Lymphocoeles in renal homograft recipients. Seven lymphocoeles have complicated 158 cadaver and 18 related live donor transplants performed over six years. The purpose of this study is to review the clinical, diagnostic and therapeutic problems encountered with lymphocoeles at this centre. Presentation was insidious, delayed (50 days post-op), and manifested by one or more of the following: palpable rectal or supra-pubic mass; unilateral leg oedema; recurrent urine infections with radiographic evidence of obstruction; filling defect in bladder on routine IVP. Possible pathogenetic factors: transplants performed on side of functioning Scribner shunts (6/7 cases); severe rejection episodes with graft lymphatic leak (1/7 cases). Differentiation from urinomas, haematomas, perinephric abscesses or other causes of obstructive uropathy were facilitated by: needle aspiration; IVP and cystogram, serial ultrasound sonography. Lymphangiography was not used. Treatment was conservative in three, repeated aspirations were performed in two and formal drainage procedures were required in three patients. Repeated cyst aspirations resulted in serious infections in both patients. Marsupialisation into the peritoneal cavity failed in one. 1) The graft should be anastomosed on side opposite a functioning shunt. 2) Lymphocoeles have an occult presentation and should be actively sought for as they may produce urinary obstruction. 3) Serial ultrasound is an excellent method of diagnosis and follow-up. 4) Unless urinary obstruction is present management should be conservative as spontaneous resolution may occur. 5) Ideal surgical management is problematical. Repeated needle aspirations should be approached with caution. Lymphocoeles are an uncommon but well documented complication of renal transplantation (Schweizer et al, 1972; Koehler et al, 1972; Christiansen et al, 1974; Rashid et al, 1974). They represent definite hazards and can either directly or indirectly contribute to morbidity or even mortality in the post-transplant patient. They must be differentiated from other pelvic masses such as urinomas, haematomas and perinephric abscesses as they all require different modes of treatment. As a rule, the diagnosis of one from another is straightforward, but as certain clinical features are shared, differentiation can on occasions be more difficult. In order to clarify some of these problems and outline a mode of therapy, a study was carried out in patients who have presented with lymphocoeles in our unit.


Hypertension after renal transplantation. The incidence of hypertension defined as a mean diastolic pressure above 90 mmHg has been evaluated in 85 transplanted patients with a follow-up ranging from 3 to 78 months. The proportion of hypertensive patients rises during the first three months and stabilises subsequently around 60 percent. Over the years hypertension fluctuates so that one-third of the initially hypertensive patients become normotensive, whereas one-third of the initially normotensive patients become hypertensive. The main single aetiological factor is renal failure. No clear relationship was found between prednisolone dosage and hypertension. Renal artery stenosis was found in 2.4 percent of the cases. Finally no single aetiological factor was found in one third of the hypertensive patients. It is speculated that in some of them, minute intrarenal vascular lesions are responsible for the hypertension and lead ultimately to decreased renal function.


Plasma renin activity (PRA) and plasma aldosterone (PA) in hypertensive kidney allograft recipients. Basal and stimulated plasma renin activity (PRA) and plasma aldosterone (PA) were measured in 13 hypertensive and 16 normotensive patients with kidney allografts one to nine years after transplantation. In both groups no significant differences were observed between mean basal and stimulated PRA and PA values. Therefore, we conclude that abnormal renin secretion might not be the main factor causing hypertension in renal allograft recipients. Other mechanisms seem to be involved in the pathogenesis of hypertension in these patients.


Kidney preservation by continuous hypothermic albumin perfusion without membrane oxygenation. Continuous hypothermic albumin perfusion in the new Gambro device utilising surface oxygenation of the perfusate was studied in 20 consecutive human kidneys at the Transplantation Clinic in Gothenburg. The results were compared with previous results of kidney storage using simple hypothermia and continuous perfusion with membrane oxygenation. The mean preservation time was increased from eight and 24 hours in the previous material to 30 hours in the studied group. Immediate onset of function occurred more frequently after surface oxygenation and all kidneys perfused for the longest period of 30 to 48 hours, had immediate onset of function. No increased LDH release was observed after prolonged perfusion. Delayed onset of function could in most cases be attributed to prolonged warm ischaemia time in which cases also increased LDH release was observed. Continuous albumin perfusion using surface oxygenation was found to be equally efficient in clinical practice as the previously used system with membrane oxygenation.


Effect of organ preservation in cadaver kidney transplantation. Hypothermic pulsatile perfusion did not adversely affect long-term renal allotransplant function and did not result in an increased rate of rejection. Thus, we can conclude that perfusion had little effect on the immunogenicity of renal allografts. The incidence of acute tubular necrosis was directly related to the length of warm ischaemia and perfusion time. However, long-term renal function was not influenced by acute tubular necrosis. Perfusion is a safe and reliable way of preserving cadaver donor kidneys until transplantation.


Alteration of polynucleotide secondary structure by ribosomal protein S1. Ribosomal 30S protein S1 causes disruption of the secondary structure of certain pyrimidine-containing polynucleotides. Helical poly(U), poly(C, U), and neutral and acidic poly(C) are stoichiometrically converted by S1 to structures indistinguishable from their partially or completely thermally denatured forms, as revealed by circular dichroism. Of the several double- and triple-stranded helical polynucleotides tested that contain one polypurine strand and at least one polypyrimidine strand, only the conformation of the DNA.RNA hybrid, poly(A)-poly(dT), is perturbed. In the presence of S1, this hybrid undergoes a transition to a new structure that has a circular dichroism spectrum unlike either the native or thermally denatured forms. Intercalated ethidium bromide is released from poly(A)-poly(dT) by S1, confirming the occurrence of a conformational rearrangement. The translation inhibitor, autintricarboxylic acid, completely inhibits the action of S1 on polypyrimidines, but has no effect on the conformational perturbation of poly(A(-poly(dT). The possible relation between these observations and the biological function of protein S1 is discussed.


Ribosomal proteins of Escherichia coli that stimulate stringent-factor-mediated pyrophosphoryl transfer in vitro. Guanosine tetra- and pentaphosphate, (p)ppGpp, can be synthesized in vitro in a reaction containing only the enzyme (stringent factor), salts, and substrates (nonribosomal system). This reaction is greatly stimulated upon addition of methanol (methanol system) or by ribosomes, mRNA, and tRNA (ribosome system). Here we show that several ribosomal proteins alone stimulate the synthesis of (p)ppGpp in the presence of stringent factor (protein system). The optimal ionic conditions for the ribosome and protein systems are identical. The concentration of ribosomes or any stimulating ribosomal protein required for saturation of a given concentration of stringent factor is similar. Fifty of 54 ribosomal proteins were tested for stimulation in the protein system; 15 proteins showed high activity, seven of these from the 30S ribosomal subunit and eight from the 50S subunit. The physiological relevance of this finding is discussed.


Synthesis of yeast histones in the cell cycle. The yeast, Saccharomyces cerevisiae, contains four types of histones resembling histones H3, H2b, H2a, and H4 of animal cells. These proteins are synthesized primarily, if not exclusively, in the S-phase of the cell cycle. This result is discussed with reference to the insensitivity of ongoing DNA replication in yeast to inhibitors of protein synthesis.


Protein-protein interaction in transport: periplasmic histidine-binding protein J interacts with P protein. A component of the high-affinity histidine transport system in Salmonella typhimurium, the periplasmic histidine-binding protein J, interacts with another transport component, the P protein. A mutant J protein, with a defective interaction site but intact histidine-binding site, can function in histidine transport if an appropriate compensating mutation is introduced in the P protein. The interaction between the J and P proteins is an obligatory step in transport. The significance of this interaction and of the involvement of the P protein in multiple transport functions is discussed.


Morphogenesis of the bacterial division septum: a new class of septation-defective mutants. A new class of mutants of Salmonella typhimurium (lkyD mutants) are described. The mutants are defective in morphogenesis of the division septum, and are characterized by a failure of the outer membrane to invaginate despite normal ingrowth of the cytoplasmic membrane and murein layers of the growing septum. The cell envelopes of the mutants show a significant decrease in the bound form of murein-lipoprotein and a corresponding increase in the free form of the lipoprotein. This suggests that the morphogenic defect may result from a defect in formation of covalent bonds between the free lipoprotein of the outer membrane and the murein of the nascent septum.


DNA synthesis in vitro dependent upon phiX174 replicative form I DNA. Extracts of Escherichia coli strains infected with bacteriophage phiX174 catalyze DNA synthesis dependent on double-stranded, circular phiX174 replicative form I (phiX RFI) by a semiconservative process. The reaction required Mg++, ATP, all four dNTP, and exogenous phiX RFI DNA as template and yielded phiX RFI and phiX RFII. The reaction was inhibited by nalidixic acid and novobiocin but not by rifampicin. DNA synthesis required the phiX174 gene A product and E. coli gene products dnaB, dnaC(D), dnaG, and rep.


Ribonuclease P substrate specificity: cleavage of a bacteriophage phi80-induced RNA. RNase P can cleave in vitro a bacteriophage phi80-induced RNA which is 62 nucleotides long [M3 RNA, G. Pieczenik et al. (1972) Arch. Biochem. Biophys. 152, 152-165] to yield two specific fragments 25 and 37 nucleotides long. As is the case for another substrate of RNase P; the precursor to Escherichia coli 4.5S RNA, the cleavage site in M3 RNA is at the end of a long double-stranded region immediately adjacent to a single-stranded segment. Similar nucleotide sequences span the cleavage site in both substrates. These and other features of the reaction of RNase P with M3 and 4.5S precursor RNA are different from some aspects of the reaction of this enzyme with tRNA precursor molecules. A qualitative scheme is presented that is directed towards the understanding of the differences in RNase P cleavage site specificity for these substrates.


