Immunochemical characterization of mature and immature glomerular basement membrane. 20 kidneys from premature infants (27th to 38th weeks of gestation), 5 kidneys of mature newborns and 5 kidneys of children between 5 and 15 years of age were obtained at necropsy and glomerular basement membranes (GBM) isolated. The isolated GBMs were degraded by papain and the degradation products were characterized by immunoelectrophoresis applying an antihuman GBM antiserum from the rabbit. GBMs of children between 5 and 15 years showed in each case 3 precipitation lines distributed from the alpha-gamma-zone. The examined newborns and 17 premature infants presented two precipitation lines only, moving with alpha 1-mobility and beta-gamma-inter-region. 3 premature infants showed a pattern with 2--4 different precipitation lines of different mobility, maybe interpretable as a result of bacterial digestion. On the grounds of these findings we postulate that the GBM is, from an immunochemical point of view, immature at birth and in the late fetal life becoming mature in the child with about 5.


Assessment of ventilation-perfusion inequality by aADN2 in newborn infants. The contribution (Qo/Qt) of gas-filled air spaces with reduced ventilation-perfusion ratio (VA/Qc) to the production of total venous admixture in nondistressed premature infant and newborn infants with transient tachypnea was assessed by the aADN2 and AaDo2. The mean value for Qo/Qt in both nondistressed prematures and infants with transient tachypnea was 0.08. In both groups this represented about 30% of total venous admixutre.


Effects of low-dose prenatal corticosteroid administration on the premature rat. Administration of dexamethasone (0.2 mg/kg/day) to the pregnant rat on days 19 and 20 of gestation has been found to have marked effects on the body and organ weight of fetuses delivered 1 day prematurely on day 21 of gestation. Longer-term dexamethasone treatment earlier in gestation (days 14-18) had even more pronounced effects on body and organ weights in rat fetuses delivered three days prematurely. Dexamethasone treatment for 2 days prior to delivery had no effect on the survival of 1-, 2- and 3-day premature rats. The marked inhibitory effect on organ and body weight observed in the premature rats resulted from prenatal steroid therapy approximating that used in human pregnancies (dexamethasone 0.2 mg/kg/day for 48 h prior to premature delivery).


Human fetal respiratory movements: a technique for noninvasive monitoring with the use of a tocodynamometer. A tocodynamometer applied to the maternal abdomen is used for monitoring human fetal respiratory movements (FRM). This provides a recording of fetal chest wall movements from which observations and measurements relating to fetal respiratory physiology may be made. The FRM must be differentiated from materanal vascular and respiratory movements, as well as fetal movements and cardiac pulsations. The technique lends itself to extended periods of observation, since it does not transmit energy to the fetus as in other techniques. The simplicity of the technique, combined with the use of monitoring devices already available in most hospitals, warrants further observation of this method of respiratory movement monitoring in the developing fetus.


Neonatal changes in the plasma levels of cortisol, cortisone and aldosterone in the calf. Plasma levels of cortisol, cortisone and aldosterone were measured during the first 20 days of life in 10 healthy calves. Cortisolemia, high at birth, decreased from birth to day 15. Changes in plasma cortisone were similar to those of cortisol. The value of the cortisol/cortisone plasma ratio increased from birth to day 8 and remained steady until day 20. A positive correlation was found between plasma levels of cortisol and cortisone, during the 6- to 20-day period; no correlation was observed before that. These results raise the question of whether, as is assumed in the human, maternal cortisol would cross the placenta with conversion to cortisone in the bovine. Plasma aldosterone increased from day 1 to day 3, and decreased steadily until day 20 when its level was very low. Negative correlation found between the values of aldosterone and sodium led us to think that natremia regulation by this hormone could be functional in the neonatal calf.


Effect of development on the gangliosides of rabbit brain. The effect of growth and development on the DNA and ganglioside-NANA of the rabbit forebrain, cerebellum and brainstem was studied. Animals were killed at 1 day of age and at intervals up to 180 days. The growth rate of each part of the brain fell during the first 30 days, but showed a spurt at about 40 days. The absolute amount of DNA reached its mature value by about 40 days. In the forebrain, the deposition of ganglioside-NANA rose sharply to a peak value at 50 days, falling to 120 days and rising again to 180 days, whereas in the cerebellum and brainstem the amount rose almost steadily to a mature value at 90 and 120 days, respectively. In the forebrain, the proportion of GD1a and GM1 showed a reciprocal rise and fall, respectively, during the first 10 days after birth, subsequently falling and rising to near mature values by 50 days. GD1a was the major ganglioside in the mature forebrain, whereas GT1 and GD1b were the major gangliosides in the mature cerebellum and in the mature brainstem, respectively.


Plasma thyroid hormones and cholesterol in the newborn of genetically different types of cattle in a tropical environment. The patterns of plasma concentrations of thyroxine (T4), triiodothyronine (T3) and cholesterol were determined in tropically adapted (ZX) and temperate (SH) breeds of cattle in the first 6 days of their lives in a tropical environment. T4 concentrations were high at birth and fell to within normal adult values at 6 days of age. In contrast, plasma cholesterol levels were low at birth and increased daily to the highest values on day 6. T3 levels increased from birth to maximum values at 12 h after birth and then declined progressively. The T4/T3 molar ratios were high at birth and decreased to lower values on day 2. T4 and cholesterol levels were  higher (p less than 0.001) in ZX than in SH calves, and in calves born in winter were higher (p less than 0.001) in females than in males. There were significant (p less than 0.001) animals within-breed differences in all parameters. The results are discussed with reference to the use of physiological and biochemical indices for the early selection of cattle suited to tropical conditions.


Malonyldialdehyde formation, oxygen consumption, fatty acid composition in newborn platelets stimulated by thrombin. The release reaction, the formation of malonyldialdehyde (MDA), the pattern of oxygen consumption, and the variation in fatty acid composition after addition of thrombin (1.67 U/ml) have been investigated in newborn platelets, comparing the obtained data with analogous values showed by adult platelets assumed as normal controls. Newborn platelets showed a release reaction 20% lower than that of controls. MDA formation, even in the presence of NEM and the burst in oxygen consumption, resulted to be similar in newborn and adult platelets (p greater than 0.3); the burst was also similar after the addition of thrombin (10 U/ml) in the presence of antimycin and aspirin. The ratio between formed MDA and oxygen consumption was 1:10 in adult platelets while it was 1:15 in those of newborns. The study of fatty acid composition demonstrated that in newborn platelets at rest, arachidonic acid is significantly in a higher concentration than in controls and that it decreases after stimulation with thrombin. It is concluded that the pathway of prostaglandins is normally stimulated by thrombin in newborn platelets.


Organic acids in urine from preterm infants. The organic acid excretion was studied in urine samples from 26 preterm infants on the 1st and 5th days of life and the results compared to those obtained in 5 samples from full-term neonates. Gas-chromatography-mass spectrometry with a computer system was the method used in this work. The acids tabulated were those more closely related to lactic acidosis and the Krebs cycle. Great variations were found in the excretion of these acids in preterm infants in contrast to the very homogeneous pattern obtained in full-term neonates.


Integrated cardiovascular responses to combined somatic and visceral afferent stimulation in newborn piglets. Mean aortic pressure, arterial flow and heart rate response to interactions of afferent stimulation of the sciatic nerve (SNS) and carotid sinus stimulation by infusion (CSI) or inhibition by bilateral common carotid occlusion (BCCO) were studied in 25 newborn piglets under halothane-N2O anesthesia. Combined stimulation of the somatic and visceral afferents produced no heart rate changes. Combinations of pressor stimuli (BCCO and high frequency SNS) showed facilitation; femoral and renal resistances increased. However, combinations of depressor stimuli (CSI and low frequency SNS) showed occlusion. In combinations of pressor with depressor stimuli, the pressor pattern of responses dominated. Thus, dissimilar types of excitatory afferent inputs are capable of evoking facilitation in the neonatal cardiovascular regulatory system.


Light- and electron-microscopic studies on the gastric parietal cells in perinatal rats. Effects of fetal and neonatal oral administration of milk. Perinatal changes of the gastric parietal cells were studied under normal and various experimental conditions. Histologic examination revealed that the parietal cells appeared markedly increased in number from late fetal to early neonatal days. When premature newborn rats were delivered by cesarean section and were nursed by foster mothers for 1 or 2 days, the degree of increase of these cells reached nearly that in the normal neonates. On the other hand, in fetuses retained in utero 1 day beyond the normal gestation, these cells appeared not increased in number. When these postmature fetuses were delivered, the parietal cells turned to increase in number in a degree similar to that in the normal neonates. Milk given to the premature newborn rats caused 6 h later a marked increase in the number of the parietal cells. Milk given to fetuses in utero also caused an increase of these cells. The results suggest that the development of the parietal cells in perinatal rats is accelerated by the intake of milk and that the fetal parietal cells are ready to respond to milk given at least 1 day before birth.


Developmental pattern of pulmonary lipoprotein lipase in growing rats. The developmental pattern of pulmonary lipoprotein lipase (LPL) activity was measured in growing male and female rats from the neonatal period to the adult age. The pulmonary phospholipid content showed a sharp increase at term from premature low level. At the same time the LPL activity increased markedly showing thereafter a decrease at 1 week of age and increasing thereafter to the adult age. Also the phospholipid content was low at 1 week of age. Thus the pulmonary phospholipid content and LPL activity change in the same way during the development indicating possibly that the LPL by supplying free fatty acids for the phospholipid biosynthesis may be one of the rate-limiting enzymes in the pulmonary surfactant synthesis.


Pulmonary aeration after unilateral fetal ligation of pulmonary artery in neonatal rabbits. When the pulmonary artery was ligated at the gestational age of 30 days, 9 out of the 17 rabbit fetuses had vital lungs and in 7 of these the lungs were aerated after breathing for 15 min to 1 h. Ligation before this gestational age caused necrotic lungs in all 13 rabbit fetuses. On the basis of this we can conclude that the bronchial circulation is not sufficient to ensure vitality of the fetal lung and the pulmonary circulation does not play a major role in the primary aeration of the lungs at birth.


