Vagal tone and effect of vagotomy on the circulatory response to arterial hypoxia. The influence of vagotomy on resting vagal tone arterial Po2, the heart rate and blood pressure responses to different grades of hypoxia was studied in three species of anesthetized animals. Vagotomy without hypoxia produced a sustained increase in heart rate of dogs but not in rabbits or sheep. In the dogs, where this was studied more fully, heart rate showed sustained increase over several hours with no significant change in blood pressure or arterial Po2. It is concluded that there is species difference in the resting vagal tone during anesthesia. The relationships between graded arterial hypoxia with heart rate and blood pressure have been determined with and without intact vagus nerves. Before vagotomy hypoxia significantly increased the heart rate of dogs and sheep and reduced that of rabbits. Vagotomy decreased the bradycardia observed in rabbits, but did not change the response to hypoxia in dogs and sheep. The greater increase in heart rate of dogs calculated statistically and were due to the pre-existing resting vagal tone. After vagotomy, heart rate response to graded arterial hypoxia was increased rather than decreased in all animals.


Antagonism of calcium-induced contractions by some non-specific spasmolytics in depolarized smooth muscles. The effects of papaverine MgCl2, cocaine, DNP, KCN and khellin on responses of some rabbit and rat tissues to CaCl2 were studied in vitro in a depolarizing medium. Guinea pig taenia coli preparation was used for comparison. In rabbit tracheal chain and vas deferens and guinea pig taenia coli preparations all spasmolytics shifted the concentration-response curves of CaCl2 to the right without affecting the maxima or slopes. In rat tracheal chain and vas deferens preparations all spasmolytics shifted the concentration-response curves of CaCl2 to the right. Furthermore all agents (except cocaine in tracheal chain preparations) depressed the maximum responses. The slopes were unaffected in either preparations. The initial competition and subsequent noncompetition observed in certain tissues is discussed in the light of the reported poor capacity of some tissues to retain Ca++ and the absence of releasable firmly bound Ca++ (11).


Relation of PTC responses and secretor status to blood groups. Blood groups (ABO, Rh-including sub-types M-N, Duffy), secretor status and ability to taste Phenylthiocarbamide (PTC) were investigated in 102 medical students of Delhi University, and the distribution was found similar to that observed in the north Indians. Both faster and secretors had highest percentage in AB, O and in rr, while the lowest values were obtained in B and R1r.


Effects of buphenin on the rat portal vein. The vasodilator and tocolytic substance buphenin (10 mumol/l) stimulated the spontaneous phasic activity of some (8 out of 18) isolated rat portal vein preparations; 0,1-1 mmol/l buphenin diminished or abolished the activity in all preparations. The isotonic and isometric tonic contractions of portal vein in response to adrenaline, noradrenaline and phenylephrine (0,1-1 mumol/l) disappeared almost completely after addition of buphenin in equimolar concentrations, whereas acetylcholine contractions persisted. The beta-adrenergic blocking agents propranolol and dichloisoprenaline (10 mumol/l) only slightly antagonized the inhibitory effect of buphenin on the contractile responses to catecholamines. It is concluded that buphenin exerts dual action upon rat portal vein: the drug partially stimulates the beta-receptors and partially blocks the alpha-adrenergic receptors.


Peak expiratory flow rate in South Indian adults. Peak Expiratory Flow Rate (PEFR) was measured with a Wright Peak Flow Meter in 851 healthy men and women of two categories; Group I--students and staff of the Medical College constituting the middle income group, and Group II--healthy individuals from the poorer class with an income of less than Rs.200/-per month, forming the lower income group. In both categories women had much lower values than men, and in both sexes the values in the subjects of the poor income group was significantly lower. The PEFR was found to correlate best with height in subjects below 30 years, and with age in older subjects. The mean values, standard deviations and regression equations are given for the different groups. Present values are also compared with some western and Indian data.


Phagocytic response of leucocytes in secretors and non-secretors of ABH (O) blood group substances. Secretor status of healthy young volunteers in the age group of 18-22 years and having similar socio-economic background was determined by standard agglutination inhibition test of the saliva. Phagocytic response of leucocyte was worked out by in vitro suspension technique and average number of cocci engulfed by leucocytes calculated in secretors/non-secretors of each blood group. Leucocytes of non-secretors of O and AB seem to have more and highly significant ingestion power as compared to secretors. Non secretors in group A & B also show more phagocytic activity. Relatively different concentration of the components of the blood group substances in secretors/non-secretors seems to affect phagocytic activity of the leucocytes.


Sialic acid in human semen.

Sialic acid in human semen. Sialic acid of seminal fluid of eighty two human subjects has been studied in relation to infertility. Normozoospermic group had highest sialic acid content (94 mgm/100 ml of the fluid) and was significantly different from other groups. The lowest sialic acid level was observed in necrozoospermic group (54 mgm/100 ml of the fluid). Azoospermic (62 mgm/100 ml) and vasectomised group (73 mgm/100 ml) had 33 and 22 percent less sialic acid level respectively than normozoospermic group. For the pooled observation sialic acid was found to be correlated (r = 0.282, significant at 5 percent level) with the total sperm count.


A study of dynamic lung functions in textile workers. The current study was done to determine the normal ventilatory dynamic indices in healthy male textile workers and to observe the influence of exposure to cotton dust. Toshiniwal's Expirograph is used to record the Forced Vital Capacity tracing and from this tracing, other Forced Expiratory Volumes like FEVO.5, FEVO.75 and FEV1.0 are calculated. The data was statistically analysed and compared with the values reported by various other workers. It was observed that all functional parameters showed a decline with age, both in the control as well as the exposed group. The mean values in the exposed group were generally lower than the controls, and the difference was larger and statistically significant in the subjects of 40-49 year age-group, may be because they were exposed to cotton dust for a long duration.


Non-competitive inhibition of serum acetylcholinesterase (E.C.3.1.1.7) by vacor (N-3-pyridyl methyl-N'-P-nitrophenyl urea) in bandicoot rats. Single dose (1 mg/rat) administration of VACOR (N-3-pyridyl methyl-N'-nitrophenyl urea) produced significant paralytic symptoms in rats. Such rats which lived for one week were sacrificed and serum AChE was extracted and purified by Sephadex column chromatography. The serum enzyme from the normal rats showed the existence of two isozymes on polyacrylamide gels which could be resolved through column chromatography. Both the isozymes showed non-competitive inhibition with VACOR in vitro; but to a varied degree. The ACh concentration increased by 70-75% in serum and 95-100% in erythrocytes of the poisoned rats. VACOR thus affects ACh hydrolysis thereby causing an accumulation of ACh in the serum of poisoned rats.


Spermicidal activity of some halides.

Spermicidal activity of some halides. Though most of the metallic ions are spermicidal in action, the present investigation emphasises the spermicidal activity of anions. Among the inorganic compounds screened at 4 concentrations (0.01%, 0.1%, 1% and 5%) halides are mainly spermicidal, except NaCl, KCl & CsCl which are spermiostatic; sulphates and nitrates are mainly spermiostatic except ZnSO4 at 1% concentration and above; CuSO4, Al2 (SO4)3, Uo2(NO3)2.6H2O and AgNO3 at 5% concentration where they become spermicidal.


Pathogenic synergism between Treponema hyodysenteriae and other selected anaerobes in gnotobiotic pigs. Gnotobiotic pigs were orally exposed to various anaerobes at 6 to 9 days of age and similarly inoculated with Treponema hyodysenteriae B204 3 to 6 days later. Watery diarrhea and fecal excretion of large quantities of mucus and some fibrin clots were observed 4 to 20 days after inoculation with B204 if other anaerobes were present. Colonic lesions characteristic of swine dysentery were observed when B204 was present with Fusobacterium necrophorum, three strains of Bacteroides vulgatus, a Clostridium species, and Listeria denitrificans individually and when some of these microbes were present in various combinations, but not when B204 was present alone. These results are consistent with the conclusion that T. hyodysenteriae is the primary pathogen in the etiology of swine dysentery and that the presence of one or more other anaerobes is a prerequisite for expression of pathogenicity of T. hyodysenteriae. This prerequisite can be met by a variety of anaerobes.


Crossed immunoelectrophoretic analysis of two antigen extracts of Thermoactinomyces candidus. A pyridine extract antigen and a double-dialysis antigen (DDA) obtained from Thermoactinomyces candidus were analyzed by crossed immunoelectrophoresis. In addition, the heat lability, pronase sensitivity, and isolectric points of the components of the DDA were determined. By using antisera raised against crude pyridine extract antigen, two immunogenic components were resolved by crossed immunoelectrophoresis. A similar analysis of DDA using antisera raised against crude DDA revealed 15 immunogens. All but six components were heat labile, whereas pronase had little effect on the number of resolvable components. Intermediate gel crossed immunoelectrophoresis using antiserum raised to whole spores detected six immunogenic components, four of which were also detected by the anti-DDA serum. A total of 19 bands were obtained when the DDA was subjected to flatbed isoelectric focusing on polyacrylamide gels. The isoelectric points for the various components were found to range from 3.5 to 5.7. Crossed immunoelectrophoresis using isoelectric focusing in the first dimension yielded at least 16 immunogenic components. Six components with isoelectric points falling in the range of 4.5 to 6.4 were found to be resistant to heat. A comparison with antigens obtained from other thermophilic actinomycetes is presented.


Septum and adrenocortical function.

Septum and adrenocortical function. Dorsal septum is an intermediary centre in between the hippocampus and hypothalamus and it has got inhibitory influence over the hypothalamo-pituitary-adrenal axis. Stimulation of the dorsal septum manifested with fall in adrenocortical output whereas its lesion has opposite response. Ventral septum is a facilitatory area regarding activation of the hypothalamo-pituitary-adrenal axis. It is a balancing centre lying in between the higher central nervous system structures and the hypothalamus. Stimulation and lesion of the ventral septum led to rise and fall in adrenal venous 17-OHCS output respectively. Adrenocortical response to stress of burn was not blocked or inhibited following lesion of the dorsal as well as ventall septum.


The role of thyroid in clinical disorders of hypothalamo-pituitary adrenocortical axis--a prelminary communication. The study of thyroid function in clinical conditions associated with the disorders of the hypothalamio-pituitary-adrenocortical axis indicated overt hypofunction of thyroid in all the three cases of Cushing's disease and subclinical hypo-or low normal function of thyroid in most of the cases of adrenogenital syndrome. It was suggested that hypo or low normal function of thyroid might facilitate excess elaboration of ACTH through CRF by swaying the balance of neurotransmitters at hypothalamus in favour of serotonin.


