[Effects of lesions in the pontine tegmentum on the sleep stages in the rat]. 1. Limited coagulations of the locus coeruleus and subcoeruleus nuclei have been performed in rats and the sleep-waking cycle was continuously monitored during 9 days. The cortical and diencephalic noradrenaline content was mesured at the termination of the experiment, on the 10th post lesion day. 2. The bilateral destruction of the locus coeruleus is followed by the appearance of a uro-genital syndrome consisting of hema turia, bladder distension and penile erection. The states of sleep are disturbed during the first two days (increase of slow-wave sleep and decrease of paradoxical sleep times) and thereafter return to normal. Additionally, an hyperthermia appears during the third experimental day. The cortical and diencephalic noradrenaline content decrease to 70%. 3. The simultaneous lesion of both locus coeruleus and subcoeruleus nuclei is followed by the appearance of an aphagia adipsia syndrome in addition to the uro-genital syndrome. After these lesions, it is no long possible to find paradoxical sleep episodes in polygraphic recordings while the amount of slow wave sleep is normal. Cortical and diencephalic noradrenaline content decrease more than 50%. 4. In normal rats direct injection of 6 hydroxydopamine directly in both locus coeruleus and nuclei subcoeruleus had no discernable effects either on the behaviour or on the states of sleep. The cortical noradrenaline content decreased 30% below control values. 5. These results are consistent with but do not prove the hypothesis that part of the pontine tegmentum might play an important role in triggering paradoxical sleep episodes. The role of these regions in the regulation of internal temperature, food consumption and bladder motricity is also discussed.


Once daily dosage beta-blockade: antihypertensive efficacy of slow release oxprenolol as related to renin and age. A single daily dose antihypertensive therapy with a new slow-release (SR) form of the beta-adrenoceptor blocking agent oxprenolol was as effective as a standard tid beta-blocker regimen in maintaining therapeutic effects over 24 hours. The good overall response rate (target larger than or equal to mmHg diastolic) of 67% was achieved in eight of the 11 high renin patients and 16 out of the 20 normal renin ones; the five low renin patients, who were also older, proved to be non-responsive. In terms of age, 83% of the patients aged under 40 years showed a reduction in diastolic pressure to larger than or equal to 95 mmHg, this percentage being significantly better than the 50% response rate in the 40--56-year-olds. In nine of the 12 beta-blocker non-responders the diastolic blood pressure was reduced to larger than 95 mmHg by adding a diuretic, and in four of the nine, all of them low renin patients, this effect persisted in response to diuretics alone. Oxprenolol SR suppresses renin acutely (59%) and chronically (62%), and it blunts the renin stimulatory effects of diuretics.


The effects of saralasin, an angiotensin II antagonist, on blood pressure and the renin-angiotensin-aldosterone system in normal and hypertensive subjects. Blood pressure reduction with saralasin infusion was seen only in hypertensive patients with abnormally elevated basal plasma renin and angiotensin II levels, and after sodium depletion the reduction in blood pressure was more marked. In normal subjects, and in hypertensives with plasma renin and angiotensin II levels within the normal range, there was no marked fall in blood pressure across saralasin infusion regardless of the sodium status of the individual. Plasma aldosterone concentration fell during saralasin infusion in those subjects with high baseline renin and angiotensin II levels. This fall occurred in the sodium replete and deplete states. In the normal subjects, and those hypertensives with normal plasma renin levels, there was no fall in aldosterone in the sodium replete state. However, after sodium depletion the expected rise in aldosterone was abolished during saralasin infusion, the plasma aldosterone falling to within the normal sodium replete range, rising again after the saralasin infusion was stopped. This study supports the concept of a direct role for renin and angiotensin II in the maintenance of hypertension in those subjects with elevated basal plasma renin. Plasma aldosterone would appear to be controlled, at least in part, by the prevailing plasma angiotensin II level in those subjects with elevated basal levels of angiotensin II; that is in high renin hypertensives, and in normal subjects and normal renin hypertensives who are sodium deplete.


Angiotensin II blockade in patients with essential hypertension. Patients with essential hypertension were sodium deprived by five days on a 10 mM sodium diet and were then infused with an incremental infusion of saralasin, a competitive inhibitor of angiotensin II. Patients with normal renin hypertension showed no change in lying or standing blood pressure during the infusion of saralasin. Angiotensin II is not, therefore, directly maintaining blood pressure in these patients when sodium deprived by diet, and is therefore unlikely to be playing any direct role in maintaining their blood pressure on their normal sodium intake. Patients with low renin hypertension showed a significant rise in blood pressure during saralasin infusion. Saralasin may be a further method of distinguishing low renin hypertensives from other hypertensives if they are infused when sodium deprived by diet.


Follow-up of renin in essential hypertension. In a prospective study of patients with essential hypertension, plasma renin levels showed a progressive increase with longer follow-up. This was associated with a parallel increase in renal vascular resistance. Arterial blood pressure and plasma volume did not change significantly during follow-up. In patients where the hypertension was complicated by myocardial infarction there was a comparatively greater increase in renin levels and renal vascular resistance which may be attributable to chronic reduction of cardiac output.


Centrally acting alpha-adrenoceptor agonists in hypertension: mechanisms and their role in therapy. Experimental work in animals has shown that both methyldopa and clonidine lower the blood pressure predominantly by an action on the central nervous system. This action is due to alpha-adrenoceptor stimulation by clonidine and by alpha-methyl-noradrenaline. The evidence for a central site of action for these drugs in man is indirect but persuasive. Both drugs lower blood pressure and heart rate without causing much postural or exercise hypetension. Sympathetic responses like the overshoot of pressure following Valsalva's manoeuvre are reduced but not abolished. Failure of ejaculation in the male is much less common than with drugs that are known to blockade sympathetic adrenergic neurones in the periphery.


Attitudes of Australian psychiatrists toward certain aspects of psychotherapy. An 81-item questionnaire was mailed to all Australian fellows and members of the Australian and New Zealand College of Psychiatrsits (May, 1973 listing). The questionnaire obtained background data, therapeutic school, and 5-point ratings on therapeutic techniques, goals of psychotherapy, helpfulness of various therapist attributes, and opinions on some theoretical issues from a sample of 275 respondents. Similar studies are underway in Great Britain and the United States, and comparisons among the three samples will be done at a later date. Data from these studies will also be used as a base line for study of changes in subsequent years.


Community Push: a community-oriented evaluation programme in a psychiatric ward. Evaluation of mental health programmes is a neglected area in New Zealand. This paper describes a community-oriented, experimental programme designed to provide a model for evaluation in the context of an inpatient psychiatric unit. Its primary objective is to improve patient care. This is achieved by emphasizing real-life needs, and dealing with these by a series of clearly specified steps involving goal-setting. Community resources, especially volunteers, are used. A variety of evaluative data are produced and the overall result is a "self-correcting" programme which is appreciated both by patients and staff.


Season of birth in schizophrenia: an Australian study. The authors have studied the season of birth in schizophrenics comparing those born in both southern and northern hemispheres. Their findings do not support the notion of seasonal variations claimed by other authors. The clinical significance of reports published in the literature is questioned.


The use of the role construct repertory grid in studying changes during psychotherapy. A case study including a detailed principal component analysis of repertory grids is reported in illustration of the use of grid method in the evaluation of psychotherapy. Grid method covers areas not accounted for by more symptom-bound criteria. Some of the problems of comparability and interpretation are discussed.


Wider perspectives in the behavioural treatment of anorexia nervosa: a case study. Hospital-based operant conditioning programmes have been reported as the most effective treatment available for anorexia nervosa. Two refinements of these techniques are outlined and illustrated in this case study. In the first, the external controls on the patient's activities imposed by the operant programme are relaxed in stages as weight increases, allowing the patient to assume progressively more self-control. The second entails re-educative therapy designed to develop adequate covert and behavioural responses for coping with the psycho-social consequences of weight gain and with other environmental stresses.


A heterosexual transvestite club: psychiatric aspects. An Australian club for heterosexual transvestites, the Seahorse Club, is described. Emphasis is given to the history and activities of the club and the behaviour of members at club meetings. Indications for referring transvestites requesting medical help to the club are discussed.


Moral behavior, an invitation to enquiry. The term Moral Behavior is used to designate that behavior which best promotes the cooperation and peaceful coexistance of human beings. The present and future behavior of Executives and Legislators is to a great extent dependent on the moral behavior of those involved with or controlled by authoritative figures. The subject of Moral Behavior has been written about by many disciplines. However, the subject has not been reviewed on a multidisciplinary basis looking to the possibility of making definite recommendations in areas which might effect positive changes.


Affinity of sphingomyelin in myelin proteolipid of bovine brain white matter. A preparation of proteolipid, the principal component of the myelin sheath, was obtained from the bovine brain white matter with satisfactory reproducibility. Much of the lipid portion, containing most of the component sphingomyelin, was removed by precipitation with a mixture of ethanol and ether, and the precipitate fraction exhibited a preferential affinity for sphingomyelin. Since phosphatidylcholine, which did not show so much combining affinity for the precipitate fraction, exhibited an enhanced interaction by means of hydrogenation of the fatty chains, it is assumed that the affinity of sphingomyelin depends on the hydrophobic region of the molecule. Sphingomyelin is considered to interact with a complex formed by the ionic linkage between the basic protein and acidic phospholipid, which is obtained by further removal of the lipid portion from the precipitate fraction by dialysis.


A case of vasculo-Behcet's syndrome.

A case of vasculo-Behcet's syndrome. A case of Behcet's syndrome with vascular complications is presented. This case had a familial occurrence of Behcet's syndrome. His vascular complications were deep vein thrombophlebitis of both legs, aneurysms of the left common iliac artery and the left femoral artery and the occlusion of the left subclavian artery. He was successfully operated on for the aneurysms. This paper discusses the problems accompanying the aneurysm of Behcet's syndrome. The authors pointed out that the subclavian steal syndrome may be diagnosed as neuro-Behet's syndrome and stressed the importance of vascular survay in Behcet's syndrome when the patient complaints of thrombophlebitis.