Balance of net base in the rat. V. Effects of oral ammonium chloride loading. The physiology of oral ammonium chloride loading was studied in four groups of male weanling rats weighing about 100 g and fed either standard ground Rostock rat food (containing 317 mmol net base/kg) or ground barley (containing only 20 mmol net base/kg). One group of animals on the Rostock diet received oral supplements of ammonium chloride (approximately 32 mmol . kg-1 . day-1) sufficient to provide a net zero rate of oral net base intake. In this group, ongoing fecal net base excretion caused net acid to be absorbed at an average rate of 15 mmol . kg-1 . day-1. The mean rate of renal net acid excretion rose markedly (by 29.4 mmol . kg-1 . day-1); and over an 8-day balance period the animals were able to maintain near-normal balances of net base. During a subsequent 8-day recovery the pattern of mineral turnover returned to normal. Even in the barley-fed rats, gastrointestinal net acid absorption was observed. These animals suffered a 61% reduction in the rate of body growth, but the overall rate of net base retention, per kilogram of mass gain, was close to the reference value. Finally, the combination of barley and ammonium chloride led to weight loss, positive net acid balances (8.5 mmol . kg-1 . day-1), and a maximal rate of renal net acid excretion (50.8 mmol . kg-1 . day-1). Some implications for the metabolism of organic acids are discussed.


Effect of nicotine on the development of fetal and suckling rats. Nicotine, administered at a dose of 100 micrograms/kg/day from day 14 of gestation, did not affect maternal food intake, weight gain, length of gestation, litter size or fetal development; however, a daily dose of 1 mg/kg led to smaller litter size and higher incidence of stillbirth. Continued maternal administration of nicotine (100 micrograms/kg/day) until 12 days post partum did not affect newborn growth (body weight and length and size of heart and lung) during the first week after birth; during the second week, however, the nicotine-treated group lagged behind the controls. The stomachs of pups of nicotine-treated rats contained less food than those of controls; this difference increased with age, becoming more than 40% at 12 days. We suggest that lower milk production of nicotine-treated rats interferes with the normal development of the offspring during periods of rapid growth.


The effect of tricyclic antidepressants on cerebral fluid dynamics. Tricyclic antidepressants are thought to act primarily via effects on adrenergic neurotransmitters. Recent research supports the concept that a major function of the central adrenergic system is the modulation of cerebral fluid dynamics. Based on this concept, studies in the rat were conducted to assess the effects of these drugs on cerebral capillary permeability and flow by quantitating changes in the extraction fraction of water (Ew). Amitriptyline and nortriptyline produced significant increased in Ew for the total forebrain (from control values of 0.67 to experimental values as high as 0.99) while protriptyline had no effect on Ew. The amitriptyline-induced increase in Ew occurred at doses which produced plasma levels (500 ng/ml) near the range defined as therapeutic in depression studies. The magnitude of the effect was similar for both amitriptyline and nortriptyline representing a 35--40% increase over control values. The effects were uniformly observed throughout the forebrain: rostral telencephalon, caudal telencephalon, and diencephalon.


Calcium: bivalent cation in the bivalent psychoses. Decreases in cerebrospinal fluid (CSF) calcium accompany mood elevation and motor activation in depressed patients undergoing treatment with ECT, lithium, and total sleep deprivation. Similarly, decreases in CSF calcium occur during acute psychotic agitation or mania. On the other hand, periodic recurrences of such agitated states are accompanied at their onset by transient increases in serum calcium and phosphorus. Several observations suggest that such serum ion shifts may trigger the more enduring and opposite shifts in CSF calcium and, in turn, the manic behavior. Progressive restriction of dietary calcium was earlier reported to mitigate and finally abolish both rhythmic rises in serum calcium and periodic agitated episodes in one psychotic patient. Lithium, which decreases the efficiency of alimentary calcium absorption, may function similarly. Conversely, a modest oral calcium lactate supplement (approximately one additional Recommended Daily Allowance of dietary calcium) seemed to slightly intensify agitation in six patients. Dihydrotachysterol (DHT), an analogue of vitamin D, which more exactly mimics the increase in both serum calcium and phosphorus, appeared in at least one periodically psychotic patient to trigger and opposite shift in CSF calcium. Moreover, in eight patients, manic symptomatology appeared de novo or grew significantly and substantially worse during 2 to 6 weeks of oral DHT administration. On the other hand, in 12 patients, subcutaneous injections of synthetic salmon calcitonin (SCT) decreased serum calcium and phosphorus, increased CSF calcium, and decreased agitation while augmenting depressive symptomatology. SCT also decreased quantified motor activity, frequency and severity of periodic agitated episodes, serum CPK and prolactin, and nocturnal sleep, while DHT or calcium lactate had opposite effects on the same parameters.


Dopamine-beta-hydroxylase in the cerebrospinal fluid: relationship to disulfiram-induced psychosis. Cerebrospinal fluid (CSF) dopamine-beta-hydroxylase (DBH) activity in 32 male alcoholics was measured using a modification of the radioenzymatic method of Molinoff et al. In most, the CSF was obtained before treatment with disulfiram, while in others it was obtained while they were on the drug (250 or 500 mg). As expected, treatment with this reversible DBH inhibitor had no effect on the activity of the enzyme measured in our in vitro assay. However, low pretreatment DBH activity was found to correlate with adverse reactions to disulfiram. Mean DBH activity of four individuals who went on to become psychotic on disulfiram was 0.13 +/- 0.02 nmole/ml per hr (mean +/- SEM). An additional four individuals who developed dysphoric but nonpsychotic reactions had a mean DBH of 0.23 +/- 0.03. Both these values were significantly lower than the mean DBH activity of the remaining 24 individuals treated with disulfiram who had no adverse side effects, 0.53 +/- 0.06 p less than 0.02 and p less than 0.05, respectively, 2-tailed t-test.


d-Amphetamine: effects on memory in a depressed population. The effect of intravenous d-amphetamine on memory functions in a group of depressed patients was examined in a double-blind placebo-controlled study. Active drug administration resulted in an increase in verbal free recall but no change in cued recall, suggesting specific effects on memory processes. The level of psychological processing of the presented stimulus was shown to interact with drug-induced facilitation of recall. Improvement in memory of more shallowly processed material under amphetamine related significantly to subjects' base-line indices of noradrenergic function. Drug-induced changes in mood did not correlate with improvement in cognitive functioning. The interrelationships between biochemical determinants of mood and memory are discussed in light of these findings.


Somatosensory and auditory evoked potential studies of functional differences between the cerebral hemispheres in psychosis. Evidence of lateralized hemispheric dysfunction in schizophrenia was previously found with a measure of visual evoked potential (VEP) wave-shape stability. The purpose of this study was to determine whether the VEP findings would extend to the auditory and somatosensory modalities. Measures of wave-shape stability were computed for auditory (AEP) and somatosensory (SEP) evoked potentials, recorded from one EOG and 14 scalp leads. Subjects were 74 unmedicated patients (49 schizophrenics, 25 nonpsychotics) and 27 nonpatients; two sets of age- and sex-matched comparison groups were formed. Main findings were: (i) Overtly psychotic schizophrenics exhibited lower than normal stability in left hemisphere AEPs (15-100 msec poststimulus). (ii) Both overtly psychotic and latent schizophrenics showed lower than normal wave-form stability, bilaterally, in the later epoch of AEPs (101-450 msec poststimulus). (iii) A subgroup of overt schizophrenics (other than chronic paranoid or chronic undifferentiated) had lower than normal stability in SEPs (15-100 msec) evoked by right median nerve stimuli and recorded from the right (ipsilateral) hemisphere. It was concluded that only the AEP results augment the previous VEP evidence indicating left hemisphere involvement in schizophrenic dysfunction.


Psychological characteristics corresponding to low versus high platelet monoamine oxidase activity. From an original sample of 375 college students and employees studied for platelet MAO activity, 66 subjects representing the lower and upper deciles of the sample were contacted for further study, including administration of the booklet form of the MMPI. We analyzed what psychological characteristics might be associated with differences in MAO activity and attempted to cross-validate these characteristics by using them to predict the separability of low vs. high MAO subjects. Each subject was randomly assigned to one of two groups in which the low and high MAO subjects were balanced for sex. For 16 women in group A, a MAO scale discriminated low and high subjects with 100% accuracy. For 18 men in group A, a separate MAO scale discriminated with 94% accuracy. To cross-validate these results, the two scales were applied to another population; both discriminated low and high MAO women and men with a combined 97% accuracy. The thematic content of the two scales is discussed in the light of other reports on the psychological characteristics of low and high MAO subjects, including the apparent relationship between the scale content and the clinical features of bipolar affective disorder.


Familial biochemical and clinical correlates of alcoholics with low platelet monoamine oxidase activity. This study substantiates previous reports that low platelet MAO activity is associated with alcoholism. The results also indicate that low platelet MAO activity in alcoholic probands is associated with a higher prevalence of psychiatric hospitalization in first-degree family members as well as alcoholism and suicide attempts among alcoholics. Psychiatrically ill family members of the alcoholic probands with low platelet MAO activity also demonstrate low enzyme activity whereas the well family members have normal enzyme activity.


The mimicking of mania in "benign" herpes simplex encephalitis. This paper reports on a relative rarity, the case of a 41-year-old male who, after receiving an original admission diagnosis of clear-cut acute mania, actually turned out to be suffering from herpes simplex encephalitis. Interestingly enough, his illness was unusually "benign" in the sense that at no time during massive cycling bipolar mood disturbances did any clinically apparent neurological signs and symptoms or other serious somatic complications or any psychopathology pointing to an acute organic brain syndrome appear. Karl Bonhoeffer's often forgotten but still relevant clinical insights on acute organic psychoses are then discussed in the light of recent research attempting to link manic states and infectious illness.


Succinylcholine drug interactions during electroconvulsive therapy. Electroconvulsive therapy (ECT) is frequently described as being almost free of absolute contraindications. However, drug interactions with succinylcholine pose potential hazards to which this paper calls attention. In addition to its neuromuscular-blocking action, succinylcholine has other acetylcholine-like effects. Drugs which inhibit cholinesterase activity or which inhibit acetylcholine release or synthesis may produce prolonged respiratory paralysis when combined with succinylcholine. The increasing longevity of the population receiving chemotherapy for physical ailments implies that greater numbers of these patients may also become candidates for ECT and therefore be at risk for adverse drug interactions with succinylcholine. Of particular importance to the psychiatrist are the various psychotropic drugs that have been reported to interact with succinylcholine. Precautions in using drug combinations and treatment of complications are described.