Production of hydroxyl radical by human alveolar macrophages. Stimulated human alveolar macrophages were demonstrated to oxidize B-methyl proprionaldehyde (methional) or 2-keto-4-thiomethylbutyric acid to ethylene (C2H4). Agents which are believed to scavenge the hydroxyl radical (.OH), sodium benzoate, and mannitol, as well as scavengers of superoxide anion (O2-) or hydrogen peroxide, decreased C2H4 production, implicaing .OH as the oxidizing radical. Differences in C2H4 rpoduction, as well as oxygen uptake and O2- release between human alveolar macrophages and polymorphonuclear leukocytes, were also documented.


Aggregation and adherence of Streptococcus sanguis: role of human salivary immunoglobulin A. Fourteen freshly isolated strains of Streptococcus sanguis were obtained from the dental plaque of five healthy adults. Whole saliva was collected concomitant with the plaque isolates from the five subjects, and a second whole saliva sample was collected 10 weeks later. All possible combinations of the first five saliva samples, the second five saliva samples, and 14 strains of bacteria were tested for aggregation. Of the 140 combinations examined, 108 of 140 (77%) of the strains aggregated with the first saliva samples and 95 of 140 (68%) aggregated with the second saliva samples. Overall, 72% of the strains aggregated with both the first and second saliva samples. Removal of immunoglobulin A (IgA) from these same salivas resulted in 38 of 108 (35%) of the aggregates decreasing in intensity with the first saliva samples and 27 of 95 (29%) of the aggregates decreasing in intensity with the second saliva samples. No aggregates increased in intensity with saliva samples when IgA had been removed. Removal of IgA from saliva also resulted in a mean decrease of 46% in adherence of S. sanguis to hydroxyapatite coated with the IgA-deficient saliva. Several strains of S. sanguis were shown to aggregate strongly with human salivary and colostral IgA. In addition, S. sanguis strain S7 showed a 31% stimulation of adherence to hydroxyapatite precoated with human salivary IgA over the uncoated controls. Stepwise removal of IgA from saliva resulted in a decrease in aggregation intensity from strong (4+) to weak (1+ to 2+). Similarly, the adherence of S. sanguis to hydroxyapatite coated with these saliva samples decreased linearly as the salivary IgA was depleted. Alternatively, the addition of a small quantity of salivary IgA (20 mug/ml) to progressively diluted saliva maintained a high level of adherence and strong aggregation until the saliva dilutions reached between 1:8 in the adherence experiments and 1:32 for the aggregations. These data indicate that salivary IgA may play an important role in the microbial ecology of human dental plaque formation.


Relationship between host age and susceptibility to oral colonization by Actinomyces viscosus in Sprague-Dawley rats. The colonization of Actinomyces viscosus strain Ny-1R on the molar teeth of conventional and ex-germfree rats of various ages fed either a high-sucrose diet, a high-glucose diet, or laboratory chow was studied. Conventional rats directly after weaning and up to 30 days of age are less susceptible to experimental infection by strain Ny-1R than are older rats regardless of the test diet. The relationship between host age and susceptibility to infection is also demonstrable in ex-germfree rats fed a high-sucose diet. Host factors responsible for the differences in susceptibility were investigated. The results from these studies do not implicate host antibodies, host indigenous flora, or host saliva. In other studies, it was demonstrated that within the mouths of rats, strain Ny-1R preferentially colonizes in the pits and fissures of the molar teeth rather than on the dorsum of the tongue or on the vestibular mucosa. In short-term experiments, it was found that strain Ny-1R attaches to the first molars of 40-day-old conventional rats to a greater extent than it attaches to the first molars of 20-day-old rats. The differences in attachment and subsequent colonization of strain Ny-1R in 20- and 40-day-old rats may be related to the varying amounts of the reduced enamel epithelium and connective tissue present in the fissures of the molar teeth.


The role of adrenal and pineal glands on the hypothalamo-pituitary axis in adult male rats. Although there have been reports on the effects of adrenal and pineal gland secretions on the hypothalamus and the pituitary, the maintenance of rhythmicity by these glands has not been reported so far. The present data deals with the alterations in the periodicity of hypothalamo-pituitary axis after the surgical removal of either adrenal, gonad or pineal in adult male rats. The data indicated an alteration in the 24 hour pattern of hypothalamic content of LHRH after adrenalectomy, castration or pinealectomy. In adrenalectomy group, the in vitro responsiveness of pituitary decreased at 0600 h and 100 h as compared to the intact rats, resulting in a low amplitude of LH circadian rhythm. The pituitaries of pinealectomized rats showed increased sensitivity at 1000 h and 1800 h which resulted in two peak LH concentration at those time intervals. Further, pinealectomized rats showed a selective five fold increase over 24 hr in serum FSH concentration as compared to intact rats suggesting dissociation in the release of FSH and LH.


Brain-pituitary-adrenal interrelationship in closed loop intestinal obstruction in man. Effects of stepwise removal of brain, midbrain section and frontal leucotomy in dogs after the same type of stress. Volvulus shows high plasma 17-OHCS level and after operation there is a progressive fall. Brain-pituitary-adrenal interrelationship has been studied in experimental dogs using a different type of stressor i.e. closed loop intestinal obstruction. Midbrain section blocks the adrenocortical response. Frontal leucotomy leads to increased response after acute distension of the closed loop. Acute hypothalamectomy does not lead to blocking of the adrenocortical response to stress.


Ultrastructure of gliding bacteria: scanning electron microscopy of Capnocytophaga sputigena, Capnocytophaga gingivalis, and Capnocytophaga ochracea. When examined by both light and scanning electron microscopy, Capnocytophaga gingivalis, C. sputigena, and C. ochracea displayed three distinct growth zones: the original streak, an intermediate zone, and the advancing edge, or halo zone. On Trypticase (BBL Microbiology Systems)-soy-blood agar, the cells translocated by gliding. C. gingivalis and C. sputigena formed large, irregular isolated colonies, while C. ochracea formed a more confluent cell mass. The cells within the streak zone and in most of the intermediate zone were heaped into mounds, with the individual cells displaying a definite flow pattern, the latter characteristic of C. sputigena and C. gingivalis. The halo zone consisted of tracks of cells which appeared to have translocated back upon themselves, or were restricted in their outward movements by adjacent cells. Also present within the halo zone were small aggregates of cells, referred to as pioneer colonies. The cell surfaces of C. gingivalis and C. ochracea were smooth and free of any apparent extracellular material, whereas C. sputigena was covered with a thick amorphous material, as well as long, thick, cell surface-associated fibrils.


Inhibition of adsorption of Streptococcus mutans strains to saliva-treated hydroxyapatite by galactose and certain amines. Adsorption of all of eight strains of Streptococcus mutans to saliva-treated hydroxyapatite (S-HA) surfaces was inhibited by galactose and melibiose, but not by other neutral sugars tested. This observation supports the hypothesis that lectin-like components participate in the attachment of these streptococci to salivary glycoproteins on saliva-treated hydroxyapatite surfaces. Adsorption of all strains was also inhibited by iodoacetate and spermine; other amines tested reduced adsorption of some strains, but not others.


Genetic control of the murine corneal response to Pseudomonas aeruginosa. Inbred mouse strains differ in susceptibility to intracorneal challenge with Pseudomonas aeruginosa. Genetic studies indicate that resistance to corneal infection is dominant over susceptibility and is controlled by autosomal genes, at least one of which is located outside of the H-2 locus. On the basis of genetic complementation studies, the susceptible strains BALB/c and C57BL/6 each bear one resistance gene, since the F1 hybrid (BALB/c X C57BL/6) was uniformly resistant to infection.


Use of antibodies to purified Newcastle disease virus glycoproteins for strain comparisons and characterizations. The H/N and F1 glycoproteins responsible for hemagglutinin/neuraminidase (H/N) activity and fusion (F1) activity were purified from several Newcastle disease virus strains and used to produce antisera. These antisera can be used to clearly distinguish the virus strains by a number of techniques including radioimmunoassay, and so provide a means of classifying new virus isolates. The variations detected between strains are not related to field virulence.


Effect of cell-mediated immune factors on the replication of an attenuated temperature-sensitive mutant of vaccinia virus. Studies of the in vivo multiplication of an attenuated temperature-sensitive strain of vaccinia virus (ts2) indicated that temperature sensitivity alone could not account for the attenuation. Immunodepressive treatment of intracerebrally inoculated mice had a dramatic stimulatory effect on the multiplication of the attenuated strain and suggested that establishment of ts2 infection in the mice was hindered by host defense mechanisms mediated by cellular elements. Experiments carried out in vitro with the 51Cr release assay showed that cells infected with the ts2 mutant represented more susceptible targets to the cytotoxic action of immune spleen cells than cells infected with the parent vaccinia strain. Moreover, it appeared that ts2 replication, compared with wild-type replication in vitro, was more inhibited by the immune spleen cells. Although this work did not evaluate the role of specifically sensitized lymphocytes within the lesions, indirect evidence suggests that lymphocytes could cause a more effective halt in ts2 virus multiplication than in wild-type multiplication.


Virulence of temperature-sensitive mutants of Sindbis virus in neonatal mice. The virulence in neonatal mice of temperature-sensitive (ts) mutants of Sindbis virus was determined by measurements of mean survival time and 50% lethal dose after intracerebral injection. For 11 ts mutants, mean survival time was determined by the ribonucleic acid (RNA) phenotype, RNA+ mutants killing the mice sooner than RNA- mutants for the same titer of virus injected. Mortality caused by seven ts mutants was, with one exception, correlated with the proportion of revertants recovered after death. A82, a presumed double mutant showing low reversion, showed no detectable lethality. The pathogenicity of this mutant could be detected by inhibition of weight gain, which was proportional to the titer of virus injected. A low-level persistence, independent of the titer injected, occurred up to 7 days after injection. This was followed by complete clearance. It is concluded that the virulence of Sindbis virus may be considerably altered by mutation, and that this is related to events occurring at the cellular level.