Cell-free synthesis of rat preproinsulins: characterization and partial amino acid sequence determination. Whole nucleic acid fractions of isolated rat islets of Langerhans greatly stimulate incorporation of radioactive amino acids into protein in a wheat germ ribosomal system. Approximately 30% of the synthetic product is precipitated with antisera to insulin or proinsulin. Characterization of this material by gel chromatography and sodium dodecyl sulfate-polyacrylamide gel electrophoresis indicates a molecular mass of 11,500 daltons. Trypsin digestion releases intact A chain as well as tryptic fragments of the C-peptides and B chains of the two rat proinsulins. Automated sequence determination of labeled cell-free product purified by immunoprecipitation discloses the presence of 23 additional amino acids NH2-terminal to the B chain sequence of proinsulin. The partial amino acid sequence of this extension is as follows: NH2-X-Leu (Lys) Met-x-Phe-Leu-Phe-Leu-Leu (Lys) Leu-Leu-x-leu-X-X-X-X-X-X-X-X-proinsulin. On the basis of the above evidence we have designated this peptide preproinsulin.


A chromosomal gene required for killer plasmid expression, mating, and spore maturation in Saccharomyces cerevisiae. "Killer" strains of Saccharomyces cerevisiae are those that harbor a double-stranded RNA plasmid and secrete a toxin that kills only strains not carrying this plasmid (sensitives). Two chromosomal genes (kex1 and kex2) are required for the secretion of toxin by plasmid-carrying strains. The kex2 gene, which maps at a site distinct from the mating-type locus, is also required for normal mating by alpha strains and meiotic sporulation in all strains. Strains that are alpha mating-type and kex2 fail to secrete the pheromone alpha-factor or to respond to the alpha-factor II pheromone which causes a morphological change, but they do respond to alpha-factor I which causes G1 arrest in alpha cells. Strains that are alpha mating-type and kex2 show no defect in mating; pheromone secretion, or response to alpha-factor. Diploids that are homozygous for the kex2 mutation, unlike wildtype or heterozygous diploids, fail to undergo sporulation, with the defect occurring in the final spore maturation stage. These same defects in the sexual cycle are present in all kex2 mutants independent of the presence of the "killer" plasmid.


Characterization of 2-mum DNA of Saccharomyces cerevisiae by restriction fragment analysis and integration in an Escherichia coli plasmid. Electrophoretic analysis of EcoRI and HindIII restriction fragments of 2-mum supercoiled DNA of Saccharomyces cerevisiae indicated that this class of DNA is heterogeneous and probably consists of two types of molecules. Integration of the 2-mum yeast DNA in E. coli plasmid pCR1 directly showed that existence of two types of molecules as each of these could be individually inserted into separate bacterial plasmids. The difference between the two types of 2-mum circles is due to an inversion of about 1.6 X 10(6) daltons. The inversion is flanked by a reversed duplicated sequence of 0.45 X 10(6) daltons. Possible implications of this structure are dicussed.


Biogenesis of mitochondria: molecular mapping of the mitochondrial genome of yeast. We have developed a new procedure for the detailed molecular mapping of any allele of the yeast (Saccharomyces cerevisiae) mitochondrial genome. The procedure employs a collection of different genetically characterized petite strains whose genomes have been physically defined by molecular hybridization. The map position of an allele is within the DNA segment common to all defined petites that can be shown by marker rescue to retain the locus. The same collection of petites can be used to locate the positions of mitochondrial rRNA and tRNA cistrons and DNA fragments produced by restriction endonucleases.


Mouse spleen lymphocyte bactericidal and peroxidase activities: enhancement by whole body x-irradiation. A 20,000 g pellet obtained from the homogenate of CD1 mouse spleen cells has measurable peroxidase and bactericidal activities. Whole body x-irradiation stimulates the in vitro peroxidative and bactericidal activities of the spleen cells. These cells do not phagocytize. However, addition of polystyrene latex particles to spleen cells from non- or x-irradiated mice, increases glucose oxidation. The extent of this stimulation (three- to fourfold) is less than that of PMN (six- to tenfold). Interaction between particles and lymphocyte surface may be the cause of this stimulation. The increased bactericidal activity due to x-ray is attributed mainly to an increase in the peroxidase activity of the lymphocytes. Surface (membrane) action rather than phagocytosis may be involved in the bactericidal process. The spleen lymphocyte peroxidase is distinct from myeloperoxidase in several respects.


Cannula system for local stimulation of the rat brain. The cannula design permits microinjection and push-pull perfusion, plus the use of a pressure probe for intraventricular placements.


Beam hardening in x-ray reconstructive tomography. As a polychromatic X-ray beam passes through matter, low energy photons are preferentially absorbed, and the (logarithmic) attenuation is no longer a linear function of absorber thickness. This leads to various artifacts in reconstructive tomography. If a water bag is used, the nonlinear attenuation in bone causes a distortion of the bone values and a spill-over inside the skull, or 'pseudo-cortex' artifact. If no water bag is used, there is an additional effect due to the varying thickness of soft tissue which causes a depression of interior values, or 'cupping'. Both artifacts can be remedied by additional prefiltering of the beam and by applying a linearization correction to the detector outputs.


Neurophysiology of locomotor automatism. It had long been known that the decapitated cock can cross a yard. During the last century an automatic mechanism controlling stepping movements has also been found in other vertebrates. The system controlling locomotion has many features similar to these systems controlling other natural movements: respiration (28), micturition (98), scratching (154), mastication (33), etc. Today we know that there are spinal automatisms for each limb generating its stepping movements. Activity of these automatisms depends essentially on the afferent inflow from the moving limbs. There also is interaction of the limbs during locomotion that promotes their coordination. The existence of two descending systems with different functions in the control of locomotion (Fig. 1) also can be considered as an established fact. Activity of a number of neurons involved in the control of locomotion has been studied directly during locomotion in decorticate, thalamic, and mesencephalic cats. To explain the experimental data at hand, several hypotheses of organization of the spinal automatism of stepping have been forwarded: a chain-reflex hypothesis, a hypothesis of two reciprocal half-centers, and a ring hypothesis (Fig. 2). Although general features of the system controlling locomotion are more or less clear, many questions are not yet answered. It is unknown what relative contributions to motoneuronal activity are made by proprioceptive reflexes versus influences from the automatism of stepping. Furthermore the structure of the spinal stepping automatism is not known. It is not clear if the spinal stepping automatisms of the forelimbs are as potent as those of the hindlimbs. The descending system responsible for activation of the spinal automatism of stepping has not yet been identified in direct experiments. The inputs and outputs of the subthalamic and midbrain "locomotor" regions have not been found, and we know almost nothing about intrinsic interaction of neurons in these regions. The role of inhibitory thalamic influences is scarcely known. Finally, we have no data concerning the influence of either cortical (42, 186) or visual mechanisms in locomotor control.


Transport of molecules across renal glomerular capillaries. Direct measurements of the pressures and flows governing the formation of glomerular ultrafiltrate have been made possible in recent years by virtue of 1) the discovery of rats and monkeys possessing glomerular capillaries on the renal cortical surface, accessible to micropuncture, and 2) technological advances that permit measurement of intracapillary hydraulic pressure and assessment of the change in colloid osmotic pressure along the glomerular capillary network. Based on these direct measurements, evidence has been obtained to indicate that glomerular capillary hydraulic pressure and hence the net driving force for ultrafiltration are lower than previously believed. By the efferent end of the glomerular capillary network, net filtration of fluid ceases, owing to a reduction in the net driving force to zero. Evidence in the rat indicates that the process of ultrafiltration is highly dependent on glomerular plasma flow rate. Studies in rats with surface glomeruli have also made possible an assessment of the factors that govern the transport of macromolecules across the highly specialized capillary network. In addition to molecular size, transcapillary movement of macromolecules is influenced by the glomerular filtration rate, since total transport reflects the combined contributions of convection as well as diffusion. Molecular charge has also been found to be an important determinant of the transport of macromolecules, very likely contributing to the marked restriction to the transcapillary movement of albumin. This electrostatic restriction to the transport of polyanions such as albumin, by some fixed, negatively charged component(s) of the glomerular capillary wall, is markedly reduced in primary glomerular injury. Evidence indicates that glomerular injury results in loss of these fixed negative charges from the capillary walls, providing an attractive explanation for the enhanced filtration of albumin, and hence the proteinuria, observed in a variety of glomerulopathic states.


Spatial patterning of response to odors in the peripheral olfactory system. The low odor specificities of the olfactory receptors suggest that odor recognition depends on the simultaneous activity in an ensemble of receptor neurons. This ensemble could conceivably code quality without reference to the point of origin of each input on the receptor sheet. However, the nose-to-bulb projection appears sufficiently precise to provide the bulb with a topographical map of the receptor sheet although it is poorly delineated in the anteroposterior plane. (It is also known that the morphological changes that follow prolonged exposure to odors are more differentiated in the coronal than in the anteroposterior plane.) Furthermore, it is clear from work at both epithelial and bulbar levels that a spatiotemporal pattern of excitation is generated by odor stimulation of the receptor sheet and that this pattern differs for different odors. This evidence, then, supports the view that there is a spatial component to odor quality coding. This spatial pattern has two elements. One is imposed and depends (at least in part) on differences in the retentivity of different odorants by the mucous sheet, which has powerful sorptive properties. It effectiveness seems particularly weak for odorants with relatively long retention times. The second component is inherent and depends on the tendency of receptors with similar peak odor specificities to aggregate in the same region (or regions) of the epithelium. Different odors or groups of odors maximally excite different regions, which may overlap. The imposed component could not, in itself, provide an adequate mechanism for odor recognition, partly because many compounds have comparable or even identical mean retention times (e.g., enantiomeric isomers). The inherent component, on the other hand, possesses this potential. However, either or both forms of patterning may cooperate with a third nonspatial mechanism (based on differential responsiveness of receptors to different odors) in coding odor quality.


Treatment or punishment? A nineteenth-century scandal. In psychiatry the relationship between treatment and punishment is variable and ambiguous. It has always been possible to employ physical methods of treatment for punitive ends, against which the introduction of liberal policies is no complete safeguard. Indulging one's personal animosities towards a difficult or violent patient has always been condemned, but the motives of a psychiatrist may be particularly easily misconstrued. These inherent risks in a psychiatrist's situation are illustrated by a case from the 19th century.


A note on classifying phobia.

A note on classifying phobia. The increasing interest in the treatment of phobias underlines the need for clarifying their definition and classification. A brief historical note highlights some of the difficulties which have been, and still are, encountered.


