Kinetics of conformational changes in tRNA Phe (yeast) as studied by the fluorescence of the Y-base and of formycin substituted for the 3'-terminal adenine. The kinetics of the melting transitions of tRNA Phe (yeast) were followed by the fluorescence of the Y-base and of formycin substituted for the 3'-terminal adenine. As judged from differential UV absorbance melting curves the formycin label had virtually no influence on the conformation of the tRNA. A temperature jump apparatus was modified to allow the simultaneous observation of transmission and fluorescence intensities by two independent optical channels. The design of a temperature jump cell with an all quartz center piece is given. The cell is resistant to temperatures up to 90 degrees C; it provides high optical sensitivity, low stray light intensity and the possibility of measuring fluorescence polarization. The T-jump experiments allowed to discriminate between fast unspecific fluorescence quenching (r less than 5 musec) and slow cooperative conformational changes. In the central part of the temperature range of UV-melting (midpoint temperature 30 degrees C in 0.01 M Na+ and 39 degrees C in 0.03 M Na+, pH 6.8) two resolvable relaxation processes were observed. The corresponding relaxation times were 20 msec and 800 msec at 30 degrees C in 0.01 M Na+, and 4 msec and 120 msec at 39 degrees C in 0.03 M Na+. The Y-base fluorescence shows both of the relaxation effects, which almost cancel in equilibrium fluorescence melting, because their amplitudes have opposite signs. From this finding the existence of some residual tertiary structure is inferred which persists after the unfolding of the main part of tertiary structure during early melting (midpoint temperature 24 degrees C in 0.03 M Na+). In the fluorescence signal of the formycin also the two relaxation effects appear. Both of them are connected with a decrease of the fluorescence intensity. From the results a coupled opening of the anticodon and acceptor branches is concluded.


Campomelic dwarfism.

Campomelic dwarfism. The campomelic syndrome is a short-limb, usually fatal, neonatal dwarfism. It is characterized by bowed lower limbs, especially the tibia, usually associated with a cutaneous dimple over the anterior skin. There is delayed calcification of the epiphyses and delayed mineralization of the spine and pelvis. The cartilages of the tracheobronchial tree are hypoplastic, contributing to death from respiratory problems. Other associated abnormalities are unusual appearing facies, cleft palate, absent olfactory nerves and talipes equinovarus. Less commonly seen are cardiac, renal and brain anomalies.


[Properties of the F' factors formed in crosses of E. coli Hfr donor cells with recipient cells by means of defects in recombination]. Meriploids isolated from the crosses of donor cells HfrH, KL-96, KL-99 and the recipient cells AB 2463 recA carried sex factors of different structures (different in length) and activities: 1) typical F1-factors with the proximal chromosomal markers; 2) "long" F1-factors of different structures with defective genes, which controlled sensitivity to phagef2; 3) "long" F1-factors of different structures with defective genes, which controlled conjugation transfer. Chromosomal markers can be incorporated into the sex factor regardless of their position in respect to the sex factor in the initial Hfr cells. Defects of the sex factor proper in the genome are accompanied by the loss of some chromosomal genes incorporated into the sex factor. At the same time the typical F'-factors preserve their structure completely.


[Origin of Luciani periods during the effects of acetylcholine and eserine on the automation of Purkinje fibers]. Experiments were conducted on the isolated rabbit hearts with a complete atrio-ventricular block. It was shown that under the effect of acetylcholine (1.10(-7)-2.10(-6)g/ml) or eserine (1.10(-7)-2.10(-6)g/ml) there can occur Luciani periods which disappeared under the action of atropine (1.10(-6)g/ml). With the aid of microelectrodes it was revealed that Luciani periods appearing under the effect of acetylcholine or eserine were caused by periodic depression of automation of the Purkinje's fibers. This automation depression is regarded to be the result of a relative insufficiency of the active ionic transport processes.


Cell cycle dependency of a T-cell marker on lymphoblasts. A T-cell marker was expressed by the leukemic lymphoblasts of a 14 years old boy. After 14 days of cultivation, a permanently growing lymphoblastic cell line JM, which manifested the T-cell marker over the whole period of subcultivation, was established from the blood. In vitro synchronization experiments showed that this important cell marker in the G1 phase of the cell cycle is expressed on the surface of the blasts to a reduced degree, compared to the level in the other cell cycle phases.


An other look at iron: role in host pathogen interaction. Iron, as participant of many biological processes is a prerequisite for life. Uptake, internal transport and storage by organisms is handled by highly specialized chemical systems endowed with strong metal binding affinities. Apart from the homeostatic function of iron-binding compounds they appear of significance for inter-species interactions. Thus, by tight binding transferrin withholds the iron from invading microorganisms required for their optimal growth. This bacteriostatic property of the iron transport protein is however partially overcome by small molecular substances synthesized by bacteria and successfully competing for the metal. The balance of such interaction is a complex one. Yet, strong evidence points to the crucial importance of the amount of iron offered by a host to infecting agents for determining the fate of bacterial disease.


From poor farm to medical center: a century of library services to the Los Angeles County/University of Southern California Medical Center. As its centennial approaches, the history and development of library services to the patients and professional staff of the Los Angeles County/University of Southern California Medical Center is traced from the early days when the library was housed in the cafeteria of the dispensary to its present position of being first point of access to library service for one of the largest teaching hospitals in the country. Its recent affiliation with the Norris Medical Library of the University of Southern California School of Medicine is explained. The change in emphasis from patients' library to health sciences library is illustrated, and the contribution of the library to the Cumulative Index to Nursing Literature is detailed.


Reliability of plethysmography, the single breath oxygen test, and spirometry in population studies. Three thousand five hundred and twenty-eight residents of a census tract in Los Angeles, California underwent pulmonary function testing in a mobile laboratory (the Breathmobile). Tests included respiratory questionnaire, electronic spirometry, the single breath O2 test and body plethysmography. The reliability and sensitivity of the tests performed in the Breathmobile was measured by repeating the same tests and others on a 3% probability sample at the University of California at Los Angeles Pulmonary Function Laboratory. The reliability of the FVC and FEV1 was excellent; of the FEF 25-75% and the FEF 50-75% -- good; and of the VTG, RA and delta N2 -- reasonably good. As yet the reliability of the closing volume fraction is inadequate in our study. Grouping by individual reported symptom complexes identified different groups of people. The questionnaire and the forced expiratory flow rates identified the most people as having decreased respiratory function. Selection of the best breath or average of the two best breaths affected results of spirometry very little.


Cross-hand, cross-finger neurovascular flap: a preliminary report. As a preliminary report we present a case of severe injury of the dominant left hand in a 19-year-old girl. Reconstruction constituted a cross-arm flap initially, a palmaris longus tendon graft and finally a cross-hand, cross-finger neurovascular flap.


Free groin skin flaps.

Free groin skin flaps. The operative technique of free groin flap transfer is described and some typical results presented. The overall complete success rate in 47 cases was 80 per cent, but complete necrosis only occurred in II per cent of the transferred flaps.


Free groin flaps: their vascular basis.

Free groin flaps: their vascular basis. By studying the vascular base of flaps raised from cadavers we obtained a basic knowledge of free groin flaps for clinical application. The method of selection of the nutrient vessels in 70 free groin flaps based on this knowledge has been described.


Inosculation of vessels of skin graft and host bed: a fortuitous encounter. From the combined procedures of skin stereomicroscopy of in situ grafts in rats, graft removal and supravital intracardiac injection of a contrast medium, the data suggest that the revascularisation of skin grafts is an orderly sequence of events which include: active invasion of the graft dermis by the ingrowing host capillary sprouts; development of anastomoses between the graft and host vasculatures; entry of blood into the graft through the vascular anastomoses by 48 hours after transplantation.


A method of prominent ear correction.

A method of prominent ear correction. Modifications of the Mustarde technique for prominent ear correction are described, making this more widely applicable with less complications.


An investigation of space and space-time clustering in a large sample of infants with neural tube defects born in Cardiff. Altogether 406 infants with neural tube defects born in Cardiff between 1956-71 were investigated for evidence of space-time clustering and 100 similarly affected infants, together with matched controls born in Cardiff between 1964-66 were investigated for evidence of spatial clustering. No evidence of excessive prevalence in either dimension was observed.


A statistical review of controlled trials of imipramine and placebo in the treatment of depressive illnesses. A method of reviewing a series of clinical trials by extracting the basic data in the form of 2 x 2 tables and analysing these by Fisher's two-tailed Exact Test is described, and illustrated by published imipramine-placebo trials. The results suggest that the benefit of this drug in patients with endogenous depression who have not become institutionalized is indisputable, and that further drug-placebo trials in this condition are not justified. Two of the three trials of imipramine in neurotic depression gave results showing significant improvement. Possible explanations of the apparent failure of this drug in groups of patients with undifferentiated depression are discussed.


Matrix calculi.

Matrix calculi. Matrix calculi are an uncommon form of urinary tract concretion. They must be considered in the differential diagnosis of a radiolucent mass within the renal collecting system or ureter. The clinical and radiographic features of three cases are presented and the literature of matrix calculi is reviewed.


Duodenotomy defect.

Duodenotomy defect. Radiographic changes in the duodenum after duodenotomy are discussed. Two types are noted. One is a polypoid mass, the other is a convex deformity at the lateral wall of the descending duodenum. The radiographic findings are explained by the surgical technique used for duodenotomy.


Short-term cadaver kidney preservation.

Short-term cadaver kidney preservation. 200 consecutive human cadaver kidneys were preserved using 6 different techniques. Some attempt was made in the clinical situation to assess donor pre-treatment and postoperative specific recipient treatment to encourage immediate renal function. Provided the warm time was less than 60 min and the cold time less than 12 hours, intraarterial flushing with a crystalloid or colloid solution combined with pre-treatment of the donor and postoperative fluid load/frusemide drive to the recipient gave the best results.


Urinary tract infection and wound infection in kidney transplant patients. The frequency of urinary tract and wound infections was studied in 53 patients most of whom had received kidneys from donors without heart action. Urinary infection was demonstrated soon after the transplantation in 46 out of 47 with functioning kidneys. Recurrent infections took place during the first 3 months and still half of the patients were infected or under treatment 6 months after the operation. The urinary infection seems mainly to arise via indwelling catheters. Wound infections were demonstrated in 18 out of the 53 patients and in addition abscess formation took place in 9 of these. In the majority of the infected wounds previous infected drains were demonstrated. In all, 36 of the patients had infected drains, the use of which therefore is to be avoided.