The psychological effects of dopamine-beta-hydroxylase inhibition in normal subjects. Acute administration of the dopamine-beta-hydroxylase (DBH) inhibitor, fusaric acid, combined with L-dopa, 500 mg, produced discernible psychological abnormalities in normal subjects. These were not found after L-dopa alone, or after placebo. The changes, lasting a few hours, were manifested by significant increases in "total psychopathology," and in a number of subscales on the Brief Psychiatric Rating Scale. Changes were also found in mood ratings on adjective checklists, and inkblot tests. A variety of effects were found on psychiatric interview. Since DBH does not occur in dopamine neurons, it is likely that the psychological effects were due to changes in dopamine or norepinephrine in norepinephrine neurons.


3-Methoxy-4-hydroxyphenylglycol and primary depression: clinical and pharmacological considerations. Pretherapeutic urinary excretion of 3-methoxy-4-hydroxyphenylglycol (MHPG) was studied in 25 primary depressed patients. The results indicate that: (i) There exists a wide variability among primary depressives with respect to MHPG excretion. (ii) Age of onset together with polarity of the disease may account for the nonhomogeneous division of the patients according to MHPG levels. (iii). The other variables considered, with the possible exception of motor activity, do not explain the dichotomy between high or normal and low MHPG levels, even though it is possible that they influence MHPG excretion to some extent, with the consequent possibility of errors in subclassification of the patients at the boundaries between the two groups. (iv) The correlation between motor retardation and low MHPG excretion is positive, but probably due to a frequent association between this motricity state and primary depression of bipolar early onset type. (v) Treatments with chlorimipramine and, to a lesser degree of specificity, with amitriptyline are particularly indicated in patients with normal or high MHPG. Some practical and theoretical implications deriving from these data are briefly discussed.


Epileptic phenomena induced in the cat by the antidepressants maprotiline, imipramine, clomipramine, and amitriptyline. The epileptogenic properties of four tricyclic antidepressant drugs: maprotiline, imipramine, clomipramine, amitriptyline, were investigated in locally anesthetized cats immobilized with gallamine and supplied with neocortical, hippocampal, and reticular recording electrodes. The drugs were infused intravenously at a constant rate (0.5 or, in some cases, 0.25 mg/kg per min) up to a final dose of 45 mg/kg. Already in small doses (1 to 5 mg/kg) all four antidepressants produced local signs of epileptiform pathology. Generalized sustained discharges occurred, on the average, at between 20 and 25 mg/kg with all four drugs. Imipramine and amitriptyline, after the first or first few generalized discharges, led to a pattern of repeated short generalized seizures alternating with silent periods. Maprotiline invariably produced this later alternating pattern only after a 10- to 30-min period of a seminormal high amplitude pattern. Clomipramine assumed a position between maprotiline on the one hand and imipramine and amitriptyline on the other. Starting at doses of 2-4 mg/kg, imipramine, clomipramine and amitriptyline, all three being norepinephrine and serotonin uptake inhibitors, induced a high amplitude "sleep" pattern. Maprotiline, a  norepinephrine uptake inhibitor, which is thought devoid of serotonin-uptake inhibiting properties, led to high amplitude slow waves only with doses of at least 12.5 to 15 mg/kg.


Material effects in shear-induced hemolysis. A rotating-disk apparatus for shearing blood was employed to compare 22 materials for their tendency to cause hemolysis during standardized low-stress (130 dynes/cm2 maximum) laminar flow conditions. Rigid plastics, hydrogels, and carbons were among the materials tested. Time-independent ranking of the materials was possible for 75% of the data; these rankings correlated linearly (for polymers) with the critical surface tension gammac over the range 20--46 dyne/cm, with low gammac being associated with low hemolysis. Surface morphology was also found to influence hemolysis. Roughness in the 1--15 micron range had a distinct effect on hemolysis kinetics for polyethylene surfaces. This suggest that failure to find time-independence in 25% of the material rankings can be attributed to inadequate control of the roughness variable. It also emphasizes the importance of surface morphology, as well as surface chemistry, as a biocompatibility parameter.


Observations on shear-induced hemolysis. New data are reported on chemical and mechanical factors affecting the hemolysis of blood in a rotating-parallel-disk apparatus used in biomaterials studies described elsewhere. The hemolytic potential for a blood is found to correlate with plasma components LDH and total triglycerides existing prior to shear. Antibiotics are shown to suppress hemolysis, unrelated to bacterial action. The kinetics of measured hemoglobin release are analyzed in terms of a red cell population having a distribution of fragilities, sample storage age, and possible hemoglobin adsorption. Blood/gas interfacial effects are examined by varying the gas and the extent of interface, and found to be minimal under normal testing conditions. Several geometric and dynamic parameters are varied to illustrate the complexities of engineering design and scale-up.


Characterization of homogeneous and pseudocomposite homopolymers and copolymers for articular cartilage replacement. Semicrystalline swollen polymeric networks are prime candidates for biomedical applications. Purity, controlled structure, easy preparation, non-biodegradability and improved mechanical properties are some of their most important characteristics. New articular cartilage simulants in the form of hydrogels with surface hydroxyl groups have been developed and characterized. The mechanical properties and physical behavior of these materials are described by high elastic moduli, ultimate tensile strength and elongation at break, low tear propagation resistance and excellent friction properties. Crystallinities vary between 15% and 35% and the crystallites are stable within the range of practical applications. The hydrogels show no permeability to hyaluronic acid and can be grafted with cationic monomers or polymers to form boundary lubricant layers. Techniques have also been developed for the preparation of deformable pseudocomposites consisting of layers of swollen semicrystalline and amorphous polymer.


Comparative studies of hemoperfusion devices. II. Pressure drop and flow uniformity tests. One resin-based hemoperfusion device and three charcoal-based hemoperfusion devices were tested to determine their pressure drop and flow uniformity characteristics. Measurements were made on pressure drop versus flow rate using distilled water and on pressure drop versus time using bovine blood. Effluent concentration curves obtained after the step-change introduction of a high molecular weight dye solution to each unit were used to determine the priming volumes of the devices and were interpreted to yield information regarding the uniformities of flow in each device. The pressure drop and priming volume values for the resin-based device were significantly higher than the corresponding values for the charcoal-based units.


Calculation of blood velocity and pressure in stenosed renal artery considered as a Venturi tube. The authors propose using a Venturi tube as a model of stenosed renal artery; they can thus calculate blood velocity and pressure in the stenosed part from estimated renal flow, systemic pressure and the hydraulic characteristics of the model.


Migraine. A platelet hypothesis.

Migraine. A platelet hypothesis. This paper presents evidence for my hypothesis that the diverse features of a migraine attack, both during the prodromal and the headache phases, become explicable if migraine is caused by a primary abnormality of platelet behaviour. This hypothesis places migraine among the most common disorders of the blood.


Further investigations about actinomycin D action on mouse erythropoietin responsive cell. Repeated injections of 100 micrograms/kg/day of Actinomycin D entirely eradicated erythropoiesis in normal mice. The study of the effect of graded Actinomycin D doses on the erythropoiesis displayed a reproducible dose-effect relationship. The same relation appeared in the action of various Actinomycin D doses on the response to erythropoietin in hypertransfused-mice. To decide whether Actinomycin D had destructive or inhibitory action on its target cell, myleran was used. A single injection of myleran reduced the pluripotent haematopoietic stem cell (CFU) and the erythropoietin responsive cell (ERC) in polycythemic mice to around 1% that of the controls. When repeated injections of erythropoietin restored a transitory ERC population in the absence of CFU, Actinomycin D to the doses of 90 and 120 micrograms/kg-mouse/day did not prevent the erythropoietin effect on self replication of ERC. This result directly showed that Actinomycin D acted on the ERC by selective inhibition of their differentiation without cytotoxic effect.


Inborn hypouricemia due to isolated renal tubular defect. Inborn hypouricemia due to isolated renal tubular defect is a rare disorder. Thus far eight documented families with this condition have been reported. In reviewing the data on these families, hyperuricosuria was found to be a constant associate of the hypouricemia, and hypercalciuria, mainly of the absorptive type, was frequently associated. Urolithiasis appears to be common. The mode of inheritance of this hypouricemia was autosomal, probably recessive. The magnitude of renal urate clearance and the effects on it of probenecid and pyrazinamide suggest the inborn renal hypouricemia to be of two types, due to defective re-secretory tubular urate reabsorption and to total defective tubular urate reabsorption. The question of the renal tubular abnormality for urate transport being the primary defect or secondary to an abnormal metabolite is discussed.


Immuno-heterogeneity of the calcitonins of hypercalcemia, breast and lung cancers and medullary carcinoma of thyroid. Four antisera raised in the goat have very different properties: all recognized the immunoreactive calcitonin (iCT) of medullary carcinoma of the thyroid (MCT), one the response of normal subjects to induced or endogenous hypercalcemia and 2 others a different molecular species which occurs in half the patients with cancer of breast and 3/4 of patients with cancer of the lung. The latter two antisera are most sensitive to the 22-32 sequence of human calcitonin. Depending on the antiserum used, 4 or 7 peaks of immunoreactivity are found in eluates by column chromatography or stimulated serum from MCT. Not all elevated levels of iCT in serum are diagnostic of MCT and ectopic production by lung and breast cancer must be considered. Presence of higher levels of iCT with greater amounts of cancer tissue and undetectable levels after surgery or radiotherapy when using antisera which require intact molecule of calcitonin for recognition suggest the possibility that sequential calcitonin levels with differentiating antisera may be helpful in assessing the extent of disease and response to therapy.


