RNA-dependent DNA polymerase activity of RNA tumor virus. VI. Processive mode of action of avian myeloblastosis virus polymerase. Purified avian myeloblastosis virus (AMV) polymerase consisting of alpha,beta subunits has been shown to act processively in catalyzing DNA synthesis primed with 34S AMV RNA oligo(dT), poly(A)-poly(dT), and poly(I)-poly(dC). DNA transcripts prepared with 34S AMV RNA-oligo(dT)14 and AMV polymerase (alphabeta) have been shown to have a molecular weight of 1.05 X 10(6), or approximately one-third the size of the 34S RNA genome. Polymerase subunit alpha acts nonprocessively with the above templates.


Antilymphoblast globulin in renal transplant patients. No allergic reactions. The incidence and type of allergic reactions to antilymphoblast globulin (ALG) and their relationship to skin testing, histamine release, and serum levels of ALG and anti-ALG antibodies were studied prospectively in 50 patients receiving high-dose ALG therapy intravenously for the first two weeks after renal transplantation. No clinically apparent allergic reactions occurred in the patients studied.


[The safety evaluation of fradiomycin-gramicidin S troches "Meiji" (author's transl)]. The troches "Meiji" contain fradiomycin (neomycin), an aminoglycoside antibiotic, and gramicidin S, and are effective against gram-negative and -positive bacteria. In this paper the safety evaluation of the troches is reported. In this study male guinea pigs of Hartley strain were used, and fradiomycin (FRM) and gramicidin S (GRMN) were administered orally for 35 days consecutively except Sunday. The PRYER'S reflex test was carried out with frequency range of 10,000 approximately 15,000 Hz before, during and after the administration. After the last administration the animals underwent vital perfusion with physiological saline and then with Wittmack's fixative. Bilateral temporal bones were removed and fixed in the same fixative for several days. Using a conventional method, serial celloidin horinzontal sections were prepared and stained with hematoxyline-eosine to observe histopathological effect of the medicines on the organs of CORTI. The results were as follows: 1) There were no remarkable differences in the treated animals from the initial states. No animal died at all the doses tested. 2) All of the guinea pigs received 10 and 50 mg/kg of FRM and 4 and 20 mg/kg of GRMN for 35 days indicated positive pinna reflex in the extensive frequency range of 10,000 approximately 15,000 Hz. There was no remarkable damage in the organ of CORTI on histopathological examination. 3) It was concluded from these results that the troches are highly safe.


Mouse virulent strain of Staphylococcus epidermidis. Relation of antiphagocytic activity to the protection-inducing antigen. Using 10(9) or 10(7) colony-forming units of a strain of Staphylococcus epidermidis (strain 1142) in saline or 5% mucin, respectively, 90 to 100% of mice died within 24 to 48 hr after intraperitoneal challenge infection. These organisms gradually multiplied in the peritoneal cavity when injected intraperitoneally into mice, while the mouse avirulent strain (strain 1124) rapidly decreased and no organisms were found there 20 hr after injection. This strain was capable of inducing resistance against challenge with homologous strains. The resistance appeared as early as the first week and disappeared the 4th week after the immunization. However, no resistance was induced with strain 1124 against challenge with strain 1142. Also, hyperimmune rabbit serum prepared with strain 1142 passively protected against challenge with homologous strain in mice. The protective antibody was absorbed out with homologous organisms but not with strain 1124. Subsequently, a surface substance was obtained from strains 1142 or 1124 by the method of Morse. The 1142 surface substance was capable of inducing a resistance against challenge with the homologous strain but not with the 1124 surface substance. Also, this substance absorbed the protective antibody in hyperimmune rabbit serum prepared with the homologous strain but not with the 1124 surface substance nor with the Smith surface antigen extracted from the Smith strain of Staphylococcus aureus. Conversely, the protective antibody in rabbit anti-Smith strain serum against challenge with the homologous strain was absorbed with the Smith surface antigen but not with the 1142 surface substance. In the agar diffusion test, the 1142 surface substance and the Smith surface antigen produced single precipitin lines only against homologous antisera. Biochemical analysis of the 1142 surface substance showed that the substance contained neither nucleic acids nor proteins but is composed of hexosamine, glycerol, phosphorus, alanine, glycine and phenylalanine.