Effect of the methyl methacrylate-tributylborane sealant in preventing occlusal caries. A newly developed pit and fissure sealant, named Enamite, was studied technologically and clinically. Major ingredients of the sealant are a solution of 3% 2-hydroxy-3-beta-naphthoxypropyl methacrylate in methyl methacrylate and poly (methyl methacrylate) powder, using tributylborane as an initiator. In comparison with other commercially available sealants, Enamite showed much greater adhesiveness to enamel, which was confirmed by scanning electron micrographic observations. The sealant was applied to 161 first molars in 99 children, aged 6-8 years, to determine the caries preventive as well as the caries retardation effect. Among the treated teeth, 98 were intact and the remaining had incipient caries. The right side teeth of each subject was assigned to the test side and the other side served as a control. Each child was evaluated every 6 months by clinical exploration and bite-wing X-ray survey. At the final examination, the electric conductivity test was also used for the caries detection. After 2 years the sealant was effective in preventing 57.1% of the occlusal caries on treated compared with control teeth. When evaluation was made by including the caries retardation effect--teeth initially carious but remaining sealed after 2 years were counted as effective--, the sealant was effective in preventing or retarding 96.3% of the occlusal caries.


Observations on two cases of change in the dental arch and occlusion during the period of changing dentition. The object of this study was to know what changes take place on the dental arch during the changing dentition. For this purpose, two excellent cases were observed from six to twelve years of age, and the following results were obtained from its observation. Enlargement of dental arch was observed till the shedding of the deciduous second molar. In the anterior segment, not only the increment of the arch width but also the labial inclination and/or movement of the permanent incisors was noted in conjunction with the eruption of these teeth. These tendencies were slightly observed during the eruption of the permanent canine. In the buccal segment, the space for the permanent buccal teeth increased during the time of eruption of the permanent canine and first premolar, and this increase made it possible for these teeth to align normally.


Histopathologic and roentgenologic studies on the effects of irradiation on the human mandibles. The present study deals with the pathologic change of the mandible following radiation therapy for oral cancer, histopathologically and roentgenologically. The results are summarized as follows: 1) As the resorptive change of the cortex and the trabeculae, irregular and bizarre resorption and enlargement of the lacunae were observed, 2) The grade of injury of the osteocytes was described by the percentage of the number of the lacunae, which were empty and in which the nuclei of the osteocytes could not be seen. Consequently these results correspond considerably well with the clinical aspects. 3) Osteophytes in the spongy and compact bone were observed, and also narrowing and plugging of the Haversian canal and the canal of Volkmann with mineral were seen as the sclerotic change. 4) Thickening of the tunica intima, obstruction, disarrangement of the elastic fibers and distruption of the vessels were observed in the inferior alveolar artery, the arterioles, and also occlusion, which gave various appearances, in the vessels within the Haversian canal and the canal of Volkmann was seen. 5) The following four groups, based upon the radiographic change, were classified as: Group I, irregular osteolytic change; Group II, marked osteosclerotic change; Group III, irregular mixture of osteolytic and osteosclerotic change; and Group IV, no remarkable change.


Laboratory and clinical evaluation of a new volume ventilator. A three phase laboratory and clinical evaluation of a new fluidically controlled volume ventilator (Ohio 550) was undertaken to determine if this more compact, less complex and less costly unit retained the multiple advantages which have been established for volume ventilators in the continuous ventilatory support of patients in respiratory failure. Inspired volume, peak pressure, and flow rates were continuously monitored while a "test lung" was ventilated with its "effective compliance" reduced, and ambulatory patients with varying degrees of obstructive and restrictive ventilatory impairment were ventilated with the 550 respirator. Since adequate tidal and minute volumes were achieved under these conditions of markedly altered breathing mechanics, ten patients in acute respiratory failure requiring mechanical ventilation were managed with the 550 respirator. Aside from the absence of a sighing device, not considered by the authors to be a major disadvantage, the mechanical characteristics, inspired oxygen control and alarm systems were judged satisfactory and compared favorably with the volume ventilators currently available. The fluidic control system is expected to enhance the reliability and minimize the maintenance required of this respirator.


Study of markers of human erythroid differentiation in hybrid cells. Somatic cell hybrids exhibiting co-expression of the globin genes of two species were generated by fusion of mouse erythroleukemia cells with Chinese hamster or human marrow erythroid cells. In contrast, extinction of the mouse globin genes occurred in hybrids formed between the erythroleukemia cells and human fibroblasts. Direct detection of the human globin genes in human X mouse fibroblast hybrids was achieved by annealing of DNA from these cells to human globin complementary DNA. This method was developed to permit the chromosomal assignment of the human globin genes.


Behaviour of leukocyte acid phosphatase in various chronic diseases. Leukocyte acid phosphatases were investigated in 146 patients with different chronic diseases. The method of investigation used was that of Kaplow and Burstone slightly modified by the authors in what regards the pH of the incubation medium. Normal or slightly increased scores were observed in the granulocytic series of patients with chronic myeloid leukemia. In patients with rheumatoid arthritis, chronic hepatitis, lupus erythematosus disseminatus and chronic lymphocytic leukemia a moderate enzymatic activity was generally observed in the lymphocyte and more marked in severe forms of disease. A marked increase of the enzyme activity was observed in patients with myeloma. The possibility of a correlation between the intensity of enzyme activity and immunoglobulin formation is discussed.


Nitroblue tetrazolium (NBT) test in children with acute lymphoblastic leukemia or malignant lymphomas. In sixty children with acute lymphoblastic leukemia, Hodgkin's disease or lymphosarcoma 121 determinations of the NBT test were performed in various periods of disease. All the children studied were free of infectious complications. In acute lymphoblastic leukemia the NBT test values were low during relapses of the disease and increased above normal values in the period of remission. In the group with Hodgkin's disease an increase of the NBT test values was always associated with the active stage of the disease. No significant differences between the relapse and the remission period were found in children with lymphosarcoma.


Immunoglobulin and granulocyte cytochemical reactions in L-asparaginase treated children with acute lymphoblastic leukemia. The dose-dependent effect of L-asparaginase (Crasnitin, Bayer) on the serum IgG, IgA and IgM content was studied in 14 children with acute lymphoblastic leukemia. This effect was less evident in the intracellular metabolism of peripheral blood granulocytes (studied by the NBT test), in the myeloperoxidase and alkaline phosphatase activities and in the serum glycogen and lipid content.


The sealing of fissures in a school dental programme. An examination was made of 817 children, mean age 6.9 years. Of their first permanent molars 42.4 per cent were assessed as suitable for fissure sealant. Of these teeth 522 were sealed and compared with contra-lateral controls after one year. The retention rate of and the mean application time for the sealant are presented and discussed.


Dental health education in the South Australian school dental programme. The role of dental health education as part of the school dental service is reviewed. Activities which promote dental health education and which involve school children, their parents, and dental therapists are also reviewed and comments are made on their evaluation. The effects of these programmes on the children's dental health, their health practices and their attitude to dental care is summarized.


Dental conditions in high school students, Sydney, 1972. Dental examinations of 1,895 first year students of nine Sydney metropolitan State high schools were carried out in 1972. The schools were chosen from three socio-economic areas representing upper-middle, lower-middle, and working class groups. Minimal differences were shown in the prevalence of dental diseases, treatment needs, and dental practices between the upper-middle and lower-middle socio-economic groups. The working class group showed a higher prevalence of dental caries, gingivitis, and treatment needs and reported different dental health practices from the other groups.


Comparative studies of artificial respiration sets for babies and infants. In experiments on appropriately modified manikins the action and effectiveness of artificial respiration sets for infants Penlon (British production) and Ambu (Danish production) were compared. The tidal volume, pressure and characteristics of respiratory phases, rebreathing, oxygen concentration, safety systems and their effect on ventilation were assessed. It was found that better ventilation parameters for the needs of resuscitation of newborns and babies can be obtained using the Ambu set, particularly when compliance is lower and bronchial resistance is higher. The Ambu set is simple, easy and safe to use.


Phase identification of dental amalgam using transmission electron microscopy. Dental amalgam specimens were polished and afterward etched by an acid iodine solution. The replicas were obtained by the vacuum coating technique. The electron micrographs indicated that it was possible to identify the silver-mercury (gamma1) and tin-mercury (gamma2) intermetallic compounds formed during amalgam setting.


The probable significance of hypertriglyceridaemia in viral hepatitis. It is proposed that the raised serum glutamic pyruvic transaminase activity (SGPT) in viral hepatitis reflects an adaptive increase in glutamic pyruvic transminase in muscle for the increased transamination of alanine for post-absorptive glucose homeostasis. However, in a disease where the SGPT is elevated for four to six weeks, muscle cannot be an indefinite source of alanine unless it could, concurrently, resynthesize alanine. Since the two substrates of muscle are glucose and fat, fasting blood sugars, serum triglycerides and SGPT were estimated weekly, for one month, in 12 children with viral hepatitis. This was done to see if there was evidence of increased substrate availability for alanine synthesis, and whether any relationship existed between increased substrate availability and SGPT. The results show that there is a relationship between triglycerides and SGPT. This suggests that the hypertriglyceridaemia, by providing substrate to meet the energy requirements of muscle, spares glucose for alanine synthesis to maintain the alanine content of muscle. The paper suggests the existence of a glucose-alanine-pyruvate-glucose cycle in viral hepatitis and also reviews evidence for increased ammonia uptake by muscle, in liver diseases associated with raised SGPT, to support the concept of amino acid synthesis.


Xylose-1-14C absorption test: the use of urine, serum and breath analysis, and comparison with a colorimetric assay. The xylose absorption and excretion test has been reassessed in controls and patients with coeliac disease. Xylose has been assayed in both serum and urine colorimetrically and by liquid scintillation counting using xylose-1-14C. The excretion of 14CO2 in breath following administration of xylose-1-14C has been measured. Liquid scintillation counting is a simple and reliable method for the measurement of xylose absorption. Serum xylose levels, urinary xylose excretion, or breath 14CO2 in isolation were poor screening tests for mucosal disease. The use of serum levels and urinary excretion in combination improved the discriminatory value of the test though small gut biopsy was more reliable.