BCG immunotherapy in previously treated malignant melanoma patients. Eighteen patients with histologically confirmed metastatic malignant melanoma were treated with intradermal BCG. Before starting immunotherapy their immunocompetence was tested in vivo and in vitro. Four of 15 (27%) achieved complete regression, and two (13%) a regression of more than 50%, after systemic BCG. All three patients treated with perinodular injection of BCG had complete regression of treated as well as some of untreated nodules. Treatment was unsuccessful in 9 patients. Five of them (33%) had a disease stabilisation for more than 5 months. The results of BCG immunotherapy were compared with those of chemotherapy alone. The immunotherapy patients had longer remissions and survived longer than those treated by chemotherapy. All patients had repeat skin tests with PPD after BCG but showed no significant improvement in tuberculin reactivity. Despite, their clinical condition often being improved after BCG. We conclude that BCG may be of considerable benefit to malignant melanoma patients.


Pregnancy-associated alpha 2-glycoprotein (alpha 2-PAG) and various acute phase reactants in rheumatoid arthritis and osteoarthritis. Pregnancy-associated alpha 2-glycoprotein (alpha 2-PAG) concentrations have been measured in matched sera and synovial fluid samples obtained from 36 patients with rheumatoid arthritis and 10 patients with osteoarthritis. Levels of alpha 2-PAG in serum and synovial fluid were significantly higher in rheumatoid arthritis than in osteoarthritis. Calculation of the synovial fluid/serum ratios for alpha 2-PAG gave results which are explicable only if this protein were being synthesised locally. In a longitudinal study of 15 patients with rheumatoid arthritis, concentrations of alpha 2-PAG did not reflect disease activity, unlike those of the classical acute phase reactants, C-reactive protein and caeruloplasmin.


Decreased calcium content in patients with digoxin intoxication. The platelet calcium content, the plasma calcium level and the serum digoxin were examined in 90 individuals divided into the following four groups : I -- patients with digoxin intoxication; II -- treated with digoxin; III -- treated with digoxin and furosemide, and IV -- control subjects. The patients with digoxin intoxication showed a lower platelet calcium content as compared to subjects of the other groups (p less than 0.001), whereas the serum digoxin level was significantly higher than in the patients of groups II and III (p less than 0.001). Since the examination of the platelet calcium level is a relatively simple and rapid procedure, with reliable results, its use as a routine method in the determination of digoxin intoxication is suggested.


Electrophoretic mobility of Sézary syndrome lymphoid cells. The variations in electrophoretic mobilities found in different lymphocyte populations present in circulating blood of three patients with Sézary syndrome have been studied. Evidence is given for variations in electrophoretic mobilities being a function of the cytological type of the pathological cells found. The existence of a significant increase of "null" cells is shown, which seem to correspond to Sézary cells.


The suicide technique in vitro for granulocytic progenitor cells (CFC) by application of hydroxyurea (HU) to low concentrations of human bone marrow cells. A suicide technique applicable to human bone marrow granulocytic progenitor cells has been previously described (3). This study discusses the conditions for its use on bone marrow aspirates poor in cells. When the number of cells exposed to hydroxyurea (HU) is proportional to the quantity of HU it is possible to avoid artifacts due to HU toxicity. This technique can repeatedly reproduce a 40--50% suicide. To obtain this result we suggest using a 6.10(-6) mM/ml/cell HU concentration.


On the mechanism of the tetrahydropteridine cofactor oxidation in aerobic and H2O2-peroxydase media. It is commonly postulated that the enzymatic hydroxylation of phenylalanine, tyrosine and tryptophan involves the concomitant oxidation of a tetrahydropteridinic cofactor to an unstable quinonoid product, converted to the initial compound under the catalytic action of dihydropteridine reductase. We now report UV, NMR, mass spectrum and spectroscopic studies of 2-amino-4-hydroxy-6,7-dimethyl-5, 6, 7, 8-tetrahydropteridine oxidation process either by atmospheric O2 or by the H2O2-peroxidase system. No quinonoid form was visualized and, moreover, the spectral characteristics of UV absorbance spectra, initially reported as specific for the quinonoid form, are related to other oxidation products whose formation is explained here.


Inhibition of murine bone marrow colonies growth by adenosine containing nucleotides. The effect of various compounds: NAD+, NADP+, Adenosine Diphospho-Ribose, Nicotinamide, Ribose 5 Phosphate, Adenosine, cAMP, cGMP, on the growth of granulocytic and erythroid mouse bone marrow colonies (CFUc and CFUE) was evaluated. The substances were either added directly to the semi-solid culture system, to obtain a continuous exposure during colony growth, or preincubated for various times with bone marrow cells before plating. The results indicate an inhibitory effect on the number of both colonies of several adenosine containing compounds. The effect is concentration dependent and irreversible. CFUE and CFUC show different sensitivity to the inhibition.


Kidney 15-hydroxy-prostaglandin-dehydrogenase activity during the development of experimental hypertension in the rat. 15-hydroxy-prostaglandin-dehydrogenase (PGDH) activity was studied in rat kidney homogenates during the development of hypertension, within 20 days after left renal artery constriction by a solid silver clip. In the ischemic kidney PGDH activity increased at day 6, reached maximum at day 10, then progressively at day 15 and returned to normal levels at day 20. No difference was found between contralateral kidneys and kidneys of normotensive control rats. Variations of PGDH activity did not seem to be related to either renal perfusion pressure or renin production. Increased PGDH activity may be a consequence of an enzyme induction following increased PG-synthetase activity, or it could be viewed as a defence mechanism, according to the hypothesis of a prohypertensive effect of PG in the rat.


Adverse effects of interferon treatment on the life span of NZB mice. NZB mice treated with interferon from birth and for over a year, display early some characteristics of the autoimmune disease. In these animals, mortality is clearly higher than in controls. Their death occurs 3 to 6 months before that of mice injected with a "mock" preparation.


Determination of free glycerol on human skin surface. In water soluble substances obtained by water extraction from human skin surface, free glycerol was detected by gas chromatography mass spectrometry. A selected ion monitoring method was employed to measure low concentration of free glycerol and the mean amounts were found to be about 0.7 microgram cm-2 on the cheek and 0.2 microgram cm-2 on the forearm and sole.


Comparison of radioimmunoassay and gas chromatographic mass spectrometric assay for d-amphetamine. Quantification of low levels of psychotropic drugs (10(-7) to 10(-9) g ml-1) in small volumes of plasma requires sensitive and accurate methods. Validation of these methods is best achieved by comparing results obtained using several techniques. In this study, amphetamine levels in plasma were measured using gas chromatography mass spectrometry and radioimmunoassay. Correlation of the results obtained by the two methods was found to be positive and high (R = 0.9822). The average coefficient of variation between assays for gas chromatography mass spectrometry was 5.8% and for radioimmunoassay was 12.3%, while the average coefficient of variation within assays for gas chromatography mass spectrometry was 4.9% and for radioimmunoassay 6.9%. Although gas chromatography mass spectrometry was 1.9 times more sensitive than radioimmunoassay, for most purposes, the convenience of the radioimmunoassay method outweights the technical superiority of gas chromatography mass spectrometry.


A sensitive method for the simultaneous determination in biological fluids of imipramine and desipramine or clomipramine and N-desmethylclomipramine by gas chromatography mass spectrometry. A procedure is described which permits the simultaneous determination of imipramine and desipramine or clomipramine and N-desmethylclomipramine in serum or plasma for concentrations in the range of 1-200 ng ml-1. Detection limits of 0.2 ng ml-1 for imipramine and 0.1 ng ml-1 for desipramine were demonstrated with a signal-to-noise ratio maintained at 2:1 or better. The method relies on the derivatization of the secondary amines with heptafluorobutyric anhydride and is based on the combined use of gas chromatography, electron impact mass spectrometry and computerized data handling. The assaying procedure is specific, accurate and precise. It is suitable for routine analyses and has sufficient sensitivity to permit monitoring the drug and metabolite levels in human plasma or serum resulting from a single therapeutic dose.


Determination of uracil and thymine and their nucleosides and nucleotides in picomole amounts by gas chromatography mass spectrometry selected ion monitoring. A stable isotope dilution method is presented by which uracil (Ura) and thymine (Thy) can be determined with high precision and sensitivity at the picomole level utilizing stable isotope dilution and gas chromatography electron impact mass spectrometry in the selected ion monitoring mode. [15N2]Ura and [2H3]Thy served as internal standards. The molecular ions as well as the [M-CH3]+ ion fragments of silylated Ura and Thy (Ura-TMS and Thy-TMS) were suitable for the assay which provides evidence of specificity, if identical results are obtained at both ions. Nucleosides and nucleotides of Ura and Thy were determined following quantitative hydrolysis in 6 N HCl at 180 degrees C for two hours. Other hydrolysis procedures did not give satisfactory results. Levels of free Ura and Thy were measured in human and rat plasma after solvent extraction with a sensitivity of 20-40 pm ml-1 demonstrating ready applicability of the assay method to biological samples. The potential physiological role of circulating Ura and Thy is discussed.


Plasma quantitation of warfarin and warfarin alcohol by gas chromatography chemical ionization mass spectrometry in patients on warfarin maintenance therapy. A quantitative method has been developed to measure plasma concentrations of warfarin and warfarin alcohol. The analytical procedure uses deuterated analogues as internal standards, and the technique of selected ion monitoring following gas chromatography methane chemical ionization mass spectrometry of the 4'-methyl ethers of warfarin and warfarin alcohol. Concentrations of warfarin and warfarin alcohol have been measured in plasma samples from 43 patients maintained on chronic warfarin therapy and compared with the 'apparent warfarin' concentration as measured by a fluorometric procedure. The study demonstrated a high degree of correlation between the gas chromatography mass spectrometric derived sum of the individual concentrations of warfarin and warfarin alcohol, and the 'apparent warfarin' concentration determined from a spectrofluorometric assay.


Identification of urinary metabolites of flavanone in the rat. The urinary metabolites of flavanone in the rate were investigated using a gas chromatographic mass spectrometric method employing an OV-1 capillary column. Forty-three metabolites were detected and the most prominent of these were identified. The most common metabolic reactions were reduction of the keto group and hydroxylation at the 3- or 6-positions. Little hydroxylation occurred in ring B. The major metabolites were flavan-4 alpha-ol, trans-3-hydroxyflavan-4 beta-ol, 6-hydroxyflavanone and 6-hydroxyflavan-4 beta-ol. Gas chromatography analysis of underivatized flavanone metabolites, especially with stainless steel columns, results in the formation of dehydrated products including flavone, flav-3-ene and flavanone itself.