[The vulnerability of the human atrium. I. Correlations between vulnerability, sinus node recovery time and intraatrial conduction time (author's transl)]. Using the extrastimulus method in 100 patients, premature impulses were applied during the relative refractory period of the right atrium. Depending on the atrial response to these impulses we divided our patients in the following 3 groups: Group A: no repetitive firing (61 patients); group B: 1 to 5 additional atrial extrasystoles with a total duration of maximum 1.5 s (27 patients); group C: runs of atrial flutter or fibrilation for at least 8 s (12 patients). The statistical analysis of the following parameters: age, PA interval, absolute and corrected sinus node recovery time did not show any significant difference between the 3 groups. These results suggest that the investigated parameters are of no great importance in the genesis of the atrial vulnerability.


Surgical versus medical treatment in disease of the left main coronary artery. Data from 179 patients with a significant lesion of the left main coronary artery were reviewed to compare survival with and without bypass graft surgery. 149 patients were treated with bypass grafting. Of 38 patients treated medically, 24 were suitable for surgery but either had been evaluated before the widespread use of bypass grafting procedures or preferred medical treatment. Major prognostic factors in this group were comparable to the surgical patients. The survival-rate was consistently higher for the surgically treated group and differed significantly (P less than 0-02) for the total duration of follow-up. At twelve months, 89% of the surgical group were alive, but only 73% of the comparable medical group; at twenty-four months, survival-rates were 86% and 65% respectively. These findings, corroborated by other data, suggest that surgery prolongs life for these patients.


Is the adrenergic control of renin release dominant in man? Two beta-blocking agents with different properties were used to define the adrenergic component of the renin release which follows orthostasis. Five normal young subjects were tilted to 85 degrees for 30 min on four separate occasions. In two control studies the release of renin, as indicated by changes in plasma-renin activity, was highly reproducible. The effects of intravenous oxprenolol and intravenous propranolol, were then compared under the same experimental conditions. Oxprenolol attenuated the renin response in all subjects without completely abolishing it. Propranolol completely abolished the renin response. The difference in the ability of these agents to suppress renin release may be related to the presence (oxprenolol) or absence (propranolol) of intrinsic sympathomimetic activity. The increased rate of renin release in orthostasis seems to be mediated entirely by the adrenergic nervous system.


Oestrogen profiles of parous and nulliparous women. Women who bear their first child at an early age have lower breast-cancer incidence-rates than do women who are older at first birth or who remain nulliparous. The urine "oestriol ratio", the concentration of oestriol relative to the sum of the concentrations of oestrone and oestradiol, is inversely related to a population's breast-cancer rate. To evaluate the relationship between these two breast-cancer risk indicators the urine oestriol ratio was determined for recently delivered uniparous women aged 19-23, 25-27, and 29-34 years and nulliparous women of comparable ages. In the follicular phase, the youngest parous women had an oestriol ratio 40% higher than, and significantly different from, the ratios of all other groups which were otherwise quite similar. In the luteal phase, the oestriol ratio of the youngest parous women was again distinctively raised and generally the oestriol ratios of parous women were higher than those of nulliparae. The results are not explained by differing frequencies of ovulation among the groups or by confounding from several breast-cancer risk indicators. These findings support the hypothesis that oestrogen metabolism, as reflected by the urine oestriol ratio, is a determinant of breast-cancer risk.


Isolation of influenza virus from liver and muscle biopsy specimens from a surviving case of Reye's syndrome. Influenza virus (A/Ohio/7/76) was demonstrated by haemagglutination and by direct electron microscopy in chick embryo fluids inoculated with liver, muscle, cerebrospinal fluid, and nasotracheal secretions obtained from a boy with Reye's syndrome, 8 days after the onset of the upper-respiratory-tract symptoms and at the height of neurological and hepatic involvement. This finding accords with the hypothesis that Reye's syndrome may be an epiphenomenon of influenza-virus infection. It is postulated that the pathogenesis of Reye's syndrome may be related to the other influenzal eipiphenomena including influenzal pneumonia in previously healthy persons and influenza-associated myopathy, both of which, like Reye's syndrome, become clinically evident about 7 days after the first clinical signs of influenza.


Portal hypertension in vinyl-chloride production workers. Portal hypertension was seen in seven patients who had been involved in the production of vinyl-chloride monomer for 4-15 years. Four presented with bleeding oesophageal varices. In liver biopsy specimens non-cirrhotic portal fibrosis was inconspicuous and was seen more clearly on wedge rather than needle biopsy specimens. The intrahepatic venous pattern was hardly distrubed. Three patients have done well following shunt surgery. In one patient an angiosarcoma developed, but fibrosis was a more common lesion and was probably not pre-malignant.