Follow-up studies on liver disease associated with HBsAg carriers. Eight male subjects who were initially studied in 1972 with liver biopsy because of HBsAg carrier status were re-studied two years later with liver biopsy, clinical examination and standard liver function tests. Three of the eight subjects remained antigen positive and had continuing liver disease, this being either chronic active hepatitis or chronic persistent hepatitis. two subjects became HBsAg negative and their liver biopsies returned to normal. One subject became HBsAg negative but his biopsy disclosed chronic active hepatitis with cirrhosis in the presence of normal liver function tests. While persistence of the antigenaemia is associated with persisting liver disease, the converse is not true in that the disappearance of the antigen does not necessarily imply an improvement in liver disease. Liver biopsy remains the only reliable means of assessing liver disease as biochemical tests of liver function and the clinical findings may be of little value.


Detection of vesicoureteric reflux using radionuclide micturating cystography. Radionuclide micturating cystography (RMC) has been compared with the standard micturating cystourethrogram for detecting vesicoureteric reflux (VUR). Of 16 renal tracts with VUR radiologically classified as gross all had reflux demonstrated on RMC and in 15 of these the reflux reached the renal pelvis. Eight of the 12 renal tracts with moderate VUR and three of four with slight VUR were shown to reflux on RMC. RMC should prove valuable for following the course of patients with VUR treated surgically or conservatively because of the lower gonadal radiation dose resulting from this technique compared with the conventional radiological method.


Duodenal ulcer--does it exist in Australia aborigines? Analysis of barium meal examinations performed at the Darwin Hospital on 742 non-Aboriginal patients showed that 82 (11.5%) had duodenal ulcers. A similar analysis of barium meal examinations performed on 94 Aboriginal patients at the same hospital did not reveal any duodenal ulcers. Aboriginal patients form 22% of the local population and 18% of the hospital admissions. Therefore, it is suggested that duodenal ulcer is an uncommon disease in the Aboriginal population of the Northern Territory of Australia.


Studies on serum amylase in normal man and in acute pancreatitis. Amylase isoenzymes in serum, urine, saliva, jejunal juice, and pancreatic tissue were separated by isoelectric focusing. Isoamylase patterns obtained indicated that the majority of amylase activity in normal serum is of salivary gland origin. Pancreatic amylase is characteristically predominant in acute pancreatitis. The increased renal clearance of amylase in acute pancreatitis may be partly due to the increased proportion of the smaller molecular weight pancreatic amylase. However, a demonstrated increase in the renal clearance of salivary amylase in acute pancreatitis suggests a renal cause also. Autopsy pancreas samples devoid of TAME (p-tosyl arginine methyl ester) esterase activity (e.g. trypsin and plasma enzymes such as thrombin and plasmin) had isoenzyme patterns different to those samples with free proteolytic activity. Incubation of TAME esterase free pancreas with trypsin caused conversion of the former isoamylase pattern to one with the predominant isoenzymes focusing coincident with the predominant peak in serum from acute pancreatitis, jejunal aspirate, and TAME esterase positive autopsy pancreas. Such conversion suggests that pancreatic amylase is synthesized in a form different from that found in the intestinal lumen and serum.


The significance of lowered jejunal disaccharidase levels. Disaccharidase estimations on 115 consecutive jejunal biopsies are reported. The patients were divided into four groups: 1. Normal jejunal biopsy light microscopy, not milk intolerant, 82 cases. 2. Normal jejunal biopsy light microscopy, milk intolerant, eight cases. 3. Patients with giardiasis, 11 cases. 4. Coeliac disease patients, 14 cases. The lowest disaccharidase levels were found in coeliac disease, with giardiasis cases showing intermediate levels. Poor correlation of lactase levels with milk intolerance was found. Three cases in Group 1 showing lowered lactase levels were given metronidazole and showed remission of clinical symptoms, raising the possibility that they had undiagnosed infections with Giardia lamblia.


Effect on respiration of diazepam, chloropromazine and haloperidol in patients with chronic airways obstruction. The effect on respiration of diazepam, haloperidol and chloropromazine in patients with chronic airways obstruction was studied on ten patients by the modified rebreathing method of ventilatory response to carbon-dioxide. The two parameters of the ventilatory response studied were: (a) the slope expressed as litres/minute/mmHg CO2 and (b) minute ventilation at a computed pCO2 57 mmHg (VE 57). A significant decrease in either of these parameters indicated respiratory depression. Following administration of 10 mg diazepam intramuscularly to ten patients a significant depression of respiration was observed in five patients. Administration of 50 mg chloropromazine intramuscularly to eight patients significantly depressed respiration of three patients. A significant depression of respiration was not observed in any of the ten patients given 5 mg haloperidol intramuscularly. These results indicate that the lack of significant respiratory depression from an intramuscular injection of 5 mg of haloperidol to patients with severe chronic airways obstruction makes it a safer drug, for the management of acute psychotic episodes in such patients, than 50 mg of chloropromazine or 10 mg of diazepam given intramuscularly.


Diabetic peripheral neuropathy: nerve conduction studies before, during and after carbamazepine therapy. Fifty-four patients with diabetic peripheral neuropathy were treated with carbamazepine for a period of one year. Clinical assessment and nerve conduction velocity studies (NCV) were done periodically. Forty-nine patients had symptomatic relief of all sensory manifestations but NCV remained essentially unchanged. Untoward effects of the drug were frequent but transitory. It was concluded that carbamazepine is a dependable drug for the treatment of symptomatic diabetic sensory polyneuropathy.


Severe haemolytic anaemia complicating infectious mononucleosis. The case record of a patient suffering from infectious mononucleosis, complicated by severe haemolytic anaemia, with overt intravascular haemolysis, is reported. Investigation of such cases usually shows a high titre of cold agglutinins with anti-i specificity. In the case reported, the results of serological investigations were atypical, and suggested that cold agglutinins with anti-L activity (rather than anti-i) were predominant in the aetiology of the haemolysis.


Extensive primary lymphoma of the gastrointestinal tract. A case of extensive primary lymphocytic lymphoma (lymphosarcoma) of the gastrointestinal tract is reported. At the time of presentation the patient had diffuse involvement of the gastrointestinal tract from the stomach to the ano-rectal junction. Malabsorption was present. Pre-treatment immunologic studies showed elevated serum IgA and IgG, but impaired humoral and cellular immunity. Death occurred 13 months after diagnosis.


Double pylorus: a complication of chronic gastric ulcer? A case of double pylorus with a chronic ulcer in one of the two channels is described. The patient, a middle-aged man with active rheumatoid arthritis, required partial gastrectomy to allow continued treatment of the arthritis with anti-inflammatory drugs. Detailed histological examination of the surgical specimen revealed features consistent with intramural penetration of an ulcer across the pyloric ring, resulting in a gastro-duodenal fistula. The findings provide further support for the hypothesis that the double pylorus is an acquired lesion, which occurs as an uncommon complication of chronic peptic ulcer.


The haemolytic uraemic syndrome and oral contraceptives. A case of haemolytic uraemic syndrome is described in a young woman in whom the illness was apparently precipitated by the change from a low to a high oestrogen containing oral contraceptive agent.


The role of intensive care units.

The role of intensive care units. The indications for intensive care are discussed. Selection of patients should be based upon the apparent reversibility of disease processes and the likelihood of producing worthwhile relief of suffering. Admission statistics for one II-bed unit are also presented, and survival rates exceeding 90% of three "model" conditions-namely, fat embolism, tetanus and Gullain-Barré syndrome-are reported. The hospital costs for treating critically ill patients are approximately three times those for treating the "average" patient.


Patient monitoring.

Patient monitoring. Optimum results are obtained in the care of the critically ill patient if efforts are directed to maintaining the internal environment in a state as near normal as possible. This cannot be done without the use of basic monitoring procedures. Complex investigations may have a legitmate and necessary role as research tools. There is, however, a real risk of complex procedures becoming an end in themselves in general intensive therapy units, where they are apt to distract overworked nurses and medical attendants from the care of their patients. It is important, therfore, for clearcut indications for various monitoring procedures to be defined, and in this paper an attempt has been made to outline alogical approach to the monitoring of critically ill genral surgical patients admitted intensive therapy units.


The rational use of blood.

The rational use of blood. A rational approach to the use of blood entails careful assessment of blood loss in the individual patient and a clear awareness of the advantages and disadvantages which may follow the use of whole blood. The use of red cell concentrates in preference to whole blood has therapeutic and immunological advantages for a majority of patients. Predictable changes which follow massive transfusion must be assessed and appropriate steps taken to minimize any undesirable results in the patient. A protocol for emergency transfusion is outlined.


Disseminated intravascular coagulation.

Disseminated intravascular coagulation. Disseminated intravascular coagulation (DIC) is a syndrome of deposition of platelet-fibrin thrombi in the microcirculation, with consumption of platelets and clotting factors and possible clinical features of bleeding or thrombosis or both. It may be produced by activation of coagulation, platelet aggregation or endothelial damage. It is not a primary disease, but a common and important complication of many serious illnesses, especially sepsis, carcinoma and obstetrical accidents. Shock and acidosis are frequent precipitating factors, and vitamin K deficiency is a common complicating factor. DIC usually produces no clinical features, but it may give rise to bleeding, ischemic organ damage or shock. Although its clinical contribution is often difficult to separate from that due to the underlying disease, DIC remains the commonest cause of a generalized bleeding tendency in acutely sick patients. Laboratory confirmation consists of the demonstration of thrombocytopenia, coagulation impairment, hypofibrinogenamia, raised levels of fibrin degradation products, and positive results of para-coagulation tests. The most important therapeutic measure is control of the underlying disease, but replacement therapy and heparin may be required, especially if bleeding is significant and the process is not acute and self-limited.


Selective surgery for carcinoma of the rectum. The importance of selecting the best operation for each patient in the management of carcinoma of the rectum is emphasized. Selection must be based upon many factors, including the level of the lesion, and the mode and extent of spread. Using these important guidelines, the place of local excision, tube resection, and abdominal resection with anastomosis by the trans-sphincteric approach are discussed and the techniques described.


A fifteen-year study of breast cancer in Tasmania. Seven hundred and seventy-nine patients presenting with breast cancer in Tasmania between 1930 and 1975 have been studied. No comparisons of different treatment have been made, but overall survival has been assessed. Median survival in the group was only 3-3 years, but 30% of patients were still alive at ten years. Other factors assessed in relation to survival were axillary node involvement, site, size, age, parity, breast feeding and place of birth.


Bilateral carcinoma of the breast.