Psychiatric symptoms during l-dopa therapy for Parkinson's disease and their relationship to physical disability. Fifty patients attending a neurological outpatient clinic for Parkinson's disease were assessed by standardized methods for both physical and psychiatric symptoms. The patients then received treatment with L-dopa with carbidopa or anticholinergic drugs and/or amantadine. During the following six-month period the subjects were assessed at intervals, both physically and psychiatrically. Forty patients were followed up for the full six-month period. The severity of physical signs and affective symptoms was shown to be significantly related at several stages of the investigation. Initially, the patients showed a high psychiatric morbidity. During treatment, 22 patients developed a depressive disorder, 12 or which had a history of previous depressive episodes. By contrast, of the 11 patients who showed very few affective symptoms during follow-up, none had a history of depression. Of the 22 patients with a depressive disorder, only two were in the anticholinergic/amantadine group, compared with nine and 11 in the other groups. L-dopa was not an effective antidepressant agent. The probable relevance of the findings of the study to the management of patients with Parkinson's disease is outlined.


Effects of progressive relaxation on sleep disturbance: an electroencephalographic evaluation. Subjects with reported sleep-onset disturbance were given progressive relaxation training, placebo, or no-treatment. All three conditions showed significant improvement in daily reported sleep onset over the duration of the study. Between-condition effects were limited to relaxation superiority over no-treatment on Stage 1 sleep, and over placebo on postquestionnaire items and sleep-latency reports at 1-year follow-up.


Life-history tactics: a review of the ideas. This review organizes ideas on the evolution of life histories. The key life-history traits are brood size, size of young, the age distribution of reproductive effort, the interaction of reproductive effort with adult mortality, and the variation in these traits among an individual's progeny. The general theoretical problem is to predict which combinations of traits will evolve in organisms living in specified circumstances. First consider single traits. Theorists have made the following predictions: (1) Where adult exceeds juvenile mortality, the organism should reproduce only once in its lifetime. Where juvenile exceeds adult mortality, the organism should reproduce several times. (2) Brood size should macimize the number of young surviving to maturity, summed over the lifetime of the parent. But when optimum brood-size unpredictably in time, smaller broods should be favored because they decrease the chances of total failure on a given attempt. (3) In expanding populations, selection should minimize age at maturity. In stable populations, when reproductive success depends on size, age, or social status, or when adult exceeds juvenile mortality, then maturation should be delayed, as it should be in declining populations. (4) Young should increase in size at birth with increased predation risk, and decrease in size with increased resource availability. Theorists have also predicted that only particular combinations of traits should occur in specified circumstances. (5) In growing populations, age at maturity should be minimized, reproductive effort concentrated early in life, and brood size increased. (6) One view holds that in stable environments, late maturity, broods, a few, large young, parental care, and small reproductive efforts should be favored (K-selection). In fluctuating environments, early maturity, many small young, reduced parental care, and large reproductive efforts should be favored (r-selection). (7) But another view holds that when juvenile mortality fluctuates more than adult mortality, the traits associated with stable and fluctuating environments should be reversed. We need experiments that test the assumptions and predictions reviewed here, more comprehensive theory that makes more readily falsifiable predictions, and examination of different definitions of fitness.


Ultrasonic "B" scanning in the diagnosis of complications in renal transplant patients. B-mode ultrasonography has been used in the evaluation of complications following renal transplantations. The main indications for examining the patient are decreased renal function, clinically suspected abscesses, or suggestions of a mass in the region of the transplant. In most patients, worsening renal function is due to rejection. In 10 of 50 patients, however, lesions such as lymphoceles, postoperative hematomas, abscesses, and urine leakage were diagnosed. Ultrasonography proved to be a noninvasive and reliable method for the assessment of these complications.


Carcinoembryonic antigen and skin test reactivity in tumor radiotherapy. Serial carcinoembryonic antigen (CEA) levels were obtained from 122 cancer patients. In a random selection, the levels in 67 of these patients were compared with clinical response to radiotherapy. Skin tests were also performed for histoplasmin, tuberculin and mumps. CEA levels, skin-delayed hypersensitivity reaction (DHR) and clinical tumor response were evaluated and correlated. Clinical response of tumors to radiotherapy was more often seen in patients with positive skin tests, but no correlation was observed between skin test reactivity and CEA response curves.


Detection of upper abdominal abscesses by radionuclide imaging. An improved means of detecting upper abdominal abscesses using the dual radionuclide subtraction technique was applied to 51 patients. 67Gallium citrate was used in the localization of the lesion and 99Tc-labeled human albumin microspheres and 99Tc sulfur colloid were used for subtracting out the interfering background from normal organ concentrations. The procedure provided the parameter capabilities for localization of the abscesses as well as information on their shape and size. Compared to nonsubtraction Ga procedures, 53% more abscesses were diagnosed using the subtraction technique.


Recurrent renovascular hypertension. Report of an unusual case. A 7-year-old girl with histologically proved fibromuscular dysplasia underwent renal autotransplantation with prompt return of the blood pressure to normal. Two months later, immediately after tonsillectomy, severe hypertension recurred with marked narrowing of the previously patent anastomosis. After 4 weeks on antihypertensive therapy, the patient became normotensive again and remained so for 18 months, with marked widening of the anastomosis. It is possible that this complication might be explained on an immunologic basis.


Papillary necrosis in kidney transplant patients. Of 158 renal transplant recipients, 75 underwent excretory urography at some point during a six-year period, 24 hours to 7 years after transplantation. In 11 patients, renal papillary necrosis (RPN) was found. RPN was associated in 9 patients with one or more disease entities known to be the etiologic factor to RPN in nontransplanted kidneys. In 2 patients, previous rejection episodes were the probable case for RPN. Renal papillary necrosis, a rather late complication with renal allograft, was demonstrated in this population on an average of 28.1 months after transplantation.


Evaluation of sellar and parasellar masses by computed tomography. Computed tomography is the method of choice for initial evaluation of patients with potential suprasellar masses. In our experience, CT has proved completely reliable for detecting or ruling out the presence of a suprasellar mass, the direction and degree of parasellar extension, and the presence of any calcific or cystic component of the lesion. When multiple cut CT has been negative, further diagnostic studies have proved unrewarding. When CT has been positive, additional studies have been required in some cases to rule out aneurysm prior to craniotomy.


Localized cryptococcal osteomyelitis.

Localized cryptococcal osteomyelitis. Cryptococcal infection of the skeletal system alone is rare. The authors report a case of osteomyelitis caused by Cryptococcus neoformans involving the distal humerus and skull, with roentgenographic and scintigraphic findings and pathological confirmation.


Flexural pseudolesions of the duodenum.

Flexural pseudolesions of the duodenum. A collection of barium simulating an ulcer, or a negative defect simulating a mass, frequently occurs at the junction of the first and second portions of the duodenum. This appearance may be related to several factors, including (a) distortion produced by flexion,  (b) sphincter function, and (c) an extrinsic impression. Several such patients have had negative findings on endoscopy. The defect can be distinguished from a true lesion by its characteristic location and its variable appearance on different projections.


Computed tomography in the diagnosis of extra-axial posterior fossa masses. Extra-axial posterior fossa masses can be diagnosed reliably by computed tomography (CT) in most cases. Acoustic and trigeminal neurinomas, meningiomas, cholesteatomas, and other extra-axial masses can usually be distinguished from intra-axial masses by asymmetric widening of the basal subarachnoid spaces, bone destruction, continuity of the tumor mass with the tentorium or bone, and more sharply defined margins. Multiple-cut study of the posterior fossa improved visualization of the fourth ventricle and basal cisterns. Interpretation of cisternal changes in association with changes in the fourth ventricle and abnormal attenuation coefficients permits accurate diagnosis of posterior fossa masses.


Computed tomography of granulomatous basal arachnoiditis. Clinical findings are often insufficient to diagnose basal arachnoiditis and conventional neuroradiological techniques often fail to demonstrate the inflammatory process. Computed tomographic (CT) scans, however, usually can demonstrate the circle of Willis, and the basilar, sylvian quadrigeminal, and vermian cisterns. Cisternal anatomy can also be delineated on the CT scans by metrizamide cisternography. CT scanning may prove to be the most accurate and sensitive radiographic test for basal arachnoiditis. Findings in three patients are reported.


Computed tomography: demonstration of contrast medium within cystic tumors. Two cases demonstrated that intravenously injected contrast medium entered cystic lesions. It appears that both vascular opacification and transgression of the blood-brain barrier play major roles in contrast enhancement.


Computed tomography in adrenoleukodystrophy. Correlation of radiological and histological findings. Computed tomograms (CT) demonstrated symmetrical low-density lesions in the white matter of the posterior portion of the cerebral hemispheres in a 9-year-old boy with adrenoleukodystrophy (Schilder's disease). Biopsy of the brain in an area that appeared normal on the CT scan showed profound loss of myelinated fibers and oligodendroglia; the white matter had been replaced by a rather loose acellular stroma consisting of astroglial cells and blood vessels.


Meningomyelocele and syringohydromyelia. Some radiological aspects. Twenty meningomyelocele patients with nonfunctional ventricular shunts or no shunts were studied radiologically. This group was compared to a second group of 4 patients with functional shunts. The various techniques are compared and discussed. Pantopaque ventriculography is a potentially dangerous procedure. Radioisotope ventriculography appears to be a safe and useful method of diagnosing syringohydromyelia. Ventricular decomposition by means of a shunt appears to be an effective treatment.


Overutilization of radiological examinations. Overutilization of radiological studies has become a significant economic consideration in this country. The reasons for unnecessary examinations include indirect financial benefit to physicians, medicolegal considerations, inadequate history provided to the radiologist, and simply inappropriate requests. In many radiological examinations, the indications are controversial or unknown. Recent Professional Standards Review Organization legislation will probably diminish overutilization of radiological studies, both directly through peer review and indirectly by providing comparison statistical data to facilitate better assessment of the value of individual examinations. The final common pathway of the radiological examination is the radiologist, who has the right and the duty to refuse studies, particularly when they involve risk to the patient.


On cats and the territorial imperative.

On cats and the territorial imperative. Of all the medical innovationes of our era, computed tomography is undoubtedly one of the most fascinating, and many nonradiologists are seeking entry into the field. If CT is to remain a radiological specialty, we must act to ensure that our training and experience are adequate to meet this new challenge.