Septic shock.

Septic shock. The problems associated with septic shock are highlighted, including those which arose during a 3-year prospective study. Mortality in the first year of the study was 71 per cent, falling to 38 per cent in the third year. The reasons for this fall are detailed. The pattern of survival times changed over the 3 years, giving rise to the longer term complications such as stress bleeding, multiple organ failure and superadded infection.


Prediction of kidney viability before transplantation. A patient who receives a kidney transplant which fails suffers a physical and psychological disaster. Almost one-third of the kidneys transplanted in the United Kingdom are primary failures; many others function only after a delay, and the long term prognosis for these kidneys is poor. There is a need to identify kidneys which will function immediately after transplantation, those which will function after a delay and those which will never function. Such identification is seldom possible from the history. By continuous hypothermic perfusion we can identify a group of kidneys which will probably never function. The perfusate lactate level predicts which of the remaining kidneys will function immediately and which will not. Kidneys which function immediately after transplantation have a very much better long term prognosis after transplantation than those with delayed onset of function.


A controlled clinical trial of three methods of closure of laparotomy wounds. A controlled clinical trial was conducted of three methods of closing elective paramedian laparotomy wounds--catgut layer suture alone, catgut layer suture with tension sutures and wire sutures alone. Three hundred and twenty-four patients were entered in the trial. The combined incidence of wound dehiscence and subsequent incisional herniation in patients who did not manifest overt dehiscence in the immediate postoperative period was significantly higher after catgut layer suture alone (14 per cent) than after catgut layer suture with tension stitches (4-8 per cent) or wire sutures alone (0-9 per cent). There seemed to be more wound sespis and sinus formation associated with catgut layer suture and tension sutures than with either of the other methods of closure. In 4 patients a wire suture had to be extracted, because of sinus formation in 2 and on account of pain in 2.


Controlled clinical trial comparing early with interval cholecystectomy for acute cholecystitis. The traditional management of acute cholecystitis is initial conservative treatment with antibiotics followed by elective cholecystectomy. Although early cholecystectomy has often been advocated, there has been only one randomized controlled clinical trial comparing the two methods of treatment. This paper reports the preliminary results of such a trial in which 32 patients have been studied so far. Of the 17 patients managed conservatively, there was a misdiagnosis in 2 (11-8 per cent). In the remaining 15 patients with acute cholecystitis 3 (20 per cent) required urgent operation because of failure of medical treatment. Elective cholecystectomy was not technically difficult. Of the 15 patients treated by early cholecystectomy, there was a misdiagnosis in 1 (6-8 per cent). Surgery was technically difficult in 2 patients but cholecystectomy was possible in all. The former 2 patients required blood transfusion, but in the remainder the estimated blood loss was only slightly more than in the elective group. There was no mortality in either group nor any complication directly attributable to the biliary surgery. The incidence of minor postoperative complications was only slightly greater in those treated by early operation. The length of postoperative stay was similar in both groups but those treated conservatively spent an average of 11 more days in hospital. The preliminary results indicate that those treated by early cholecystectomy spend less time in hospital and avoid the complications of failed conservative treatment without the added risk of increased postoperative mortality and major complications.


The role of surgery in the management of Hodgkin's disease. The marked improvement in the prognosis of patients with Hodgkin's disease has resulted from advances in radiotherapy and chemotherapy. Success with these treatments depends upon accurate knowledge of the extent of the disease. Clinical assessment of the presence of abdominal disease is unreliable. Exploratory laparotomy with splenectomy, multiple lymph node biopsy and liver biopsy will reveal that preoperative assessment of the extent of the disease is inaccurate in 30 per cent of cases. The information obtained prevents relapses from undiagnosed abdominal disease and ensures that inappropriate radiotherapeutic treatment is not given to patients with disseminated disease.


Measurement of the immune response to an allograft: amino acid incorporation by peripheral white blood cells in man. The uptake in vitro of 3H-thymidine and of 3H-uridine by white blood cells freshly taken from the recipients of renal transplants has been followed at regular intervals during the period of the patients' hospitalization. In addition, groups of subjects without renal failure undergoing operation and of patients on chronic dialysis have been studied. Of 33 patients undergoing rejection of their kidney, 28 showed a marked rise in the incorporation of thymidine over the period of rejection. However, a similar rise appears to accompany episodes of inter-current infection.


Experimental studies on the pathophysiological responses of the newborn to injury. Experimental studies are reviewed which show that there are significant differences with age in both the local and general responses to injury. The results seem to confirm the belief in the striking ability of the newborn to withstand injury and suggest that one important aspect of this resistance is an increased ability to compensate circulatory hypovolaemia.


Atenolol and bendrofluazide in hypertension. The effect of atenolol, a new beta-1-adrenergic receptor blocking agent, was studied in a double-blind cross-over trial in 24 carefully selected hypertensive outpatients. After a four-week run-in period on matching placebo each patient received atenolol 200 mg/day, atenolol 400 mg/day, a combination of atenolol 200/mg day with bendrofluazide 5 mg/day, and bendrofluazide 5 mg/day alone, according to a random sequence. Atenolol at either dose produced a significantly greater reduction in all blood pressure levels except standing systolic pressure than bendrofluazide alone. There was no statistically significant difference between the effects of the two atenolol doses on either blood pressure or pulse rate. The addition of bendrofluazide to atenolol resulted in a further significant lowering of the blood pressure. A significant effect of thiazide on weight was noted. The study shows that atenolol, a cardioselective beta-blocker of similar potency to propranolol in animals but without membrane-stabilizing or partial agonist acitivity, is an effective and well-tolerated hypotensive agent.


Continuous positive airway pressure and mechanical ventilation by facemask in newborn infants. During a nine-month period 24 newborn infants were treated with continuous positive airway pressure (CPAP) or mechanical ventilation delivered through a facemask. The mask was held in place in a way that minimised trauma and distortion of the head. The median birth weight of the infants was 1096 g and their median gestational age 29 weeks. The usual reason for treatment was hyaline membrane disease or recurrent apnoea due to inadequate control of breathing. Twenty-one of the infants survived. The technique was simple to apply and complications were minimal. We suggest that it may have advantages over other methods of applying CPAP or mechanical ventilation to infants mildly affected by respiratory illnesses and that it should be useful in avoiding endotracheal intubation or reducing the length of time that infants with more serious illnesses are intubated.


Controlled trial of sodium valproate in severe epilepsy. In a double-blind crossover trial sodium valproate or placebo was added to the existing anticonvulsant treatment of 20 patients with chronic uncontrolled epilepsy. Sodium valproate 1200 mg/day significantly reduced the frequency of both tonic-clonic and minor seizures in these patients. Only mild and transient side effects occurred (drowsiness, ataxia, and nausea), and these may have been due to the effect of adding sodium valproate to existing phenobarbitone or phenytoin treatment. Further controlled trials are needed to assess more fully the efficacy of this drug in various types of epilepsy.


Low-dose heparin prophylaxis against fatal pulmonary embolism. A prospective randomised controlled trial in 500 patients over the age of 50 who were undergoing major surgery showed that low-dose subcutaneous heparin was an effective prophylactic measure against fatal pulmonary embolism. None of the 252 patients who received perioperative heparin cover died of fatal pulmonary embolism while eight of the 236 who did not receive heparin prophylaxis died of fatal pulmonary embolism. These results were statiscally significant (P less than 0.01).


Effects of oxygen and nitrogen on the character of T. pallidum is subcutaneous chambers in mice. Nitrogen and oxygen gases were injected into mouse subcutaneous chambers which contained virulent Treponema pallidum. The effect of each gas on the viability and survival of T. pallidum in an in vivo system was determined. In comparison with the effects in nontreated control mice, injection of nitrogen enhanced both motility and survival time, but oxygen exerted a deleterious effect.


Evaluation of a sustained-release oral tetracycline in non-specific urethritis. A double-blind trial of oxytetracycline (Imperacin-I.C.I.) and tetracycline hydrochloride in a sustained-release formulation (Tetrabid-Organon) was carried out on 259 men suffering from non-specific urethritis. Patients who had NSU in the preceeding 3 months were excluded from the trial. The response to treatment assessed at 10 days was favourable in ninety patients out of 129 (35 per cent.) who received oxytetracycline and in 89 patients out of 130 (34 per cent.) who received Tetrabid-Organon. Eight patients in each group required re-treatment and the remainder failed to attend for follow-up. At 4 weeks after treatment one (1-3 per cent.) of 74 patients treated with Tetrabid-Organon and twenty (37-7 per cent.) of patients treated with oxytetracycline required further treatment. A large proportion of patients who were free of signs and symptoms at the first follow-up failed to return at 4 weeks, so that the true rates of cure at 4 weeks are difficult to assess. In a field such as venereology, the twice-daily administration of medication offers distinct advantages over a four-times-daily regime. This study suggests that Tetrabid-Organon, a tetracycline designed specifically for twice-daily dosage, is more effective than standard oxytetracycline, given twice daily, in the treatment of NSU. It was satisfying to find that the traditional advice concerning abstention from sexual activity and alcohol consumption during the treatment of NSU has a sound basis. The study showed a close correlation between recurrence of NSU and failure to follow such advice. It would be interesting to investigate the means by which alcohol consumption may act to delay recovery.


Behavioural effects of electrical stimulation of the hypothalamus of the goldfish (Carassius auratus). Food-satiated goldfish were stimulated in tanks containing food on the surface of the water and on the bottom of the tank. Various components of the feeding response were seen, and complete feeding was observed, which was elicited from sites in the postero-medial hypothalamus. Evidence is put forward to support the supposition that the full response was due to a change in feeding motivation, rather than to changes in sensory or motor factors. Other types of behaviour, such as fin movements and swimming, could not be identified as part of any normal ethological sequence. However, vertical movements and gas-spitting responses indicated a possible hypothalamic control of buoyancy. None of the behaviours observed was seen to change in a social context.