Disproportionate elevation of the immunoglobulin G1 concentration in cerebrospinal fluids of patients with multiple sclerosis. We determined immunoglobulin G (IgG) subclass concentrations and studied their distributions in the cerebrospinal fluids of patients suffering from multiple sclerosis, other inflammatory neurological diseases, and non-inflammatory diseases of the nervous system in comparison with a control group. In addition, the four subclass concentrations were measured in serum specimens of the multiple sclerosis and control groups. These data were correlated with the extent of local IgG synthesis in the subarachnoid spaces of the patients belonging to the different groups. We found a selective elevation of the IgG1 subclass in the cerebrospinal fluids of multiple sclerosis patients, and there was only a very small overlap of the IgG1 ranges of the multiple sclerosis and control groups. No major differences were detected between the IgG subclass distributions in different courses of multiple sclerosis nor between multiple sclerosis and control sera. The group with non-inflammatory diseases showed a uniform elevation of all four subclasses and a greater overlap with the normal range. This latter feature was combined with an elevated IgG1 concentration in the group with other inflammatory diseases. It is concluded that locally synthesized IgG in the cerebrospinal fluids of multiple sclerosis patients consists mainly of IgG1.


Interaction of diphtheria toxin with phosphorylated molecules. The binding of diphtheria toxin to 125I-labeled cell surface glycoproteins from hamster thymocytes was shown to be inhibited by nucleotides. The relative effectiveness of the nucleotides (at 5 mM) was found to be thymidine triphosphate greater than adenosine triphosphate greater than guanosine triphosphate greater than uridine triphosphate greater than cytidine triphosphate. When adenine-containing compounds were used, the relative effectiveness was determined to be adenosine tetraphosphate greater than adenosine triphosphate greater than adenosine diphosphate greater than adenosine monophosphate. In addition, tetrapolyphosphate, tripolyphosphate, inositol hexaphosphate (phytic acid), and the highly phosphorylated proteins casein and phosvitin were also shown to be potent inhibitors of the binding of diphtheria toxin to 125I-labeled cell surface glycoproteins. Diphtheria toxin was shown to bind directly to 125I-casein; this binding was also inhibited by the highly phosphorylated compounds and was decreased by pretreatment of the 125I-casein with alkaline phosphatase. These results suggest that diphtheria toxin binds to regions of high phosphate density and raise the possibility that the site on the cell surface glycoproteins to which diphtheria toxin binds might be polyanionic in nature.


Disseminated gonococcal infection in mice. Gonococci do not readily cause disseminated infection in mice. To simulate some of the conditions leading to disseminated gonococcal infection in women, we suspended gonococci in mucin plus hemoglobin and studied the development of gonococcal bacteremia. The mucin-hemoglobin mixture was used because the menstruum appears to be involved in dissemination of gonococci from the genital tract during menstruation. Mice did not die after massive inocula of 10(9) gonococci given intraperitoneally in broth, but when gonococci were suspended in mucin (15%) alone, the 50% lethal dose was 10(8.4) and in 15% mucin plus 4% hemoglobin (M/H), the 50% lethal dose fell to 10(6.6). Sublethal doses produced local peritonitis and transient bacteremia. With larger inocula the local peritoneal infection progressed to fatal septicemia. Studies of the mechanism by which M/H lowered the 50% lethal dose showed that systemic clearance mechanisms were compromised, but not enough to account for the total decrease in the 50% lethal dose. If gonococci were given intravenously after intraperitoneal inoculation of M/H, sequestration of gonococci in the peritoneal cavity occurred, suggesting an effect on local peritoneal defenses. The effect on neutrophils appeared most significant, since numbers of neutrophils in the peritoneal fluid were decreased in the presence of M/H and neutrophils were destroyed by M/H in vitro. The serum bactericidal system was not affected. We conclude that M/H promotes gonococcal bacteremia by interference with phagocytosis and intracellular killing of gonococci. The model simulates the disseminated gonococcal infection cases in women which follow pelvic inflammatory disease in its progression from local peritonitis to transient or lethal bacteremia and in factors (mucin and hemoglobin) which enhance infection.


Simple and rapid procedure for the selective removal of lysozyme from human saliva. A simple and rapid method is described for the removal of lysozyme from human whole salivary supernatant. Saliva specimens were adsorbed with Micrococcus lysodeikticus. The saliva so treated was depleted of 95% of the lysozyme activity. Changes in total protein, lactoperoxidase, lactoferrin, immunoglobulin A, and the proportions of several anionic proteins were less than 10%. It is concluded that adsorption of saliva with M. lysodeikticus is a suitable procedure for the preparation of saliva that is selectively deficient in lysozyme.


Cytotaxin receptors of neutrophils: evidence that F-methionyl peptides and pepstatin share a common receptor. Pepstatin, a chemotactic microbial pentapeptide, competes with f-Met-Leu-[3H]Phe for binding to human neutrophils. Furthermore, porcine neutrophils, which neither specifically bind nor respond chemotactically to the synthetic f-methionyl peptides, also fail to respond chemotactically to pepstatin. These results suggest that pepstatin shares a receptor on the neutrophil with f-methionyl peptides, despite their completely different amino acid compositions. The specificity of this cytotaxin receptor may therefore be broader than expected and depend on ligand characteristics distinct from primary structure.


Aryl hydrocarbon hydroxylase inducibility in lung cancer patients undergoing radiotherapy. Aryl hydrocarbon hydroxylase (AHH) inducibility was studied in cultured lymphocytes from 21 healthy control subjects and from 15 lung cancer patients selected for radiation therapy. AHH inducibility of the patients was measured prior to, during and at the end of radiation therapy. Four of 15 patients had values comparable to the healthy controls. Cellular DNA and protein measurements of cultured lymphocytes were the same for patients and healthy controls. There was no significant difference in the percentage of lymphoblast formation and percentage of cell survival between the two groups. Radiation therapy reduces the number of lymphocytes in vivo and the amount of lymphoblast formation in vitro. AHH inducibulity is signifcantly lowered by radiation in the patients who had very high inducibility at pre-treatment level. DNA and protein contents of cultured lymphocytes did not change during radiation therapy.


Serum, pituitary and urine concentrations of prolactin and growth hormone in eight strains of mice with varying incidence of mammary tumors. Eight inbred strains of mice with varying incidences of spontaneous mammary tumor were compared in regard to prolactin and growth hormone concentrations in sera, pituitary glands and urine. Serum prolactin was compared under basal conditions as well as after stimulation with perphenazine. Both hormones were measured with specific, homologous radioimmunoassays. Although some strains having a high incidence of mammary tumors had high levels of prolactin in sera, urine and pituitary glands, neither basal nor perphenazine-induced serum concentrations showed a consistent pattern across mouse strains that correlated with the incidence of mammary tumors. Growth hormone levels in sera, pituitary glands and urine also had no characteristic pattern that applied to all strains studied. The ratio of prolactin depleted from the pituitary gland to prolactin detected in serum after perphenazine injection, which reflected the metabolic clearance rate of prolactin, was highest in two strains with a high incidence of mammary tumors and relatively lower in low-tumor strains. These results suggest that if prolactin plays a part in mammary tumor development in mice, its mechanism varies with strains: while hyperprolactinemia may be the means in some strains, a peculiarity in the metabolism of the hormone may be more important in others.


Contribution of macrophages to interactions between tumor cells and other tissues assessed in an in vitro system. The modification of the tissues surrounding solid tumors is usually attributed exclusively to interactions between the normal tissues and the cancer cells in the tumor, in spite of the fact that tumors contain many different types of non-cancer cells including macrophages. As an experimental model for some facets of the cellular interactions between tumor and normal tissues, we have assessed the individual contributions of macrophages and cancer cells to the differential inhibition of neural retina (NR) cell aggregation by co-culturing NR cells with small numbers of macrophages or cancer cells alone, as well as with both natural (ascites tumors) and artificial mixtures. Cells from human colonic adenocarcinoma inhibited NR aggregation to a greater extent than normal colon mucosa. Aggregation of NR cells was inhibited by macrophages from mice and rats, and to a greater extent by cancer cell suspensions of mouse Ehrlich and rat Walker 256 lines from spinner culture or in the ascites form. Combinations of macrophages and cancer cells indicated that their inhibitory effects were neither additive nor synergistic. Cell-free media from macrophages and cancer cell cultures were equally effective inhibitors of aggregation. The results suggest that the interaction between a malignant tumor and the surrounding normal tissue can be modified by cancer cells, tumor macrophages and their products.


The relationship between sister chromatid exchange, chromosome aberration and gene mutation induction by several reactive polycyclic hydrocarbon metabolites in cultured mammalian cells. The ability of three ultimate matabolites of benzo(a)-pyrene and of 7-bromomethylbenz(a)anthracene to induce 8-azaguanine mutants, sister-chromatid exchanges and chromosome aberrations has been investigated. 7 beta,8 alpha-dihydroxy-9 alpha,10 alpha-epoxy-7,8,9,10-tetrahydrobenzo(a)pyrene was shown to be an extremely efficient inducer of both mutants and sister-chromatid exchanges at 100% survival, whereas its geometrical isomer, 7 beta,8 alpha-dihydroxy-9 beta,10 beta-epoxy-7,8,9,10-tetrahydro-benzo(a)pyrene and benzo(a)pyrene-4,5-oxide were comparatively weak. The potency of this compound, as both a mutagen and a sister-chromatid exchange inducer, gives further evidence that it may be the important carcinogenic metabolite of benzo(a)pyrene. 7-Bromomethylbenz(a)anthracene was a moderate mutagen and inducer of sister chromatid exchanges. Comparisons of the relative potencies of these four chemicals as inducers of both mutations and sister chromatid exchanges have indicated that these two phenomena are not directly related. The induction of sister chromatid exchanges also appears to be independent of the induction of chromosome aberrations.


Analysis of chromosomal proteins of fractionated chromatin from rat liver and transplantable hepatocellular carcinomas. The chromosomal proteins from a number of transplantable hepatocellular carcinomas (THC) induced by a single carcinogen or its derivatives and varying greatly in their growth rates were examined by sodium dodecyl sulfate (SDS) polyarcylamide gel electrophoresis. Before extraction and analysis of proteins, chromatin from hepatomas, as well as from normal and regenerating liver was fractionated into rapidly and slowly sedimenting gradient components. Ten non-histone chromosomal proteins (NHCP) present in the tumors and ranging in molecular weight from 220,000 to 55,000, were absent from normal liver. Further, each rapidly growing tumor possessed more non-histone protein bands in the most rapidly sedimenting chromatin fractions than did corresponding, slowly growing tumor fractions. A number of single protein occurrences common only to normal liver and/or rapidly or slowly growing tumors were also found. In contrast, NHCP banding patterns of rapidly growing 70% hepatectomized rat liver were identical to those of non-dividing liver. Of particular interest was the finding that the prototypic "minimal deviation tumor" 9618A varied more in its  NHCP-banding pattern when compared to liver than did those tumors which were rapidly growing and poorly differentiated. These studies represent an initial attempt at seeking NHCP which might be uniquely related to the malignant process.