Prostaglandins and aspirin therapy in Bartter's syndrome. A young patient with Bartter's syndrome was treated for three months with 100 mg/kg/day of aspirin to inhibit prostaglandin synthesis. Clinical symptoms resolved and serum-potassium increased from 2-9 to 3-5 mmol/l. Urinary excretion and plasma concentration of prostaglandins E and F were significantly reduced during aspirin therapy. Plasma-renin activity declined from 85 to 20 ng/ml/h (normal 1-5-4 mg/ml/h) and hyperaldosteronism was corrected. These results suggest that overproduction of prostaglandins has a central role in the pathogenesis of Bartter's syndrome.


Total hip replacement in renal transplant recipients with aseptic necrosis of the femoral head. Aseptic necrosis of the femoral head is a complication of renal transplantation which seriously delays the rehabilitation of the patient despite otherwise successful transplantation. Of 187 renal allograft recipients, 8 underwent 14 total hip replacements. The most severe postoperative problem was an easily reducible dislocation. All patients were relieved of their severe preoperative pains and all were greatly improved in mobility and strength. Renal function was not altered in any patient. It is therefore suggested that total hip replacement be recommended in such cases at an early stage so that the patient may be spared prolonged suffering and may be returned to a programme of post-transplant rehabilitation.


A suppressor T-cell defect in tropical splenomegaly syndrome. Serum-IgM is always abnormally high in tropical splenomegaly syndrome. It is postulated that patients with this disease have an abnormal immunoglobulin response to malaria because they lack effective T suppressor cells. This defect may be genetically determined, thus explaining the tribal and familial aggregation of the disease. Hypermacroglobulinaemia is associated with the formation of large amounts of high-molecular-weight immune complexes. These complexes are important in the pathogenesis of the clinical features of the syndrome.


Rational choice of penicillins and cephalosporins based on parallel in-vitro and in-vivo tests. Because of the unavailability of strictly comparable data, seven representative penicillins and the five cephalosporins currently used in Britain were evaluated in parallel, both in vitro and in vivo. Penicillin sensitive and resistant strains of Staphylococcus aureus and Proteus mirabilis were the main test organisms. Minimum bacteriocidal concentrations of cloxacillin, flucloxacillin, cephalothin, and cephazolin in serum were much higher than conventional minimum inhibitory concentrations in the absence of serum. Cephalexin and cephradine showed the smallest divergence in these values. Staph, aureus beta-lactamase caused least damage to methicillin and cephradine, whereas enzymes from Escherichia, Klebsiella, and Bacillus cereus had least effect against cephradine followed by cephalexin. In mouse protection experiments, highly protein-bound antibiotics had relatively low efficacy. Cephradine had the highest mean activity followed closely by cephaloridine and cephalexin. From the data, cephradine was the cephalosporin of choice, and firm decisions were also made about the choice of penicillins.


The management of stillbirth: coping with an unreality. With about 1 stillbirth occurring in every 80 deliveries, stillbirth is a common tragedy. Yet it is an event which, by common consent, is cloaked in secrecy, and which by its very nature seems unreal. There are thus strong forces operating on the bereaved mother and her family, and on the professionals who care for them, to keep the crisis of stillbirth hidden away, therby in fact hindering the mourning and healing process. Bourne has produced statistical evidence to show that family docotrs are astonishingly reluctant to know or remember anything about the patient who has had a stillbirth. I would like to put forward some suggestions for helping doctors to overcome their reluctance to face the problem of stillbirth.


"Anabolic" effects of methandienone in men undergoing athletic training. After failure to confirm an anabolic action of testosterone and its derivatives in rats, methandienone ('Dianabol', an "anabolic steroid" used by athletes) has been given to 11 athletic men during a course of weight-training, in a double-blind, crossover experiment. The dose of methandienone was 100 mg/day for 6 wk. Body weight and composition, muscular strength and performance, and indices of endocrine function were studied. Compared with the placebo period, on methandienone the subjects gained weight (mean 3-3 kg +/- 0-6 kg) and accumulated a disproportionately large amount of potassium (420+/-68 mmol); the increase in weight was confined to the lean part of the body, and the muscles increased in size. Strength and performance improved over each training period, but not significantly differently on drug and placebo. On the drug, plasma-cortisol concentration and urinary cortisol excretion increased, and plasma-testosterone decreased. Although the weight and body-composition changes may demonstrate an anabolic action of methandienone in man, they may alternatively have been caused by an increase in intracellular fluid, and the question of anabolic action therefore remains open.