The naming of neurons: applications of taxonomic theory to the study of cellular populations. For many purposes, biologists must study large brains through groups of similar neurons, since these populations - not individual cells - are the smallest units for which exact counterparts can be recognized unequivocally across a series of brains. One who surveys singel neurons, by whatever techniques, may discern major aspects of a tissue's organization by classifying the elements studied, thereby performing an exercise in taxonomy at the cellular level. The discovery of neuronal types is best achieved by imitating the naturalist who seeks new biological species: a large sample of cells is gathered by a regular, widely effective method, and an effort is made to understand the biases in the sampling procedure; a numerous and diverse set of features is observed for each neuron encountered; and the cell sets recognized are described in agreement with the polythetic concept of natural groups. The resulting multidimensional population descriptions, the most useful of which include the temporal information available through electrophysiologic recording, may be quite powerful for testing circuit hypotheses about the large nervous system.


Experimental immunohistochemical studies on the localization and distribution of substance P in cat primary sensory neurons. With the indirect immunofluorescence technique of Coons and collaborators the occurrence of substance P (SP)-like immunoreactivity was studied in spinal ganglia (L6-S1), the spinal cord (L6-S1) and the pad skin of the hind paw of the cat. In untreated cats a very dense network of SP-positive fibers was found in the spinal cord in Lissauer's fasciculus, in laminae I-III and a rather dense plexus was seen in the ventral horns, in the area around the central canal (laminae X) and in the medial parts of laminae VI and VII. SP-positive fibers were also observed in the connective tissue under the epithelium of the skin. However, in untreated cats no specific immunogluorescnece was observed in the spinal ganglia, dorsal roots or certain large peripheral nerve trunks. After certain experimental procedures such as local application of colchicine or compression of the dorsal root close to the spinal ganglion, SP-positive fluorescence was observed in a rather small number of neuronal cell bodies and in fibers. The fluorescent material was observed in the peripheral parts of the cytoplasm and the cell bodies were exclusively of the small type. Ten days after transection of the dorsal roots a marked decrease in the number of SP-positive fibers was observed in the substantia gelatinosa but not in the ventral horns. The present results give strong evidence for the occurrence of SP in a certain population of primary sensory neurons and support earlier findings that SP may act as a transmitter or modulator in these neurons.


Membrane-bound S-100 protein on nerve cells and its distribution. In this study we present data supporting a heterogeneous distribution of the brain-specific S-100 protein on nerve cell plasma membranes from isolated neurons. This has been shown in a previous study by immunoelectron microscopy using peroxidase-conjugated anti-S-100 antiserum and in this study by immunofluorescence using fluorescein-conjugated anti-S-100 antiserum, the specificity of which is discussed. Incubation of the cells at +23 degrees C or at +4 degrees C did not change the distribution pattern of S-100 over the cell membranes, nor did incubation in antimetabolites, or incubation with univalent Fab fragments. We conclude that the membrane-bound S-100 protein with its heterogeneous and polar distribution on the nerve cells is a sign of a protein differentiation of the neuron.


Comparative studies in synaptosome formation: preparation of synaptosomes from the ventral nerve cord of the lobster (Homarus americanus). A flotation method for preparing synaptosomes, previously developed for work with squid nervous tissue, has now been successfully applied to the ventral nerve cord of lobster. Perhaps due to the greater content of connective tissue, homogenization of the lobster nerve cord was more difficult than with squid optic lobes and the yield of synaptosomes was lower. The synaptosomes fraction showed a 3.8-fold enrichment of bound acetylcholine relative to the homogenate and was almost 10 times richer in acetylcholine than a guinea pig cerebral cortical synaptosome fraction. The lobster synaptosomes accumulated choline rapidly when incubated at room temperature in sea water, and showed a high degree of occlusion of lactate dehydrogenase, thus confirming that they are sealed structures. The lobster can thus be added to the wide range of species from whose nervous systems synaptosomes can be isolated, and merits further study as a possibly rich source of cholinergic synaptosomes.


Distribution of protein-bound radioactivity in brain slices of the adult rat incubated with labelled leucine. The distribution of protein-bound labelled leucine in brain cortex slices, prepared from adult rats by various methods and incubated with [14C]- or [3H]leucine, was investigated by autoradiography. In the first and second slices a marked gradient of incorporated radioactivity from the cut surface to the slice interior was observed. Very high labelling of leptomeningeal cells and vessels enhanced further the inhomogeneity of radioactivity distribution. Light microscopic examination of incubated slices revealed morphological alterations of neurones, especially in the vicinity of the cut surface. The comparison of grain density over neurones and their satellite glia indicated markedly higher incorporation into the latter. The ATP level in slices at the end of incubation reflected the method of slice preparation and morphological integrity. Inhomogeneity of incorporated radioactivity distribution in brain slices contrasted with the uniform labelling of cortical cells in vivo, and may represent at least one reason for the low estimates of protein synthesis rate in brain cortex slices.


Processing of E. coli tRNA precursors.

Processing of E. coli tRNA precursors. Our results indicate that RNase P has a very general role in the processing of tRNA precursors in E. coli, being responsible for the cleavage of virtually all precursor molecules at a site corresponding to the 5' end of the mature tRNA, and that at least two other RNases play specific roles in precursor processing. One of these, which may be RNase II, is responsible for removing extra nucleotides from the 3' end of tRNA precursors. The other, which we call RNase P2, is an endonuclease that cleaves precursors in spacer regions between different tRNA sequences; this enzyme is involved in the processing of large multimeric precursors.


Demineralization of bone matrix: observations from electron microscope and electron-probe analysis. Displacement or removal of mineral during the processing of calcified tissues for electron microscopy is a recognized phenomenon. An electron microscope analysis has been made of artefactual mineral loss during ultramicrotomy of osteogenic tissue. It is concluded from morphological investigation and the use of electron diffraction that this loss of crystalline mineral during sectioning can considerably change the morphology of calcified tissues and may lead to inaccurate interpretation of cell and matrix morphology. Electron probe X-ray microanalysis has been used to demonstrate in a semi-quantitative manner, the artefactual loss of calcium and phosphorus. Problems of specimen preparation for such analytical work are discussed.


A modification of the Bird Mark VIII ventilator to deliver continuous positive pressure breathing and intermittent mandatory ventilation. A Bird Mark VIII ventilator was modified to produce a simple and inexpensive C.P.P.B. and I.M.V. circuit. A Bain Breathing Circuit allowed the manifold to be placed near the ventilator. The negative pressure and flow to the injector produce C.P.P.B. The continuous flow of the Mapleson D Modification furnished constant inflow to provide humidified fresh gas to the reservoir and the patient circuit for I.M.V. An accompanying graph illustrates suggested flow rates and CO2 elimination (Figure 2).


Air bypass voice prosthesis for vocal rehabilitation of laryngectomees. An air bypass voice prosthesis and the refinement of a surgical technique has been developed. It involves a one-stage, low retrograde cervical esophagostomy that is functionally and cosmetically feasible since it permits hidden use of the device and eliminates fistula tract stenosis; and the problem of aspiration is eliminated. Most importantly, it provides a natural speech mechanism without any training period. Patients can regain immediate speech following installation of a voice prosthesis with a minimum of maintenance required. Ultimately, they have demonstrated greater self-reliance and developed a high degree of self-esteem which has enabled them to resume a normal way of life.


Specific features of laryngeal carcinoma involving the anterior commissure and the subglottic region. The anterior commissure may be a line or an area with the same vertical extension as the vocal cords anteriorly. If it is an area it may laterally be bounded by the "maculae flavae". The subglottic region includes the under surface of the vocal cords corresponding to the mucosa covering the conus elasticus and the mucosa inferiorly to the lower border of the cricoid cartilage. Serial sectioning has proved that the weak spot of the laryngeal framework is the anterior midline as far as early tumor invasion of cartilage and extension of tumor outside the larynx through the cricothyroid membrane is concerned. Despite many unfavorable anatomico-pathological points at this site, radiotherapy gives at least as good results as those reported with conservative (voice conservation) surgery. Primary subglottic carcinomas are rare. In a series of 110 serially sectioned laryngectomy specimens only four were classified as subglottic. These tumors possess specific characteristics: an extensive circumferential growth, cartilage invasion, and spread outside the larynx through the cricothyroid membrane, to trachea or to the hypopharynx. Twenty-four tumors were classified as glottic-subglottic. Three of these invaded the thyroid cartilage and seven spread outside the larynx through the cricothyroid membrane. Vocal cord fixation occurred in all four subglottic and in six of the glottic-subglottic tumors. The thyroarytenoid muscle was most freqeuntly invaded. Thyroid gland invasion did not occur in any of the subglottic tumors. A metastatic focus of tumor was observed in one lobe of the thyroid in the glottic-subglottic group. Two neck dissections were performed in the subglottic group and one of these contained a metastatic carcinoma. Eleven neck dissections were performed in the glottic-subglottic group and three contained metastatic tumor.


Effects of age and of fasting on the responsiveness of the insulin-secreting mechanism of the islets of Langerhans to glucose. Insulin responsiveness to glucose of isolated islets of Langerhans was studied in 'younger' and 'older' rats after feeding and fasting for various lengths of time. In 'younger' rats, after prolonged fasting (168 h) the threshold for glucose-stimulated insulin secretion was increased. This was not evident in islets from 'younger' rats fasted for 48 or 89 h. Reductions in increments of insulin secretion with increments in glucose, in the maximum insulin secreted and in the total extractable insulin of the islets were apparent after fasting for 48, 89 and 168 h as compared with islets from fed rats. In 'older' rats, prolonged fasting caused an increase in the threshold for glucose-stimulated insulin secretion, reduced incremental insulin secretion, reduced maximum insulin secretion and reduced total extractable insulin. However, the responses of islets from fed 'older' rats were similar to those of fasted (168 h) 'younger' rats. The threshold levels were similar, and there were no significant differences between increments in insulin secretion, maximum insulin secretion and insulin content of the islets. These experiments show that the responsiveness of islets of Langerhans in rats can be altered by age and fasting.