Butaclamol hydrochloride in newly admitted schizophrenics. Butaclamol hydrochloride, a new type of antipsychotic drug, was evaluated by an uncontrolled study of 13 newly admitted schizophrenic patients. The drug had antipsychotic effects as well as a strong propensity for evoking extrapyramidal side effects. With the maximal daily doses of 30 mg used in this study, therapeutic results obtained were probably somewhat less than optimal.


[Vision in fish. An historical and analytical bibliography]. A collection of about 1100 references dealing with the history of the study of Vision of Fishes is compiled, from the earliest mentions to the present. These were chosen selectively on the basis of their relevence. The chronologically arranged bibliography places each of the references in one or more of the following categories: Structure, Behaviour, Development, Ecology, General and Physiology, Publications which started a new trend of technique and reviews are also indicated. Some extracts and quotations, particularly from the older literature, considered interesting are included. This compilation is intended to provide an overall view of the evolution of the subject and its multiplicity.


The nucleated erythrocyte: a model of cell differentiation. The process of erythropoiesis is characterized by several distinctive features which render it a very useful model of cell differentiation. Mature erythrocytes arise from stem cells in a series of intermediate stages which are fairly well defined both on morphological and on biochemical grounds. During this development, the erythrocytes genome is gradually inactivated and the cell becomes geared to the production of primarily one gene product, hemoglobin. Recently, erythropoiesis has been closely studied in avian species since it has become technically possible to fractionate the blood of anemic birds into high-yield populations of young, developing and mature red cells. Attention has focused on patterns of RNA synthesis including globin m-RNA, in relation to cytoplasmic constitutents becoming modified for reduced activity. From the point of view of gene regulation, erythrocyte development is especially interesting in non-mammals, where in contrast to mammals, even fully mature red cells retain their nuclei. These erythrocytes rank among the most extreme examples of cell specialization and gene repression known. The nuclei of avian erythrocytes and others, contain a tissue-specific histone protein in addition to the more usual complement of vertebrate histone. This histone (H5, V, F2c) has been extensively investigated with a view to linking its presence to structural and molecular changes involved in the condensation and repression of red cell nuclei. The evidence to dat suggests that H5, in conjunction with tissue-specific changes in non-histone proteins, may be responsible for keeping the genomes of nucleated erythrocytes permanently inactive.


Observations on the association of pathogenic Escherichia coli with small intestinal villi of pigs. Pathogenic Escherichia coli were observed in association with microvilli of piglets experimentally infected with E coli O149:K91,K88a,c, but the bacteria were only rarely observed actually in contact with microvilli. The association of E coli with villi occurred most commonly in the ileum and least commonly in the duodenum: in some pigs, it was only observed in the ileum. The proliferation of pathogenic E coli in the small intestine and their association with villi commonly coexisted, although each phenomenon was also observed independently. It is suggested that the villous association of pathogenic E coli is not a prerequisite for their proliferation.


An indirect haemagglutination test for the detection of antibody to Nairobi sheep disease virus. An indirect haemagglutination test was developed for the detection of antibody to Nairobi sheep disease virus and shown to be specific and highly sensitive. The optimum conditions necessary to achieve maximal sensitivity were determined. Sheep and goat sera were tested in parallel with an indirect fluorescent antibody test and close correlation of results was demonstrated.


Observations on the epidemiology of contagious bovine pleuropneumonia: Mycoplasma mycoides in urine. During field epidemiological investigations into an outbreak of contagious bovine pleuropneumonia. Mycoplasma mycoides var mycoides was detected in the urine of 14 out of 19 infected cattle. The titres of the organism ranged from 10(1) to 10(8) organisms per ml of urine. The main factor affecting the excretion was the severity of the disease.


Application of the Limulus amoebocyte lysate test to the detection of gram-negative bacterial endotoxins in normal and mastitic milk. The Limulus in vitro endotoxin assay was evaluated as a possible method for the prompt detection and measurement of endotoxins of Gram-negative bacteria in milk. Quantitative results were obtained following 1 h incubation of Limulus lysate and 10-fold dilutions of milk from normal quarters and from quarters of cows with clinical mastitis. This test was capable of detecting endotoxins associated with acute coliform mastitis. A positive Limulus reaction was recorded at dilutions ranging from 1: 10(4) to 1: 10(9) of milk from quarters affected with clinical mastitis due to coliform bacteria. Milk from normal quarters and from clinical mastitis cases due to Gram-positive bacteria was consistently negative to the test when diluted 1:10(3).


Differential diagnosis of ventilatory disorders with the help of volume/flow diagram. Volume/flow (V/v) diagrams obtained from 82 healthy and pulmonary diseased subjects were analyzed. A formula had been worked out on the basis of determined slow vital capacity, for the calculation of maximum forced expiratory flow (VEmax). The expiratory volume/flow curves were used for the computation of lung conpliance (C1). These calculated values of VEmax and C1 were highly correlated to the measured values. It is concluded that these calculated values would provide a good index for the preliminary differential diagnosis of the pulmonary disorders.


Metabolic acidosis in status asthmaticus. Blood gases and acid-base balance were measured in a group of patients in status asthmaticus. Simple or combined metabolic acidosis was found in 37.9% of the patients. In 25 of these, lactic acid (LA), pyruvic acid (PA) and LA/PA were increased. Increased glycolysis and anaerobic respiratory muscle glycolysis during extreme airways obstruction may be instrumental in these changes. Base deficit, not accounted for by organic acid increase, may be dependent on previously present hypocapnic hyperventilation. Possibly hyperlactemia provoked by hyperventilation may be exaggerated in severe asthma.


Pulmonary vascular response to ventilation hypercapnia in man. The effect of ventilation hypercapnia on pulmonary circulation in man was investigated through separate studies. In the first study on 44 patients with little or no airway obstruction and 20 normal men, 5% CO2 breathing produced (a) significant rise in pulmonary artery pressure (PAP), (b) no significant change in cardiac output, (c) rise in pulmonary vascular resistance, (d) rise in brachial artery pressure (BAP) and (e) no change in wedge pressure (WP). The rise in PAP was more pronounced after 2 min of 10% CO2 breathing in 12 bronchitics. The scond study was carried out in 39 bronchitics and 22 normals while breathing 10% CO2 for 1 min and showed that pulmonary vascular response was independent of systemic vascular response, in that BAP rose later and came back earlier to original level during CO2 breathing. In the third study on 26 severe bronchitics and 15 normals the observed rise in PAP during 10% CO2 breathing was independent of H-ion concentration in the blood since PAP continued to rise even when pH was maintained at air breathing level by intravenous injection of 130 mEq of sodium bicarbonate in 250 cm3 of 5% glucose solution. This study also confirmed the findings in the first study that there was minimal rise in cardiac output, no rise in WP, while PAP and pulmonary vascular resistance rose significantly during ventilation hypercapnia. The responses were pronounced compared with those observed in the first study with 5% CO2. It is postulated that the responses might be due to direct action of CO2 on muscular pulmonary arteries.


Comparative study of the ventilatory responsiveness to CO2 in bronchitic and emphysematous patients with chronic respiratory failure. The comparative ventilatory responsiveness to CO2 was studied in 13 chronic bronchitics and 14 emphysematous patients, all exhibiting respiratory insufficiency and with FEV1 less than 1,500 ml. The gas inhaled was enriched with oxygen (F1O2 =0.6) and contained 6% CO2, and measurements were taken when the patients had reached a stable state. The ratio delta VE/deltaPaCO2, which represents the ventilatory responsiveness to CO2, was higher in the emphysematous patients (1.18+/-0.51 liters-min-1. Torr-1) than in the bronchitics (0.76+/-0.34, p less than 0.025), but the deviation on either side of the mean was large in each group. The ventilatory responsiveness to CO2 was proportional to the initial PaCO2, FEV1, total airways resistance, total pulmonary work and especially to inspiratory mechanical work done on the lung ( r=-0.73, p less than 0.001). The difference in ventilatory responsiveness to CO2 between the bronchitic and emphysematous patients may be explained by the difference in energy expended in breathing. It was not possible to exclude an effect due to a difference in sensitivity within the respiratory centers, since inspiratory mechanical work was not measured during CO2 inhalation. It was thought likely that mechanical factors play a triggering role, in that they cause a fall in ventilatory responsiveness to CO2 and hypercapnia, the latter causing the central hyposensitivity which maintains the retention of CO2.


Clinical value of rebreathing test in obstructive lung diseases. The ventilatory response to CO2 inhalation, using rebreathing method, was studied in normal subjects and in patients with bronchial asthma and chronic obstructive lung disease. The patients with lung disease had flatter CO2 response curves. However, it the ventilation was expressed as a fraction of the maximal voluntary ventilation, the difference between normal subjects and patients disappeared. The reduced ventilatory response of these patients may be of mechanical origin and not depending on reduced CO2 sensitivity. The high lung volume of these patients may be the mean factor of the mechanical disadvantage of thoracomuscular system.


Inhibition of allergen-induced bronchospasm in patients with reversible bronchial obstruction by a new xanthone derivative. Six patients with allergic asthma were studied in bronchial challenge tests with their specific antigen. In five cases 7ioxo-7-thiomethoxyxanthone-2-carboxylic acid, sodium salt (OTMX), a new xanthone with mediator-release inhibitory properties, given as an inhaled solution under 'single-blind' conditions, protected against the immediate-type bronchospastic response. This protection was statistically significant (p = 0.016) at the highest dose level used. Late reactions which occurred in two patients were unaffected by the compound.


Bronchopulmonary aspergillosis. An epidemiological study in a hospital population. In order to determine the incidence of bronchopulmonary aspergillosis in patients with other types of pulmonary pathology, 586 in-patients, out-patients and controls were examined during the period 1968-1970 in Baguley Hospital, Manchester, England. It was found that from the 344 in-patients and out-patients with other pulmonary pathology, 6 had a definite diagnosis of allergic aspergillosis. 1 had pulmonary aspergilloma while 53 other patients demonstrated some evidence of bronchopulmonary aspergillosis. These 53 patients had insufficient criteria to be classified in one of the recognised forms of aspergillosis. The number of controls examined was 242, none of whom were found to have allergic or other forms of aspergillosis. Eleven of these had a positive immediate skin test the other test being negative. In addition to the above groups 534 patients with bronchial asthma attending the out-patient department, were investigated with multiple intradermal tests, including Aspergillus fumigatus. Positive intradermal Aspergillus test was found in 130 of the patients with bronchial asthma. This investigation showed that the bronchopulmonary asperigillosis is more prevalent in patients with a pulmonary disease than in persons without this pathology.