Immunochemical characterization of tumor-associated surface antigens on a Moloney leukemia virus-lymphoma, MBL-2. Tumor-associated surface antigens (TASA) on a Moloney leukemia virus (M-MuLV)-induced lymphoma, MBL-2, in C57BL/6 mice (B6) were characterized. The surface proteins of MBL-2 cells were selectively radioiodinated and then extracted by Nonidet P40. The solubilized materials were then reacted with a variety of antisera: monospecific antisera to murine leukemia viral proteins (anti-gp69/71, anti-p30, anti-p15, anti-p12 and anti-p10), sera from B6 which regressed murine sarcoma tumors induced by murine sarcoma virus (anti-MSV) and a rabbit anti-MBL-2 antiserum. The resulting radioimmune precipitates were analyzed and compared in sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). The following results were obtained. (1) Among all anti-viral protein antisera tested only anti-gp69/71 was active and detected a protein doublet of gp69/71 and its degradation fragments of 42,000 and 35,000 daltons. (2) Radioimmune precipitates prepared with anti-MSV showed a SDS-PAGE pattern similar to that seen with anti-gp69/71. This result indicated that the surface antigen detected by the anti-MSV serum on MBL-2 tumor cell was probably a viral envelope antigen. (3) The rabbit anti-MBL-2 serum detected on the cell membrane an antigen of approximately 95,000 daltons which was tumor-associated and did not appear to be related to virion components. The anti-MBL-2-serum still reacted with the 95,000 dalton antigen after absorption with disrupted M-MuLV virus and with gp69/71 and p30 purified from the virus.


Lung tumors from PuO2-ZrO2 aerosol particles in Syrian hamsters. Syrian golden hamsters were given PuO2/ZrO2 particles via inhalation and/or Pu-laden ZrO2 ceramic 10-micron diameter microspheres lodged in the capillary bed of the lung. The mean initial lung burdens ranged from 8 nCi to 143 nCi for the six experimental groups of animals. Significant numbers of primary lung tumors (5-50% per group) were induced in those animals that received inhalation exposures. Additional alpha radiation administered via Pu-laden intravenous microspheres had little or no effect on tumorigenesis or the production of non-neoplastic, degenerative changes in the respiratory tract.


Anti-tumor potential of retinoic acid: stimulation of immune mediated effectors. Data are presented on the effects of retinoic acid (RA) treatment on the in vivo growth of tumors in two mouse strains. Inhibition of tumor growth as a result of systemic RA injection was observed in three out of seven tumor models. Using adult thymectomized, lethally irradiated and fetal liver (A x TFL) reconstituted mice, we found that inhibition of tumor growth is not due to direct toxic effects of RA but rather appears to be the result of stimulation of thymus-dependent immune-mediated effectors to suppress tumor growth. Results suggest that only strongly immunogenic tumors are sensitive to in vivo retinoid inhibition.


Active specific immunotherapy of murine leukemia. I. Irradiated tumor cell vaccine. This report describes a new animal model for active, specific, systemic immunotherapy of leukemia. Mice were challenged (day 0) with 10(3) viable LSTRA cells and treated later with a vaccine containing 10(7) irradiated LSTRA cells. Four intraperitoneal or intravenous vaccine injections, on days 2, 9, 16 and 23, caused significant prolongation of survival; single injections by the same routes had inconsistent effects. Vaccine was not effective against a higher initial challenge dose, when given later in the course of tumor growth, when given intradermally or when used in weanling mice. The therapeutic effect was specific since a vaccine composed of an antigenically unrelated leukemia was ineffective. These results suggest that LSTRA is suitable for studying active, systemic, specific immunotherapy.


Active, specific immunotherapy of murine leukemia. II. Adjuvant effect of Corynebacterium parvum. We have previously shown that irradiated LSTRA cells (LX) were immunogenic and could prolong survival of mice bearing LSTRA tumors. This study demonstrated that addition of Corynebacterium parvum to the LX dramatically improved the strength of tumor immunity. In pretreatment-challenge experiments, C. parvum augmented the immunogenicity of 10(6) LX given intradermally, with an optimum dose of 0.14-1.4 microgram C. parvum per mouse. In therapy experiments (intraperitoneal vaccine treatment after tumor cell challenge), the therapeutic effect of 10(7) LX was improved by admixture of C. parvum, leading to a larger number of cured mice, permitting treatment of a larger challenge inoculum, and allowing later initiation of treatment than was possible with LX alone. Optimal dose of C. parvum for therapy was 1,400 microgram per mouse. Presensitization to C. parvum or use of repeated vaccine injections did not further improve the therapeutic effect. Cure of tumor-bearing mice by the mixed vaccine was tumor-specific. These results suggest that C. parvum is a potent adjuvant for use in active, tumor-specific immunotherapy.


Augmentation of natural killer activity by pyran copolymer in mice. Treatment of older mice with pyran copolymer, a known interferon-inducer, was found to result in a rapid boosting of cell-mediated cytolytic activity against YAC-1 tumor target cells. The effector cells were characterized as being non-adherent and were presumed to be natural killer (NK) cells. Augmentation occurred in various lymphoid organs and was detectable 2-3 days after drug treatment. Differences in the levels of boosted activity among the lymphoid organs resulted when the route of administration was varied. The degree of augmentation was largely independent of the dose of pyran, but did vary among different strains of mice. Augmentation, moreover, was followed by a rapid decline by 5-7 days.


A surgical approach for the infected diabetic foot. Three hundred cases of major infection of the foot in diabetic patients are analysed. Based on our experience we have been able to define certain criteria which we have found useful in the management of these cases. It is felt that an aggressive surgical approach with careful surgical technique and the appropriate antibiotics can avert major radical amputation.


External fixation of unstable pelvic fractures. The Hoffmann external fixator was used to stabilize unstable pelvic fractures in 56 patients with multiple injuries. It was applied under general anaesthesia and the dislocated pelvis reduced and secured with a single tie bar. In 16 cases residual dislocation of less than 1.5 cm was noted after the reduction and the reduced position was maintained in 48 out of 51 cases, a minor redislocation occurred in the remaining 3 patients. Few complications could be attributed to the method, infection was noted in one patient, the iliac crest was fractured in one case and an exostosis of the iliac crest occurred in one youth. Forty-three patients were symptom free with regard to the pelvis at the time of review whereas 5 patients had residual pain and 3 diffuse symptoms. The technique of application is simple but requires two surgeons at the time of reduction and fixation of the pelvis.


Treatment of the femoral shaft fracture with a curved heat-treated COP clover-leaf nail. The commonly used straight intramedullary nail has certain limitations and disadvantages. Following radiographic and metallurgical studies we have developed a curved heat-treated clover-leaf nail using a newly developed precipitation hardening stainless steel (COP). The nail is bent with a slot on the convex side and the radius of curvature is 115 cm which corresponds to the anatomical antero-lateral convexity of the human femur. The nail has been satisfactory in clinical use since 1971 and has provided not only more stable internal fixation but also allowed fixation of fractures beyond the middle third of the shaft.


Preoperative normovolaemic haemodilution with dextran 70 as a thromboembolic prophylaxis in total in hip replacement. The effect of preoperative normovolaemic haemodilution with dextran 70 in 57 patients undergoing total hip replacement for osteoarthritis, was evaluated with respect to the production of thrombosis and pulmonary embolism. The patients were randomly allocated to one group undergoing preoperative haemodilution and one control group receiving 500 ml dextran 70 during operation and again on the second postoperative day. Before operation blood was replaced by dextran 70 to lower the hematocrit to between 25 and 30. The blood drained from the patients was used to replace blood lost at operation. Between 10 and 14 days after operation the patients were examined by perfusion lung scan, chest radiography and bilateral phlebography. Twelve patients also had 133Xe ventilation scans. The incidence of deep vein thrombosis in the two groups did not differ significantly. Pulmonary embolism was significantly decreased in the preoperative haemodilution group. One patient in the control group had clinical symptoms of, and died from, pulmonary embolism.


The treatment of arthritis of the shoulder joint by double osteotomy. This paper presents the new operations of double osteotomy of the shoulder for the treatment of painful arthritis. The procedure consists of osteotomy without displacement of the necks of both the scapula and the humerus. Sixteen patients who have had this operation have been followed for one to nine years (average 2 years 11 months). The results show good or excellent pain relief in 13 patients and a substantial increase in active abduction in 13 patients. Complications were few and none were serious. A possible reason for the reduction of pain is suggested and the advantages of this operation over arthrodesis and total shoulder replacement are discussed.


Biomechanical study of the pitching elbow. Medial-tension injuries of the pitching elbow are well recognized. One contributing factor is the extreme valgus which has been noted to occur during the acceleration phase of throwing. It is hypothesized that breaking pitches generate higher medial loading because of the pronation and supination required to impart spin to the ball. The pitching motion is a complex action of all body segments to produce maximum linear and angular acceleration of the ball. The purpose of this study was to correlate elbow loading with pitching style. We measured the forearm segment for axial and tangential (varus-valgus plane) acceleration using accelerometers attached to the forearm and hand. Muscle activity was measured by EMG. Forearm rotation was assessed by stroboscopic photography. Despite different delivery styles when throwing breaking pitches, each pitcher demonstrated patterns of muscle activity and acceleration which were similar. Deceleration forces were lower than acceleration forces. Pronation and supination were documented and contribute to the direction of ball spin. Accelerometers can be used to evaluate pitching mechanics. We suggest that the main factors causing an elbow injury are the amount of throwing and the force with which the ball is thrown.


A study on tension signs in lumbar disc hernia. The laminae were removed from the lower lumbar spines of five cadavers within four hours of death. A short length of rubber tube was inserted between the nerve roots and the lumbar disc and the tension monitored using semiconductor pressure transducers. The angulatory stresses exerted on the lumbar nerve roots during tension sign tests were found to correspond to clinical experience.


Spinal osteotomy to correct kyphosis in spinal tuberculosis. Twenty-seven patients with severe tuberculous kyphosis have been treated at the National Murayama Hospital between 1966 and 1977. We have undertaken curettage of the foci and vertebral osteotomy through an anterior approach, followed by gradual correction with a halo pelvic distraction apparatus and subsequent vertebral fusion. Choice of this method depends upon the age of the patient, the degree of kyphosis before correction, and the presence of concomitant lesions. Details of postoperative management are given and their importance is emphasized. The major risks of correction are discussed and precautions suggested.