Factors affecting the immunizing activity of ribosomal fractions isolated from Mycobacterium tuberculosis var. bovis strain BCG. Levels of antituberculous immunity similar to those induced by live BCG vaccine were detected in CF1 mice immunized with ribosomal fractions isolated from Mycobacterium tuberculosis var. bovis, strain BCG, and challenged 3 weeks later with the virulent H37Rv strain of Mycobacterium tuberculosis var. hominis. The activity of the crude ribosomal preparations was found to be a function of the immunizing doses and the immunity induced by 1.0-mg doses remained at the same high level after 4 weeks of storage at 4 degrees C but decreased markedly thereafter. Dialysis and lyophilization had no detrimental effects on the activity of the crude preparations whereas purification by column chromatography on Sephadex G-200 annihilated their biological activity. Crude low-polysaccharide-containing preparations were found inactive even at the 1.0-mg dose level and results of experiments performed with crude ribosomal fractions of varying polysaccharide contents strongly suggest that polysaccharides, or RNA-polysaccharide complexes, may play an important role in the induction of immunity with crude ribosomal fractions isolated from the BCG strain of Mycobacterium tuberculosis var. bovis.


Envelope proteins in Neisseria.

Envelope proteins in Neisseria. The proteins of the cell envelope of Neisseria sicca strain ATCC 9913 have been examined by SDS - polyacrylamide gel electrophoresis. Some 20 proteins were resolved from the total envelope fraction, and nearly all of these were found to be localized in the outer membrane. Preparations of the "free-endotoxin" fraction differ from the outer membrane only in lacking a few minor proteins. The behavior of several of the envelope proteins on electrophoresis can be modified by changing the temperature of sample solubilization, and also by alteration of the growth medium. Experiments with phosphate-limited cultures showed that certain periplasmic proteins are closely associated with free endotoxin. Mutations which result in altered outer membrane permeability to antibiotics were found to cause changes in cell envelope protein composition. A comparison of the envelope proteins of eight species of non-pathogenic Neisseria showed that each had a characteristic composition. A classification of the organisms based on the relatedness of the protein patterns seen on SDS-polyacrylamide gels was in close agreement with classifications based on more usual methods.


Isolation and partial characterization of an Escherichia coli mutant resistant to colicin A. An Escherichia coli K12 mutant resistant to colicin A-CA31 apparently through loss of its receptor sites has been isolated and partially characterized. Resistance to colicin A was accompanied with a decreased sensitivity to colicins L-398 and E2-CA42, and to acridine dyes. The mutant strain displayed the same general pattern of tolerance or sensitivity as the parent strain towards eight antibiotics, colicins C, D, E1, E3, F2, F3, G, I, K, and N; phages T1, T2, T5, T6, T7, F2, lambda vir, P1kc, phi 80, and BF23; and to methylene blue, triphenyltetrazolium chloride, ethylenediaminetetraacetate (EDTA), deoxycholate, and sodium dodecyl sulfate. Conjugation and transduction experiments showed that a locus controlling resistance to colicin A-CA31 mapped at 21 min on the genetic map of this E. coli K12 strain.


A replica-plating method for the identification of Micrococcaceae. A procedure of replica plating is described whereby all isolated colonies of Micrococcaceae can be identified with relative ease and rapidity. The method is as accurate as the recommended procedure, but permits a more complete and economical analysis of cutaneous flora in large-scale surveys. In this system, Baird-Parker carbohydrate medium was found somewhat superior to standard medium as was incubation at 35 degrees C instead of the customary 30 degrees C. Baird-Parker's broth medium for acetoin production yielded more positive results than did commercial medium, although the reactions were less distinct. However, an agar acetoin test medium was found as good or perhaps even better than Baird-Parker's medium. The classification schemes of Baird-Parker and Bergey's Manual were contrasted in the analysis of data.


Variation in the lethal response in mice to yeast-like and pseudohyphal forms of Candida albicans. The lethal response in mice to yeast-like cells of Candida albicans grown for 3, 6, or 9 h in a defined minimal culture medium was more severe than that observed with corresponding pseudohyphal preparations. This differential effect could be only partially correlated with the greater number of viable units in respective yeast-like cultures. No significant differences between yeast-like and pseudohyphal syspensions were detected when turbidity-mass ratios were examined. The injection of physiological saline suspensions containing increasing quantities of yeast-like cells resulted in proportional decreases in mouse survival times. Conversely, when comparable experiments were conducted with pseudohyphal preparations no significant decreases in survival times occurred. The data indicate that these differences in the lethal response cannot be explained solely on the basis of a variation in the number of viable units or cell mass in corresponding yeast-like and pseudohyphal preparations. Factors contributing to this phenomenon may therefore include altered susceptibilities to host defense mechanisms in the early stages of the infectious process as a result of differences between these yeast-like and pseudohyphal inocula.


The survival of Escherichia coli from freeze-thaw damage: permeability barrier damage and viability. The effect of cooling rate and subsequent warming rate on survival of lactose-limited Escherichia coli was investigated. As previously reported, in the slow cooling rate range, a peak of survival was noted at 8 degrees C/min with survival decreasing as the cooling rate was increased or decreased from this value. Minimal survival was noted at 100 degrees C/min; increasing the cooling rate above 100 degrees C/min increased survival. At cooling rates greater than 200 degrees C/min, the survival became dependent on subsequent warming rates. Permeability damage, as measured by release of UV-absorbing material, potassium and beta-galactosidase, and increased accessibility of glucose-6-phosphate dehydrogenase to its substrates, was dependent on the cooling rate when cells were frozen in either water or saline. For cooling rates less than about 8 degrees C/min, there was minimal permeability damage to cells frozen in water. However, at rates greater than this value, damage and viability were related; the lower the viability the more the damage to the permeability barrier. The relationship was strengthened by the observations that protectants which increased survival reduced damage as well and that at ultrarapid cooling rates where survivals were dependent on warming rates, the extent, of damage was likewise dependent on the warming rate. Saline frozen cells were damaged by freezing and thawing more than comparable water-frozen cells over the whole cooling rate range. At cooling rates less than 8 degrees C/min, frozen in water, permeability damage of cells frozen in saline increased as the cooling rate decreased. As the cooling rate was increased from 8 degrees C/min, the damage increased as viability decreased. The relevance of these findings to the two-factor hypothesis of cell death is discussed.


Three antimicrobial metabolites from Aspergillus caespitosus. Aspergillus caespitosus NRRL 5769 growing in broth containing small amounts of sitosterol produced substance(s) with greater inhibitory activity against Candida albicans ATCC 10231 than in broth without sitosterol. Subsequent isolation, purification, and structural elucidation yielded 5,6-dihydro-5(S)-acetoxy-6(S)-1,2-trans-epoxypropyl)-2H-pyran-2-one (asperline (1), compound I) and two new metabolites. These were 5,6-dihydro-5(S)-acetoxy-6(S)-(1,2-trans propenyl)-2H-pyran-2-one (compound II) and 5,6-dihydro-5(R)-acetoxy-6(S)-(1,2-trans-epoxy-propyl)-H-pyran-2-one (compound III). These three metabolites showed anti-microbial activity against C. albicans and against specific bacteria, fungi, and a trichomonad.


A technique for obtaining linear heat-survivor curves with Staphylococcus aureus and its application to the assay of sublethal heat injury. Staphylococcus aureus was grown in a complex (HK) medium either by a batch technique or by a modified batch technique after growth in a chemostat. These cultures were heat-treated at 52 degrees C, and counted on trypticase soy agar (TSA) or trypticase soy agar containing 7.5% NaCl (TSAS). When linear heat-survivor curves were obtained decimal reduction times (D52 degrees C) could be calculated from the TSA counts and pseudodecimal reduction times (D' 52 degrees C) from the TSAS counts. The D or D' values of batch-grown cells varied from 22 to 133 min and from 3 to 12 min, respectively. With cells grown by the modified technique the values were less variable (D was 22-51 min and D' was 3-7 min). D and D' values could be calculated from the same heat treatment in two of the six estimations with cells grown by the modified technique.


The brain, the heart and taurine.

The brain, the heart and taurine. This paper reviews some recent developments concerning the "non-essential" amino acid Taurine. It is shown that taurine is important in metabolic regulations within the heart, muscle and brain. Particular attention is paid to the neuropharmacology of taurine, such as its possible role in epilepsy.


Comprehensive mental health care in a pediatric dialysis-transplantation program. The dialysis-transplantation (D-T) program at The Hospital for Sick Children, Toronto has a mental health component directed by a psychiatrist and a social worker. As of Jan. 1, 1975, 53 kidney transplants had been carried out on 44 children. Patients and their families are counselled continuously by the psychiatrist and the social worker before, during and after transplantation. Members of the multidisciplinary team meet regularly to plan treatment for the children. Mental health issues are an integral part of team discussions and help determine D-T program policy. Psychological preparation, mental health consultation, therapeutic intervention and continuous counselling prevent many of the mental health problems that plague a D-T program.


Hepatitis B surface antigen (HBsAg) infection in a hemodialysis unit. II. Factors affecting host immune response to HBsAg. Serum from 86 hemodialysis patients, 105 healthy hospital staff "at risk" and 160 regular hospital staff was screened for hepatitis B surface antigen (HBsAg) and antibody (anti-HBs). The combined prevalence of HBsAg and anti-HBs was higher in the staff of the artificial kidney unit (57.7%) than in the hemodialysis patients (33.7%). The healthy subjects with HBsAg infection responded significantly more often by producing anti-HBs compared with the hemodialysis patients. Twelve of 29 (41.4%) hemodialysis patients with HBsAg infection produced anti-HBs, while 17 (58.6%) remained positive for HBsAg. This differential response could not be attributed to age, sex, time spent undergoing hemodialysis, delayed cutaneous reactivity or response to phytohemagglutinin (PHA) or pokeweed mitogen (PWM). However, a much larger proportion of patients with HBsAg than with anti-HBs had previously received blood transfusions (88.2% v. 33.3%). Our results indicate that development of the chronic HBsAg carrier state or production of anti-HBs in uremic patients may be influenced by the route of immunization or the dose of antigen, or both. Although uremic patients maintain normal in vitro response to PHA and PWM, they may have depressed immunity in vivo because of a decreased total number of T-lymphocytes.