[Polyradiculoneuritis in a diabetic patient. Ultrastructural study of a biopsy of a peripheral nerve]. We have made a study of a case of polyradiculoneuritis occurring in a diabetic. Clinically, symptoms were very similar to those in classical Guillain-Barré syndrome and respiratory complications necessitated a stay in a Respiratory Resuscitation Centre. Recuperation was slow but practically total. Ultrastructural changes noted in the roots and the peripheral nerves of patients suffering from Guillain-Barré syndrome are similar to those occurring in experimental allergic neuropathies. These changes are specific as the myelin takes on a fishnet appearance and, more important, the myelin is attacked by the projection of a mononucleate cell which has passed through the cytoplasm of the Schwann cells. We did not find this in our case. On the other hand, the lesions we found consisted of a mixture of common segmental demyelinization and axonal lesions, associated with marked Schwann cell hypertrophy coiled around most of the myelinized fibres. Such aspects are very like those found in certain diabetic neuropathies. The existence of significant microangiopathy which was present in this case is also an important, though not a decisive factor. We consider, therefore, that the syndrome of polyradiculoneuritis exhibited by this patient corresponds more closely to diabetic neuropathy than to a classical Guillain-Barré syndrome.


[Fertile amenorrhea associated to diabetes insipidus]. A case of diabetes insipidus is presented which appeared in a 13 year old girl associated with hormone-resistant amenorrhea; she went through two normal pregnancies and partutition at 22 and 25, indicating a fertile amenorrhea. During a total of 17 years of observation the amenorrhea persisted, with the exception of a few normal menstruation periods at the beginning of the disease. She remained permanently under treatment with pitressin tannate. Repeated administrations of estrogens, gestagens and chorionic gonadotrophin, had no effect. An endometrial biopsy revealed a presecretory phase. Acidophilic index in vaginal smears as well as serial determinations of urinary pregnanodiol indicated cyclic changes. Daily determinations of urinary pregnanodiol indicated cyclic changes. Daily determinations of plasma gonadotrophins during 28 days revealed normal levels, with normal FSH pulse and ovulatory type peak of LH. An LH-RH test gave marked and characteristic increase of both hormones. The data indicate the integrity of the hypothalamo-hypophyso-ovaric system, with cyclic changes and formation of corpus luteum, vaginal trophism and endometrial changes, concordant with the two normal pregnancies. In this case, the amenorrhea can only be explained by alteration of the usual endometrial vascular changes. The coexistence of diabetes insipidus and fertile amenorrhea is discused in relation with the possible participation of vasopressin in the mechanism of menstruation.


[Clinical trial with glypentide. Comparison with the hypoglycemic activity of other sulfonylurea compounds]. In 53 sulphonylurea-treated diabetic patients, the activity of glypentide and the patients' general tolerance of the drug were studied. The results show that the new oral hypoglycemic drug has a similar, and superior in many instances, activity to other similar drugs such as glybenclamide and glypizide, and to the activity of the classical sulphonylureas (chlorpropamide and carbutamide). The patients' tolerance of the drug was excellent. No digestive disorders, undesirable side effects or hypoglycemias were seen in the patients. Analysis of lipid levels showed that glypentide induces a significant decrease in total lipid and cholesterol values, being this action more marked in patients with normal body weight non-treated with a hypocaloric diet.


Sulindac in osteoarthrosis of the hip.

Sulindac in osteoarthrosis of the hip. Sulindac (400 mg/day) has been compared with ibuprofen (1200 mg/day) in 40 patients with osteoarthrosis of the hip, over an eight-week period, in a double-blind controlled clinical trial. The two drugs were comparable in terms of patient preference, effects on hip movements, and toxicity. Sulindac showed superior analgesic properties to ibuprofen, resulting in a significantly greater reduction in pain on weight-bearing and with passive movements (P less than 0.01).


A trial of micro-encapsulated and enteric-coated aspirin in rheumatoid arthritis. In a trial of 48 patients with rheumatoid arthritis, enteric-coated aspirin (4.55 g daily( and micro-encapsulated aspirin (4.50 g daily) proved to be equally effective in reducing morning stiffness, relieving pain, increasing grip strength, reducing ESR, and reducing the need for additional analgesic tablets, compared with placebo. Reduction of joint tenderness was also found, but this was not statistically significant. Proximal interphalangeal joint circumference altered little during the trial. Tinnitus and deafness were commoner with enteric-coated aspirin, but gastric side-effects were similar. Of 39 patients completing the trial, there was an equal patient preference for enteric-coated aspirin and micro-encapsulated aspirin. Salicylate side-effects necessitated withdrawal of six patients from the trial and dose reduction in nine patients. It was concluded that the efficacy and side-effects in rheumatoid arthritis of both aspirin preparations were similar.


A controlled trial of the analgesic effects of Floctafenine against placebo in osteoarthrosis. Floctafenine 200 mg four times a day was compared with placebo in 30 out-patients with osteoarthrosis in a double-blind controlled study. There was a significant patient preference for, and a greater relief of pain with, floctafenine. Pain on walking and joint stiffness after sitting were significantly less on floctafenine. There were no differences in side-effects between floctafenine and placebo.


Diagnostic value of computer-assisted quantitative radioisotope angiocardiography. The cardiac cavities and large vessels were studied by radioisotope angiocardiography with 99mTc-labelled albumin, using a gamma-camera linked to Med-II, with subsequent digital scanning and analysis by coloured video unit (VDP2) of the areas of iso-activity. The results are illustrated of 8 cases selected from the aggregate case histories of 78 patients (1 normal, 4 congenital heart disease, 2 rheumatic, 1 cor pulmonale chronicum). The direct observation of the course of the bolus and the activity/time curves in areas of interest in the cardiac cavities and the lungs, together with the representation of the areas of iso-activity, were useful for diagnosis and physiopathological evaluation of the heart conditions in the patients.


The proliferative diseases of the lymphoreticular system. Classification and pathological features of malignant lymphomas. An histogenetic classification of lymphomas is discussed, and diagnostic criteria are proposed for these neoplasms, based primarily on their histological features and assessment of the predominant cell population in the individual lymphomas. Limitations of space ane experience have precluded more comprehensive discussions on the morphology of malignant lymphomas in relation to their immunological, functional and clinical features, prognosis and response to therapeutic agents. Since we are aware that the proposed classification and histological criteria are incomplete and imperfect if the malifnant lymphomas are considered as static entities, we wish to conclude our paper by quoting a statement made by Rappaport23: '...the clinical usefulness of any classification of reticular neoplasms is limited by their often unpredictable behaviour'.


The assay of exocrinous peptidases in clinical chemistry. The various peptidases secreted by such exocrine tissues as gastric mucosa, pancreas and prostate are usually determined by catalytic methods. Another approach utilizes immunoassay. Endopeptidases were formerly assayed with protein substrates such as hemoglobin and albumin. These techniques are increasingly replaced by more specific ones using artificial peptide derivatives as substrates, some of which allow an increase in absorbance or fluorescence to be continuously recorded. The presently available methods of assaying pepsin, pancreatic trypsin, trypsinogen and carboxypeptidase A, enterokinase and several peptidases of human sperm are reviewed.


Viral interference and interferon.

Viral interference and interferon. Viral interference is a phenomenon for which a cell infected by a virus becomes resistant toward a second outcoming infection by a superinfectant virus. Even though other mechanisms are known, it can be assumed that most cases of viral interference occurring in natural conditions are mediated by interferon, a low molecular weight protein produced by the infected cell in response to a stimulus provided by viral nucleic acid(s). The interferon produced by a cell can migrate to other cells not yet involved by the spreading infection, transmitting to them the antiviral-resistant state. Available evidence indicates that interferon acts by inducing the production of a second cellular protein, called antiviral protein, which is directly responsible for the antiviral state through some alterations of the cellular, virus-directed, proteosynthetic system. In addition to the antiviral activity, the interferon system can affect the growth of several nonviral organisms and that of tumour cells; rather controversial effects have been shown also on the immune responses; the mechanisms underlying these effects are still nuclear. However a relationship to the specific immune system is suggested also by the finding that interferon can be liberated by sensitized T-lymphocytes following antigenic stimulus. Activation of the interferon system can be operated in vitro and in vivo also by several non-viral substances of various nature, such as nucleic acids, polysaccharides, aromatic amines, etc. This fact, considering that interferon has been shown to play a critical role on the mechanisms of recovery from viral infections, may open new perspectives for their possible prophylactic and/or therapeutic use in viral diseases. This problem can be approached also by administering exogenous interferon. Encouraging preliminary results have so far been obtained either with interferon or its inducers. However, several problems of various nature have to be resolved before considering the actual use of interferon system as a wide range antiviral drug in natural viral diseases of man.


[Historical and recent data on the relationship between cerebellum and epilepsy]. Short historical review of the interrelationships between cerebellum and epilepsy, the historical background of COOPER'S intervention. The Author's personal contribution to this fascinating topic is also reminded.