Physiological effects of increased tissue pressure. The physiological effects of increased tissue pressure were studied using a model system in which known pressures were applied uniformly to the hindlimbs of rabbits for a period of 5 h. Muscle blood flow was monitored using a new argon washout technique. Muscle pO2, pCO2, and pAr were measured using a Teflon membrane catheter-mass spectrometer system. The myoneural conduction velocity served as a measure of the functional status of the limb. Higher tissue pressures led to successively greater compromise of muscle blood flow and pO2. Myoneural conduction velocity decreased significantly only when a pressure of 80 mm of mercury was applied, at which time muscle blood flow and pO2 were zero. These observations suggest that abnormalities of neuromuscular function are relatively late manifestations of a pressureinduced circulatory deficiency.


Appropriate nitroxoline dosage regimen design. Clinically used dosage regimen of nitroxoline, three times 100 mg daily, was proved to be inappropriate because the successfulness of medical treatment was rarely sufficient. Nitroxoline, used as urinary antiseptic, exhibits its antibacterial activity in concentrations higher than 6 mg/l, as demonstrated in many "in vitro" experiments. This work deals with the most appropriate nitroxoline dosage form as well as with the optimal dosage regimen design. The data were obtained by the aid of the suitable pharmacokinetic model and multiple dosing simulation on analog-hybrid computer EAI 580. From the several studied alternatives two usable dosage forms with the necessary dose and corresponding dosage interval were selected.


Pharmacokinetics of naproxen in healthy volunteers and in patients with diabetic microangiopathy. The pharmacokinetics of Naproxen administered as a single oral dose of 250 mg, have been determined in 7 healthy volunteers and 9 patients who had been diagnosed as suffering from diabetes mellitus with varying degrees of angiopathy. A two-compartment model was used to describe the biphasic decline in serum concentrations and to calculate the amount of drug in the central and peripheral compartments. In healthy volunteers the following values were obtained for various pharmacokinetic parameters: tmax = 2 hr; Cmax = 52.63 micrograms/ml; Ka = 1.893 hr-1; alpha = 0.393 hr-1; beta = 0.049 hr-1; K12 = 0.147 hr-1; K21 = 0.198 hr-1; K13 = 0.097 hr-1. In patients with severe diabetic microangiopathy, a decrease may be seen in the fraction of the dose absorbed shown by a decrease in the Cmax and the (AUC) 0--8 hr. The glomerular impairment of some patients leads to a decrease in the elimination constant.


In vitro and in vivo characteristics of some commercial phenobarbital tablets. Using an incompletely randomized crossover study design, the oral bioavailability characteristics of 7 different brands of phenobarbital tablets, USP, 100 mg was investigated in 5 adult, male volunteers. From plasma drug concentration-time data, best estimates for the bioavailability parameters of peak plasma phenobarbital concentration (Cmax) and time to peak concentration (tmax) were obtained by curve fitting and area under the plasma drug concentration-time curve (AUC) computed with the trapezoid rule. No significant difference in Cmax or normalized AUC was seen for the 7 products investigated. Additionally, a difference in tmax was observed between 2 preparations (A and E) only (p less than or equal to 0.05). All drug products met USP requirements for weight variation and tablet disintegration and all but one product (D) exhibited reasonably good and similar dissolution characteristics in simulated gastric fluid. No correlation between various in vitro dissolution parameters and in vivo bioavailability of phenobarbital could be found for the 7 phenobarbital products studied.


Treatment of hyperlipoproteinemia type II with etofibrate. Seven patients with hyperlipoproteinemia (HLP) type II (four patients with type II A and three patients with type II B), who were experienced to be resistant to hypolipidemic drugs, were treated for 6 months with etofibrate, a double-ester of nicotinic acid and clofibrinic acid, at a dose of 0.3 g t.i.d. Mean serum cholesterol level decreased by up to 18% from a pre-treatment value of 7.7 +/- 1.4 mmol/l. The reduction of serum cholesterol was due both to a decrease in very low density (VLDL) and low density (LDL) lipoprotein cholesteral by 61 and 25%, respectively (after 6 months). Furthermore alpha-LP (HDL) cholesterol increased by 8%, (after 6 months). All seven patients had previously received clofibrate and had obtained a mean decrease in plasma cholesterol by 6%. There was a slight transient increase in S-ASAT and S-ALAT simultaneous with in increase in serum urate. However, these values returned after 3 months to pre-treatment level. No influence on glucose tolerance was recorded. There were no bothersome side effects except a transient discomfort in the form of flushing or acid indigestion which occurred after 1--2 months of treatment with etofibrate.


Treatment of hyperlipoproteinemia (HLP) type II A with a new phenoxy-isobuturic acid derivative, procetofen. Eleven patients with hyperlipoproteinemia (HLP) type II A, were treated for 3 months with a new compound, a phenoxy-isobuturic acid derivative, procetofen, at a dosage of 100 mg t.i.d. Mean plasma cholesterol decreased after 3 months by 25% from a pretreatment value of 10.3 +/- 0.7 mmol/l (p less than 0.001). The reduction of plasma cholesterol was apparently due not only to a decrease in LDL, as expressed from a marked reduction (15%) of the major LDL apolipoprotein moiety, apolipoprotein B, but also presumably to a decrease in VLDL as reflected from a marked reduction (45%, p less than 0.05) in plasma triglycerides. Furthermore, a marked favourable increase (28%, p less than 0.001) in HDL major apolipoprotein moiety, apolipoprotein A, was observed. No disagreeable side-effects were recorded, except for a skin rash in one patient.


Effect of systemic autonomic inhibition on the hemodynamic response to antihypertensive therapy with timolol. To evaluate the role of systemic autonomic tone in the hemodynamic response to beta-inhibitors, the hemodynamic effects of long-term timolol therapy were studied in hypertensive patients under two sets of conditions: at rest and after pharmacologic systemic autonomic inhibition (SAI). Hemodynamic studies were performed in every subject at the end of a 4-week placebo period and again at the end of a 9-week treatment period. The antihypertensive effect of timolol was associated with decreased cardiac output and unchanged peripheral resistance at rest and with unchanged cardiac output and decreased peripheral resistance after SAI. The hemodynamic response to SAI during the two studies was also markedly different. The findings provide evidence of increased alpha-adrenergic component of systemic autonomic tone during long-term therapy with timolol.


Serum atypical pseudocholinesterase and leprosy. The frequency of the serum atypical pseudochloinesterase variant was significantly higher (p less than 0.005) in a group of 115 lepromatous leprosy patients than in a comparison group of 133 healthy individuals. This finding corroborates the results obtained in the group of patients from India, and supports the contention that the serum atypical pseudocholinesterase is one of the possible genetic factors involved in susceptibility to leprosy.


Exploring a new type of alcoholism survey. A new type of method for surveying alcoholism and alcohol-abuse was tested in a way designed to cover about 20% of adults in a town of 50 000. The method proved able to identify types of alcohol-abuser which other survey techniques have difficulty with; it made no undue demands on respondents; and it is much more economical than conventional household surveys. However, more work is still needed on it, and for certain types of information the customary self-report is still going to be required.


Respiratory abnormalities, smoking habits and ventilatory capacity in a highland community in Papua New Guinea: prevalence and effect on mortality. The prevalence of chronic lung disease was investigated in 1284 adult residents of 11 villages situated at 1800 m in the Highlands of Papua New Guinea. Chronic cough, shortness of breath on exertion, bronchial hypersecretion, and adventitious chest sounds were increasingly common in both sexes from middle life onwards, and were associated with an irreversible obstructive ventilatory defect. Over the age of 45 years, 20% of men and 10% of women had an FEV1/FVC % less than 60%. The prevalence of active asthma was 0.25%. The smoking of home-grown, air-cured tobacco was not associated with chronic respiratory symptoms or reduction of ventilatory capacity. Smoking was, however, associated with recent cough symptom, bronchial hypersecretion and adventitiae. Mortality over the subsequent 5 years was increased 2--3 fold in those with adventitiae, but was not related to smoking status. The aetiological relevance of wood smoke in the houses and acute chest infections remains to be clarified.


Iodization and thyroid status in relation to stillbirths and congenital anomalies. Thyroid status is known to have an important bearing on the ability of a woman to conceive, and to bring a normal infant to term. Thyroid status has changed in a number of previously iodine deficient countries as a result of recent iodization programmes. In this study, examination has been made of changes in the rates of two pregnancy outcomes in Tasmania, a State of Australia, namely, stillbirth and infant death due to congenital anomalies. Tasmania began iodine supplementation in 1950. Stillbirth rates declined more rapidly than in Australia as a whole, but show a peak associated with the peak of iodine-induced thyrotoxicosis in 1966. Congenital anomalies causing death show an initial rise in the early 1950s. It is suggested that this is due to persistence of iodine deficiency in the foetus after maternal iodine status improved sufficiently to allow term delivery of a live infant. The later fall coincides with the reaching of reproductive age by the first cohort of Tasmanian women who had been iodine sufficient since childhood, who would therefore not deprive their own foetus of iodine. Examination of trends in New Zealand, Switzerland and Finland, which have each introduced iodization programmes, confirms the largely beneficial effect of iodine supplementation on the rate of infant death due to congenital anomalies.


The relationship between infant mortality rates and medical care and socio-economic variables, Chile 1960-1970. Infant mortality rates (IMR) have traditionally been considered useful as health status indicators, and changes in these rates are thought to reflect changes in both medical care services and socio-economic circumstances. In order to explore this relationship of IMR with medical core and socio-economic factors in a developing country, Chilean health zone data for the decade 1960--1970 were used to construct 25 variables which were then classified into groups representing antenatal-obstetric services, acute and preventive medical services and socio-economic variables. In an analysis which involved developing a series of linear multiple regression equations for each year of the decade 1960--1970 with IMR as the dependent variable, the percentage of births with professional attention proved to be the stronger variable.


A methodology for determining high risk components in urban environments. A method of data collection and analysis is proposed for identifying environmental indicators significant to community health. The methods were applied to a study of child mortality in the city of Cali, Colombia. Pridit analysis (principal component analysis of ridits) is described. The methods have potential usefulness for monitoring and health care planning.