Role of 67gallium citrate scanning in the management of non-Hodgkin's lymphoma. 67Gallium scans were performed as part of the initial evaluation in 45 patients with non-Hodgkin's lymphoma. Eighteen of these patients underwent staging laparotomy and splenectomy. In addition, scans were performed either shortly after therapy was completed or during subsequent followup in 10 patients. The initial scans were found most useful for patients with histiocytic lymphoma: in detecting sites of involvement above the diaphragm and the high para-aortic/mesenteric region, and when tumors were greater than 2 cm in diameter. The addition of 67Ga scanning to the pre-operative clinical evaluation reduced the number of incorrectly staged patients from 8 to 4. Reversion of previously positive 67Ga scans to negative in 3 patients with suspected persistent or recurrent disease was associated with fibrosis and no lymphoma when biopsied. Five other patients had histologically documented positive 67Ga scans post-therapy; in 1 the 67Ga scan was only definitive noninvasive procedure. Despite the occurrence of both false-positive and false-negative 67Ga scans, this procedure appears to be a useful supplement to the pretreatment evaluation of patients with non-Hodgkin's lymphoma, especially the histiocytic form. Confirmation of its ability to detect high para-aortic/mesentric involvement may subsequently result in a reduction of the number of staging laparotomies necessary. For the post-treatment followup of these patients 67Ga scans may prove to be valuable noninvasive investigation.


Evolution of the team approach in breast cancer. Dr. Wendell G. Scott hailed mammography as the first significant contribution to the control of breast cancer since Halsted described the radical mastectomy in 1903. Mammography as engendered new approaches and has supplied new concepts of breast cancer. Through the tenacity of a few physicians convinced something could be done for the breast cancer patient, the team against this dread disease has gradually, but solidly, been built and continues to grow.


Nutrition in the United States, 1900 to 1974. Food and nutrient intakes are being examined for possible relationship to the occurrence or the progress of various types of cancer in man. This paper describes the state of our knowledge on the nutritional status of various population groups in the United States and on the food consumption patterns and their nutritional consequences during the 1900's. Only a few medical studies of nutritional status have been conducted on a national or even a regional basis. These extend back less than 2 decades. Dietary information is available back to the 1930's and statistical data on use of food in the United States can be found beginning with 1909. Sources of information are suggested for the use of and detailed study by the epidemiologist.


Incidence of stomach cancer and its relation to dietary habits and nutrition in Japan between 1900 and 1975. The diet of the Japanese people may be an important factor contributing to the high morbidity and morality rates of stomach cancer in Japan. Heavy rice consumption plus many salty foods in the diet are characteristic of the traditional eating habits in Japan. Fat intake and use of alcohol and tobacco are also considered possible factors. As the diet of the Japanese people changes to a more Western diet, there may be a concomitant change in the incidence of stomach cancer.


Nutrition and tumor immunity: divergent effects of antitumor antibody. Nutritional deficiency reduces antibody synthetic capacity. Antibody directed against tumor antigens, however, may serve either to heighten tumor immunity, as in antibody-dependent cellular cytotoxicity, or to diminish host resistance to cancer growth by "blocking" cell-mediated tumor immunity. Diets made deficient in specific amino acids are inimical to tumor growth, apparently through reduction of synthesis of blocking antibody. Thus, where tumor immune function is involved, complex and possibly paradoxical effects of nutritional status on tumor growth can be predicted.


Effects of dietary constituents on the metabolism of chemical carcinogens. Dietary constituents of 2 types have been shown to affect the metabolism of chemical carcinogens by the microsomal mixed-function oxidase system. Naturally occurring inducers of increased activity of this system are present in plants. Cruciferous vegetables including Brussels sprouts, cabbage, and cauliflower are relatively potent in this regard. From these vegetables, three indoles with inducing activity have been identified. These are indole-3-acetonitrile, indole-3-carbinol, and 3,3'-diindolylmethane. A 2nd type of dietary constituent affecting the microsomal mixed-function oxidase system is added phenolic antioxidant, i.e., butylated hydroxyanisole (BHA) and butylated hydroxytoluene. Studies of the effect of BHA on metabolism of bezo(a)-pyrene by liver microsomes have been carried out. BHA feeding results in microsomal changes. The cytochrome P-450 shows altered spectral characteristics, and the aryl hydrocarbon hydroxylase system of these microsomes has an increased sensitivity to inhibition by alpha-naphthoflavone. In addition, there is a decrease in binding of metabolites of benzo(a)pyrene to DNA upon incubation of these microsomes of induction of increased mixed function oxidase activity have shown that increased levels of activity protect against administration of chemical carcinogens. BHA and butylated hydroxytoluene also have been found to exert a protective effect against chemical carcinogens. Thus the constituents of the diet could be of consequence in the neoplastic response to exposure to carcinogens in the environment.


Is there a role for mitochondrial genes in carcinogenesis? Although defective respriration is not characteristic of all tumors, recent comparative studies on the ultrastructure of normal and tumor cell mitochondria indicate that in malignant cells mitochondria deviate from normal not only in relative abundance but  also in the size, form, density, and frequency of appearance of lesions. Normal and abnormal mitochondria may populate the same cell, suggesting that there may be a gradation in respiratory deficiency depending on the proportion of normal to abnormal forms. Recent advances in mitochondrial genetics suggest that aberrant mitochondria may be formed as a result of the presence of an abnormal mitochondrial genome. In analogy with the petite mutant of certain strains of yeast, animal cells may be transformed by treatment with dyes that alter the structure of their mitochondrial DNA, so that their mitochondria also become deficient in enzymes of the respiratory chain. Whether nutritional or other deficiencies are mutagenic with respect to mitochondrial DNA of animal cells is not known; nor is it known whether mitochondrial mutagenesis is causally involved in carcinogenesis. New knowledge of cytoplasmic genetics and of mitochondrial DNA and membrane structure and dynamics should encourage investigations aimed at examining the possible role of mitochondrial genes in neoplastic transformation.


Can nutrition explain the pattern of international epidemiology of hormone-dependent cancers? International data on the distribution of hormone-dependent cancers suggest that they are cancers of affluence. Their occurrence parallels that of bowel cancer fairly closely in population and less closely with regard to individual patient risk. The most plausible hypothesis, although based on extremely incomplete knowledge, is that some components of the Western high-protein, high-fat diet acting in early life make individuals prone to develop these cancers.


Breast cancer incidence and nutritional status with particular reference to body weight and height. The epidemiological literature on breast cancer is reviewed with particular emphasis on the possible etiological role of nutritional status as reflected by weight and height. The results of a prospective study and preliminary results of a population-based case-control study seem to indicate that body size or body mass rather than overweight (obesity) is a risk factor. A considerable proportion of the differences in incidence between the Netherlands and Japan can be explained by differences in body mass. The biological mechanisms mediating nutritional status and breast cancer are believed to be of an endocrinological-metabolic nature.


Hormones, nutrition, and cancer.

Hormones, nutrition, and cancer. The effects of obesity on steroid metabolism in women with breast and uterine cancer have been considered. Obesity may increase plasma estrone by two mechanisms, a higher rate of secretion of the estrone precursor, androstenedione, and a higher rate of conversion of androstenedione to estrone. Obesity may alter routes of metabolism of androgens and estrogens. The excretion of specific urinary metabolites can therefore be altered by obesity alone. Thus, steroid indices of relative cancer risk or responsiveness must be constructed with due attention to obesity, one of many important variables.


Hormone profiles in hormone-dependent cancers. Studies on the relationship of urinary excretion of androgen metabolites and estrogens to the natural history of breast cancer are reviewed. The importance of distinguishing between "within-population" studies (i.e., cancer patients versus normal controls) and "between populations" studies (i.e., low-risk versus high-risk populations) is emphasized, and it is pointed out that "qualitative" agreement (i.e. the same direction of differences) between the two types of studies must be present in order to implicate a hormonal parameter as a determinant of the natural history of breast cancer. For reasons detailed in this paper, it is concluded that the reported relationship of low urinary androgen metabolite excretion to increased risk of developing breast cancer and poor response to adrenalectomy or hypophysectomy and the validity of the "estriol hypothesis," namely, that a high urinary ratio of estriol to estrone-plus-estradiol in early life is protective against subsequent development of breast cancer, are both dubious. A new hypothesis concerning the relationship of estrogens to breast cancer risk is presented: "A period of of time, prior to age 30, during which the amount of biological availability of active estrogens' (i.e., estrone and estradiol) is diminished, protects against subsequent development of cancer." This hypothesis is shown to be compatible with the epidemiological and biochemical data. Reports concerning the influence of nutrition on endocrine parameters are reviewed. Inanition and obesity have been shown to alter steroid metabolism but it is not known whether nutritional "microdifferences" (i.e., differences between populations or individuals that are due to cultural, geographic, or socioeconomic factors, but that fall within the range of "normal" or adequate nutrition) can also alter steroid metabolism.


Experimental evidence of dietary factors and hormone-dependent cancers. Current awareness of the importance of environmental factors such as diet in the etiology of human cancer has stimulated renewed interest in animal models for studying effects of diet on tumorigenesis. Diet can influence cancer in animals by affecting the initiation or subsequent preneoplastic stage of tumorigenesis, but it has less effect on tumor growth. Caloric restriction has a general inhibitory influence on tumorigenesis. Dietary fat, on the other hand, tends to promote tumorigenesis, but only certain types of tumors, such as mammary tumors, are affected. Both caloric restriction and dietary fat appear to act primarily during the preneoplastic state, and their effects on hormone-dependent tumors may be mediated through changes in the hormonal environment. Variations in other dietary factors, such as protein, vitamins, or minerals, above the levels required for normal maintenance seem to have little influence on the genesis or growth of tumors.


Metabolic epidemiology of dietary factors in large bowel cancer. According to the hypothesis being tested by this laboratory, bacteria (in particular, certain clostridia) metabolize the bile acids to give unsaturated products that are important in the causation of colorectal cancer. In this paper, various dietary regimens are discussed in terms of their effect on the fecal steroid concentration and on the gut bacterial flora. The diets considered include high- and low-fiber, high- and low-meat, and high- and low-fat diets.