A comparison of calculation procedures for isotope dilution determinations using gas chromatography mass spectrometry. Several data reduction procedures have been used for converting isotope ratios, determined using gas chromatography mass spectrometry, into mole ratios for the purpose of quantitating organic compounds. In this report, these procedures are shown to be related under certain limiting approximations of original sample and internal standard isotope ratios. With the understanding that some of the procedures involve approximations, the incorporation of related systematic errors into calculated mole ratio values was investigated. The results indicate that certain data reduction procedures allow quantitation over wider mole ratio ranges and with internal standards which contain a significant quantity of unlabeled impurity.


Selected ion monitoring of glycospingolipid mixtures. Identification of several blood group type glycolipids in the small intestine of an individual rabbit. A novel application of selected ion monitoring was used for a mixture of non-acid glycosphingolipids of one rabbit small intestine. Earlier studies of permethylated and permethylated-reduced (LiAIH4) derivatives of model compounds have revealed a specificity and abundance of saccharide ions (terminal monosaccharide(s), disaccharide, trisaccharide, etc., and all sugars plus fatty acid) and of ceramide fragments that permit a conclusive detection of separate glycolipid species in a mixture. The sample (50-200 micrograms) was evaporated slowly (1-5 degrees C min-1 from 150-350 degrees C) from the direct inlet probe of an MS 902 mass spectrometer (electron ionization). Mass spectra with fragments up to about m/z 200 were collected on-line by a computer system. A successive partial separation was obtained for glycolipids with from one up to seven sugars. The structures of eight different compounds were identified. They all had 16:0, 22:0 and 24:0 2-hydroxy fatty acids and 18:0 trihydroxy base (phytosphingosine) as major ceramide components. The dominating complex glycolipid was a hexaglycosylceramide with a blood group B type of sequence. A blood group A type sequence was found in a second hexaglycosylceramide. In support of this, the native mixture showed blood group A and B activity. An intense peak, m/z 182, collected from methylated derivatives were evidence for a dominating type 2 carbohydrate chain of the core tetrasaccharide.


A quantitative selected ion monitoring assay for ketoprofen determination in human biological fluids. A new very sensitive method of ketoprofen [(benzoyl-3-phenyl) 2-propionic acid] determination in various biological fluids using selected ion monitoring is described. After ether extraction is acidic medium, ketoprofen and (benzoyl-4-phenyl)-2-butyric acid used as internal standard are methylated and their concentrations determined by monitoring the m/z values correponding to their respective molecular ions. Standard deviation is below 5% at 100 ng ml-1. Detection limits range from 10 ng ml-1 for urine and serum samples to 50 ng ml-1 for maternal milk specimens. This method has been applied successfully to various biological studies: pharmacokinetic profiles, bioavailability and transfer of the drug through physiological barriers.


Metabolites of loperamide in rats.

Metabolites of loperamide in rats. Following intraperitoneal administration to rats of [14C]loperamide, [carbonyl-14] 4-(p-chlorophenyl)-4-hydroxy-N,N-dimethyl-alpha, alpha-diphenyl-1-piperidine butyramide, metabolites in feces and urine were separated, and identified by means of mass spectrometry. In feces, six metabolites were identified in addition to the unchanged drug. The main metabolic pathways involved are dealkylation in the dimethyl amide moiety to give desmethyl- and didesmethylloperamide, both of which were in turn monohydroxylated either in the alpha-phenyl ring or possibly in the alpha-carbon in the piperidine ring. It is noteworthy that metabolites hydroxylated in the piperidine ring were isolated as pyridinium derivatives, possibly due to spontaneous aromatization of its 2,4-dihydroxy-4-(p-chlorophenyl)piperidine ring. In urine, only two metabolites were found and identified to be desmethyl- and didesmethylloperamide, since [14C]loperamide was excreted into urine only in a small amount.


The identification of bile acid methyl esters by gas chromatography methane chemical ionization mass spectrometry. Methane chemical ionization mass spectrometric data and gas chromatography retention parameters are reported for 31 bile acid methyl esters. The group includes both saturated and unsaturated compounds with up to three keto or hydroxyl groups. Major ions include the quasimolecular ions and fragments resulting from the loss of neutral species such as methanol, water and methane. The combination of gas-liquid chromatography retention and mass spectral data is sufficient for an unequivocal distinction among all the bile acids studied. Application of this data to the identification of bile acid metabolites is cited.


Alloimmunization following prophylactic granulocyte transfusion. Nineteen noninfected adults receiving initial induction chemotherapy for acute nonlymphocytic leukemia (ANLL) were randomized to receive either prophylactic granulocyte transfusion or platelet transfusion alone on an alternate-day schedule. An average of 11 granulocyte transfusions (range 3--19) were administered/patient with a mean dose of 11.5 X 10(9) granulocytes/transfusion. The groups were identical with respect to age, sex, number of days on study, granulocytopenic days, percent of days receiving systemic antibiotics, febrile days, complete remission rate, and incidence of minor infection. Significant transfusion reactions were much increased in the granulocyte transfusion group (7/10 versus 1/9 in controls) and were associated with the development of lymphocytotoxic antibodies (7/10 versus 4/9 controls), refractoriness to platelet transfusion, repeated fevers, and a pulmonary infiltrate in one patient. Alloimmunization to granulocytes occurred as early as the second week in some  patients complicating platelet support during induction and maintenance. No severe infections occurred in the granulocyte transfusion group while three fungal infections occurred in the controls. The high rate of alloimmunization suggests that histocompatibility considerations indicate that prophylactic granulocyte transfusion should not be routine therapy and should be studied only in investigational settings.


Prolonged hematopoiesis in a primate bone marrow culture system: characteristics of stem cell production and the hematopoietic microenvironment. Maintenance of myelopoiesis and pluripotential stem cell production for prolonged periods in vitro hitherto has been limited to mouse bone marrow culture. In an effort to adapt the system for use in higher species, particularly in human and non-human primates, studies were undertaken using the prosimian species, Tupaia glis (tree shrew). In a number of experiments the duration of sustained normal hematopoiesis observed in cultures of this species, following a single inoculum of 5 X 10(6)--10(7) bone marrow cells, with or without addition of fresh allogeneic bone marrow exceeded 1 yr. Analysis of suspension cells obtained by weekly demidepopulation of such cultures revealed production of CFU-C, differentiating neutrophils, and basophils at high levels. Direct comparison with murine cultures indicated that in both species a complex series of cellular interactions takes place within an adherent environment of marrow-derived endothelial cells, macrophages, and fat-containing cells. Certain functional and ultrastructural features served to distinguish murine from Tupaia marrow cultures, and the prolonged duration of in vitro hematopoiesis in the latter species could be attributed to a regenerative capacity possessed by its adherent hematopoietic microenvironment. The availability of this primate marrow culture system should facilitate studies of hematopoiesis, viral leukemogenesis, and transplantation biology, which have more direct relevance to man than that provided by the existing murine system.


Adhesion of normal and sickle erythrocytes to endothelial monolayer cultures. Experiments were carried out to test the hypothesis that the differences between the surfaces of erythrocytes from normal and sickle cell patients are reflected in the degree of attachment to the capillary lining. An assay was used that measured the number of 51Cr-labeled erythrocytes (normal or sickle) attaching to a monolayer of endothelium cultured from calf aortas. Under these conditions, erythrocytes from sickle cell patients adhered better to the endothelium than did those from normal patients. The results suggested that the enhanced adhesion of the sickle cells to the endothelium may be partially responsible for the increased blockage of capillaries that produce the symptoms in sickle cell anemia.


Serum erythropoietin concentration in chronic renal failure: relationship to degree of anemia and excretory renal function. By use of the fetal mouse liver cell assay, serum erythropoietin (SEp) concentration was measured in 135 patients at various stages of chronic renal failure and in 59 healthy subjects. In patients with creatinine clearances (CCr) ranging from 2 to 40 ml/min/1.73 sq m, endocrine renal function was found to deteriorate in parallel to excretory renal function. The known negative correlation between SEp and hematocrit (Hct) was not apparent, probably because of the loss of renal mass accompanying progress of anemia and renal insufficiency. In contrast, in patients with minimal variation of residual excretory renal function, as in individual patients investigated repeatedly within a short period of time, changes of Hct were always accompanied by opposite changes of corresponding SEp concentrations. Thus, patients with chronic renal failure have a sustained regulatory feedback mechanism between Hct and SEp, which probably works at a lower level.


Serum lactic dehydrogenase as a prognostic tool for non-Hodgkin lymphomas. Serum LDH levels have been found to be significantly increased in non-Hodgkin lymphoma (NHL) patients, both histiocytic and lymphocytic. The duration of survival of NHL negatively correlates with the level of serum lactic dehydrogenase (LDH), and statistical analysis reveals that patients with lower levels of LDH have a longer survival rate than the patients with higher LDH activity, irrespective of their histologic classification. The analysis of the results by the Test for Trend in Prognosis allows us to establish that the correlation of the rate of survival and LDH levels is independent from other clinical parameters.


Megakaryocyte colony formation from human bone marrow precursors. We report the growth in plasma clot culture of megakaryocyte colonies from adult bone marrow cells with the use of four different sources of erythropoietin (Ep) as the stimulating factor. A major proportion of the megakaryocyte colonies (75%) were pure, while the others were mixed, involving erythroblasts and megakaryocytes. Ultrastructural studies have shown that the maturation of megakaryocytes was essentially normal and that platelet shedding occurred. Megakaryocyte colony formation required a large number of plated cells (greater than 3 X 10(5)/ml). In the absence of erythropoietin, rare spontaneous megakaryocyte colonies could be observed, while no erythroid colonies were present. However, erythropoietin induced a fivefold increase in the total number of colonies. These data suggest that erythropoietin is involved in the differentiation of human megakaryocytes, but that it does not act alone, since another factor related to the number of seeded cells appears essential for the formation of human megakaryocyte colonies.