A mathematical model for the epidemiologic study of infectious diseases. Many infectious diseases have been hypothesized to represent common virus infections in which only small proportions of cases result in clinically recognizable disease. In order to find a method of studying this class of diseases, a mathematical model of the age distribution of clinical disease was developed using poliomyelitis as a prototype. The model is shown to fit the age distribution of reported poliomyelitis in a variety of localities before the use of artificial immunization. The true yearly rate of infection is easily estimated and ranges from .11 in rural Sweden to 1.20 in Chile. The model accounts for several major features of poliomyelitis epidemiology, including the shift to older ages and the high rate of clinically apparent disease which were frequently observed in populations which could be expected to have a comparatively low rate of spread. An examination of the age distribution of other diseases by these methods may provide a method of identifying other common infections which only occasionally result in clinically apparent disease.


Experience with an independent study programme in epidemiology and biostatistics. An independent study programme (ISP) was devised to permit self-paced learning in a combined epidemiology and biostatistics course for second-year medical students. The ISP was offered as an alternative to lecture instruction and the enrolment was restricted to 40 students out of a class of 176. The students who selected the ISP were superior to the remainder of the class with regard to MCAT scores and performance in first-year subjects. The ISP group scored higher on the examinations given in the course, including a set of 35 final examination questions which were identical for all students. This difference persisted even when the scores were adjusted for ability by use of MCAT scores. The time taken to complete the ISP varied considerably and there was no correlation between completion time and performance. Almost all the ISP students indicated satisfaction with the course and expressed a desire to have a similar option in subsequent courses.


Resting metabolic rate, weight, surface area and body composition in obese women. Resting metabolic rate was measured in 22 women with varying degrees of obesity. Body composition was estimated from total body potassium and from total body water, and creatinine excretion in urine was measured over a period of three weeks while the patients were on a creatinine and creatine-free reducing diet. Resting metabolic rate was highly significantly correlated with body weight, surface area, creatinine excretion and lean body mass calculated either from potassium or water measurements (P less than 0.001). Correlation with adipose tissue was less strong, and when multiple regression of both fat and lean on metabolic rate was performed, the relationship was seen to depend mostly on the mass of lean rather than adipose tissue. In obese people the water content of fat-free tissue is greater than that in normal subjects, so it is not valid to assume that fat content can be calculated accurately from a measurement of total body water.


The association of obesity with infertility and related menstural abnormalities in women. Historical data from 26 638 20-to 40-year women were used to study the association between obesity and menstrual abnormalities including evidence of infertility. It was found that women with evidence of anovulatory cycles, ie, irregular cycles greater than 36 days, and hirsutism, were more than 30 lb (13.6 kg) heavier than women with no menstrual abnormalities after adjusting for height and age. The percentage of women with evidence of anovulatory cycles was 2.6 per cent for women less than 20 per cent overweight, 4.0 per cent for women 20-49 per cent overweight, 5.8 per cent for women 50-74 per cent overweight., and 8.4 per cent for women more than 74 per cent overweight Women with a single menstrual abnormality including cycles greater than 36 days, irregular cycles, virile hair growth with facial hair, or heavy flow were also significantly heavier than women with normal values for these factors. A longer duration of obesity was associated with facial hair. Another analysis found that teenage obesity was greater for never-pregnant married women than for previously pregnant married women and for women having ovarian surgery for polycystic ovaries than for women having ovarian surgery for other reasons. This also supports an association of obesity with anovulatory cycles. These findings showing evidence of abnormal ovulation, menstrual abnormalities and excess hair growth in obese women may be explained by the recent studies of others demonstrating an association between obesity and hormonal imbalances.


Acute effects of nicotine on plasma free fatty acid concentrations and on the response to cold stress, in lean and obese (genotype ob/ob) mice. Lean and genetically obese (ob/ob) male and female mice were given nicotine by subcutaneous injection. Nicotine treatment was found to raise plasma free fatty acids by similar amounts in both lean and obese mice. In lean mice, nicotine caused depression of rectal temperature at ambient temperatures 22-25 degrees C and partially prevented the hypothermia in these mice when exposed to cold (o-3 degrees C). In obese mice, nicotine treatment did not alter either rectal temperature at 22-25 degrees C or the severe hypothermia on cold exposure. It is proposed that the effect of nicotine on free fatty acids is due to release of adrenal catecholamines and that this mechanism operates in both lean and obese animals. It is also proposed that, in obese mice under normal circumstances, there is a defect in the central nervous control of this adrenergic mechanism which may contribute to the observed fall in body temperature at low ambient temperatures.


Lipogenesis in vivo in lean and genetically obese (ob/ob) mice fed on diets with a high fat content. The effect of variations in the fat content of the diet on fatty acid synthesis in vivo was determined in lean and genetically obese mice, using the 3H2O incorporation technique. In both lean and obese mice the rate of fatty acid synthesis was higher between 21.00 - 22.00 h than between 09.00 - 10.00 h. When lean mice were given a high fat (low-carbohydrate) diet the rate of lipogenesis in adipose tissue and rest of carcass (whole mouse minus liver and adipose tissue) was less than in similar mice given a high-carbohydrate (low-fat) diet. In obese mice, the rate of lipogenesis in adipose tissue and rest of carcass was unaffected, but liver fatty acid synthesis was reduced. In lean mice fed on diets containing a constant percentage of carbohydrate and protein, increasing the fat content of the diet (and decreasing the proportion of cellulose) produced a decrease in fatty acid synthesis in liver, adipose tissue and rest of carcass, when the measurements were made during the night-time feeding period. During the day-time, the effect of increasing the fat content of the diet was less marked. In obese mice, dietary fat did not supress either the day-time or the post-prandial night-time rate of fatty acid synthesis. It is suggested that the hyperinsulinaemia in obese mice may be able to overcome the inhibitory effect of dietary fat on fatty acid syntheses.


Resting metabolic rate in obese and normal weight women. The relationship between resting metabolic rate and different parameters of body size was investigated among 28 female volunteers in the age group of 20--30 years. The resting metabolic rate of the subjects was determined indirectly by measuring the oxygen consumption in a closed circuit, in which the oxygen concentration was stabilised. The fat percentage of the body was determined by densitometry. The population was divided into two groups: the obese, with an average fat percentage of 33.6 and the normal-weight with an average fat percentage of 20.4. Mean values for the resting metabolic rate were 1550 kcal/24 h (6.488 MJ/24 h) for the obese and 1421 kcal/24 h (5.948 MJ/24 h) for the normal-weight group. The resting metabolic rate per kg body weight was lower in the obese than in the normal-weight persons. However, expressed per kg fat-free body mass, energy expenditure under resting conditions in the obese was higher than in the normal-weight. No single body parameter seems to be suitable in the explantation of RMR in women with substantially different fat content. The best prediction of resting metabolic rate in this population of obese and normal-weight women is obtained when both fat-free mass and fat mass are used as independent variables in a linear regression equation.


Granulocyte functions during treatment of obesity. Food deprivation is known to suppress antimicrobial defence under certain conditions. This potentially negative consequence of weight reduction treatment for obesity was studied in 11 obese patients who were treated with a mixed, balanced 600 kcal(2.5MJ)/day diet for 4 weeks. The mean body weight fell from 103 +/- 5 to 95 +/- 6 kg. The antimicrobial defence was studied before and during the diet period by analyses of polymorphonuclear granulocyte bactericidal capacity and adherence. No signs of impaired granulocyte function were found. The possibility remains that during prolonged treatment by semistarvation host defence may be impaired, especially in grossly obese patients whose antimicrobial defence may be already impaired before treatment.


Tissue ascorbic acid, fenfluramine, and changes in fat metabolism. Following initial weight gain, reduction in appetite and pronounced weight loss occurred in scorbutic unsupplemented guinea-pigs. Hepatic ascorbic acid levels were significantly reduced and cholesterol concentration increased in the liver. Fenfluramine administration caused immediate loss of weight and appetite in the scorbutic guinea-pigs, these changes being more pronounced in the males. Hepatic ascorbic acid, cholesterol and triglycerides were reduced to lower levels in the fenfluramine-treated scorbutic animals than in the scorbutic guinea-pigs receiving diet alone. In contrast, weight and appetite increased in vitamin-C-supplemented animals while they were receiving fenfluramine. Their hepatic cholesterol and triglyceride levels became significantly reduced. It has been shown that supplementary vitamin C can inhibit the anti-obesity and anorectic actions of fenfluramine and counteract its effect in raising tissue cholesterol.


Effects of a combined behavioral and pharmacological program on weight loss. The effects of an 'anorectic' drugs as an adjunct to a behavioral weight-loss programme were investigated. Four groups of 20 began an initial two weeks of instruction. Groups 1, 2, and 3 were instructed in a behavioral programme utilizing a food diary, stimulus control techniques, and reinforcement. Group 4 was instructed in a relaxation programme. Group 1 took phentermine resin 30 mg for eight weeks, followed by a placebo for eight. Group 2 took placebo for eight and phentermine for eight. Group 3 took placebo for 16. Group 4 took placebo for eight and phentermine for eight. All groups were followed for an additional eight weeks. A significant number of subjects in all behavioral groups achieved some weight loss. (A significant difference among the mean percentage body weight reduction for the three behavioral groups was also found.) In addition, a group of 'slow losers' who initially lost less than one half-pound (0.2 kg) per week and were subsequently placed on phentermine lost significantly more weight than a similar group which continued on placebo. These differences were maintained for 24 weeks.


A method of quantifying cultural ideals of beauty and the obese. A series of photographs of persons which had been varied by anamorphic lens to produce images both thinner and thicker than the originals were assessed by three experts in terms of percentage deviation from ideal body weight. Together with the photographs, five questions about preferences for body size were put to 341 persons who were also asked to assign each photograph to one of six basic categories of body weight in Puerto Rican culture.


Psychosocial aspects of extremely obese women joining a diet group. Fifty-eight women, desiring to lose at least 45 kg, participated in a diet group and completed a battery of personality inventories. Their scores differed significantly from normative data on several subscales of the personality inventories. As a group, these extremely obese women scored low on the Tennessee self-concept scales, particularly on the physical self-concept scale. On the Edwards personal preference schedule, they scored low on the deference, order, affiliation, nurturance, and endurance scales, and high on the dominance and heterosexuality scales. On the Minnesota multiphasic personality inventory, they scored high on the depression, hysteria, psychopathic deviate, and paranoia scales, and they scored low on the masculinity-feminity scale. The most striking finding was that these extremely obese women, who were not alcoholics, showed scores on alcoholism scales which are typical of an alcoholic population.