Oral trypsin-inhibitor-induced improvement of the exocrine and endocrine pancreatic functions in alloxan diabetic rats. Studies are presented dealing with the effect on the exocrine and endocrine pancreas of long-term oral trypsin inhibitor administration to alloxan diabetic rats. Three categories of rats were used: a) normal rats, b) alloxan diabetic rats, and c) alloxan diabetic rats treated with the trypsin inhibitor. 1. The concentration of amylase in both pancreas and intestinal contents were markedly decreased in alloxan diabetic rats as compared with normal rats, whereas the concentrations of lipase and trypsin(ogen) were practically unaffected by the diabetic state. 2. Trypsin inhibitor treatment of diabetic rats enhanced the concentrations of both amylase, trypsin(ogen), and lipase in pancreas and intestinal contents when compared with untreated diabetic controls. 3. Alloxan diabetic rats treated with trypsin inhibitor displayed an increased weight gain, increased pancreatic weight, and increased pancreatic protein concentration as compared with the untreated diabetic controls. 4. Alloxan diabetic rats treated for 3 or 5 weeks with the trypsin inhibitor were found to have decreased basal blood glucose levels and an increased plasma insulin: blood glucose ratio as compared to the untreated diabetic controls. 5. There was no apparent difference in the glucose elimination rate after I.V. glucose loads in diabetic rats given trypsin inhibitor and their diabetic controls. However, the insulin secretory response to the glucose stimulus was slightly improved in the trypsin inhibitor group. 6. Alloxan diabetic rats treated with trypsin inhibitor had an increased total pancreatic insulin content compared with their diabetic controls. It is concluded that long-term daily treatment with oral trypsin inhibitor in alloxan diabetic rats increased enzyme production and secretion in the exocrine pancreas, and produced an improvement of the diabetic condition of the animals. This improvement might partly be due to an increased pancreatic content and secretion of insulin.


[Malarial encephalopathy and disseminated intravascular coagulation (author's transl)]. Clinical and anatomical studies of a case of malarial encephalopathy are described in a 51 year old man. In view of the typical symptomatology it was important to ascertain an period even brief of stay in an endemic area. Only when this was confirmed the appropriate investigations could be planned (in thic case thick blood drop test) to identify the parassite. The physiopathological mechanisms through which the malarial infection causes the parenchymal lesions are considered. Such lesions according to many Authors are of ischemic nature, due to machanical obstruction of capillaries by the invaded erytrocytes with damage to the endotelial wall and thrombus formation. These lesions cause anoxic and necrotic damage of the parenchyma and, in certain cases, the appearance of serious haemorrhagic syndromes where the initial stage is the conglutination of the erytrocytes followed by disseminated intravascular coagulation syndrome. The importance of this syndrome is emphasized as well AA. the role of the association of the specific antimalarial treatment with the use of drugs against blood conglutination, thrombosis and oedema.


Gastric secretory response to different doses of carbachol and pentagastrin in man. In 6 healthy students, the gastric secretion of acid, pepsin, and IF was measured during one hour at basal conditions, and during one hour of stimulation with 0.01 mug/kg/h and thereafter during one hour of stimulation with 0.1 mug/kg/h of pentagastrin. On separate days the same dose of pentagastrin was given in combination with 0.15 mug/kg/h or 1.5 mug/kg/h of carbachol, or stimulation was performed with each of the two doses of carbachol alone. A dose-dependent relationship was found between carbachol and the output of acid, pepsin, and IF. The responses to carbachol were independent of changes in plasma gastrin concentration. The acid- and IF-secretions stimulated by the largest dose of pentagastrin were significantly increased by the largest dose of carbachol, whereas the secretion of pepsin was not. Pentagastrin and carbachol seem to interact by competitive augmentation on the gastric secretion of acid and IF.


[Piribedil in the treatment of Parkinson disease (author's transl)]. Seventeen patients with either Parkinson's disease or post-encephalitic parkinsonism were treated with Piribedil, an apomorphine-like drug, in single blind conditions for a period ranging from five weeks to twenty-four months. The analysis of the results shows that Piribedil modifies the extrapiramidal symptomatology being specially effective against the tremor either when used alone or in association with L-Dopa. The side effects noticed during treatment with Piribedil are similar to those of Apomorphine, and are dose-dependent.


Co-trimoxazole and nitrofurantoin in urinary-tract infections: a controlled clinical study. The clinical efficacies of co-trimoxazole and nitrofurantoin were compared in patients with urinary-tract infections associated with significant bacteriuria with coliform bacteria tested and found to be sensitive to both drugs. Of 27 patients treated with co-trimoxazole, 23 were cured after 10 days' treatment with 320 mg trimethoprim and 1600 mg sulphamethoxazole daily (85%). Of 18 patients treated with nitrofurantoin (200 mg/day for 10 days), 7 were cured (39%). Thus, cotrimoxazole was significantly superior (p less than 0.01) in this study. A significant (p less than 0.001) but temporary and modest rise of the serum-creatinine levels was noted after 5 days' treatment with co-trimoxazole. Such a rise was not observed in the nitrofurantoin group. Only a few minor side effects were noted in both groups.


On bacteriological problems in the REDY dialysis system. During a series of dialyses with the REDY absorbent dialysis system, samples for bacteriological examination were drawn from different parts of the system. The REDY cartridge, both unused and after dialysis, was submitted to bacteriological examination by the drawing of samples from its four layers. Bacteria grew from the different layers of the cartridge with decreasing frequency from the bottom layer upwards. There was bacterial growth both in samples taken from unused cartridges and in samples from cartridges at the conclusion of dialysis. An attempt to sterilize the bottom layer of the cartridge by irradiation had no apparent effect on the incidence of growth. There was no growth in the dialysate, while bacteria could be cultured from both sides of the membrane of the dialyzer as well as from the solution of concentrate. Bacteria are probably found in the urease layer of the unused cartridge and may multiply during dialysis, leak out into the dialysate, and be trapped in the dialyzer. It is concluded that bacteriological contamination of the system should be avoided by the use of a suitable and effective sterilization procedure.


Igg rheumatoid factor in serum of rheumatoid arthritis patients. The ability of isolated IgG and F(ab)2 fragments to agglutinate IgG-coated latex particles was used as a test of IgG-RF activity. No definite differences could be proved between controls and RF-negative RA patients, whereas the latex titres of IgG and F(ab)2 of sero-positive RA patients were higher. The IgG latex activity was recovered in the fractions between the 19S and 7S after gradient centrifugation of serum or isolated IgG at pH 7.2 and within the 7S fraction after centrifugation at pH 4.1. The dissociated IgG complexes reformed after neutralization, thus indicating a self-association of the IgG molecules.


Spongy bones in prehistoric America.

Spongy bones in prehistoric America. A well-preserved mummified child from about A.D. 1200 was recovered fron Canyon de Chelly in northeastern Arizona in 1971. Striking skull changes were found and microscopic, ultrastructural, and cytochemical studies confirm the diagnosis of porotic hyperostosis that resulted in spongy bone appearance. We suggest that a possible cause for this condition could be iron deficiency of a severity seldom found in modern societies.


Intraclonal histocompatibility in a parthenogenetic lizard: evidence of genetic homogeneity. A total of 175 skin grafts were transplanted among 20 individuals belonging to two separate populations of the parthenogenetic lizard Cnemidophorus uniparens. Of these, 98.8 percent were permanently accepted, which indicates that all individuals of each population may be genetically identical. These results further suggest that large populations or the entire species may consist of one clone derived from a single individual.


Criteria for the differentiation of dysfibrinogenemic states. A large number of families have now been described in whom affected individuals have within their plasmas an abnormal species of fibrinogen (factor I). These defects, presumably examples of the phenomenon of allotypy--i.e., the synthesis of variant forms of a normal protein--have been inherited as autosomal dominant characteristics. In the great majority of cases, clotting is abnormally slow when thrombin is added to the abnormal plasma. Sometimes this defect appears to reside in impaired release of fibrinopeptides by thrombin. In other cases, fibrinopeptide release proceeds normally, but aggregation of fibrin monomers is impeded. In the latter instance, aggregation may be abnormally slow or, once it begins, it may proceed at a normal rate. Curiously, a bleeding tendency is more likely to occur in patients in whom fibrinopeptide release is impaired, while dehiscence of operative wounds rarely complicates dysfibrinogenemias associated with impaired aggregation of fibrin monomers; thrombosis has been described in both groups of patients. Most of the reported cases may be distinguished by functional criteria and by the physicochemical behavior and biochemical nature of the abnormal protein. Additonally, one family has been described in which plasma clots abnormally rapidly upon addition of thrombin, and two others in which crosslinking of fibrin by fibrin-stabilizing factor (factor XIII) is defective.


Placenta previa and preeclampsia complicating the management of renal transplant patients. Presented are three patients who have delivered full-term normal infants after renal transplants from living related donors. One patient had a placenta previa with excessive vaginal hemorrhage. Another patient manifested preeclampsia. Management of these and other complications should be aggressive and thorough with special precautions taken to preserve graft function. In our patients, pregnancy was not harmful to the renal transplant. No fetal complications from immunosuppressive drugs were noted and the patients' dosage requirements did not change. Counseling regarding family planning is essential in patients with renal transplant.


Correction of extensive neck contractures with local flaps and split- and full-thickness grafts. A technic of combined split-thickness and full-thickness skin grafts and local flap closure for extensive deep cicatricial neck contractures is presented. The head and neck are mobilized by excision of limiting tissues. The lateral neck skin is mobilized to be rotated anteriorly as flaps, and a full-thickness skin graft is applied to the central neck. Split-thickness skin grafts are placed below the full-thickness graft and flaps, and also above the full-thickness graft over the horizontal part of the neck. The success of this technic relies upon the limited contracture of full-thickness skin grafts, mobilization of lateral neck tissue, and consideration of regional units of the neck. This relatively simple operation results in a dramatic and lasting improvement of the neckline, good range of motion of the head and neck, elimination of multiple operative procedures, and early rehabilitation of the patient.


Aggressive treatment of acute respiratory insufficiency. Treatment of patients with severe acute respiratory insufficiency included application of end-expiratory pressure to an optimal level, precise cardiovascular monitoring, and adaptation of conventional respirators to provide intermittent mandatory ventilation. Of 90 patients with acute respiratory insufficiency secondary to trauma, sepsis, or complicated surgery, 65% survived. Mortality appeared to be independent of the level of end-expiratory pressure required. The goal of therapy was maximal reduction of intrapulmonary shunt without significantly decreasing cardiac function. In the group requiring more than 20 cm H2O end-expiratory pressure, shunt decreased from 48% at 5 cm of positive end-expiratory pressure to 21% at the optimal level. In only 6% of the entire group was significant pulmonary dysfunction present at the time of death. Most deaths (75%) were deemed secondary to failure of multiple organ systems, occurring late in the hospital course. Pneumothorax was recorded in 10% of the entire group. Acute respiratory insufficiency should be rapidly reversible in most cases if aggressive measures are employed with the intent of reversing functional impairment rather than improving arterial oxygenation to "satisfactory levels."