Dense (aged) circulating red cells contain normal concentrations of adenosine triphosphate (ATP). The densest 0.1%--1% of circulating red cells were separated from fresh blood, and the ATP content of a representative sample of such cells was determined. The dense ("old") cells had decreased amounts of ATP relative to unfractionated cells. However, the dense cells were also smaller, and the concentration of ATP in these cells was the same as in controls. Therefore, it seems unlikely that loss of cellular ATP is a causative factor in removal of senescent red cells from the circulation.


Erythroid colony stimulating and inhibiting cells in peripheral blood of transfused dogs: separation of function by velocity sedimentation. We have previously shown that the addition of normal dog peripheral blood lymphocytes (PBL) to cultures of allogeneic marrow increases the number of marrow-derived erythroid colonies (EC), but that PBL from transfused dogs usually inhibit EC growth from marrow of the transfusion donor. In this study, the cells in normal dog PBL responsible for stimulating EC growth were shown to sediment in a narrow peak at 4.30 mm/hr. A similar population of stimulating cells exists in transfused dogs and can be separated, on the basis of size, from cells that inhibit EC growth. EC-stimulating cells from transfused dog PBL sediment at 3.3--5.0 mm/hr, while cells responsible for inhibition are larger and sediment more rapidly at 5.4--8.1 mm/hr. These data demonstrate that cells capable of stimulating allogeneic EC are present in transfused dogs, but their stimulating ability is masked by the presence of EC-inhibiting cells. Thus, coculture experiments designed to test lymphocyte/marrow cell interactions may miss significant but opposing effects if unfractionated cells are used.


Leukocyte alkaline phosphatase in malignancies. The leukocyte alklaine phosphatase (LAP) levels were determined in 183 patients with malignant diseases and 71 normal controls. The median LAP scores were 64 units (range 0 to 290) for the patients and 55 (range 2 to 158) for the controls, respectively, and no significant difference could be established. When analyzed according to primary malignancy, only in patients with Hodgkin's disease (n = 14) was the median value higher than normal (p less than 0.001). In patients with distant metastases (n = 48), higher LAP levels were demonstrated (M = 76, range 21 to 290) as compared to patients with no evidence of metastases (M = 53, range 0 to 229), (p less than 0.01). Thus, LAP activity has very limited value in the diagnosis of malignancies. Its elevation in the presence of malignant disease might, however, indicate metastases.


Congenital dyserythropoietic anemia type I: report of a pair of siblings in Japan. This is the first case of two siblings with congenital dyserythrobpoietic anemia (CDA) type I to be reported from a Japanese family. Both of these cases showed characteristic morphological aberration of erythroid precursors, ineffective erythropoiesis, and negative acidified serum test. The ultrastructural study of erythroblasts also revealed characteristics quite compatible with CDA type I.


Erythrocyte agglomeration and survival studies in citrate-phosphate-dextrose (CPD) units. We have previously reported increased tendency to agglomeration in CPD-stored erythrocytes. In the present study we investigated the deterioration pattern of fresh units, as detected by agglomeration, free hemoglobin levels, ATP levels, osmotic fragility, and certain enzymatic activities. When the negative test was converted to a positive one, the 24-h survival values of these units were determined by autotransfusion. A positive agglomeration occurred while viability was still above 70%. Fresh units had high ATP levels and negative agglomeration while old units had low ATP levels and positive agglomeration. However, in intermediate-storage units, no definite correlation between ATP and agglomeration was found. Agglomeration seems to reflect the degree of changes in stored erythrocytes. However, further studies are needed before this test may serve for prediction of post-transfusion viability.


Human cold agglutinins against "cryptic" erythrocyte antigens. Two examples of human IgM cold agglutinins agglutinated human RBC only after enzyme treatment in vitro. Proteases were optimally effective, neuraminidase was also effective. The cold agglutinins did not coat native RBC but were directed against "cryptic" RBC determinants. The cold agglutinins belonged to the anti -I/-i complex indicating a "new" type of I/i determinants. They were strongly accessible to cold agglutinin interaction on native RBC of a patient with congenital dyserythropoietic anaemia. Enzyme treatment of RBC was shown to be not only suited for defining cold agglutinin specificities but also essential for detecting the "new" type of cold agglutinins, obviously causing autoimmune haemolytic anaemia in vivo.


A haemagglutination inhibition test kit for routine analysis of erythropoietin. A commercially available haemagglutination inhibition test kit for routine analysis of erythropoietin was shown to be unable to detect elevated levels of serum Epo.


Results-oriented management though MBO.

Results-oriented management though MBO. Management by Objectives (MBO) as it has been implemented in the Houston Academy of Medicine--Texas Medical Center Library is described. That MBO must be a total management system and not just another library program is emphasized throughout the discussion and definitions of the MBO system parts: (1) mission statement; (2) role functions; (3) role relationships; (4) effectiveness areas; (5) objective; (6) action plans; and (7) performance review and evaluation. Examples from the library's implementation are given within the discussion of each part to give the reader a clearer picture of the library's actual experiences with the MBO process. Tables are included for further clarification. In conclusion some points are made which the author feels are particularly crucial to any library MBO implementation.


A regional cooperative acquisition program for monographs. A cooperative acquisition program for monographs for the twelve resource libraries in Region IX of the Regional Medical Library Network is described. Each of the participating libraries has agreed to purchase all books of an assigned publisher which fall within a prescribed subject-format profile. It is hoped that this will help to reduce unnecessary duplication and contribute toward the development of resources in the region.


Medical school graduates' retrospective evaluation of a clinical medical librarian program. This paper reports on the results of a survey of sixty-six graduates of the University of Missouri-Kansas City (UMKC) School of Medicine conducted in the spring of 1977. The graduates were questioned about their present library use behavior and their restrospective perceptions of the clinical medical librarian (CML) services which they received as medical students at UMKC. The results show that these young physicians, after regular association with other, more tradional medical library services, hold very positive impressions of the CML program. The graduates also typically credit the CML'S with helping them to learn to use library resources effectively. These retrospective perceptions of the CML match the short-term benefits reported in other studies of similar programs.


New library buildings: the Health Sciences Library, Memorial University of Newfoundland, St. John's. The new Health Sciences Library of Memorial University of Newfoundland is described and illustrated. A library facility that forms part of a larger health sciences center, this is a medium-sized academic health sciences library built on a single level. Along with a physical description of the library and its features, the concepts of single-level libraries, phased occupancy, and the project management approach to building a large health center library are discussed in detail.


Cooperation strengthens small hospital libraries in a rural area of New England: a five-year experience. Before 1970, library facilities and services at the small hospitals in rural Vermont were essentially nonexistent. Similar findings were later encountered along the Connecticut River in New Hampshire and in a small area of upstate New York. The Hospital Library Development Services program was established at the University of Vermont's Dana Medical Library to improve these conditions. Financial assistance was received from the National Library of Medicine, and by the end of 1974, thirty-three hospitals had staffed libraries. Earlier that year it has been decided to begin emphasing cooperation among the developing libraries, including the production of union lists and regular meetings of staff members from geographically proximate hospital libaries to plan and implement various activities. An additional one-year award from NLM was received in 1975. Results achieved during and after the period of grant support are reported. Cooperation among hospital libraries is seen as a feasible and beneficial undertaking provided that the participating libraries are internally supported and developing.


Male infertility.

Male infertility. The modern management of male subfertility is based on recognition and correction of the underlying defect. Treatment starts nonspecifically with improvement in the general environment of spermatogenesis and any surgical abnormalities are dealt with. If supplementary endocrine treatment is necessary it is given rationally after estimation of pituitary and testicular hormone levels. The presence or absence of antisperm antibodies is established and their effect on sperm behaviour is observed before and during treatment. Progress in understanding the complex processes involved in human reproduction requires careful observation of accurately defined facts. Much research remains to be done.


Ambulatory ECG monitoring.

Ambulatory ECG monitoring. The development and widespread application of 24-hour ambulatory ECG monitoring in the last 15 years represent major advances in cardiology. It is the most sensitive method of detecting arrhythmias and allows objective evaluation of such abnormalities and their response to treatment as the patient continues the activities of daily life. Information on prognosis and early diagnosis in patients with coronary artery disease has been obtained but more data and a greater understanding of their relevance in normal populations are necessary. Until then the significance of the findings in many situations, especially in asymptomatic patients, will remain speculative and decisions on whether or not to institute therapy will continue to be somewhat arbitrary.


High-dose propranolol in schizophrenia.

High-dose propranolol in schizophrenia. Eight male schizophrenics were treated in an open study with d.l. propranolol. The dose was increased by 160 mg/day until a maximum of 2,400 mg/day was achieved on day 15, and this remained constant until day 21. Seven patients showed significant clinical evidence of psychiatric improvement, while the incidence of toxic side-effects was low. There was wide inter-patient variation in plasma levels of propranolol. Despite a significant increase of plasma propranolol between day 15 and day 21 of the study, there was no significant change in serum prolactin.


Motivation, responsibility and sickness in the psychiatric treatment of alcoholism. Two dominant themes of alcohological thinking and practice are considered in this paper; the disease concept and the concept of motivation. Both are examined in terms of (a) the rights, obligations and responsibilities associated with different types of illness and degrees of severity, and (b) the routine care and treatment of alcoholism in two out-patient alcoholism clinics. The allocation of responsibility and attribution of motivation in psychiatric alcoholism consultations are examined. Finally, the relationship between responsibility allocation, motivation attribution and judgements of a potentially moral nature is considered. It is concluded that a Mutual Participation model of sickness behaviour and doctor-patient relationship is operative in the psychiatric treatment of alcoholism, based upon patients' self-responsibility and strength of character (will-power). In this respect, the psychiatric treatment of alcoholism contrasts with other (particularly non-psychiatric) conditions and treatments.


Averaged evoked responses in relation to cognitive and affective state of elderly psychiatric patients. Averaged cortical evoked responses to auditory and somatosensory stimuli were recorded in elderly depressives, dements, patients with a combination of depression and dementia and normal elderly controls. The subjects were also given a battery of cognitive tests and clinical ratings at stated intervals. The latency of the auditory response was significantly longer in dements than in controls. Depressives had intermediate latencies which did not return to normal after recovery. Although somatosensory stimulu produced the results that pointed in the same direction, the mean response latencies were not statistically significant. Mixed cases were too few for separate statistical analysis but their latencies fell between those of the dements and those of the depressives. Significant correlations emerged between latencies of auditory responses and some cognitive tests, but not with measures of depressive symptomatology. The delay in response to auditory stimuli may be a useful adjunct to diagnosis: in depressives it may reflect organic cerebral change playing a part in the emergence of depressive symptoms in old age.