Further leads on metabolic epidemiology of large bowel cancer. Studies in metabolic epidemiology have shown that the dietary intake of high fat affects the composition of the intestinal bacteria and their metabolic activity as well as the levels of certain neutral sterols and bile acids that may act as tumor promoters for the colon. A strong association has also  been established between microbially modified bile acids and  cholesterol metabolites and the risk of colon cancer among different populations. The patients with colon cancer had high concentrations of fecal bile acids and cholesterol metabolites compared with the controls. It remains to be shown whether this established association is causative in nature.


Cancers of the pancreas and biliary tract: epidemiological considerations. The epidemiological patterns for pancreatic and biliary cancers reveal more differences than similarities. Pancreatic carcinoma is common in western countries, although 2 Polynesian groups (New Zealand Maoris and native Hawaiians) have the highest rates internationally. In the United States the disease is rising in frequency, predominating in males and in blacks. The rates are elevated in urban areas, but geographic analysis uncovered no clustering of contiguous counties except in southern Louisiana. The origin of pancreatic cancer is obsure, but a twofold increased risk has been documented for cigarette smokers and diabetic patients. Alcohol, occupational agents, and dietary fat have been suspected, but not proven to be risk factors. Except for the rare hereditary form of pancreatitis, there are few clues to genetic predisposition. In contrast, the reported incidence of biliary tract cancer is highest in Latin American populations and American Indians. The tumor predominates in females around the world, except for Chinese and Japanese who show a male excess. In the United States the rates are higher in whites than blacks, and clusters of high-risk counties have been found in the north central region, the southwest, and Appalachia. The distribution of biliary tumors parallels that of cholesterol gallstones, the major risk factor for biliary cancer. Insights into biliary carcinogenesis depend upon clarification of lithogenic influences, such as pregnancy, obesity, and hyperlipoproteinemia, exogenous estrogens, familial tendencies, and ethnic-geographic factors that may reflect dietary habits. Noncalculous risk factors for biliary cancer include ulcerative colitis, clonorchiasis, Gardner's syndrome, and probably certain industrial exposures. Within the biliary tract, tumors of the gallbladder and bile duct show epidemiological distinctions. In contrast to gallbladder cancer, bile duct neoplasms predominate in males; they are less often associated with stones and more often with other risk factors. In some respects, bile duct and pancreatic tumors are alike. The male predominance of both tumors, an association between cholecystectomy and pancreatic cancer, and other considerations have prompted the notion that the same biliary carcinogens may affect the bile duct, ampulla of Vater, or, by reflux, the pancreatic duct. Various epidemiological and interdisciplinary approaches are needed to further clarify the origins of biliary tract and pancreatic cancers, but nutritional studies hold special promise in laying the groundwork for prevention of these tumors.


Developments in the epidemiology of stomach cancer over the past decade. The history of stomach cancer epidemiology is reviewed. The introduction of migrant population studies in the 1960 decade that described the critical role of exposures to this disease in early life was a key event. Companion pathology studies have indicated different epidemiological patterns for 2 histological entities, intestinal and diffuse type carcinomas, and confirmed an excess of intestinal metaplasia in populations at high risk to stomach cancer. Recent results suggest that epidemiology of stomach cancer can be transformed into the epidemiology of precursor lesions, and introduction of the fiberoptic gastroscope makes technically feasible detailed studies of the relationship of precursor lesions to suspect factors, including diet, in selected geographic areas. Nitroso compounds have been identified as candidate carcinogens and the epidemiological, pathological, and chemical data display signs of internal consistency. Feeding experiments with N-methyl-N'-nitro-N-nitrosoguanidine have led to animal models that permit a coordinated epidemiological-experimental approach to stomach cancer.


Role of trace elements in cancer.

Role of trace elements in cancer. The review considers trace elements including fluorine, copper, manganese, zinc, cobalt, chromium, selenium, molybdenum, tin, vanadium, silicon, and nickel from the standpoint of their role as either inhibitory or causative agents of cancer and also the possible use of their assay in biological fluids as diagnostic or prognostic aids in patients with cancer.


Dietary factors and special epidemiological situations of liver cancer in Thailand and Africa. Incidence patterns of primary liver cancer in Swaziland and Uganda have been compared with frequency of contamination of dietary staples by aflatoxins. Geographical regions or tribal groups with elevated cancer incidence were associated with increased frequency of contamination. In further studies, aflatoxin ingestion has been quantitatively measured in populations in Thailand, Kenya, and Mozambique, in subgroups of which the incidence of primary liver cancer varied over a wide range. In each instance, elevated cancer incidence was associated with highest levels of aflatoxin intake. In view of the potency of these compounds as liver carcinogens in many animal species, these data collectively suggest that the aflatoxins are also carcinogenic for man and that regular ingestion of foods heavily contaminated with aflatoxins increases the risk of liver cancer in human populations.


Mutagenicity of nitrofurans, nitrothiophenes, nitropyrroles, nitroimidazole, aminothiophenes, and aminothiazoles in Salmonella typhimurium. Thirty-two heterocyclic compounds, including 24 nitroheterocycles, 7 aminoheterocycles and derivatives, and 1 thiophene lacking a nitro group, were tested for mutagenic activity in Salmonella typhimurium TA 98 and TA 100. All the nitroheterocycles (11 new), including nitrofurans, nitrothiophenes, nitropyrroles, and 1 nitroimidazole, were mutagenic in TA 100; 13 were also mutagenic in TA 98. 5-Nitro-2-furoic acid, a noncarcinogen, was mutagenic in TA 100. Seven carcinogenic nitroheterocycles were mutagenic in both strains. Seven aminoheterocycles (4 new), aminothiophenes and aminothiazole derivatives, and 1 thiophene without a nitro group were not mutagenic. Both TA 98 and TA 100 were uvrB and lacked the ability of excision repair of DNA. Among the 24 mutagenic nitroheterocycles, only 13 compounds exhibited bacterial killing effects, suggesting that more than 1 mechanism may be involved in the interaction of nitroheterocycles with bacterial DNA.


Increased expression of a normal lymphocyte membrane antigen on chronic lymphatic leukemia cells. Rabbit antisera against a 3 M KCl extract from lymphocytes isolated from tonsils were found to detect an antigen of the normal lymphocyte membrane that on chronic lymphatic leukemia cells is increased in quantity. This increase seems to be specific for chronic lymphatic leukemia. A discrepancy was found between the results obtained with complement-dependent techniques and with methods wherein no complement is used. In complement-dependent methods, the antisera showed a much weaker reaction with normal lymphocytes than would be expected from the amount of antigen present, as established by other methods.


The reactivity and carcinogenicity of aflatoxin B1-2,3-dichloride, a model for the putative 2,3-oxide metabolite of aflatoxin B1. Aflatoxin B1-2,3-dichloride (AFB1-Cl2) was synthesized as a model for the probable ultimate carcinogen, aflatoxin B1-2,3-oxide. As expected for aflatoxin B1-2,3-oxide, AFB1-Cl2 has an electrophilic carbon 2; it decomposed in water (half-life of 0.5 min in 10% dimethyl sulfoxide, pH 7.4) with the formation of 3-chloro-2,3-dihydro-2-hydroxyaflatoxin B1 and 2,3-dihydro-2,3-dihydroxyaflatoxin B1. AFB1-Cl2 formed covalent adducts with DNA and RNA with retention of one-half of the chlorine; the major products apparently contained glycosidic bonds between carbon 2 of the aflatoxin residues and nitrogen or oxygen atoms in the nucleic acids. Polyguanylic acid was the most reactive homopolymer toward AFB1-Cl2. AFB1-Cl2 was less reactive toward mononucleotides than toward polynucleotides. The major adducts formed on incubation of AFB1-Cl2 with protein contained little chlorine and could have resulted from alkylation of primary amino groups or from reactions with the hydrolysis products. Similarly, incubation of AFB1-Cl2 with amino acids apparently resulted in Schiff base formation between primary amino groups and the dialdehyde rearrangement forms of the hydrolysis products of AFB1-Cl2. AFB1-Cl2 was much more active than aflatoxin B1 in inducing sarcomas at the s.c. injection site in rats, in the initiation of papillomas on the skin of mice, and in the induction of lung tumors in mice. AFB1-Cl2 was also highly mutagenic for Salmonella typhimurium TA 98 and TA 100. Aflatoxin B1 and its 2,3,-dihydro- (aflatoxin B2), 2,3-dihydro-2-hydroxy- (aflatoxin B2a), 2,3-dihydro-2,3-dihydroxy-, and 3-chloro-2,3-dihydro-2-hydroxy- derivatives were inactive in the mutagenicity tests; and the latter four compounds were also inactive as initiators of papillomas of the skin in mice. The structures of the macromolecular adducts of AFB1-Cl2 formed in vitro, the carcinogenicity of this electrophile, and the lack of carcinogenicity of its hydrolysis products indicate that alkylation of nucleic acids is a critical reaction in tumor induction with this carcinogen and aflatoxin B1.


The significance of nonspecific injury for colon carcinogenesis in rats. A purse-string suture was put into the rat's cecum to form a "diverticulum." When the thread cut this stitch, the resultant extensive necrotic zone healed for a long time. The presence of a foreign body (ligature) provided a permanent source of injury to the cecal mucosa. The lesions caused an increase in [3H]thymidine-labeled epithelial cells in the adjacent tissue detected by means of microautoradiographs. A postinjury injection of 1,2-dimethylhydrazine resulted in a marked increase in the rate of cecal tumor incidence (from 23 +/- 2.8% under ordinary conditions to 87 +/- 6% and 96 +/- 4% in different experimental series). The rise in tumor incidence following injury may be due to the entry of a greater number of stem cells into the mitotic cycle at which stage they seem to be responsive to carcinogenic influences.


Selective cleavage of glycosidic linkages: studies with the polysaccharide component of Shigella dysenteriae type 6 lipopolysaccharide. The polysaccharide component obtained from the lipopolysaccharide of Shigella dysenteriae type 6 was subjected to milk hydrolysis with acid, and the products were fractionated on Sephadex G-50. An acidic hexosaminoglycan and a core oligosaccharide fraction were obtained, the former containing D-glucose, D-galactose, 2-acetamido-2-deoxy-D-galactose (in the ratios 1:1:1), and an unidentified acidic component (X). The hexosaminoglycan was N-deacetylated and then hydrolysed and deaminated to give 3-O-(2-amino-2-deoxy-beta-D-galactopyranosyl)-D-galactose (1), identified as the N-acetyl derivative (2), and 2,5-anhydro-3-O-(6-O-alpha-D-galactopyranosyl-alpha-D-glucopyranosyl)talitol (3). On the basis of the structure of 2 and the methylation-analysis data for the polysaccharide and 3, together with that for the determination of linkage configurations by chromic anhydride oxidation, the hexosaminoglycan is considered to have the repeating structure (see article).