Cardiopulmonary resuscitation by lay people. The survival-rate in 75 of 631 patients with cardiac arrest in whom resuscitation was started outside hospital by lay people was 36%. Only 8% survived when attempts at resuscitation were delayed until the arrival of an ambulance team which included an anaesthetist and a specially trained nurse. These data show the importance of anoxia-time (time from cessation of circulation to initiation of resuscitation) to the chances of survival after resuscitation) to the chances of survival after resuscitation, and support the idea that lay people should be taught and encourage to perform cardiopulmonary resuscitation.


Drug-induced encephalopathy in patients on maintenance haemodialysis. In five patients who had been on chronic maintenance haemodialysis for more than eight months a syndrome involving altered consciousness, asterixis, and abnormal electroencephalogram developed after they had been given flurazepam and diazepam. All five patients were adequately treated by haemodialysis. Hepatic, pulmonary, and cardiac decompensation were not present. The encephalopathy and other abnormalities cleared when the drugs were withdrawn. Symptoms were also produced by accidental rechallenge.


Parasites and asthma in Tanzanian children. It has been claimed that parasitic infestation suppresses the development of asthma. Eight Tanzanian schoolchildren in whom asthma was confirmed by the demonstration of exercise-induced bronchospasm were found in an ascaris-endemic area of rural Tanzania. Faecal parasites were found equally commonly in the children with asthma and the ninety-seven non-asthmatic controls. The prevalence of asthma (3.3%) in the school under study was comparable with that found in developed countries.


HLA genotyping by using spermatozoa: evidence for haploid gene expression. Serologically defined HLA-A and HLA-B antigens are expressed in a haploid manner on the surface of spermatozoa. This enabled the HLA-genotypes of four men to be determined by using sperm. This technique will mean that the HLA genotype of potential male graft recipients and others can be determined more easily and even when families are not available. These findings also provide strong evidence that some cell products are encoded by a haploid genome.


Extra-amniotic prostaglandin E2 and the unfavourable cervix. A small dose of prostaglandin E2 suspended in a viscous medium was instilled as a single application into the extra-amniotic space of patients with unfavourable induction features the day before planned induction in an attempt to improve the condition of the cervix. Two groups of 15 patients were studied, one receiving prostaglandin E2 250 mug suspended in methyl ethyl cellulose ('Tylose') 6% solution, and the other tylose alone. Cervical status did not change in those receiving tylose alone, whereas a significant improvement occurred in 14 out of 15 patients receiving the prostaglandin. Labour began before formal induction in 1 patient receiving tylose and in 8 receiving prostaglandin.


Hypophosphataemia: A complication of "innocuous dextrose-saline". Plasma and urinary phosphate levels were studied before and after operation in 13 patients undergoing uncomplicated major surgery. The maintenance intravenous fluid in six patients was 0.9% saline and in the other seven patients it was 4% dextrose with 0.18% saline. Although the plasma-phosphate fell in both groups, reaching minimum on the second postoperative day and then returning towards normal, it was significantly lower in the group receiving dextrose on the second, third, and fourth postoperative days when the levels were below the normal range. It is suggested that when dextrose-saline solutions are indicated in postoperative patients the addition of phosphate to the solution should be considered.


Bone-mineral estimation by computer-assisted transverse axial tomography. The technique of computer-assisted transverse axial tomography has been exploited by minor modification of an E.M.I. brain scanner to determine measurements of bone-mineral content in distal radius and ulna. Such measurements are possible independent of adipose tissue subcutaneously or within the bone and irrespective of bony contour. Preliminary studies suggest that the accuracy and precision justify further longitudinal studies in the exploration of trabecular bone within vertebral bodies by whole-body computer-assisted tomography.


Necrotising enterocolitis of the newborn--is it gas-gangrene of the bowel? Necrotising enterocolitis (N.E.C.) of the newborn is thought to be caused by ischaemia of the bowel. This would favour the conversion of clostridial spores, which can occur very early in the intestinal tract of newborns, to toxin-producing, invading bacilli. The histology of resected gut specimens from 6 of 7 N.E.C. patients who had undergone operation was similar to that in cases of gas-gangrene of the bowel and that in experimentally provoked pneumatosis cystoides intestinalis. In one case Clostridium perfringens type A was cultured in great number by anaerobic technique. The clostridia in these cases may have played an important role in the development of N.E.C.