Bilateral carcinoma of the breast. A review of patients treated at the Peter MacCallum Clinic, Melbourne, between 1968 and 1973 inclusive, revealed 76 cases of primary carcinoma involving the opposite breast. Twenty-one of these occurred synchronously, when they were usually associated with elderly patients, a strong family history and an increased delay in presentation. The behaviour of these tumours was unremarkable, though the survival of the patients may have been less than those with single lesions, and in accord with the doubled risk of distant spread and local recurrence. Fifty-five patients with metachronous lesions did not present initally with features which would help to identify them as being prone to this double pathology. About 50% of the second carcinomas occurred within five years, but the remainder developed at intervals which were in several cases longer than 20 years. The patients did not present earlier on the second occasion, and several had advanced lesions. There was no evidence that the behaviour of the second carcinoma was influenced by immunological factors or patient susceptibility. Implications with regard to management are outlined, and the importance of long-term follow-up with regular examination is emphasized.


The possible relationship between mammary dysplasia and breast cancer. The literature concerning a possible association between benign mammary dysplasia and breast cancer is reviewed. Prospective studies confirm a higher increase in the incidence of breast cancer in patients with clinically and biopsy proven benign mammary dysplasia than in those in whom it has not shown to be present. A plea is made for active follow-up of these patients.


The outpatient diagnosis of breast lumps. A plan of management, based on a personal experience of 421 cases, has been developed for the outpatient diagnosis of breast symptoms. In the majority of patients the presence of absence of malignancy can be established with a high degree of certainty before biopsy, and benign masses can be safely excised on an outpatient basis. Only those patients whose breast symptoms and findings suggest malignancy need be admitted to hospital and prepared for major breast surgery. This plan has been shown to be safe, while avoiding unnecessary hospital bed occupancy.


The early diagnosis and treatment of congenital dislocation of the hip. In 1964, a screening programme was commenced in South Australia to diagnose and treat congenital dislocation of the hip in the neonatal period. The purpose of this paper is to present the findings of a statistical review of cases seen at the Queen Victoria Hospital during 1971 and 1972. Related factors, and the recommended method of treatment, are discussed, along with problems of early diagnosis and treatment of newborn children found to have unstable hips.


Pyogenic osteomyelitis of the spine.

Pyogenic osteomyelitis of the spine. The records of 30 patients who had suffered from vertebral osteomyelitis were reviewed. They conformed to a constant pattern, though varying in tems of: (i) the severity of the disease due to host-organism interrelationship; and (ii) age distribution. Causative organisms could not always be identifed, though all lesions settled with conservative measures of rest and antibiotics. A high proportion of the patients who were followed up for more than one year were back at work. The anatomical distribution of the lesions can be explained by our knowledge of the vascular supply to the vertebral bodies.


Cervico-mediastinal lymphangioma.

Cervico-mediastinal lymphangioma. Two cases of cervico-mediastinal lymphangioma ppesenting in adults are reported. In one the lesion originated in the mediastinum and only when advanced showed extension into the neck. The other was associated with a cervical cystic hygroma. Both wwer relieved by one-stage excision. Although they are benign, the tendency of these lesions is to become progressively larger, and to infiltrate between the vital structures in the neck and mediastinum. These features, and the importance of early surgery, are illustrated by the patients we now report.


Ureterocalycostomy in the management of renal and ureteric trauma: report of a case. The operation of ureterocalycostomy, although rarely indicated, may occasionally be most useful, and constitute a desirable alternative to removal of an injured kidney. A case of renal transection with avulsion at the pelvi-ureteric junction, managed successfully by carrying out this procedure, is now reported.


The anterior approach to the adrenal gland. The traditional approach to the adrenal gland is via a loin incision. While this is frequently the ideal approach for unilateral disease if both adrenals are to be examined or removed the surgeon must choose between bilateral loin incisions and a transabdominal approach. A bilateral posterior approach may be made with the patient is a prone, semi-jacknife position. This, however, is often unsuitable for sick patients, and of course does not permit the surgeon to perform a laparotomy or simultaneous oophorectomy if this is considered necessary. We feel, therefore, that an anterior approach merits serious consideration.


Operative pancreatography.

Operative pancreatography. The results of operative pancreatography in 32 patients with pancreatitis are reported. The main pancreatic duct was successfully and adequately demonstrated in 30 patients: in 29 by cannulation of the major ampulla, and in one by direct needle puncture of the duct. No films were obtained in one patient, and in another only  the accessory duct could be demonstrated. There was thus a high rate of technical success, but the frequency of gross abnormalities of the major pancreatic duct was low, except in those patients with traumatic pancreatitis. These results are relevant to the assessment of the value of endoscopic retrograde cholangiopancreatography in pancreatic disease.


Breast loss and delay in breast cancer diagnosis: behavioural science in surgical research. By the use of the methods of behavioural science, a study of women's attitudes to breast cancer and to breast surgery was carried out to provide firm data which might begin to settle the argement regarding conservative surgery for breast cancer. Conscious fears, including that of mastectomy, were found to have no significatn influence on the time that a woman takes to report the presence of a breast lump to her doctor, or to commence the practice breast self-examination. The length of delay is determined by unconscious, non-rational processes, and other factors beyond her control. Rational argument, therefdore, such as that earlier diagnosis will permit more conservative surgery including partial mastectomy, will not influence women to present any earlier or to practise breast self-examination.


A brief review of the concepts related to certain modern analytical methods and their use in medical science. A number of sophisticated analytical methods are avialable in Australia and are in current use in medical research. Some basoc knowledge is required to understand the concepts behind their use, and expertise is necessary for interpretation of the results. In this brief review, the principles behind a number of modern analytical methods such as emission spectroscopy, electron microprobe, mass spectroscopy, infra-red spectroscopy, and X-ray diffraction, have been described in simple terms. These techniques may be used in the analysis of biological specimens. a number of illustrations of their use in medical research have been given.


Stimulation of renin secretion by frusemide and diazoxide in the isolated rat kidney. 1. The effect of diazoxide (17-3 micronmol min-1 g-1) and frusemide (0-12 micronmol min-1 g-1) on renin secretion was examined in the isolated perfused rat kidney. These substances are potential renal vasodilators with opposite effects on urine sodium excretion. 2. Both agents significantly increased renin secretion rate above control values. In the case of frusemide this was not altered by ureteric occlusion and presumed absence of urine flow. 3. Mean renal perfusion pressure decreased to the same extent with diazoxide and frusemide infusion as in the control experiments and no additional vasodilatory effect was observed on the basis of changes in flow rate of perfusate. 4. These observations identify an intrarenal site of action for diazoxide and frusemide on renin secretion. The apparent independence of this stimulatory action on renal vasodilation and urine flow suggests a direct effect on the renin-producing cell.


Inter-relationship between autoregulation of glomerular filtration rate, tubuloglomerular feedback and juxtaglomerular renin activity in normotensive and hypertensive rats. 1. Reduction of renal perfusion pressure from 133 mmHg to 117 mmHg in control rats did not induce a significant change of kidney glomerular filtration rate (GFR) or nephron GFR determined in distal tubules. In contrast, nephron GFR measured in proximal tubular segments (NGFR-P) fell significantly. 2. Qualitatively the same response of filtration rate to changes of arterial blood pressure was found in the chronically clipped kidneys of Goldblatt hypertensive rats after acute removal of the clip. 3. In contrast, autoregulation of kidney GFR, NGFR-D and NGFR-P was abolished in the contralateral kidneys of Goldblatt hypertensive rats. 4. Microperfusion studies showed that tubuloglomerular feedback regulation of NGFR was present in the renin-rich ischaemic kidneys of Goldblatt rats after removal of the constricting clip, but greatly attenuated in the renin-depleted contralateral kidneys. 5. These data indicate that tubuloglomerular feedback participates in establishing renal autoregulation, possibly by mediation of the renin-angiotensin system.


Effects of carotid occlusion and clonidine on renin secretion in anaesthetized dogs. 1. Sympathetic reflexes were activated by carotid occlusion in anaesthetized dogs in which changes in renal perfusion pressure were prevented. This produced a prompt and reversible increase in plasma renin activity. 2. Administration of clonidine decreased plasma renin activity, arterial pressure and heart rate and blocked the renin secretory and blood pressure responses to carotid occlusion. 3. These results support the hypothesis that the suppression of renin secretion by clonidine is a consequence of the decrease in sympathetic activity produced by this drug.


[Neuropsychic manifestations of loaiasis. A clinical case of potomania]. The authors report a case of polyurodipsic syndrome in the course of a loasis. The patient recovered after a carbamazide treatment. The authors discuss the neuro-psychic symptoms in filarioses and their induction mode.


Effects of aldosterone and spironolactone on arterial renin in rats. 1. The metabolic role of arterial angiotensin I-forming enzyme (i.e. renin activity) was studied in total homogenates and in subcellular fractions of the aorta of normotensive and hypertensive rats. 2. Angiotensin I-forming enzyme was measured in (a) uninephrectomized rats rendered hypertensive with D-aldosterone and sodium chloride (10 g/l drinking solution, (b) rats treated in the same manner but with the addition of spironolactone, and (c) control rats. 3. Hypertension developed in aldosterone-treated rats within 3-6 weeks and was associated with decreased plasma and renal renin values. Total aortic renin activity was up to sixfold higher in the hypertensive animals than in control animals and there was an increased ratio of supernatant to microsomal renin activity in the aorta. 4. In spironolactone-treated rats blood pressure and total aortic renin concentrations were comparable with those in the control rats. 5. The results support the hypothesis that renin generated at local vascular sites, which is independent of circulating renin levels, contributes to regulation of blood pressure.


The role of sodium retention in Goldblatt 2-kidney hypertension in the rat. 1. Infusion of angiotensin II antagonist failed to restore the blood pressure of short-term Goldblatt 2-kidney hypertensive rats to normal levels before and after sodium restriction. 2. The blood pressure of both normal and sodium-restricted Goldblatt 2 hypertensive rats remained elevated 6 h after bilateral nephrectomy. 3. The residual hypertension found during antagonist infusion and after bilateral nephrectomy is not maintained by the renin-angiotensin system or sodium retention.