Anticoagulant-induced necrosis of skin and subcutaneous tissues: report of two cases and review of the English literature. Two cases of necrosis of skin and subcutaneous tissues in patients taking oral anticoagulants are reported, and the English literature is reviewed. The mechanism of coumarin necrosis remains unknown. Most patients are women and the lesions are most common on the abdomen, buttocks, thighs, and breasts. Simple mastectomy is the usual treatment for a breast lesion. Although some cases have been reported in which the skin lesion has healed despite continued anticoagulant therapy, curtailing its use is recommended. Heparin has not been associated with skin necrosis, however, and may be desirable if continued anticoagulant treatment is necessary.


Comparison of indoramin and methyldopa in hypertension. A comparison of indoramin and methyldopa in the treatment of mild and moderate essential hypertension in 31 White middle-aged patients was made by means of a double-blind crossover trial. Equally satisfactory control of systolic and diastolic blood pressure, in the standing and supine positions, was achieved by both drugs. With a mean dose of 158 +/- 9 mg per day of indoramin the average fall in lying and standing blood pressures was 16/6 and 16/8 mmHg respectively. Equivalent values for methyldopa, with a mean dose of 1 540 +/- 90 mg per day, were 21/8 and 16/13 mmHg. Values for the two drugs are not significantly different. Also, there were no significant differences between the two drugs in their effect on the heart rate or in the incidence of side-effects.


Endoscopic evaluation of the effect of Ulcerone and placebo on duodenal ulcers. Fifty courses of tripotassium di-citrato bismuthate (Ulcerone) and placebo were administered to ambulant patients with duodenal ulcers in a double-blind trial for 6 weeks. Duodenoscopy was used for initial assessment and to judge improvement. The ulcers of 20 out of 30 patients (67%) healed completely with Ulcerone treatment for 6 weeks, while another 7 patients showed partial improvement. The ulcers of 4 out of 20 patients (20%) on placebo showed healing. The difference is highly significant (chi2 = 20,0; P less than 0,001). Ulcerone is a collodial bismuth substance which is said to act by coating the ulcer by becoming incorporated into granulating tissue at an acid pH. No side-effects of Ulcerone occurred. It is considered to be a safe and effective oral therapeutic substance for ambulant patients with duodenal ulcers.


The temporary colostomy.

The temporary colostomy. The indications for a temporary transverse colostomy are examined in the light of a year's experience of the Stomatherapy Service at Groote Schuur Hospital. A surgical technique, which employs primary colocutaneous suture and which may be used in both emergency and elective situations, is described.


A comparison of tilidine hydrochloride and morphine in the treatment of postoperative pain. Intramuscular injections of 10 mg morphine or 100 mg tilidine hydrochloride were administered in a double-blind fashion and in random order to 40 patients after minor surgical operations. The therapeutic effect of each analgesic was assessed by comparing the severity of pain immediately postoperatively with that 1, 2, 3 and 4 hours after injection of the relevant analgesic. Tilidine and morphine relieved pain to a similar degree. Within the limits of the protocol followed, morphine appeared superior to tilidine in some tests. No major side-effects occurred.


Serial scintigraphy during isolated renal perfusion. A quantitative standard of radioactive impulse activity can be determined as an indicator of renal functional ability during renal transplantation and after perfusion by simple methods. Hippuran excretion is nearly absent at temperature below 8 degrees C but is still measurable and rises with every degree above 4 degrees C. If there is no evidence of Hippuran excretion at 8 degrees C, this will indicate a degree of renal damage. The examination for non-pulsatile, stored kidneys similar to the method employed by Collins appears perfectly satisfactory to us. The radioactive substances do not necessarily damage the organ because the kidneys are washed out rapidly. Similar radioactive materials can be used in pre-operative preservation and during the postoperative periods as a means of control and diagnosis without additional personnel or expenditure. In the past, false values have been obtained, owing to spasm when albumin base solutions have been used. When spasm is noted, repeated measurements should be done to determine if the spasm is true, or the result of organ damage. The basic correlation between organ weight, organ blood flow and scintigraphic impulse rates will give an initial estimate of organ activity, even when the condition of the donor kidney is unknown. Follow-up sequential scintigrams provide information regarding the suitability of the organ for transplantation.


Myocardial infarction and the evolution of the intensive coronary care unit. From the start of the 1960s it became increasingly evident that sudden death with acute myocardial infarction was owing to reversible derangement in heart rhythm rather than to gross myocardial damage. Patients at risk were placed in specialised areas, intensive coronary care units (ICCUs), and their heart rhythms were continuously monitored. Initially, the prime function of the ICCU was to resuscitate a patient who had suffered cardiac arrest. Since the survival rate after resuscitation was low, no obvious reduction in mortality was noted in the early ICCU. As intensive care evolved, better resuscitation techniques became available, understanding of the terminal arrhythmic mechanism improved, and the prevention of cardiac arrest by aggressive and prompt treatment of the minor warning arrhythmias became feasible. With these developments, the ICCU appeared to show a reduction in the mortality of acute myocardial infarction. It is argued that the 'supposed' decrease represents a 'real' decrease. This is on the basis of the consistency and similarity of all ICCU results throughout the world over a period of 7 years, coupled with the fact that cardiac arrests (which were initially reported to occur in 10%-20% of patients) had been eliminated. The principles of modern intensive coronary care have been equally well utilised in small community hospitals and in large academic hospitals. Thus, the extension of soundly-based management can have application in situations which, by force of circumstances, are far from ideal. An outstanding feature which emerged early on, was the high incidence of arrhythmias recorded by continuous monitoring. The percentage frequently quoted was 80% and above. Emphasis was placed on the dangerous ventricular arrhythmias, including the ventricular premature systole. The atrial arrhythmias were considered to be of lesser clinical significance.


Extra-abdominal transplantation of the pancreas. Extra-abdominal pancreatic transplantation is a feasible surgical procedure. Transplantation of the pancreas without duodenum and with pancreatic duct-to-ureter anastomosis had better results than combined pancreaticoduodenal transplantation in the same position. The alternative extra-abdominal approach offers more definite advantages, such as ease of performance, location and identification of complications, than does the usual intra-abdominal technique.


A simple technique for closure of temporary cystostomy. To overcome the problem of persistent urinary wound discharge after prostatectomy with temporary cystostomy, a simple suture technique is introduced. Two monofilament nylon sutures are inserted through the abdominal wall, tangentially to the dome of the bladder, together making a purse-string suture around the cystostomy. The sutures are left untied until the top catheter is removed. Then they are tied and subsequently removed along with the skin stitches. The technique has fulfilled its purpose in 19 consecutive patients without giving rise to any complications.


An interpretive review of lymphoma of the stomach. Lymphoma of the stomach may exist as a primary lesion or as a manifestation of generalized or systemic lymphoma. The primary lesions constitute approximately 3 per cent of all malignant lesions of the stomach and outnumber all other types of non-epithelial malignant lesions. The cause is not known. Gross characteristics often resemble carcinoma, and like carcinoma, the primary lesion may affect other structures by direct extension, may seed to peritoneal surfaces, may metastasize to lymph nodes near or far, and may be borne by the blood to liver, lung or bone. Diagnosis begins with clinical suspicion by the physician, is supported by the results of roentogenographic and gastroscopic studies, and is finally established by a positive study of biopsy specimens obtained with or without laparotomy. Improvements in both gastroscopic instruments and their use promise to increase greatly the accuracy of preoperative diagnosis. Pseudolymphoma of the stomach, a rare type of inflammatory lesion, may, on occasion, offer a difficult differential diagnosis from that of lymphoma. The clinical approach to the lesion, whether the diagnosis is histologically proved or not, is the same as for suspected carcinoma. A laparotomy is usually necessary to determine the possibility of surgical cure, unless distant spread or systemic involvement can be established by other means, such as a distant lymph node containing the disease or a positive needle biopsy of the liver. When a cure seems possible, resection is favored by most surgeons, even though it entails total gastrectomy or multiple organ resection. Opinion is divided as to whether or not a curative resection should be followed routinely by irradiation, although irradiation is generally favored by palliation of lesions not amenable to resection. Transgastroscopic biopsy and gastroscopic follow-up study may permit radiation to be tested as the only form of treatment of favorable lesions. At the present time, chemotherapy should be reserved for lesions not controlled by operation or irradiation. Stage for stage, the outlook for lymphoma of the stomach is about twice as favorable as that for carcinoma. No generally accepted classification of lymphoma exists as yet. Correlations between prognosis and microscopic characteristics are not close, except for the generally favorable outlook for lymphocytic lymphoma.


Use of a questionably viable flap as a full thickness skin graft after mastectomy. Questionably viable skin flaps may be used as full thickness grafts after mastectomy. It is suggested that the procedure described can help reduce the incidence of flap necrosis after mastectomy and yield a more acceptable cosmetic result.


Contributions of electron microscopy to the study of corneal pathology. Most of the electron microscopic studies of pathological corneas have been done only recently. Keratoplasty has been the most important source of specimens for ultramicroscopic investigation. With the introduction of electron microscopic techniques, we have been able to confirm many light microscopic studies in pathological corneas. This contribution has been most valuable in the identification of the sites and types of pathological changes in corneal dystrophies and degenerations. This review of electron microscopic studies describes the present concepts on the nature of the histological changes in dystrophies and degenerations of the anterior and posterior corneal layers and corneal stroma. It also includes a review of some corneal inflammatory conditions as well as metabolic disorders affecting its transparency.


Morphological changes induced during fixation of Mycoplasma mycoides for electron microscopy. Only spherical mycoplasmas 0.6-0.9 mum diam were observed by darkfield microscopy in single cell suspensions prepared from exponential broth cultures of Mycoplasma mycoides var mycoides and Mycoplasma mycoides var capri. Similar cells were seen in pseudoreplicas by electron microscopy and they are considered characteristic of the morphology of M. mycoides. When the mycoplasmas were fixed by the addition of 10% formalin to the suspensions or washed, centrifuged cells were fixed by glutaraldehyde, filamentous and ring forms were observed in electron micrographs. These are not considered typical of the morphology of M. mycoides but are artifacts produced during the preparation of the mycoplasmas for electron microscopy.