Psychological impediments to weight loss. An understanding of the possible psychologic impediments to weight loss can promote improved therapeutic intervention for the obese patient. Certain psychological tasks are imposed by chronic medical illness including obesity. The universal stresses that accompany medical illness, the basic threat to self-esteem and sense of intactness, the fear--of loss of love and approval, of loss of control of function, of injury to body parts, of pain, and of guilt--all become psychological impediments thwarting weight loss and its maintenance. The physician's awareness of these psychological stresses helps him identify areas of necessary support.


Effects of physical conditioning on cardiorespiratory function, body composition and serum lipids in relatively normal-weight and obese middle-aged women. The primary purpose was to investigate the effects of a 12-week (4 day/week) physical conditioning program on cardiorespiratory function, body composition, and serum lipids (cholesterol and triglyceride concentration) in sedentary, middle-age women. A secondary purpose was to clarify the influence of excessive body fatness on the conditioning response. Forty-two 29 to 47-year-old premenopausal women volunteered; four were excluded and two dropped out, leaving 36 who completed the study, ie, 23 obese (O) (greater than 30 per cent fatness, mean = 38 per cent) and 13 lean to normal (N) (less than 30 per cent body fatness, mean = 25 per cent). The conditioning program included a 10-minute warm-up, 15 to 25 minutes of walking-jogging at an individually prescribed training heart rate corresponding to 75 per cent of maximal oxygen intake (VO2max) and a five-minute recovery period. Heart rate and systolic blood pressure at a given submaximal work load decreased in both N and O. VO2max increased (P less than 0.001 in both groups. The average increase in O was 15.0 per cent and 18.9 per cent and in N 12.6 per cent and 12.7 per cent when VO2max was expressed inlitre .min-1 and cm3.kg-1.min-1 respectively. HRmax remained unchanged in N, but decreased slightly (P less than 0.01) in O. Body weight remained essentially unchanged in N, yet decreased (P less than 0.001) in O. The sum of ten skinfolds decreased significantly (P less than 0.001) in both groups, but with a greater reduction in O. Fatness decreased slightly in N (P less than 0.05) and more in O (P less than 0.001) while fat-free weight remained unchanged in both groups. The conditioning program had no effect on serum lipids in either group. Thus, a physical conditioning program of moderate intensity affected obese and leaner women in a similar fashion.


Pilot electromyographic studies of resting oral activity in obese and normal subjects. Subjects were placed alone in a room where purposeful oral activity such as eating, talking and smoking was not permitted, while activity such as pursing the lips sucking on cheeks, grimaces etc was measured by a specially designed electromyometer. This was done via electrodes attached to the peri-oral area and was recorded in a standardized fashion. In contrast to expectations, total resting activity in the obese did not differ significantly from that of normals. However, the two groups differ in that the time lapse prior to major peaking is significantly shorter in normals than in the obese. Analysis of patterns of both obese and normals suggests cyclic activity of approximately 120 min duration, and this was confirmed with a small group of ten obese subjects. The implications of these findings, in terms of previous work on oral cycles in the obese as well as implications for future research, are discussed.


Short-term effects of energy density on salivation, hunger and appetite in obese subjects. Obese patients were admitted to a metabolic unit for weight loss. On two paired-test days subjects were given disguised preloads of 100 kcal (0.42MJ) or 300 kcal (1.26MJ). When presented with a meal one hour after the preload, subjects salivated more and reported more hunger, but not appetite, after the low compared to the high preload. A different group of 14 subjects were given preloads of the same energy content (200 kcal, 0.84MJ) on paired-test days. On one day they took 1 g methyl cellulose with 100 ml water drink immediately before the preload. Neither the energy-dilution effect of the water, nor the effect of the methyl cellulose caused a significant decrease in salivation, hunger or appetite scores one hour after the preloads of equal energy content. These results show that salivation and hunger are inversely related to short-term changes in energy intake in obese subjects. Alterations in energy density without changing energy intake or the ingestion of methyl cellulose have no effect on salivation, hunger or appetite.


Effect of hypervitaminosis A on tongue muscles of the rat. A morphometric study. Daily administration of 200 I.U. vitamin A/gram body weight to rats, for a period of 10 days, causes generalized hypertrophy of the tongue muscles. The data were confirmed with morphometric techniques, consisting of increased cytoplasm and decreased nuclei and empty spaces, obtained by the Chalkley technique, nuclei of similar volume, obtained with the use of karyometry, and larger areas of cross-sections of muscle fibers.


Bioassay of vitamin A in liquid supplements. Vitamin A bioassay techniques based on liver storage in the chick were adapted for the assay of vitamin A in molasses based liquid supplements for cattle. Methods of administering the assayed supplement to the chicks were: 1) direct dosing of the supplement via four crop infusions at hourly intervals and 2) ether extraction, suspension in cottonseed oil with solvent removal in vacuo followed by direct crop dosing. The last method allowed a larger dosage with fewer analytical problems. Five sequential extractions were required for 97% recovery of the vitamin A from the molasses supplement. With the higher dosage range, the variance of response was a function of dose level. Transformation to a log dose - log response curve allowed a linear plot with homogeneity of variance. Detection of a 10% loss of vitamin A potency (P less than .10) was estimated to require 27 chicks per treatment by the slope ratio bioassay procedure.


The effect of megadose ascorbate on some haemopoietic factors in the young guinea pig. The effect of oral administration of megadoses of ascorbate was studied on some haemopoietic factors in young apparently normal guinea pigs. Supplementation of 150 mg of the vitamin for 7 days resulted in significantly increased haematocrit value and haemoglobin concentration. Total and unsaturated iron binding capacity were also increased in association with elevated plasma iron concentration. The difference of these results from the control animals, however, was not statistically significant. The improved haematological status in guinea pigs by ascorbate treatment could be attributed to haemoconcentration rather than to an effect of iron metabolism.


Vitamin C and the anti-obesity effect of fenfluramine. Increasing doses of fenfluramine were given to female guinea-pigs on a scorbutogenic diet with or without Ascorbic Acid (AA) supplementation. AA alone increased weight and appetite, hepatic and plasma AA. AA deficiency reduced weight after an initial rise. 10 mg/kg fenfluramine in association with the diet produced a gain in weight. Larger doses caused weight loss and reduced appetite. These effects were prevented by AA supplementation. Fenfluramine reduced hepatic and plasma AA significantly in comparison with the animals receiving the diet alone, or the diet with AA supplementation in the absence of fenfluramine administration. It is concluded that AA release plays an important role in the anti-obesity and anorectic actions of fenfluramine.


Riboflavin nutriture of oral contraceptive users. A Cross-Sectional and Follow-UP study of young women taking oral contraceptive agents (OCA) revealed no significant adverse effect of OCA Bon riboflavin nutriture. Three of 33 women in the Cross-Sectional study had biochemical evidence of deficiency, while only 1 of the 12 women in the Follow-Up study developed biochemical deficiency after a period of 3 months. The biochemical riboflavin status showed no relationship with the duration of OCA use. Dietary riboflavin intake was adequate in the majority of the subjects and revealed no correlation with activity coefficient of erythrocyte glutathione reductase activity.


Effect of oral contraceptive agents on thiamin status. A cross-sectional and follow up study of oral contraceptive agent (OCA) users revealed no adverse effects of OCA on erythrocyte transketolase activity (ETK) or thiamin pyrophosphate effect (TPP effect). In the cross-sectional study group, thiamin intake was below the recommended in only 19.2 per cent subjects and thiamin intake/100 kcal/day revealed a significant negative correlation with TPP effect. Routine prophylactic administration of thiamin was not indicated in OCA users.


[Flavonoids and pycnogenols].

[Flavonoids and pycnogenols]. Pycnogenols is the term put forward by the authors to designate flavan-3-ol derivatives, so as to distinguish these substances, upon chemical and pharmacological grounds, from the heterogeneous group of flavonoid compounds.


[Liver concentrations of water-soluble vitamins in rats treated, alone or in combination, with potassium metabisulfite, tannic acid, and ethanol]. Rats given tannic acid (3.2 p. 100 in diet) have lower biotin and total ascorbic acid liver contents (after 2 months), later they have higher vitamin B6 contents (after 6 months on the same diet). After 6 months riboflavin liver content is higher when ethanol replaces an equal amount of carbohydrate energy; this effect is reinforced by tannic acid. However liver vitamins contents was not affected by bisulfite.


Metabolic studies in rats under glucose and glycerol loading. It has been found in rats that 40% glycerol, when added to standard diet, reduces the food intake and thus prevents weight gain. The subcutaneous application (40 mg/kg three times daily) has no effect. Under pair feeding conditions the oxygen consumption, the RQ value and body weight remain unaffected as compared with controls receiving glucose. It is concluded that reduction of body weight induced by glycerol feeding is due to reduced amount of food intake and not due to any alterations of energy metabolism.


Effect of lead on certain aspects of protein metabolism. Administration of lead acetate (3.4 mg/100 g of body weight) by daily intraperitoneal route for 4 days in albino rats caused an increase in size of the liver and kidney. There was diminution of the protein content of the liver. Concentration of DNA decreased to a slight extent and protein/DNA ratio remained unaltered in liver and kidney. There was elevation of the concentration of RNA in both the organs. Protein/RNA ratio was reduced. RNA per unit amount of DNA was found to be increased and the activities of RNase and DNase in both the organs were reduced. There was also diminution of plasma protein level. The possible significance of these changes has been discussed.


Effect of oral contraceptive usage on zinc and copper in serum and hair. Zinc and copper concentration in serum and hair were determined in 12 women before the initiation of oral contraceptive therapy and after a period of 3 months and 6 months. A significant elevation in serum copper occured after the usage of oral contraceptive for 3 months. The taking of oral contraceptive agent (OCA) for a subsequent 3 month period caused no further significant increase in serum copper concentration. No significant effect of OCA on serum zinc and on hair concentration of these trace elements was noted. Further study is indicated to establish the significance of these on overall metabolism and on clinical consequences.


Retrograde pancreatic venography after reduction of the arterial visceral flow: an experimental study. To evaluate techniques for retrograde pancreatic venography similar to epinephrine renal venography, 35 dogs had transjugular portography before and after the infusion of various doses of vasopressin systemically or selectively into the superior mesenteric and celiac arteries, or after occlusion of the distal thoracic aorta. Increased filling of the peripheral portal branches resulted, but none of the techniques provided diagnostically useful enhanced pancreatic visualization.