Salt, frusemide and renin in severe experimental renal hypertension. 1. Sodium-deficient diet failed to alter development and maintenance of severe renal hypertension produced in the rat by ligation of the aorta between the renal arteries. 2. High sodium diet did not alter the early phase of this hypertension, but significantly decreased blood pressure elevation in the late phases. 3. The decrease in blood pressure produced by high sodium intake does not appear to be mediated by renin suppression. 4. Frusemide effectively reduced blood pressure and renin at all phases.


Casual, basal and supplemental blood pressures in 519 first-degree relatives of substantial hypertensive patients and in 350 population controls. 1. The casual blood pressure is the sum of the relatively stable basal pressure taken under defined conditions of rest and the labile supplemental pressure (casual minus basal), which represents the response to the current degree of physical, mental and probably metabolic stimulation. 2. The basal and supplemental blood pressures behave differently and it seems likely that different factors are involved in their pathogenesis. 3. The 5 and 8 years follow-up mortality is closely related to the basal pressure but not to the supplemental pressure. 4. The rise with age in the basal blood pressure is greater in the relatives of substantial hypertensive patients than in population control subjects. 5. Above the age group 30-39 years there is an increase in the rate of rise of the mean basal blood pressure with age among the first-degree relatives of hypertensive patients. In a population control group an acceleration in the rate of rise of the mean basal blood pressure with age also occurs but a decade or more later than in the relatives of hypertensive patients. 6. In males the mean supplemental pressures (systolic and diastolic) do not rise appreciably with age and the mean supplemental pressures of first-degree relatives and control subjects do not differ appreciably. 7. In females the mean supplemental pressures rise with age but, except after age 60 years, the pressure rise in first-degree relatives is only a little greater than in control subjects. 8. When hypertensive patients with similar casual blood pressures are compared the basal blood pressures are higher in patients with glomerulonephritis than in essential hypertensive patients. 9. In the first-degree relatives of substantial hypertensive patients high-ranking basal blood pressures occur much more frequently than in general population control subjects. 10. The close resemblance of the blood pressures in like twins indicates that genetic or familial factors have an important influence on blood pressure, and on the occurrence of frank hypertension.


Exchangeable sodium in experimental hypertension in rats. 1. Total exchangeable sodium was measured in rats by a radio-sodium equilibration method, before and after the production of hypertension by clipping the left renal artery, with or without contralateral naphrectomy. 2. Clipping of one renal artery with removal of the other kidney produced severe hypertension with no significant changes in exchangeable sodium or plasma renin levels. 3. Clipping of one renal artery without contralateral nephrectomy produced severe hypertension in some animals, but little change in blood pressure in others. The animals which developed severe hypertension had a marked increase in exchangeable sodium with a concomitant rise in plasma renin; the animals with smaller rises in blood pressure did not have these changes. 4. The fact that both plasma renin levels and exchangeable sodium levels increase according to this method, suggests that hypertension in the two-kidney model is renin-dependent.


Cardiac output changes during experimental renal hypertension in the rabbit. 1. The haemodynamic changes during the development of hypertension in rabbits have been studied for 1 week before and 4-5 weeks after sham-operation (thirteen rabbits) or bilateral renal cellophan wrapping (thirteen rabbits), Doppler flowmeters being used to measure cardiac output. 2. There was a significant but transient rise in cardiac output on post-operative day 4 in six of thirteen sham-operated rabbits and six of thirteen renal-wrap rabbits before development of hypertension. Both groups showed the same rise in mean cardiac output of 10%. The reise in cardiac output was more transient than in other species, and was not essential for subsequent development of hypertension.


Ventricular performance after onset of renal hypertension. 1. In renal hypertensive dogs, the slope of the relation between either stroke volume or cardiac output and end-diastolic pressure is shifted to the right of the normal curves. 2. The maximum to which stroke volume or cardiac output can be raised during loading is significantly less. These changes in cardiac performance appear to be unrelated to the severity of hypertension.


Lowering of blood pressure, plasma renin substrate, cholesterol and triglyceride by portacaval anastomosis in rats fed on a 60% sucrose/5% lard diet. 1. Portacaval anastomosis was carried out in ten rats fed on a 60% sucrose/5% lard diet, which induced moderate hypertriglyceridaemia, mild hypercholesterolaemia and normotension. 2. Plasma triglyceride was decreased to 45% of concentrations observed in ten pair-weighed control rats. 3. Plasma cholesterol concentrations were reduced to 58%, renin substrate to 70% and aortic blood pressure to 80% of control values by portacaval shunt surgery. 4. Individual blood pressures were directly related to plasma renin substrate concentrations.


Studies on the effect of angiotensin II and of Des -angiotensin II on blood pressure, plasma renin activity and plasma aldosterone in the dog. 1. The effect of infusions of equimolar doses of angiotensin II (AII) and of Des -angiotensin II (heptapeptide) on plasma renin activity, blood pressure and plasma aldosterone were compared in normal anaesthetized dexamethasone-suppressed dogs. 2. Plasma renin activity was equally suppressed by both compounds. The increase in blood pressure induced by the heptapeptide averaged 43-62% of the increase during AII infusions. No significant differences in aldosterone increase were observed between AII and the heptapeptide. Plasma aldosterone, however, dropped significantly faster in heptapeptide-treated dogs after the end of the infusions. 3. Sar -Ala -angiotensin II (saralasin, 400 pmol min-1 kg-1) suppressed plasma aldosterone that was stimulated by heptapeptide (20 pmol min-1 kg-1) completely. The same angiotensin antagonist had only a moderate effect on plasma aldosterone stimulated by AII. After stopping the antagonist infusion, plasma aldosterone rose significantly higher in dogs infused with AII than in those receiving the heptapeptide. 4. The results demonstrate differences between the effects of AII and the heptapeptide both on blood pressure and on plasma aldosterone. They do not support the hypothesis that the heptapeptide may be the main mediator of aldosterone secretion.


An investigation of the prolonged pressor response to renin in the nephrectomized rat. 1. In an investigation of the prolonged pressor response to renin that develops after nephrectomy, angiotensin I dose-response curves and rat renin clearances were studied in nephrectomized rats and paired sham-nephrectomized control animals under pentobarbitone anaesthesia. 2. Both threshold and slope of the angiotensin I dose-response curves were decreased at 15-27 h after nephrectomy. 3. The ratio of renin clearance (determined during renin infusions) in the nephrectomized rat to that in the paired sham-nephrectomized control animals was 0-49+/-0-03 (SEM), P less than 0-001 (n = 12 pairs). 4. Both factors contribute towards the prolongation of the blood pressure increase after intravenously administered renin in the nephrectomized animal.


Evidence against inhibition of the renin-angiotensinogen reaction by des-angiotensin substrate in the rat. 1. The possible inhibitory effect of des-angiotensin I substrate on the renin-substrate reaction was studied. For this purpose rat angiotensinogen was purified 50-fool from plasma of nephrectomized rats. Des-angiotensin substrate was prepared from the purified angiotensinogen preparation by reaction with immobilized hog renin (coupled to Sepharose). 2. In kinetic experiments it was found that desangiotensin I substrate in concentrations of 0-225 and 0-45 micronmol/l has no influence on the reaction between rat renin and rat angiotensinogen.


Delayed onset and reduced severity of adrenal-compression hypertension in rats treated with digitoxin. 1. Bilateral compression of adrenal glands combined with unilateral nephrectomy and followed by imposition of a high sodium chloride intake caused severe hypertension in all rats, accompanied by enlargement of the heart, kidneys and adrenal glands, atrophy of the thymus and severe nephrosclerosis. 2. Digitoxin treatment delayed the onset, reduced the incidence and ameliorated the magnitude of the hypertensive response in such rats; it also reduced the degree of cardiac hypertrophy, the severity of nephrosclerosis and completely prevented enlargement of the adrenals and kidneys or atrophy of the thymus.


Anti-hypertensive action of DL-alpha-tocopharyl esters in rats. 1. Oral administration of DL-alpha-tocopheryl nicotinate (EN) (0-04 or 0-2 mmol day-1 kg-1) or DL-alpha-tocopharyl acetate (EA) (0-2 mmol day-1 kh-1) delayed the progress of hypertension in unilaterally nephrectomized rats, which were treated with deoxycorticosterone and salt, and in genetically hypertensive rats (SHR) which were given sodium chloride solution. Suppression of body weight gain, incidence of pneumonia and mortality were reduced by treatment with EN or EA. 2. Severe hypertension in old SHR (9 months)  further progressed, when drinking water was replaced by sodium chloride solution, and four out of ten of these animals died of cerebral haemorrhage during 4 weeks. The administration of EN or EA prevented the increase in blood pressure and incidence of stroke.


Humoral response and blood pressure regulation during hypercapnia and haemorrhage in dogs. 1. The blood-bathed organ technique was used to study the release of catecholamines, angiotensin II and prostaglandin-like (PL) substances into the circulation during hypercapnia and after haemorrhage in anaesthetized dogs. 2. Elevated blood concentrations of noradrenaline, angiotensin II and prostaglandin-like substances have been detected during both experimental conditions. 3. The rise of arterial blood pressure during hypercapnia and after haemorrhage was associated with elevated concentrations of angiotensin II in the blood and could be abolished by inhibition of the angiotensin I-converting enzyme with SQ 20881. 4. The compensation of arterial pressure during both stresses was significantly impaired by release of prostaglandin-like substances; it could be restored by inhibition of prostaglandin biosynthesis with indomethacin. 5. The results indicate that activation of the renin-angiotensin system represents the major humoral mechanism for the maintenance of arterial pressure during hypercapnic acidosis and after haemorrhage.


Evidence of altered permeability of the erythrocyte membrane for sodium and potassium ions in spontaneously hypertensive rats. 1. Erythrocyte membrane permeability to sodium and potsssium ions was studied in 8-10 weeks spontaneously hypertensive rats (SHR, Kyoto/Wistar strain), normotensive Wistar and Sprague-Dawley rats. 2. The rate of 22Na efflux from the erythrocytes and the rate constant of Na/Na exchange were considerably greater in SHR than in normotensive Wistar and Sprague-Dawley rats. This difference remained the same in rats adrenalectomized 7 days before the experiment. The maximum difference in the constants was found when the sodium-potassium pump was blocked by ouabain. 3. The accumulation of 42K in the erythrocytes of SHR (the sodium-potassium pump being blocked) took place at a considerably slower rate, and the K+ wash-out into a potassium-free medium was faster than that in the normotensive Wistar and Sprague-Dawley rats. 4. These results indicate a higher permeability of the erythrocyte membrane of SHR for Na+ and K+, compared with normotensive Wistar and Sprague-dawley strains. It is suggested that this may reflect a more widespread cell-membrane defect, which could serve as a general cause for activating the mechanisms maintaining high blood pressure.