Reality orientation and staff attention: a controlled study. A trial was carried out of Reality Orientation (R.O.) in a residential home for the elderly mentally infirm with a 'social therapy' control group, receiving the same amount of staff attention as the R.O. group, in addition to an untreated control group. R.O. residents improved more on tests of information and orientation and various aspects of memory than controls. These results support the hypothesis that the nature of staff attention is crucial and that it should encourage and reward appropriate behaviour. No differential effects of treatment were found on rating scale assessments of the resident's functioning in the home.


Problems of repertory grid analysis and a cluster analysis solution. Statistical and requirement difficulties encountered with existing methods of Repertory Grid Analysis are considered. A simple purpose-built method of Cluster Analysis is outlined, and its extension to the difficult problem of comparative analysis described.


Alcohol withdrawal states and the need for treatment. In an attempt to evaluate the clinical significance of alcohol withdrawal, the rate of symptoms and incidence of treatment were determined in 84 female alcoholics following abrupt withdrawal. Results indicated that abstinence symptoms of an emergency type (delirium tremens, convulsions) only rarely occur and require active treatment, whereas those physical and emotional disturbances frequently seen in alcohol withdrawal need very little medical help. This finding is in contradistinction to current clinical opinion.


Validity and uses of a screening questionnaire (GHQ) in the community. The 30-item General Health Questionnaire (GHQ) has been validated against the criterion of a standardized psychiatric interview in the community. Used for screening, the GHQ misclassified 25 per cent of 105 respondents, being worse for men. Specificity and sensitivity were above .70. The alternative use of the GHQ as an estimator and as an indicator of morbidity in epidemiological surveys is described and discussed.


Women who kill their children.

Women who kill their children. During a 6 year period (1970-75) 89 women charged with the killing or attempted murder of their children were examined in a female remand prison. Six types of maternal filicide were distinguished: battering mothers (36 cases), mentally ill mothers (24 cases), neonaticides (11 cases), retaliating mothers (9 cases), women who killed unwanted children (8 cases) and mercy killing (1 case). Types of filicide were compared on a number of social and psychiatric characteristics and on their offence patterns and court disposals. The operation of the Infanticide Act is discussed in the light of these findings.


Depressive classification and prediction of response to phenelzine. A variety of depressive classifications were used to predict response to four weeks' treatment with phenelzine. Better response was found in outpatients rather than inpatients, in atypical depressives, in less severe depressives with a pattern of anxiety and other neurotic symptoms, and in groups characterized as hostile and agitated. The findings, although a little patchy, gave clear support to the concept of a specific clinical group responsive to MAO inhibitors.


Pre-anaesthetic assessment and the prevention of post-ECT morbidity. The introduction of anaesthesia and muscle relaxation has made ECT relatively safe. In a retrospective study of the case notes of 367 consecutive patients receiving ECT over a two year period, chest X-ray and full blood count added no significant information and were ineffective in predicting morbidity, in contrast to physical examination alone.


The course and determinants of reactions to myocardial infarction. The growth of speculative theories about response to physical illness has not been backed by quantitative information. The introduction of standardized measures of psychological and social adjustment has allowed description and analysis of disability for 100 patients and their spouses two and twelve months after a first myocardial infarction. (1) Global measures of social outcome were found to be inadequate and misleading and therefore work, leisure, marriage and family relationships, sex and compliance were separately examined. (2) There was considerable continuity in individual reactions throughout convalescence and it was possible (3) to identify factors in the premorbid psychosocial state predictive of outcome and (4) to describe characteristic patterns of coping. (5) Outcome for spouses can be similarly described and understood. The findings have clinical applications for diagnosis, prophylaxis, treatment and the evaluation of medical care. The conclusion also extend our understanding of the basic principles underlying response to physical illness.


The predictability of thought disordered speech in schizophrenic patients. Previous research has resulted in inconsistent findings regarding the predictability of schizophrenic speech samples. It was hypothesized that the predictability of schizophrenic speech varies as a function of clinically manifest thought disorder. In an experiment based on the Cloze procedure, raters were asked to predict ten passages of schizophrenic speech and eight passages of normal speech under conditions of fourth- and fifth-word deletion. Differences emerged between the samples only for the fifth-word deletion procedure. When the schizophrenic samples were grouped according to the presence of thought disorder, thought-disordered speech was significantly less predictable than normal and non-thought disordered schizophrenic speech. Furthermore, non-thought-disordered schizophrenic speech was no less predictable than normal speech. It is concluded that schizophrenia should be more carefully defined and that thought disorder should be routinely assessed in future investigations.


Relationship between cognitive defect, affect response and community adjustment in chronic schizophrenics. The relationship between mental status and community adjustment has been examined in 100 outpatient chronic schizophrenics. Sixty-six per cent presented at least one of the signs of Schneiderian First Rank Symptoms, which, however, failed to discriminate the diagnostic subgroups. Total adjustment correlated with total mental status and appeared to differentiate the diagnostic subclassifications of schizophrenia. From the major components of mental status, anxiety and depression appear to be significantly correlated with the functioning and stress of the individual in community adjustment while primary symptoms are only peripherally correlated with adjustment.


An extension of the Random Error Coefficient of Agreement to N x N tables. Maxwell has proposed the Random Error Coefficient of Agreement (RE), as a measure of agreement for the binary case based upon the assumption of random distribution of questionable cases. The present paper presents a more general formula for RE's computation and shows how the new form is applicable to cases with more than two response categories.


Severity of psychiatric disorder and the 30-item general health questionnaire. The 30-item General Health Questionnaire misclassified 26 per cent of respondents in two samples of women who were interviewed by a psychiatrist using the Present State Examination. False negatives were likely to be women with chronic disorders, particularly anxiety states. False positives were likely to be distressed by severe physical illness, a recent adverse life event, or loneliness. Applying a higher threshold score to their GHQ responses would help to separate those with a diagnosable psychiatric disorder from those in states of distress.


Chlormethiazole abuse.

Chlormethiazole abuse. This report describes 17 cases of chlormethiazole abuse or dependence. These include one case with symptoms and signs of withdrawal and two other similar cases where undoubted dependence was combined with excessive alcohol intake. Seven other patients with alcoholism who indulged in drug-seeking behaviour involving chlormethiazole are also reported, together with a further seven abusers of various other drug who were also discovered to be taking chlormethiazole.


Consanguinity and schizophrenia in Sudan. The rate of first-cousin marriages among the patients of schizophrenics was compared with a control group in an isolated highly inbred sudanese community, no significant difference being found.


Bilateral extracranial internal carotid artery injury due to non-penetrating trauma--report of three cases. Angiographic features of three patients with bilateral internal carotid artery injury (spasm/dissection/thrombosis) due to non-penetrating trauma are reported. All three patients were involved in motor vehicle accidents. Focal-localizing neurological signs were present and the patients were suspected of having extracerebral haematomas. The diagnosis of traumatic spasm/dissection/thrombosis of the cervical portion of the internal carotid arteries was made following angiography. The need to include views of the cervical carotid arteries in cases of traumatic hemiparesis is stressed and possible effect of cranial CT scanning in these patients on diagnosis of carotid artery injury discussed.


The value of a tracer dose in predicting the kinetics of therapeutic doses of 131I in thyrotoxicosis. The kinetics of tracer doses of 131I, assessed by measuring uptake and effective half-life, correlate well with the kinetics of therapy doses. The effective half-life was measured using thermoluminescent discs fixed to the patients' anterior neck surface. This method gives results comparable with those obtained using an uptake probe, and met with a good response by the patients. Using the kinetics of the tracer dose to assist prescription of radioiodine therapy would considerably reduce the spread of absorbed doses to the glands of a group of patients. The case for attempting more exact dosimetry in this field is reviewed.


Doses to patients from pantomographic and conventional dental radiography. The increasing popularity of pantographic dental radiography and particularly its recent use for routine screening of asymptomatic patients have prompted the NRPB to compare the risks to patients from this technique with those from more conventional dental diagnostic procedures. Pantographic equipment from seven manufacturers have been investigated along with five procedures for obtaining similar information using conventional dental X-ray sets. Lithium borate thermoluminescent dosimeters located at 141 sites in the head and neck of a Rando phantom have been used to measure the mean absorbed dose to organs of interest as well as the total energy imparted to the phantom. Relative values of the energy imparted by the various techniques provide an estimate of their relative somatic risk to the patient. Pantomographic techniques were generally found to impart less than half the energy to the phantom than that given by a conventional full-mouth periapical series conducted at 45 kV, and a similar amount of energy to four bitewing intra-oral films. The restriction of the frequency of pantomographic examinations to no more than once per year during adolescence and once per three to five years during adulthood has been shown to involve only a minimal increase in the risk of somatic injury to the patient.


Radiation dose to the fetus in obstetric radiography. The mean dose to the fetus and fetal head, together with the doses to the fetal gonads and maternal gonads, have been estimated to be 107, 56, 131 and 136 mrad respectively for an obstetric prone oblique examination of the abdomen, using a rare-earth screen-film combination. The doses were derived by measuring skin doses on a series of women in late pregnancy undergoing the above examination and by using measured depth-dose information. The position of the fetus relative to the maternal skin surface was determined by ultrasonic scanning.


Lung damage in C57B1 mice following thoracic irradiation: enhancement by chemotherapy. C57Bl mice were treated with thoracic irradiation to doses in the range 12.0 to 18.9 gray. Few deaths were observed in the period 80--160 days after irradiation (an end-point of lung damage used by other investigators) and the median survival times ranged from 200 to 310 days. CBA mice treated under identical conditions predominantly died between 80--160 days and it is therefore concluded that C57Bl mice show unusually prolonged survival following this treatment. Six chemotherapeutic agents were given to C57Bl mice together with thoracic irradiation, in most cases two weeks beforehand. Adriamycin, bleomycin and cyclophosphamide enhanced the mortality of the mice. Most agents had little effect on radiation-induced skin damage.