[Iatrogenic foreign bodies in heart (author's transl)]. Two cases are reported of migrating Kirschner wires, which had been inserted for stabilisation of bony defects of the thoracic cage. The wires migrated in both patients to the heart and caused life threatening complications like pericardial tamponade, arrhythmias and cardiac insufficiency. Indications for removal of foreign bodies from the heart are discussed. Attention is drawn to the fact that the ends of Kirschner wires must be bent in order to prevent migration.


Experimental studies on the pathophysiological changes in the pancreas of rat following bilateral ligation of the parotid gland duct. The blood sugar level, blood insulin level, serum amylase level and organ amylase level in the pancreas were measured in a total of 110 rats examined at 12, 24, 48, 72, and 96 hr, and 1,2, 3, 4, and 5 weeks after bilateral ligation of the parotid gland ducts. In parallel with this functional study, light microscopic study of th=e pancreas and the parotid gland and electron microscopic observations of the pancreas obtained from the rats were performed at the respective periods. The following results were obtained: 1) The serum amylase level was most elevated in the group examined at 12 hr after ligation and it decreased gradually and returned to the normal level at 96 hr after ligation and thereafter. 2) As for the pancreatic exocrine function, the organ amylase level of the pancrease was significantly elevated in function, the organ amylase level of the pancrease was significantly elevated in the groups examined at 24 hr to 3 weeks after ligation. Electron-microscopically, hyperfunctional state in the pancreatic acinar cells was recognized as evidenced by the dilatiation of the granular endoplasmic reticulum. 3) With regard to the endocrine function of the pancreas, the blood sugar level and blood insulin level did not show and significant changes after ligation as compared with the control group. Morphologically, electron microscopy showed a decrease in electron density and swelling of the cored granules, disintegration and fusion of their limiting membranes in the beta cells. These changes are interpreted as indicating the discharge of secretory granules in the beta cells. It is concluded that an impairment of the parotid glands influences the function of the pancreas to a certain degree.


Effects of trypsin on glucose-induced insulin secretion from the perfused rat pancreas. The present study revealed that glucose-induced insulin secretion was significantly inhibited by perfusion with trypsin (10 mug/ml) in the isolated rat pancreas perfusion. However, when trypsin was interposed during perfusion of 16.6 mM glucose, glucose-induced insulin secretion was not suppressed during trypsin infusion. The insulin level was significantly lower in the trypsin treated animals than in the control after completion of trypsin infusion. The results suggest that trypsin does not attack the glucorecoptor bound with glucose but attacks the free glucoreceptor. Interestingly a biphasic pattern of glucose-induced insulin secretion disappeared by the pretreatment with trypsin. The possibility was suggested that tyrpsin prevented the initial binding of glucose to the B-cell.


Dry ice fixation of myofibrils for scanning electron microscopy. A rapid method of fixation of myofibrils using dry ice is reported. A glass slide or coverslip containing a drop of glutaraldehyde-fixed suspension of myofibrils is placed on dry ice causing the myofibrils to adhere to the glass surface. The specimens are then dehydrated through the alcohols, air dried and metal coated. This technique gives the myofibrils a corrugated appearance under the scanning electron microscope corresponding to the sarcomere banding.


Volumetric instillation of fixatives and inert substances into mouse lungs. Mouse lungs were instilled with various fixatives to establish the optimum volume necessary to fix the lung without distortion and to compare the efficacy of the fixatives. Fixation with either Stieve's or Bouin's fluid was found preferable to 2.5% and 5% glutaraldehyde, 4% neutral buffered formalin, and to a mixture of formalin and Stieve's fixative. In addition, a comparison was made between diluted Ames O.C.T. Compound and 4% aq. gelatin as supportive substances for unfixed lungs in preparation of cryostat sections and for histochemistry. A 1:2 dilution of O.C.T. was found to be superior to 4% gelatin in preparative, cutting and adhesive properties. The optimal instilled volume for mouse lungs was found to be 0.1 ml for every 7 grams of body weight, introduced at a rate of 0.1 ml per 10 seconds.


A method of permanently mounting biological tissue cleared in Herr's four-and-a-half clearing fluid. A technique which should be generally applicable for preparing permanent mounts of tissue cleared in Herr's four-and-a-half clearing fluid is described. This technique involves transferring plant or animal tissues through a series of solutions consisting of Pienarr's fixative, Herr's clearing fluid, chloral hydrate, acetone and finally polyester resin for mounting. Material prepared using this method is exceptionally transparent and well preserved, and is suitable for either phase contrast or Nomarski interference microscopy.


Preparation of fossil bone specimens for scanning electron microscopy. A method is described for preparing fossil bone specimens for scanning electron microscopy. To obtain bone surfaces suitable for study, material was embedded in Epon 812 and selected faces exposed by grinding were subjected to controlled etching with a 4:1 mixture of 5% HNO3 and 1% OsO4. Surfaces thus prepared were further processed by the so-called clearing replicas technique. As a result of this procedure the bone surfaces revealed a network of anastomosing vascular canals the innter surface of whose walls could be examined in the scanning electron microscope. By etching extremely thin ground sections of bone stuck to plastic tape the contents of vascular canals as well as osteocytes can be isolated. This method ensures the good preservation of spatial relations between bone elements essential for studies of fossil bones, which are sometimes very brittle.


Studies of osmium deposits in the carotid body of the cat. Double aldehyde fixed carotid bodies and small pieces of vagus nerve of cats were incubated in 3 mM copper sulfate and 0.5 mM potassium ferricyanide in 0.05 M acetate buffer (pH 5.6) for 30 minutes at room temperature. Several modifications of this procedure were also attempted. Tissues were then postosmicated with 2% unbuffered osmium tetroxide and heated to 50-55 C for ten minutes. Under the electron microscope carotid body cells exhibited fine osmium deposits within cisternae of endoplasmic reticulum, saccula and vesicles of Golgi complex, and cristae of mitochondria. Intense osmium precipitation was also noted in the mitochondria of nerve endings. In addition, much more intense, more conspicuous and more localized reaction was noted in the intraperiod lines of the myelin sheath of nerves. Deposits here were rod-shaped, displaying considerable variation in length. These results are discussed in the light of previous findings on osmium deposits in various tissues. It was concluded that the osmium reaction is unspecific, and that histochemical methods employing hot osmium tetroxide to amplify enzymatic activities may therefore not be reliable.


A modification of the rapid Golgi method. An extremely rapid Golgi procedure for immersion impregnation of the whole brain of the frog Rana esculenta is described. It uses an isotonic 2% osmium tetroxide solution buffered with sodium barbital at pH 7.2 that has previously been used for electron microscopy. To 15 ml of this solution 85 ml 3% potassium dichromate is added just before use. Twelve-hour treatments (6 hr in the chrome-osmium solution plus 6 hr in 0.75% silver nitrate) are sufficient to obtain consistently excellent impregnations of external brain formations. Twenty-four-hour treatments (12 hr in the chrome-osmium solution and 12 hr in the silver solution) impregnate also the deeper regions of the brain. The results show neuronal details on a clear background.


Montgomery Lecture, 1975. Changing concepts of the prognosis and management of small malignant melanomas of the choroid. Recent studies have shown conclusively that patients with small choroidal melanomas tend to have a favourable prognosis and that this, in turn, is closely related to tumour cell type, mitotic activity, degree of trans-scleral extension, and other characteristics of the tumour. It has not yet been established whether enucleation of the tumour-containing eye increases or decreases the patient's chance for survival. The frequency with which we observe late metastatic deaths among patients who had seemingly been 'cured' by enucleation indicate that host factors are most important in determining whether or not a patient will succumb to his tumour. It is possible that nonsurgical methods of treatment may be as effective or even more effective than enucleation (a) by diminishing the changes of intravasation of tumour cells, and (b) by promoting a more favourable host response to the tumour. While the total experience in management by methods other than enucleation is small, the results reported to date with photocoagulation, radiation, and no therapy are encouraging. Only after a much larger experience with prolonged periods of evaluation (more than 10 years after recognition of the tumour) will we be able to compare the results with those obtained by enucleation.


Circulating antibodies in cutaneous leishmaniasis: their detection by immunofluorescence. With the use of an indirect fluorescent antibody (IFA) test and freeze-dried antigens, circulating antibody titres of 1 in 100 or above to Leishmania tropica leptomonad forms were detected in 66-6% and 76-2% of 18 patients with active and 21 patients with healed cutaneous leishmaniasis, respectively. Cross-reactivity was observed with L. donovani and Trypanosoma cruzi antigens. Five out of 15 patients with active pulmonary tuberculosis had antibodies to L. tropica major, suggesting a possible cross-reactivity between the two agents.


Persistence and recurrence of S-antigen in Plasmodium falciparum infections in man. The persistence of heat stable malarial antigens (S-antigens) in the sera of Gambian children following treatment for severe Plasmodium falciparum infections was investigated. In most cases S-antigens ceased to be demonstrable within 7 days but in some they were detected for several weeks and their persistence correlated with both the density of parasitaemia and the antigen titre observed before treatment. An exponential loss of circulating antigen was, in the majority of individuals, accelerated by some other factor which might have been homologous antibody. Renewal of asexual parasitaemia usually resulted in reduction in the rate of antigen loss or in an increase in antigen level. When the aparasitaemic interval was a month or less the antigens associated with different parasitaemic episodes usually showed identical specificities; when the interval was longer they were usually antigenically distinct. These findings may indicate that relapse parasites usually show the same S-antigen specificities as their progenitors while parasites arising from distinct infections tend to show different specificities and could therefore support a view that considerable antigenic heterogeneity exists among the parasites that comprise P. falciparum populations in endemic areas.


Chronic malarial infection in Balb/C mice. Effect on the immune response to sheep erythrocytes and histological changes in the liver and spleen. Chronic malarial infection was established in Balb/c mice by following Plasmodium berghei yoelii with P.b. berghei infection. It was found that the IgG plaque-forming cell response to sheep erythrocytes was depressed for at least six months. A preliminary investigation of the histological changes in the spleen and liver is described. The possibility that chronically infected mice could serve as a model for the tropical splenomegaly syndrome is discussed.