Follow-up of renin in essential hypertension. 1. Twenty-three subjects with essential hypertension were followed for a period of up to 7 years. They were untreated during the investigations. 2. Plasma renin concentration was found to decrease temporarily in some subjects. The ultimate change was a gradual rise. In those subjects who suffered myocardial infarction renin tended to rise more sharply. 3. A relationship was established with the rise in renal vascular resistance, which almost invariably occurred over the years.


Solitary kidney and ageing as causes of low renin and aldosterone concentrations: relevance to "low-renin" essential hypertension. 1. As experimental models of reduced nephron population in man, (a) twelve men aged 15-32 years who had one kidney removed 1-13 years previously and (b) fourteen normotensive men aged 70-90 years were studied. Results were compared with those in eighteen normotensive men aged 18-28 years and eleven men aged 19-33 years with essential hypertension. 2. While the subjects followed a routine of normal diet and daily activity, measurements were made, after overnight recumbency and in the fasting state, of plasma volume and renin activity on one occasion in hospital and of blood pressure on five to fourteen occasions in the home. Blood pressure was also measured after standing for 2 min and plasma renin activity after 1 h standing, sitting or walking. Twenty-four hour urinary aldosterone excretion was also measured. 3. The measurements were repeated in the normotensive subjects and subjects in (a) and (b) above after 10 days of sodium-restricted diet (40 mmol of sodium/day). 4. The mean plasma renin activity (recumbent) in essential hypertensive subjects was higher than in normotensive subjects. In subjects of (a) and (b) above, it was lower than normotensive subjects, and was not increased by dietary sodium restriction in subjects of (a). 5. The mean aldosterone excretion level was lower in old normotensive subjects than in the other groups, and increased in each group after dietary sodium restriction. 6. Mean plasma volume/surface area was not different between the four groups and in normotensive, essential hypertensive and nephrectomized subjects but not subjects aged 70-90 years was negatively correlated with standing diastolic blood pressure.


High-renin essential hypertension: adrenergic cardiovascular correlates. 1. Patients with mild essential hypertension and elevated plasma renin activity, when compared with normal subjects and hypertensive subjects with normal plasma renin, demonstrated features of sympathetic nervous cardiovascular excitation, accompanied by a raised plasma noradrenaline concentration. 2. An elevated heart rate at rest, shortened cardiac pre-ejection period, and greater heart rate reduction with acute beta-adrenoreceptor blockade (intravenous propranolol) in high-renin essential hypertension were indicative of adrenergic cardiac excitation. An elevated total of peripheral vascular resistance at rest and a greater fall in peripheral resistance with alpha-adrenoreceptor blockade (intravenous phentolamine) suggested the existence of a neurogenic increase in arteriolar resistance. 3. Blood pressure was normalized by 'total' autonomic blockade (atropine plus propranolol plus phentolamine) in the hypertensive subjects with elevated plasma renin activity. 4. These findings suggest that in mild high-renin essential hypertension increased adrenergic drive to the heart and resistance vessels exists. The elevation of blood pressure is sustained predominantly by neurogenic mechanisms. The high plasma renin activity is seen as an expression of sympathetic nervous system overactivity.


Reduced plasma renin activity in essential hypertension: effects of blood pressure, age and sodium. 1. Supine plasma renin activity and its responsiveness to erect posture and frusemide were reduced in fifty-one patients with essential hypertension, compared with fifty-one age- and sex-matched control subjects. 2. Twenty-four hour urinary sodium excretion was similar in hypertensive patients nad control subjects. 2. Twenty-four hour urinary sodium excretion was similar in hypertensive patients and control subjects, but after intravenous frusemide hypertensive patients excreted significantly less sodium. 3. A significant inverse relationship between plasma renin activity and diastolic blood pressure was demonstrated in hypertensive patients and in normotensive control subjects. 4. A significant inverse relationship between plasma renin activity and age, independent of blood pressure, was shown in hypertensive patients and control subjects. 5. It is concluded that the reduced renin values found in essential hypertension are, in part, the result of the elevated blood pressure acting on the kidney.


Change in the renin dependency of blood pressure induced by volume depletion and/or propranolol therapy in hypertensive patients. 1. Plasma renin activity (PRA) and renin dependency of the blood pressure was analysed in ten patients with various forms of hypertension before and during treatment with volume depletion and/or propranolol. Renin dependency was tested by infusion of the specific competitive angiotensin II antagonist Sar1-Ala8-angiotensin II (P113). 2. The P113-induced fall of the blood pressure did correlate with the log PRA (r=0-888, P less than 0-001). This correlation was found irrespective of different types of hypertension and treatment schedules. 3. During volume depletion, PRA was stimulated and renin dependency of the blood pressure increased. Propranolol therapy suppressed PRA during normovolaemia as well as during volume depletion, and this was accompanied by a decrease of the renin dependency. 4. No incication was found that a given PRA is of special importance for blood pressure elevation in different patients. 5. Suppression of PRA by propranolol is one of the anti-hypertensive mechanisms of this drug.


The renin-angiotensin system and the pathogenesis of vascular disease in malignant hypertension. 1. The syndrome of malignant hypertension in man and animals has three fundamental components: high blood pressure, activation of the renin-angiotensin system and the rapid development of necrotizing arteriolar disease. 2. The high blood pressure can be associated with different conformations of the arteriolar microcirculation. The emergence of an arteriolar reaction pattern characterized by the formation of focal dilatations, with intervening constricted segments, is of fundamental pathophysiological importance. 3. Activation of the renin system is reflected in an increased renin secretion rate from the kidneys and an increased rate of angiotensin II generation in the pulmonary vascular bed. 4. The crucial pathogenetic process, leading eventually to severe arteriolar wall damage, is a penetration of plasmatic macromolecules into the wall of distended arteriolar segments, as observed in states of severe experimental hypertension. 5. Renin can induce vascular disease, but hypersecretion of renin is not a necessary condition for the development of hypertensive arteriolar necrosis.


Angiotensin II blockade in normal subjects and essential hypertensive patients. 1. Saralasin (Sar1-Ala8-angiotensin II), a competitive inhibitor of angiotensin II (AII), has been infused into normal subjects and patients with essential hypertension when deprived of sodium by 5 days of a 10 mmol/day sodium diet. 2. When saralasin was given by an incremental rate of infusion starting at 0-25 microng min-1 kg-1, sodium-deprived normal subjects showed a fall in standing blood pressure with no change in lying blood pressure, sodium-deprived normal-renin hypertensive patients showed no change in lying or standing blood pressure and sodium-deprived low-renin patients showed a significant sustained rise in lying and standing blood pressure. 3. These findings suggest that: (a) standing blood pressure in sodium-deprived normal subjects is angiotensin II dependent; (b)normal-renin hypertensive patients when sodium deprived by diet alone do not appear to be angiotensin II dependent (angiotensin II is unlikely therefore to be directly maintaining their blood pressure on their normal sodium intake);(c) the rise in blood pressure seen in low-renin hypertensive patients with saralasin may be a further way of distinguishing this group of patients.


Determination of renin-dependency and sodium-dependency in the three renin sub-groups of essential hypertension. 1. In all three renin sub-groups of essential hypertension, the state of sodium balance determines the degree of participation of the renin-angiotensin system in sustaining high blood pressure. 2. Even the low-renin type can become renin-dependent when sufficient sodium depletion has bee achieved. 3. The main difference between patients of these sub-groups appears to be their variable capacity to become depleted of sodium under standard dietary regimens.


Dissociation of blood angiotensin II and plasma renin activity during chronic treatment in essential hypertension. 1. Plasma renin activity and circulating amounts of blood angiotensin II were measured in twenty-six patients with uncomplicated essential hypertension. 2. Measurements were made during a control period and at 1, 4, 9 and 14 weeks of diuretic treatment with metolazone or hydrochlorothiazide. 3. Linear regression analysis indicated a progressive change in the relation of plasma renin activity and blood angiotensin II. 4. During  chronic diuretic therapy (beyond 14 weeks) blood angiotensin II had stabilized to low and relatively fixed values across a wide range of plasma renin activities.


The role of vascular capacitance in the genesis of essential hypertension. 1. Analysis of relationships between blood volume, vascular capacitance, cardiopulmonary and peripheral blood volumes, labelled albumin disappearance rate, plasma renin activity, blood pressure and age was performed in essential hypertensive males. 2. The results indicate that capacitance bed constriction probably occurs with age in essential hypertension leading to an increase in the product blood volume xvascular capacitance tone even in the presence of low blood volume. 3. A metabolic defect in the venous vascular bed along with an abnormality of regulation of renal sodium excretion is postulated.


Increased central blood volume: a poosible pathophysiological factor im mild low-renin essential hypertension. 1. Patients with mild low-renin hypertension characteristically have increased central blood volume. The total blood volume is normal; the larger central blood volume reflects a shift of the blood from peripheral to central (cardiopulmonary) segments of the capacity system. 2. A relationship between central blood volume and plasma renin activity is demonstrable during tilting in normal and hypertensive subjects. In thirteen indivicuals there was a strong correlation between the decrease of the central blood volume and the increase in plasma renin activity in response to 12 min of 35 degree head-up tilt. 3. We propose that the elevated central blood volume causes greater stretch of cardiopulmonary mechanoreceptors and this in turn depresses renin release in mild low-renin hypertension.


Significance of increase in labelled albumin disappearance rate in arterial hypertension. 1. Relationships between labelled albumin disappearance rate (LADR), plasma volume, blood volume, plasma renin activity (PRA) and blood pressure (BP) were studied in normotensive control subjects and patients with hypertension of different aetiology and severity. In essential hypertensive patients without complications an inverse linear relationship was found between blood pressure and plasma or blood volume. 2. Very close inverse correlations were found between LADR and PRA in both normotensive subjects and patients with uncomplicated essential hypertension. LADR appears to be an excellent reference standard for PRA. 3. It is postulated that LADR mainly reflects the relation between circulating fluid and vascular capacitance tone. LADR is increased in hypertension and blood volume may still be inappropriately high.