Hemodynamic effects of vasodilators across iliac stenoses in dogs. Blood flow and pressure gradients were measured in dogs across externally applied iliac artery stenoses following 3 minutes of reactive hyperemia and injection of tolazoline (0.4 mg/kg), papaverine (0.04 mg/kg), and prostaglandin E1 (0.033 micrograms/kg) into the iliac artery. Stenoses of borderline and definite hemodynamic significance at rest were produced. The gradients produced with all four modalities of vasodilatation following borderline stenosis were significantly greater than those produced with each modality before the induction of stenosis. The peak effects of all modes of vasodilatation occurred within 30 seconds, although the effects of prostaglandin E1 were continued the longest. Our results indicate that pharmacologic or reactive hyperemia can help assess the significance of borderline iliac stenoses in patients with intermittent claudication.


Embolization of the spleen for treatment of splenomegaly and hypersplenism in patients with portal hypertension. Splenectomy in cases of hypersplenism involves significant risk of serious complications, including infection, hemorrhage, portal systemic thrombosis, and necrosis of the stomach or small bowel. Alternative procedures such as transcatheter embolization have been associated with a high frequency of splenic or subphrenic abscess, preventing clinical use. We used partial splenic embolization under careful antibiotic protection to successfully treat thrombocytopenia in 18 patients, most of whom had hypersplenism and splenomegaly secondary to portal hypertension. Of the 30 embolizations performed, the only serious complications encountered were abscess in two patients (who had almost total infarction) and four cases of splenic vein thrombosis. We investigated the possible effect of splenic embolization on portal venous pressure in three patients and found no pressure change.


Natural history of sick sinus syndrome following permanent pacemaker implantation. Forty-four patients with sick sinue syndrome (SSS) who had been treated with a permanent pacemaker were followed for an average period of 39 months. Fifteen patients had bradyarrhythmia alone (group 1) and 29 had bradycardia-tachycardia syndrome (group 2). Eight patients, all from group 2, died within a short period following pacemaker implantation. They all had ischemic heart disease, congestive heart failure and a short history of the symptomatic dysrhythmia. Eleven patients developed stable chronic atrial fibrillation, which terminated the clinical syndrome. In the remaining 25 patients, all without evidence of ischemic heart disease, the dysrhythmia persisted although symptoms were successfully controlled following pacemaker therapy. Based on these observations and data obtained from other surveys, we delineated three courses of SSS: 1) a subacute course, characterized by a short-term survival; 2) a transient, self-limited course in which conversion to stable atrial fibrillation occurs; and 3) a chronic course, in which the dysrhythmia persists and permanent pacemaker therapy is indicated.


A comparison of static and dynamic exercise soon after myocardial infarction. The cardiovascular response to treadmill exercise testing and to isometric handgrip was compared in 20 selected patients three to five weeks after acute myocardial infarction. The heart rate and the heart rate-systolic blood pressure product were significantly higher during treadmill exercise than during two minutes of isometric handgrip sustained at 25% of maximum voluntary contraction. No significant difference in systolic blood pressure was noted between the two types of exercise while diastolic blood pressure was higher during isometric exercise. Asymptomatic ST-segment depression was noted in two patients during the the treadmill test and was absent during handgrip. Angina pectoris was not noted during either type of exercise. Ventricular ectopic activity was slightly more frequent during treadmill exercise. Isometric handgrip at 25% of maximum voluntary contraction may be performed safely soon after myocardial infarction and provides useful guidelines for performing many customary physical activities requiring upper extremity isometric exertion during early convalescence.


Contrast absorption and pancreatic inflammation following experimental ERCP. The effect of saline and contrast agents intraductally injected into the pancreatic duct in sufficient volume to cause acinarization was studied in normal rats and in rats with acute pancreatitis. The effect of pancreatic inflammation on the disappearance of injected contrast material was investigated by injecting meglumine diatrizoate and 125I into the pancreatic duct. The activity appeared quickly in the venous blood of normal rats (peak activity at 5 minutes after injection). In rats with sodium taurocholate-induced pancreatitis, the appearance of activity in the blood was retarded. Ninety-two percent of the rats demonstrated pancreatic atrophy or pancreatitis histologically four days following acinarization of intraductally injected saline or metrizamide, meglumine diatrizoate, or meglumine sodium diatrizoate.


2:1 atrioventricular block associated with mitral leaflet prolapse. A case of mitral leaflet prolapse associated with 2:1 atrioventricular block is described. A His-bundle electrogram demonstrated an infra-Hisian level of block. Bradyarrhythmias and sudden death in this syndrome are briefly reviewed.


The pathology of end-stage renal disease in hemodialysis patients. The pattern of the renal disease and the pathological changes were studied in the kidneys of 80 autopsied patients who were maintained on hemodialysis for periods of up to seven years. Chronic pyelonephritis was most frequently encountered (25%); next in frequency were chronic glomerulonephritis (17.5%) and nephrosclerosis (17.5%). Moderate to severe intrarenal vascular changes were seen; intimal changes were most prominent. Statistically significant differences were observed in the distribution of the initimal lesions in intrarenal vessels of different calibres. Deposits of oxalate crystals, usually in the renal tubules, were encountered in all kidneys except four. Twenty-four patients (30%) showed acquired cystic kidney disease; renal calcification was observed in 61 others. The pathogenesis of these lesions in hemodialysis kidneys and their clinical significance are discussed.


Hyponatremia in myxedema: a suggested therapeutic approach. Two patients with myxedema coma and extreme hyponatremia associated with the syndrome of inappropriate secretion of antidiuretic hormone are described. Both recovered following i.v. hypertonic saline, furosemide and thyroxine. A review of 22 cases from the literature suggests that this therapeutic approach could improve the poor prognosis in this condition.


The effect of certain variables on the tumor and tissue distribution of tracers. Part 1; Carrier. Buffalo rats bearing thigh-implanted strain-7777 Morris hepatomas were used as a model for studying the effect of carrier material on the body distribution, tumor uptake, excretion, and tumor-to-background ratios of 67Ga and 54Mn. An effort was also made to observe the changes in 67Ga and 54Mn concentrations induced by carrier in viable tumor and skeletal muscle, relative to their interstitial fluid space. This value is referred to as the Tissue Distribution Index. Carrier manipulation resulted in striking changes in the distribution of the two ions from the carrier-free state. The data also indicated a difference in the pharmacodynamics of 67Ga and 54Mn in malignant and healthy tissues which could be of importance to nuclear medicine and oncology.


Muscle pathology in idiopathic scoliosis. Muscles from patients with scoliosis were studied to determine the possible relationship between neuromuscular disease and idiopathic scoliosis. Biopsies taken from the paraspinal musculature, the gluteus maximus and other sites were examined and compared with control specimens taken from patients undergoing spinal surgery for other disorders. Morphological and morphometric examinations by light and electron microscopy revealed a wide range of pathological changes and an alteration in the normal distribution of fiber types in most muscles. Changes were mainly nonspecific, but one unusual feature in idiopathic scoliosis but not in the other types of scoliosis consisted of type I fiber atrophy in paraspinal and deltoid muscles of the concave side paraspinal muscle, the site of the maximum morphological changes. The localized muscle changes, which are disease and not deformity related, suggest that idiopathic scoliosis is a separate disease entity and that the central nervous system may be involved in its genesis.


Computed tomographic cholangiography in a canine model of biliary obstruction. The CT scanner was used to generate the time-density relationship for hepatic parenchyma following Iodipamide (Cholografin, E.R. Squibb Co., New York, N.Y.) infusion. The curves which resulted from the normal, acutely obstructed, and chronically obstructed biliary system are shown. The peak enhancement of parenchyma is seen to be blunted in acute obstruction prior to anatomic evidence of dilated ducts. This finding may be of value in the early diagnosis of obstructive jaundice.


Juvenile diabetes mellitus.

Juvenile diabetes mellitus. Population studies in Israel have shown that Jews born in Europe or America have the highest prevalence of juvenile diabetes mellitus and Jews born in Asia or Africa, the lowest. The rate in the Israel born, regardless of the father's place of birth, is intermediate between those of the other two groups. The rates for the group from Europe/American and for the Israel-born group increased during the years 1963-68, while that for the Asia/Africa group did not change. It is speculated that the differences in the rates of juvenile diabetes mellitus are related to different frequencies of certain HLA antigens in the different groups or to different associations with susceptibility genes to juvenile diabetes.


Dialysis requirements in Israel.

Dialysis requirements in Israel. Chronic dialysis is available in Israel to almost all patients who require it. During the last four years the mean number of new patients/million population per year was 44.5 (range, 39.5 to 48.6), excluding patients with systemic diseases such as diabetes mellitus and lupus erythematosus. This number is close to that estimated in a previous study--53/million per year for the years 1965-66--and the discrepancy is probably methodological in nature. The stage of equilibrium for Israel, when the net gain in patients per year approaches zero, as forecast by the European Dialysis and Transplant Association, will be reached in 1983 with 261 dialysis patients/million population. At present, the number is about 171. Inadequately treated hypertension was found to considerably affect long-term survival.


Status of hypertension treatment in Israel. A review of the records of 17 family practices in the Tel Aviv area showed that 31% of charts had no record of blood pressure readings. In other studies, only 45% of subjects with prescribed medication remained on treatment. Some of the patients who had started medication stopped going to the doctor of their own accord. Only 32% of those who remained on treatment had their blood pressure under control. Poor compliance, inadequate therapeutic regimen and high dropout rate explain the picture in Israel. A screening program for hypertension will fail if not accompanied by high-quality medical care and careful follow-up. When specially trained nurses joined doctors in the management of high blood pressure patients, a follow-up of 726 patients originally treated by a doctor alone and then by a doctor-nurse team for one year showed that the percentage of controlled hypertensives rose from 39.2 to 72.8% and the dropout rate fell from 30 to 0.65%. The adoption, on a national scale, of a doctor-nurse team approach for controlling hypertension is, therefore, strongly recommended.


Demography, morbidity and mortality in Israel: changes over 30 years. The last 30 years have seen vast changes in the size and composition of the Jewish and Arab populations of Israel. The Jewish population has increased 4 1/2 times but the proportion of aged has increased 10-fold. Infant mortality has decreased considerably and life expectancy has increased for both sexes and both populations. Patterns of morbidity and mortality have changed from those characteristic of the Middle East to those commonly seen in developed countries, with ischemic heart disease, cancer and stroke the leading causes of death.