Applications of echocardiography in acute myocardial infarction. Echocardiography has many attributes that are desirable for diagnostic and research studies in acute myocardial infarction patients. It does not alter the physiologic state being evaluated, is relatively inexpensive, and does not interfere with other hospital procedures. For these reasons, the test may be repeated frequently and used to monitor the changes after acute infarction. Useful information about left ventricular volume, diastolic pressure, and segmental wall motion may be obtained. Because echocarciographic estimates of stroke volume, ejection fraction, and velocity of circumferential fiber shortening are based on motion seen in only one "ice-pick" view of the heart, it is likely that they will be less reliable in patients with asynergy of contraction. Although a definite diagnosis of acute myocardial infarction cannot be made by echocardiography, abnormalities of wall motion may occur very early and support a clinical impression of infarction. An echocardiogram may also reveal changes suggesting ischemia or infarction (abnormal motion) in patients who have atypical chest pain and no other objective evidence of coronary artery disease.


Surgery for impending myocardial infarction, acute evolving myocardial infarction, and complications of myocardial infarction. Post-infarction ventricular aneurysm, ventricular septal defect, and mitral insufficiency are all potentially amenable to surgical intervention. In each instance the results of operation and the prognosis following operation depend largely on the extent of infarction, the status of the residual myocardium, and the interval between infarction and operation. When the residual myocardium exhibits good contractility, the results are usually good. When early operation is performed in the face of a deteriorating clinical course and with poorly contracting residual myocardium, the mortality rates are extremely high. In an effort to increase the efficiency of the residual myocardium, concomitant coronary bypass surgery should be performed whenever possible. In this difficult group, more recent supportive measures such as the intra-aortic balloon pump may be particularly helpful when utilized both before and after operation. The surgical indications and results of coronary bypass surgery in impending or acute evolving myocardial infarction are not as well defined, but it is evident that myocardial revascularization may be useful in carefully selected patients.


The acute phase of myocardial infarction. During the acute phase of myocardial infarction, two groups of patients are observed. Patients in the first group have no significant complications, and approximately 95 per cent of these patients recover fully without any specific therapy. Patients in the second group may have various complications, some of which are benign, whereas others may lead to a fatal outcome. The complications may be divided into four major types: 1. Cardiac arrhythmias and conduction defects. The tachyarrhythmias and bradyarrhythmias are the most frequently encountered complications in patients with acute myocardial infarction. Tachyarrhythmias include ventricular premature beats, ventricular tachycardia, ventricular fibrillation, supraventricular tachycardia, atrial flutter, and atrial fibrillation. Bradyarrhythmias include sinus and junctional bradycardia and various degrees of heart block. Those patients who are unable to reach a hospital and die suddenly presumably succumb to ventricular fibrillation. 2. Left ventricular failure and cardiogenic shock. In more than 33 per cent of patients with acute myocardial infarction, a third heart sound and pulmonary rales may be heard. If they are present for only 24 hours, the physical findings may indicate an alteration of left ventricular failure. However, if they persist for a few days and disappear after medical therapy, mild left ventricular failure may be present. About 12 per cent of patients have acute pulmonary edema, and 10 per cent of patients develop cardiogenic shock. These two complications carry a high mortality rate (40 per cent and nearly 100 per cent respectively). 3. Rupture of the heart. Cardiac rupture may occur in the free wall, ventricular septum, and papillary muscles. These complications, although less frequently encountered, cause a number of deaths in patients with acute myocardial infarction. 4. Thromboembolism. Under this category are included pulmonary embolism, systemic arterial embolism, and systemic venous thrombosis.


Hemodynamic monitoring in acute myocardial infarction. Hemodynamic monitoring is necessary to assess the state of ventricular performance following myocardial infarction. The methods employed require the insertion of a pulmonary artery catheter and an arterial cannula. With the information obtained thereby, appropriate therapeutic modalities may then be instituted. Hemodynamic monitoring techniques are also invaluable in the diagnosis of mitral regurgitation or ventricular septal defects complicating myocardial infarction.


Dynamics of tissue distribution of radiopotassium as affected by simulated differences in regional extraction. Simulation of tissue uptake and release of radiopotassium with a digital computer shows that tissue distribution of this diffusible indicator of regional blood flow will be essentially static during recirculation of the isotope despite large differences in regional extractions. Thus, the widely accepted view that static distribution results from homogeneous extractions may be invalid.


The duration of aldehyde fixation as a "flattening factor" of synaptic vesicles. Synaptic vesicle flattening can be induced in the excitatory mossy fibre endings of the rat cerebellum by prolonged immersion in aldehyde during fixation (with or without perfusion). The flattening is found in a greater percentage of vesicles if perfusion has been omitted before the prolonged immersion. This is discussed in relation to the various other factors that are thought to cause flattening and the important problem of the classification of different types of synapse.


Variations of mitotic activity in the adenohypophysis of male rats during a 24-hour cycle. The mitotic activity in the adenohypophysis of male rats during a 24 hours' cycle has been studied at the time of the spring equinox. The animals were killed by perfusion of fixative. The mitotic activity seems to be the combination of two elements: a relatively low and nearly constant activity with two peaks of high activity. The first one takes place at 6 o'clock (local time) with an index reaching 4.25; the second one occurs at 11 o'clock (local time) and its index is 2.09. The afternoon activity is weak with an average index of 0.56 between 1 p.m. and 9 p.m. The results are analyzed, discussed and compared with other results observed in different organs.


Fine structural distribution of microtubules in pancreatic B cells of the rat. The distribution of microtubules has been studied in pancreatic B cells of normal rats and in animals infused with glucose for various periods of time. An array of microtubules extends from the outer nuclear membrane to the plasma membrane coursing in all directions of the cytoplasmic space. Microtubules are found between profiles of the endoplasmic reticulum, cisternae of the Golgi complex and in close proximity to mitochondria and secretion granules. Insertion of microtubules in the plasma membrane is best studied in tangential sections through the plane of the membrane, the fixation of microtubules might involve microfilaments and desmosomes. The possible role of microtubules in the different phases of the secretory process is discussed.


Absence of "epitheloid cells" in AV-anastomoses (AVA) for electron microscopy. AV-anastomoses were studied in rabbit auricles. After perfusion-fixation with glutaraldehyde and post-osmication AV-anastomoses are to be identified only when serial sections are analyzed. "Epitheloid cells" were not seen in the walls of the anastomosing segments.


[Syphilitic lymphadenitis].

[Syphilitic lymphadenitis]. The authors subjected to histological examination a total of 38 inguinal lymph nodes from 35 patients. In 34 instances recent acquired syphilis was involved in one instance tertiary syphilis. The disease was in all patients confirmed by clinical examination, by evidence of Treponema pallidum in the luetic ulcer of the primary stage or in condylomas of the secondary stage and on serological examination by a positive BWR in blood or a positive TPI test.  In three instances the histological finding in the lymph node was originally erroneously interpreted as a haemoblastoma. In two other patients the histological finding in the lymph nodes drew attention to syphilis, which before has escaped clinical diagnosis. The histological picture of syphilitic lymphadenitis in the early stage of the disease is characterized by perilymhadenitis, hyperplasia of the germ centres, proliferation of reticular cells and plasma cells and often also eosinophil cells. The finding of specific structures is rare. Vasculitis is always present. In half the patients by Warthin-Starry's method treponemas were detected.


The orthomolecular treatment of cancer. III. Reticulum cell sarcoma: double complete regression induced by high-dose ascorbic acid therapy. The response of a patient with histologically proven reticulum cell sarcoma to no treatment other than large doses of ascorbic acid is described. At the time of first diagnosis, the disease was widely disseminated, and a very dramatic regression of all parameters of disease activity was induced by the continuous administration of large doses of ascorbic acid. Reduction in dosage some months later coincided with reactivation of the disease process. The reinstitution of regular high-dose ascorbic acid therapy induced a second complete remission. The case report is illustrated by serial radiographs. The significance of the therapeutic response is briefly discussed in relation to general schemes of cancer management.


Mutagenic activity of platinum and ruthenium complexes. cis-Dichlorodiammineplatinum(II) [cis-PtCl2(NH3)2] and dichlorotetrakis (dis-methylsulfoxide) ruthenium(II) [RuCl2(DMSO)4] have been tested as mutagens for strains of Salmonella typhimurium carrying the hisG46 missense mutation. Their activity, which has been compared with the activity of mitomycin C, depends on the presence in the test bacteria of the pKM101 plasmid and is affected in various ways by the function of the excision repair system. More precisely, mitomycin C is mutagenic only for strains with an intact uvr system. cis-PtCl2(NH3)2 and RuCl2(DMSO)4 are mutagens both for uvrB and uvr+ strains, but cis-PtCl2(NH3)2 is more active on the latter, while the converse is true for RuCl2(DMSO)4. It seems, therefore, that each drug interacts with DNA by a different mechanism.


Immunofluorescence method for detecting anti-myocardial antibodies, and its use in diagnosing heart disease. Demonstration of autoimmune antibodies to myocardial tissue enables one to detect and assess cardiac disease long after abnormalities in serum enzyme activities are no longer measurable. We describe and indirect immunofluorescence procedure in which cryostat sections of rat heart (ventricle) and Evan's Blue counterstaining are used to detect anti-myocardial antibodies. Sena from patients with myocardial infarct or some other cardiac diseases reveal a distinct fluorescent staining of the sarcolemmal membrane. In contrast, sera from patients with systemic lupus erythematosis demonstrate nuclear plus diffuse staining and sera from myasthenia gravis patients show a characteristic striated staining pattern. The role of anti-myocardial antibodies in cardiac disease is discussed briefly.