The effect of intravenous angiotensin II on the peripheral circulation with particular reference to its bearing on general haemodynamics. 1. Central and peripheral haemodynamic effects of intravenous infusion of angiotensin II have been investigated in ten normotensive subjects. Angiotensin II was given at the rate of 0-12-5-0 microng/min. 2. The pressor response to angiotensin II was accompanied by a significant increase in the total peripheral resistance, central venous pressure and by a marked reduction of the intravascular forearm volume and venous distensibility. Forearm circulation time was shortened. 3. Cardiac index, heart rate, forearm vascular resistance and the forearm blood flow did not change significantly in the whole group but in the individual subjects some of the variables changed markedly in either direction. 4. Direct action of angiotensin II on the vessels and its central and peripheral sympathomimetic aciton as well as the role of the baroreflex as responsible causes for haemodynamic changes after angiotensin II are discussed.


The haemodynamic response to salt and water loading in patients with end-stage renal disease and anephric man. 1. Patients with end-stage renal disease and anephric patients underwent expansion and depletion of body fluids with salt and water. This resulted in four different sequential haemodynamic patterns: (i) no significant increase in blood pressure; (ii) increase in blood pressure associated with a rise in cardiac output and no effect on total peripheral resistance; (iii) increase in cardiac output followed by a rise in blood pressure and total peripheral resistance; (iv) increase in total peripheral resistance and blood pressure without significant changes in cardiac output. 2. It is concluded that an initial rise in cardiac output is not necessary to increase-blood pressure in either anephric man or patients with end-stage renaldisease.


Primary malignant nephrosclerosis.

Primary malignant nephrosclerosis. 1. As proposed by Schürmann & MacMahon (1933), we suggest that two types of malignant nephrosclerosis exist. 2. In the type called primary malignant nephrosclerosis, renal vascular lesions precede hypertension. 3. In the second type, called secondary malignant nephrosclerosis, renal vascular lesions are considered to be the consequence of malignant hypertension.


Surgical intervention in severe and complicated renal hypertension: Report of the Sydney Renal Hypertension Group (1969-75). 1. A prospective study was undertaken in seventy-eight patients with renal hypertension (fifty-eight with renovascular disease and twenty with renal parenchymal disease), after their presentation to an advisory group as possible candidates for surgical management. 2. Vascular repair and/or nephrectomy were performed in forty-four patients, and the remainder were treated with anti-hypertensive drugs. The control of blood pressure was then assessed over periods of 6-70 months. 3. Of the patients treated surgically, fifteen (34%) were normotensive without medication and fifteen had improved blood pressure control; the morbidity rate was the same as in the medically treated group, but mortality was lower and blood pressure control was better, particularly among patients under 40 years of age. 4. Surgery undertaken primarily to conserve renal function was beneficial in four of nine patients with bilateral renal artery stenosis and severe, progressive uraemia. 5. The blood pressure response to surgical correction of unilateral renal lesions was predicted correctly by the preoperative renal vein renin ratio in fifteen of eighteen cases.


Diazoxide-induced stimulation of renin release in renal vein renin sampling. 1. The acute effect of diazoxide (150-300 mg, intravenously) on renal venous renin has been evaluated in forty-four patients with suspected renal hypertension. 2. In twenty-seven studies which showed no lateralization, diazoxide raised the mean peripheral renin to 175% of control (P less than 0-05) but the renal vein renin ratio showed an insignificant change (1-15 to 1-21). 3. In seventeen studies which showed lateralization the increase in peripheral renin was similar, but mean renal vein renin ratio increased from 1-90 to 3-52 (P less than 0-005), and the mean ratio of contralateral renal vein to peripheral renin showed no change (1-05 to 1-07), indicating persistence of contralateral suppression. 4. Diazoxide accentuates the distinction between lateralizing and non-lateralizing renal vein renin studies.


Clinical significance of plasma renin activity in human renovascular hypertension. 1. Plasma renin activity (PRA) in peripheral venous blood of patients with renovascular hypertension was found to be high (thirty-five), normal (twenty-one) and low (three). Twenty-one patients with high PRA were cured or improved after successful surgery, as were eight of eleven with normal PRA and one with a low PRA. After surgery high PRA values became normal or low. 2. A beta-receptor-blocking agent (oxprenolol) decreased PRA in twenty-eight patients (responders) and it either did not modify or increased PRA in the other fifteen (non-responders). All fourteen non-responders were cured by surgery, as were thirteen out of fifteen responders; ten non-responders became responders after surgery. Oxprenolol suppressed renin secretion of both kidneys of two patients with essential hypertension, and it either decreased (six) or did not modify (four) renin secretion from the ischaemic kidney. 3. PRA measurement in renal veins of twenty-six patients with renovascular hypertension showed that only the ischaemic kidney contributes to the peripheral PRA, renin secretion being suppressed in the contralateral kidney. The suppression of renin secretion from the ischaemic kidney produced either by nephrectomy (nine) or by aortorenal by-pass (six) normalized blood pressure. 4. Peripheral PRA values are of poor diagnostic significance and PRA unresponsiveness to a beta-receptor-blocking drug and the suppression of renin secretion from the ischaemic kidney are characteristic findings of renovascular hypertension curable by appropriate surgery.


The immediate plasma renin response to propranolol: evidence for a different mode of renin release in essential and renal hypertension. 1. The immediate short-term effects of intravenous injections of propranolol on plasma renin activity were studied in thirty-one normal subjects, 102 patients with benign essential and sixty-six patients with renal hypertension. 2. In essential hypertensive patients and normal subjects a marked fall in plasma renin activity was observed within 15 min, which was directly proportional to initial plasma renin values. In contrast, in patients with renal hypertension the fall observed was much less pronounced, or totally absent. 3. These differences in response to propranolol, which were particularly pronounced in patients with high initial renin values, suggest a dominant role of sympathetic tone at the juxtaglomerular apparatus for basal renin release in normal individuals and essential hypertensive subjects only. 4. The observations also indicate that sympathetic activity plays no part in the control of basal renin secretion in patients with renal hypertension, in whom basal renin secretion may be maintained by the renal baroreceptors.


Results and costs of investigating newly detected hypertensive patients. 1. Eighty unselected hypertensive subjects were investigated at a cost of $78.00 per patient, in a short out-patient study programme. Seven (9%) were found to have a cause for their hypertension; incidental abnormalities were found in twenty-two (28%). 2. The combination of clinical selection and planned out-patient investigation should detect all patients with secondary hypertension.


Effects of indomethacin in rabbit renovascular hypertension. 1. Indomethacin inhibits prostaglandin synthesis and interferes with renin release; these effects were studied in rabbit renovascular hypertension. 2. Ten intravenous injections (3 mg day-1 kg-1 after two initial doses of 9 mg/kg) of indomethacin were given daily to ten normal rabbits, ten rabbits with two-kidney Goldblatt hypertension (2KH), tension (1KH). Twelve appropriate control rabbits received diluent phosphate buffer without indomethacin. Plasma renin activity and plasma prostaglandin E2 were measured by radioimmunoassay. 3. In the normal group, indomethacin significantly decreased plasma prostaglandin E2 (1-15 to 0-2 ng/ml, SEM 0-2; P less than 0-01) and plasma renin activity (20 to 3 ng h-1 ml-1, SEM 1, P less than 0-01). Plasma creatinine increased slightly but the mean blood pressure was not significantly changed by indomethacin. 4. Six of ten rabbits with 2KH showed results similar to those in the normal rabbits. In four of ten rabbits in which development of 2KH was accompanied by increments in plasma renin activity (18 to 31-5 ng h-1 ml-1, SEM 3 and 4 respectively; P less than 0-01) and plasma prostaglandin E2 (1-2 to 3-4 ng/ml, SEM 0-2 and 0-4 respectively; P less than 0-05), treatment with indomethacin produced renal failure (plasma creatinine increasing to 7-6 mg/100 ml), oliguria, malignant hypertension (mean blood pressure, 168 mmHg, SEM 7-7) and death within 5 days. 5. In 1KH, indomethacin decreased plasma renin activity and plasma prostaglandin E2, but caused increased mean blood pressure (102 to 121 mmHg, SEM 4 and 6 respectively; P less than 0-01) and decreased renal function (plasma creatinine 0-9 +/- 0-04 to 3-5 +/- 1 mg/100 ml, SEM 0-04 and 1 respectively; P less than 0-01). 6. Aggravation of hypertension was conditioned by pre-existing levels of renal function and, to a lesser extent, by plasma renin activities. 7. These results suggest that prostaglandins exert a protective effect on renal function in renovascular hypertension.


Renal prostaglandin synthesis in hypertension induced by deoxycorticosterone and sodium chloride in the rat. 1. The role of renal medullary prostaglandin E has been examined in rats with hypertension induced by sodium chloride and deoxycorticosterone (salt-DOC). 2. Synthesis of prostaglandin E was normal in early salt-DOC hypertension. Indomethacin exacerbated the hypertension, and depressed synthesis of prostaglandin E equally in hypertensive and control rats. 3. Synthesis of prostaglandin E was depressed in rats with late salt-DOC hypertension. 4. The results lend support to the concept that prostaglandin E is involved in the regulation of arterial pressure.


Vascular actions of frusemide and bumetanide on the rat superior mesenteric vascular bed: interactions with prostaglandins. 1. The addition of frusemide or bumetanide to perfusion fluid inhibited the response of the isolated mesenteric vascular bed to noradrenaline. 2. Addition of prostaglandin E2 to the perfusion fluid completely restored the response to noradrenaline. 3. Inhibition of prostaglandin secretion by indomethacin with restoration of responses to noradrenaline by the addition of exogenous prostaglandin E2 prevented the inhibitory effect of frusemide or bumetanide on responses to noradrenaline. 4. The inhibitory effects of diuretics on responsiveness to noradrenaline is mediated by blockade of endogenous prostaglandin synthesis.