Effect of general practitioners' advice against smoking. During four weeks all 2138 cigarette smokers attending the surgeries of 28 general practitioners (GPs) in five group practices in London were allocated to one of four groups: group 1 comprised non-intervention controls; group 2 comprised questionnaire-only controls; group 3 were advised by their GP to stop smoking; and group 4 were advised to stop smoking, given a leaflet to help them, and warned that they would be followed-up. Adequate data for follow-up were obtained from 1884 patients (88%) at one month and 1567 (73%) at one year. Changes in motivation and intention to stop smoking were evident immediately after advice was given. Of the people who stopped smoking, most did so because of the advice. This was achieved by motivating more people to try to stop smoking rather than increasing the success rate among those who did try. The effect was strongest during the first month but still evident over the next three months and was enhanced by the leaflet and warning about follow-up. An additional effect over the longer term was a lower relapse rate among those who stopped, but this was not enhanced by the leaflet and warning about follow-up. The proportions who stopped smoking during the first month and were still not smoking one year later were 0.3%, 1.6%, 3.3%, and 5.1% in the four groups respectively (P <0.001).The results suggest that any GP who adopts this simple routine could expect about 25 long-term successes yearly. If all GPs in the UK participated the yield would exceed half a million ex-smokers a year. This target could not be matched by increasing the present 50 or so special withdrawal clinics to 10 000.


Association between raw milk and human Salmonella dublin infection. Between 1971 and 1975 the mean annual incidence of human Salmonella dublin infection in California increased more than five-fold. Investigation of the increase showed an association with exposure to raw milk in 44 out of 113 cases. Of these 44 patients, 35 had used certified raw milk from a single dairy. Faecal swabs confirmed S dublin infection in the dairy herd and the milk, and so a pasteurisation order was issued. S dublin appears to be an unusually invasive and life-threatening salmonella serotype: 65% of isolations were obtained from non-faecal specimens (mainly blood cultures), 89 patients (80%) were admitted to hospital and 22 patients died. Almost three-quarters of the patients were aged 20 or over, and half had serious underlying diseases, particularly leukaemias and lymphomas. Five patients presented with infected vascular lesions that included aneurysms with abscesses and infections of previous arterial graft sites. The public's increasing desire for a "health food" such as raw milk should be tempered with an appreciation of its attendant risk to health.


Regional organisation of neonatal intensive care in the North-west. From January 1976 to July 1978, 234 ill neonates were transported to the regional neonatal intensive care unit (ICU) of St Mary's Hospital, Manchester, from 26 maternity hospitals three to 120 miles (4.8-193.1 km) away. Ninety per cent were transferred from 15 hospitals within a 30-mile (48.3 km) radius of the ICU. Most referring hospitals had more than 2000 births a year and offered good nursing supervision of high-risk neonates in conventional special care baby units (SCBUs). In 200 of the 234 babies respiratory symptoms precipitated referral, hyaline membrane disease being the most common final diagnosis. Altogether 143 babies received definitive mechanical ventilation, and most of them were ventilated in the ambulance en route to the ICU. The neonatal survival rates for all babies and for those who received mechanical ventilation were 61% and 45% respectively. Lethal inoperable malformations and tentorial tears accounted for 23 of the 92 deaths.A crisis-orientated referral service directed towards the treatment of babies with impending or actual respiratory failure needs close collaboration between the regional ICU and referring SCBUs, with parallel development of their facilities and skills. A complementary but distinct pattern of referral is necessary to cater for those high-risk but not critically ill babies who are born in hospitals that lack staff and facilities to provide the vigilant and anticipatory care that is so necessary.


Relative costs of home and hospital confinement. The first study in a series concerned with the costs of different strategies of maternity care showed the differences between the costs of booked confinement at home, in a GP hospital for 48 hours, and in a consultant obstetric unit for 48 hours to be small. The study costed 1977 home confinements in Dudley and compared them with matched samples of hospital births. The factors that compensated, in the home booked deliveries, for the cost of hospital stay were an average of 11 extra visits from community midwives, midwife attendance for six hours at delivery, and a proportion who were transferred to hospital after receiving the extra antenatal care of a home booked delivery. This differential transfer rate is a crucial factor that merits further investigation. Family-borne costs were included in the study. The most significant was time off work by the husband. Average family costs were 68 pounds, about 30% of public sector costs. Any acceptable strategy of home confinements must provide for last-minute transfers to hospital.


Diagnostic value of routine exercise testing in hospital patients with angina pectoris. A group of patients with angina pectoris were investigated prospectively using a simple and well-recognised exercise test protocol, and S-T segment displacements during exercise were correlated with the results of coronary arteriography. Definitive exercise results in 100 patients correlated well with findings on coronary angiograms: 69 out of 70 patients with positive exercise test results had significant coronary disease on angiography, while 23 out of 30 with negative exercise test results had no significant coronary disease. In six patients a period of physical training changed indeterminate initial tests to definitive ones after the training. These results show that the use of a widely available exercise test and a light physical training programme, with rigid adherence to the protocol, can reduce the overall demand on coronary arteriography.


Serum thyroglobulin concentrations and whole-body radioiodine scan in follow-up of differentiated thyroid cancer after thyroid ablation. Measurement of serum thyroglobulin (Tg) concentrations and whole-body radioiodine scan were performed simultaneously during follow-up of 32 patients with differentiated thyroid cancer who had undergone thyroid ablation by operation and radioiodine. Almost all patients in whom serum Tg was undetectable had normal scans. Concentrations exceeding 50 ng/ml were invariably associated with residual or metastatic tumour uptake in the scan. Out of 21 observations of detectable values below 50 ng/ml, 14 were in patients whose scans showed subclinical or sub-radiological tumour uptake and seven in patients with normal scans. The sensitivity of serum Tg as a tumour marker compared favourably to that of the whole-body scan. A scan is unnecessary when serum Tg is undetectable, but in patients with detectable serum Tg concentrations, particularly if these are below 50 ng/ml, a scan is important to assess and localise tumour uptake of iodine before advising treatmet with iodine-131.


Relative contributions of diet and sunlight to vitamin D state in the elderly. In winter the vitamin D state of elderly people may reach levels associated with osteomalacia, although the disease may not be clinically apparent. A statistical correlation was observed in a group of elderly subjects during the winter between dietary vitamin D intake and vitamin D state, but the intake was generally too low to make a biologically important contribution to maintaining vitamin D concentrations. Ultraviolet light (UVL) is the primary determinant of vitamin D state in summer and winter, in winter owing to the pools of vitamin D built up during the previous summer. Plasma concentrations of 25-hydroxy vitamin D (25-OHD) in winter of 15.0-22.5 nmol/l (6-9 ng/ml) require that the concentration in the previous summer was over 40 nmol/l (16 ng/ml). To maintain plasma concentrations in the elderly above those associated with osteomalacia a mean dietary vitamin D intake of over 5 microgram/day is required. A more physiological approach, however, would be to increase exposure to UVL.


Patients' knowledge of their condition and treatment: how it might be improved. A study was carried out in which patients were asked questions to assess their knowledge of their condition and treatment, the questions relating particularly to care before siting an intravenous infusion and preoperative care. A high proportion of patients knew little about the procedure they were about to undergo. It is recommended that patients should be told more about matters relating to their condition and treatment. Written information could be given to supplement that given verbally by staff. A check list might be drawn up to ensure that patients receive all relevant information.


Fetal malnutrition--the price of upright posture? The pattern of preterm fetal growth faltering, normally seen in man, differs from that observed in animals. This type of fetal growth cannot be considered as an adaptation to facilitate birth but is more likely to be due to rapid evolution and imperfect adaptation to the upright posture. The pattern of posture and physical activity during pregnancy may therefore be an important determinant of fetal growth. Differences in intrauterine nutrition existing between social groups, usually ascribed to variations of maternal diet and nutrition, may well result from different patterns of maternal activity in the weeks preceding birth.


Spinal cord projections from the medial cerebellar nucleus in tree shrew (Tupaia glis). Electrolytic lesions were placed in the medial cerebellar nucleus in tree shrews (Tupaia glis) or in fibers issuing from this nucleus. Brains and spinal cords were processed according to Fink-Heimer procedure following survival times of 2-7 days. In control animals lesions were placed in the cerebellar cortex and, in one case, in the olfactory bulb. Degenerating fibers were seen entering the cervical spinal cord and continuing to thoracic and lumbar levels. The projection is relatively profuse in the cervical cord, becoming sparse as the fibers proceed to more caudal levels. Fibers run in the lateral funiculus, predominantly contralateral to the lesion. Some fibers are observed to travel directly through the intermediate gray matter of the spinal cord. Preterminal degeneration is seen primarily in the intermediate gray of the spinal cord. Results are discussed in relation to typical locomotor behavior of tree shrew.


Action of gamma-aminobutyric acid on hypothalamo-neurohypophysial axons. gamma-Aminobutyric acid (GABA) and the related compound, muscimol, were bath-applied to a preparation containing the rat median eminence, pituitary stalk and neurohypophysis, and are shown to reversibly reduce the amplitude, and increase the latency, of the antidromic compound action potential recorded from hypothalamoneurohypophysial axons in response to electrical stimulation of the posterior pituitary lobe. Both actions were antagonized by bicuculline, but were unaffected by strychnine. The data suggest that the peptidergic axons of the hypothalamo-neurohypophysial tract are endowed with receptors for GABA, which is believed to be synthesized and released by neurohypophysial glial cells.


Identification of direct competition for, and indirect influences on, striatal muscarinic cholinergic receptors: in vivo [3H]quinuclidinyl benzilate binding in rats. [3H]Quinuclidinyl benzilate (QNB) binds to specific muscarinic receptors of rat striatum, in vivo. The binding is saturable and displaceable by muscarinic drugs. Clozapine and thioridazine are unique antipsychotic agents with low liability for extrapyramidal side-effects, and both displaced ONB, while several other neuroleptics did not. In addition to this apparent direct competition for cholinergic receptors, morphine and amphetamine increased ONB binding by indirect influences on muscarinic receptors. In vivo QNB binding not only confirms in vitro findings, but it also detects indirect, probably transsynaptic, alterations of muscarinic cholinergic receptor dynamics.