[Digestive salmonellosis in South Vietnam]. During the period January 1969 through October 1973, rectal swabs from 13,947 diarrhea patients of all ages at infectious disease hospital and children hospital in Saigon were examined. From these specimens 610 strains of Salmonella of all group were isolated. A total of 46 serologic types were encounted. The most commonly encounted were S. paratyphi B, S. java and S. typhimurium (group B). Most of Salmonella isolated were obtained from adult gastroenteritis. We have also studied the possible relation between human and animal salmonellosis. The rodents trapped from different aera in Saigon, fish and clams collected from different markets were examined by bacteriological surveys. From these specimens, 42 strains of Salmonella were isolated for a 2,2 percent isolation rate. Our study showed that Salmonella types which were isolated frequently from animal were encounted in man.


[Effects of a unique dose of mebendazole on microfilaremia in 50 carriers of microfilaria of Wuchereria bancrofti, pacifica variety]. Treatment by Mebendazol were given to 50 patients divided in 3 groups, the first on having s single dose of 200 mg., the second one a single dose of 300 mg. and the last one a single dose of 400 mg. There was practically no unpleasant side effect. We noticed a delayed but notable effect on microfilaremia sensibly lower than diethylcarbamazine action in similar conditions. It would be interesting to try heavier doses or iterative doses.


Metabolic responses to monocomponent human insulin infusions in normal subjects and patients with liver and endocrine disease. Hypoglycaemic and growth hormone responses were studied at different steady-state plasma insulin concentrations during a graded infusion of monocomponent human insulin. The control group consisted of ten volunteer subjects. The other groups studied included women taking oral contraceptives and patients with obesity, thyrotoxicosis, myxoedema, acromegaly, diabetes mellitus (moderate and severe) and liver disease. The hypoglycaemic response was measured in two ways: (i) the percentage reduction in plasma glucose below basal, and (ii) the rate of fall of plasma glucose (Kg-%/min). Insulin sensitivity was greatest in the normal subjects and in the other groups decreased in the order thyrotoxicosis greater than oral contraceptive greater than obesity greater than myxoedema greater than acromegaly greater than liver disease. Insulin sensitivity was difficult to assess in the diabetic patients because basal plasma glucose concentrations were elevated. At any given insulin concentration, the diabetics metabolized approximately the same amount of glucose as the normal subjects but the fact that this rate of glucose turnover occurred at higher plasma glucose concentrations probably indicated insulin resistance. Within each group Kg at each dose level of insulin correlated with the steady state plasma insulin concentration during the same infusion period. Diminishing sensitivity to insulin was reflected in an increasing fasting plasma insulin and insulin/glucose ratio except in patients with diabetes. GH responses to insulin infusion in normal subjects reflected the pattern of fall of plasma glucose. In the diabetic patients GH secretion appeared to be related to the infusion of insulin and occurred before plasma glucose had fallen to hypoglycaemic levels. GH secretory patterns were within normal limits in women taking oral contraceptives and in seven of eleven patients with liver disease but were impaired in three of seven patients with thyrotoxicosis and four of five patients with myxoedema. Four obese patients had a markedly delayed but eventually normal GH response.


The HCG stimulation test in men with testicular disorders. The rise in plasma testosterone levels following stimulation with human chorionic gonadotrophin (3000 i.u./day for 4 days) has been used as a test of interstitial cell function in normal men and men with testicular disorders. The large majority of patients with testicular disorders resulting in infertility, showed a subnormal testosterone response to stimulation. The most marked impairment was noted in those patients with the biopsy appearance of germinal cell arrest and Sertoli cell only syndrome.


Incidence and significance of hyperprolactinaemia in women with amenorrhea. Serum prolactin and gonadotrophin concentrations were measured by radioimmunoassay in 106 women with amenorrhoea. Prolactin was normal in those with weight related disorders, primary ovarian failure, those with a variety of systemic diseases and in those in whom amenorrhoea followed treatment with the oral contraceptive and in unexplained primary amenorrhoea. Gonadotrophin concentrations in the above patients were normal except in those with primary ovarian failure. Prolactin was elevated in eight of forty patients (20%) with functional secondary amenorrhoea and was greatly raised in all but one of the thirteen women in this series with pituitary tumours (five of whom were studied only after treatment). Only three patients in each of the last two groups had galactorrhoea. Gonadotrophin levels were normal or slightly raised in all of the hyperprolactinaemic patients apart from those studied after hypophysectomy. Four hyperprolactinaemic patients (three with pituitary tumours and one with functional amenorrhoea) who did not have galactorrhoea have been treated with bromocriptine. Prolactin secretion was reduced in all patients and, in the two with normal gonadotrophins, ovulatory menstruation was resumed. One became pregnant in the second ovulation cycle after starting treatment. We conclude that, despite the rarity of galactorrhoea, hyperprolactinaemia is common in patients with functional amenorrhoea and in those with pituitary tumours. Treatment with bromocriptine in patients with normal gonadotrophins restores ovulation when the infertility is due to prolactin excess.


Experimental renal hypertension.

Experimental renal hypertension. The study of hypertension resulting from procedures devised to modify renal function in diverse ways has been pursued intensively in the past forty years and has contributed greatly to the understanding of hypertensive processes in man. Such procedures have included partial or complete removal of renal tissue, interference with the renal circulation and the administration of sodium and hormones promoting the tubular reabsorption of sodium. From all these studies, certain basic conclusions can be drawn. The fundamental mechanism involved in all forms of renal hypertension appears to be an alternation in the relationship between renal perfusion pressure and sodium and water excretion. The probable way in which this fundamental mechanism operates is outlined. The kidney itself is susceptible to the effects of hypertension and changes take place within it which then contribute a renal element to the hypertension whatever its primary cause.


The place of renin in the mechanism of hypertension in chronic renal disease. The history of the development of ideas on the cause of renal hypertension is first discussed. Growth of knowledge of renin and angiotensin from 1898 to the present is shown to depend upon better and more specific assays for each part of the system, which has enabled knowledge of the role of the renin-angiotensin system in various forms of hypertension to be assessed accurately. The difficulties of assessing varying levels in relation to their biological effect is stressed and the importance of the use of blockers of both renin and angiotensin is shown to mark a very large advance in the study of various forms of renal hypertension where there is a complicated relationship, still ill-defined, between renin, angiotensin, sodium and body fluid volumes.


Prostaglandins and hypertension in chronic renal diseases. The role of prostaglandin A (PG A) in the pathogenesis of renal hypertension has been studied. The concentration of endogenous PG A was measured in the peripheral plasma by radioimmunoassay in patients with chronic renal disease and in control subjects. The mean plasma concentration of PG A1 equivalents was as follows: 1. normotensive healthy volunteers (n=23): 115 +/- 15 pg/ml 2. patients in terminal renal failure on regular hemodialysis a) anephric patients (n=6): 51+/- 21 pg/ml b) patients retaining their own kidneys, all but one with hypertension (n=9): 231 +/- 51 pg/ml (P less than 0.01 versus control) 3. patients with chronic renal disease a) with hypertension (n=7): 204 +/- 60 pg/ml (P less than 0.01 versus control) b) without hypertension (n=11): 136 +/- 30 pg/ml. Renal hypertension was associated with high levels of PG A in peripheral blood. This increase is probably a secondary adaptative mechanism for the excretion of a greater fraction of the glomerular filtrate at a lower blood pressure. PG A may represent a circulating "antihypertensive hormones".


Comparison of erythromycin ethyl succinate, stearate and estolate treatments of group A streptococcal infections of the upper respiratory tract. The microbiologic and clinical responses of acute Group A beta-hemolytic streptococcal infections of the upper respiratory tract to oral treatment with erythromycin ethyl succinate, stearate, and estolate were studied in 303 patients. Streptococcal M and T typing was done on all positive cultures. The overall cure rate was 95.4 per cent, with no statistically significant differences in clearing organisms from the pharynx. Of the 285 cured patients who completed the prescribed follow-up period, 11 had recurrences between the 12th and 31st day after initiation of therapy, and five developed new infections. No cases of rheumatic fever or glomerulonephritis were encountered during a follow-up study. Eight gastrointestinal reactions and one transient rash occurred. Results with these forms of erythromycin compare favorably with published results for similar infections treated with oral penicillins.


Acinic cell cancers of the parotid gland in children. Comments based on two affected girls. Analysis of the literature and our own experiences with two pediatric cases of salivary gland tumors have yielded the following information: 1) under the age of five years, nearly all parotid tumors are mesenchymal in origin; 2) malignant tumors of the parotid during childhood occur much more often in girls than in boys; 3) mucoepidermoid carcinoma is the most common salivary gland malignancy in children; 4) the second next most common is of the undifferentiated variety; 5) acinic cell carcinoma, in general, represent fewer than 3 per cent of all salivary gland tumors, and two-thirds of these occur in females. Lymph node metastasis is rare, recurrence being usually local or blood borne; 6) Acinic cell carcinoma are rare in childhood. They are not highly malignant, yet capable of killing. Local recurrences are frequent. The best primary treatment would appear to be complete surgical excision. Blood borne metastases may develop more than 20 years after initial treatment.


The definition of radiological signs in gastric ulcer and assessment of their validity by inter-observer variation study. The initial aim was to program a computer with information on the frequency of radiological signs in benign and malignant gastric ulcers in order to obtain a percentage probability of benignancy or malignancy in succeeding ulcers in clinical practice. However, only four of the many signs described in gastric ulcer were confirmed to be of validity (i.e. reliable existence) by an inter-observer variation study using two observers and the films from 69 barium meal examinations. These were projection or non-projection of the in-profile ulcer, presence or absence of adjacent mucosal folds, good or poor definition of the in-face ulcer's edge, and extension of radiating folds to the in-face ulcer's edge. A few more remained unassessed due to insufficient numbers of relevant cases. It is condluced that: as defined in the literature the majority of radiological signs in this field are of uncertain existence; and the four that were found to be valid do not fully describe the important appearances that may be seen in benign and malignant ulcers and would be inadequate to differentiate them to a sufficiently high degree of probability.


Non-Hodgkin's lymphoma presenting with osseous lesions. Eight cases of non-Hodgkin's lymphoma presenting with bone symptoms are reported. The radiological appearances of these tumours are described. The importance of radiology in differentiating a primary lymphoma of bone from a lymphoma arising from other organs which has subsequently metastasised to the skeleton is briefly discussed.