Renal urinary kallikrein in normotensive and hypertensive rats during enhanced excretion of water and electrolytes. 1. Urinary kallikrein excreted by normal rats is significantly increased (P less than 0-001) 2 h after: (a) water loading, (b) water loading plus frusemide, 0-27 mmol (10 mg) per rat, (c) salt loading. In water-loaded rats, 5 i.u. of renin strikingly reduced kallikrein excretion (P less than 0-01) but considerably increased sodium excretion (P less than 0-001). 2. Renal kallikrein, measured by its kininogenase activity within 2 h of water loading, was significantly increased (P less than 0-05); after water loading and frusemide it was 40% decreased (P less than 0-001) and after salt loading it was reduced by approximately 50% (P less than 0-02). Renin did not change renal kallikrein. 3. Severely hypertensive (one-kidney) rats (blood pressure greater than 150 mmHg) showed no increase of urinary kallikrein after water loading, although there was a marked natriuresis, in moderately hypertensive rats (blood pressure less than 150 mmHg) urinary kallikrein was only one-third of that observed in control normotensive rats, after an equal degree of water loading.


Urinary kallikrein and plasma renin during the reversal of renovascular hypertension in rats. 1. Urinary kallikrein, sodium, potassium and water excretion, and plasma renin activity were measured before and during the reversal of experimental hypertension produced by unclamping the renal artery in rats. 2. Kallikrein excretion decreased significantly after unclamping, suggesting that it does not play a significant role in the reversal of hypertension. 3. A decrease in plasma renin activity coupled with a slight increase of sodium excretion was observed, indicating that these might participate in the reversal of hypertension.


The renal vascular lesions of severe and malignant hypertension: a light-immunofluorescent microscopy, transmission and scanning electron-microscopy study. 1. Arterial and glomerular lesions were studied in seventy-eight specimens from patients with severe or malignant primary or secondary hypertension by transmission and scanning electron microscopy and light-microscopy and immunofluorescent microscopy. 2. The lesions were classified as compensatory, decompensated and reparative. The arterial lesions of primary and secondary hypertension were qualitatively similar. Each of the microscopy techniques contributed to a better understanding of the changes.


Contribution of prostaglandins to the renal vascular supersensitivity to vasoconstrictor agents exhibited by New Zealand genetic hypertensive rats. 1. Studies were made of the effects on responses to vasoconstrictor agents of prostaglandins released from Krebs perfused isolated kidneys of genetic hypertensive and normotensive rats. 2. Prostaglandin E-like activity, detected by bioassay, was released from kidneys of both groups of rats during the vasoconstriction produced by noradrenaline, angiotensin or prostaglandin F2alpha. 3. In preparations obtained from hypertensive rats, responses to higher doses of noradrenaline or angiotensin were initially greater than those from normotensive rats and these were then reduced to a greater extent by infusion of indomethacin, which abolished release of prostaglandin E-like activity. Thereafter, in kidneys of either group, vasoconstriction to noradrenaline was potentiated by infusion of prostaglandin E2. 4. We conclude that, in rats, renal prostaglandins released in response to vasoconstrictor agents could augment the effect of such agents and in genetic hypertensive rats release of renal prostaglandins could contribute to the disease.


The effects of aldosterone and spironolactone on renal kallikrein in the rat. 1. A technique has been developed for the measurement of kallikrein 'production' in rat renal cortical cells in suspension. 2. After preparative steps, column chromatography on DEAE-cellulose yielded a peak of alpha-N-tosyl-L-arginine methyl ester (Tos-Arg-OMe) esterase activity identical with kallikrein isolated from rat urine in respect of pH optimum, effects of inhibitors, biological activity and immunological properties. 3. The nutrient medium surrounding incubated cells contained measurable kallikrein activity, which was increased by aldosterone and decreased by spironolactone. 4. The results raised the possibility that kallikrein could be an aldosterone-induced protein.


Renin-angiotensin and kallikrein-kinin systems in sodium homeostasis and hypertension in rats. 1. Urinary kallikrein excretion was measured in rats by an enzyme kinetic method employing radioimmunoassay of generated bradykinin. 2. Rats given a sodium load (NaCl solution, 20 g/l, to drink) for 28 days showed acute and prolonged significant falls in urinary kallikrein excretion associated with suppression of plasma renin and angiotensin. 3. Conversely sodium-depleted rats showed increases in urinary kallikrein excretion, associated with rises in plasma renin and angiotensin. 4. A close and significant direct relation between plasma renin activity and urinary kallikrein excretion was demonstrated. 5. The diuresis and natriuresis induced by frusemide in rats was associated with increased urinary kallikrein excretion and acute rises in plasma renin. 6. In chronic renal hypertensive rats urinary kallikrein excretion was increased only in the animals with two-kidney Goldblatt hypertension. This group was also the only group that demonstrated a significant rise in plasma renin activity.


Anti-hypertensive lipid tissue from culture of renomedullary interstitial cells of the rat. 1. Allogenic transplants of cultured renomedullary interstitial cells exert a powerful anti-hypertensive action. The blood pressure of hypertensive animals usually drops slowly over 8-12 h whereas the pulse is unchanged or reduced. 2. Lipids derived from the cultured cells exert a similar anti-hypertensive action. 3. The anti-hypertensive action of transplanted cultured cells almost certainly results from the secretion of a substance(s) that acts in the manner of a hormone. The tissue culture lipid is a prime candidate hormone. 4. The relationship of the kidney to the hypertensive state is considered to entail pro- and anti-hypertensive actions. The pro-hypertensive actions include (a) activation of the renal pressor system (mainly renin-angiotensin), (b) failure to prevent sodium and fluid overloading because of either an injured or absent kidney or the excessive action of mineralocorticoids (mainly aldosterone). The antihypertensive actions of the kidney include (a) the relief of sodium and fluid overloading through diuresis-natriuresis and (b) the action of the reno-medullary interstitial cell hormone (the antihypertensive renomedullary hormone).


Deoxycorticosterone measured by a radioimmunoassay in vivo in rats undergoing adrenal regeneration. 1. The free deoxycorticosterone pool in the rat was measured by means of a radioimmunoassay in vivo. 2. The free deoxycorticosterone pool in rats with adrenal regeneration with normal or high blood pressure was similar. 3. In rats with adrenal regeneration, the free deoxycorticosterone pool 21 days post-operatively was significantly lower than that in sham-operated control rats and returned to control values at 60 days.


Deoxycorticosterone hypertension in the pig. 1. Deoxycorticosterone acetate (DOCA) implantation (100 mg/kg) caused mean arterial pressure to rise in 5-10 days from control pressures of 100-115 mmHg to stable hypertensive values of 140-160 mmHg in approximately 1 month. In six of seven pigs elevations of mean arterial pressure were entirely the result of increased total peripheral resistance. 2. Single implants maintained serum DOCA at approximately ten times normal concentration for up to 90 days. 3. Moderate but variable decreases in serum aldosterone followed implantation. 4. Hypokalaemia, polydipsia and suppressed plasma renin activity were evident by the fifth post-implantation day and persisted thereafter. No consistent change occurred in serum sodium. 5. Noradrenaline or angiotensin caused increases in total peripheral resistance at lower threshold infusion rates in hypertensive pigs compared with control animals. 6. In isolated, perfused hind-limb preparations, hypertensive vascular beds were characterized by both functional (increased vascular smooth muscle sensitivity) and structural (elevated resistance of maximally dilated vascular bed) changes. 'Protection' from increased arterial wall stresses in hypertensive pigs prevented structural, but not functional, alterations.


Influence of spironolactone on endogenous steroid metabolism in man. 1. Mild secondary hyperaldosteronism was induced in ten healthy young males by a low sodium diet for 14 days. After 7 days on the diet, five subjects each were treated with spironolactone (group S) or triamterene (group T) daily. 2. The daily negative sodium balance was identical during the first 3 days of medication with both drugs but sodium loss was more severe during the following days in group S. Consequently, the plasma renin activity was higher during the last days of spironolactone compared with triamterene medication. 3. Changes in plasma electrolytes were similar in both groups. 4. No influence of either drug on the synthesis chain leading to cortisol was observed. 5. Plasma concentrations of deoxycorticosterone and corticosterone, however, increased considerably in group S, whereas triamterene did not influence these steroids. 6. Whereas triamterene induced a prompt increase of plasma aldosterone, an increase was delayed for the first 3 days of treatment with spironolactone. Later, plasma aldosterone concentrations rose rapidly in group S and were no longer different from those in group T. 7. Results are interpreted as being due to an initial inhibition of aldosterone synthesis by spironolactone, which is finally compensated, at least in part, by increased activation of the renin-angiotensin system.


The arteriolar lesions of steroid hypertension in rats. 1. The arteriolar lesions of rats with deoxycorticosterone (DOCA)-salt hypertension have been studied by colloidal carbon injection and light- and electron-microscopy. 2. Colloidal carbon particles enter the media of arterioles to form focal deposits when hypertension develops. 3. The focal lesions are similar to those seen after angiotensin infusion or renal artery constriction. They are characterized by endothelial damage and plasma deposition in the media. 4. Heavy deposition of carbon in the glomeruli of DOCA-treated animals was found to be caused by increased mesangial uptake and not by hypertensive vascular damage. 5. Angiotensin II concentrations fell during the development of hypertension and vascular lesions. The renin-angiotensin system was not implicated in the development of vascular damage in this form of hypertension.


The role of 11-deoxycorticosterone in human hypertension. 1. Using a newly developed and validated radioassay method, we have measured plasma 11-deoxycorticosterone concentrations in a wide spectrum of human hypertensive states. 2. Patients with essential and renovascular hypertension have normal plasma concentrations of 11-deoxycorticosterone. 3. Elevated concentrations are seen in some patients with primary aldosteronism, Cushing's syndrome, low-renin hypertension, and in adult hypertensive subjects with elevated urinary 17-ketosteroid excretion. 4. An aetiological role for deoxycorticosterone in certain forms of human hypertension appears likely.


Increased renal sensitivity to aldosterone in the potassium-loaded rat. 1. The renal response to aldosterone (urinary sodium and potassium excretion) was determined in adrenalectomized rats previously fed either a high potassium diet or a control diet. High K+ rats showed an enhanced response to aldosterone at all doses tested. 2. This enhanced response to aldosterone required the presence of the adrenal glands during the induction period, could be suppressed by a high sodium intake, but could not be induced by a low sodium diet. 3. No difference between high K+ and control rats could be detected in renal mineralcorticoid receptors, assessed by both in vivo and in vitro binding of tritiated aldosterone. 4. The method of the induction, and the mechanism of the enhanced response, remain to be defined.