Cot death and the third branchial arch.

Cot death and the third branchial arch. Congenital anomalies of the parathyroids in cases of cot death have been reported by several workers. Carotid-body hypoplasia also has been noted in typical cases of cot death. Neurally conditioned airway occlusion at the oropharyngeal level has been postulated as a precipitating factor of cot death. All these lines of evidence involve structures derived from the third branchial arch, and it is suggested that developmental arrest of this arch in early gestation may be the pathandemical basis of cot death.


Patterns of antenatal care, perinatal mortality, and birth-weight in three consultant obstetric units. Patterns of antenatal care in three selected consultant units in Britain have been analysed. The study shows that antenatal care operates differently in the three hospitals. Pregnancies resulting in perinatal deaths may not always receive appropriate obstetric care. Patients appear to be at an advantage if they receive consultant-unit care at some stage of their pregnancy.


Alcoholism amongst male doctors in Scotland. An investigation was carried out into first admissions to, and all discharges from Scottish psychiatric inpatient beds of male doctors and other social class I males who had a primary diagnosis of alcoholism. The rates were more than two-and-a-half times higher amongst doctors. Middle-aged doctors were particularly at risk, and 58% of all psychiatric hospitalisations of male doctors between the ages of 45 and 54 years were attributed to alcoholism.


Fetal outcome in trial of antihypertensive treatment in pregnancy. 242 women completed a controlled trial of methyldopa ('Aldomet') for moderate hypertension in pregnancy. Active treatment was associated with a significantly improved fetal outcome, due in part to a reduced number of mid-pregnancy abortions. There were 9 pregnancy losses in the control group, which included 4 mid-pregnancy abortions, and 1 fetal loss in the treated group. The birthweight and maturity of viable infants were similar in treated and control groups, and a detailed multivariate analysis confirmed that hypotensive treatment had no effect on fetal growth in utero. The better outcome associated with treatment was not due to the prevention of pre-eclampsia, and may be partly due to a direct or indirect effect of methyldopa on uterine activity. Methyldopa is safe to use for the treatment of hypertension in pregnancy in the context of close medical and obstetric supervision.


Modification of chronic hepatitis-B virus infection in chimpanzees by administration of an interferon inducer. Chimpanzees chronically infected with hepatitis-B virus showed transient changes in several markers of infection when treated with the interferon inducer polyriboinosinic-polyribocytidylic acid-poly-l-lysine carboxymethyl cellulose. Serum Dane-particle-associated D.N.A. polymerase, e antigen and hepatitis-B surface antigen, and intrahepatic hepatitis-B surface and core antigens diminished during treatment. Defective (D.N.A.-polymerase-negative) Dane particles increased in titre transiently during treatment; these may play a role in the modulation of hepatitis-B virus infection. Humoral immune responses in chronic hepatitis-B carrier chimps were unaffected. Interferon inducers (or exogenous interferon) may be useful for the treatment of chronic hepatitis-B virus infection.


Transmissible agents from human sarcoid and Crohn's disease tissues. Mice were inoculated with human sarcoid tissue homogenates or with a first or a second passage homogenate of mouse tissue (including 0.2 mum membrane filtrates) originating from the inoculation of human sarcoid, Crohn's disease, or control tissue homogenates. Epithelioid and giant cell granulomas were present in the footpads and/or viscera of some of the mice given homogenates originating from each sarcoid or Crohn's disease tissue 15 months after inoculation but were not present in mice given control homogenates. Among mice given homogenates originating from human sarcoidosis, granulomas were present in many organs and tissues; in contrast, a pattern of selective dissemination of visceral granulomas was found among mice given homogenates originating from Crohn's disease. This differential distribution of visceral granulomas also followed the inoculation of 0.2 mum membrane filtrates. Granulomatous responses at Kveim test sites in the ear 9-17 months after inoculation of homogenatesoriginating from human sarcoidosis or Crohn's disease were confined to mice showing granulomas in footpads of viscera. The ability of the transmissible agents to induce granulomas in mice was destroyed when sarcoid or Crohn's tissues were autoclaved or when sarcoid homogenates were stored at -20degreesC for 1 week or exposed to 60Co irradiation (2.5 MR).


HLA antigens and atopic features in steroid-responsive nephrotic syndrome of childhood. Atopic systems were more common in children with steroid-responsive nephrotic syndrome (S.R.N.S.) than in matched controls, and HLA-B12 was more common in children with S.R.N.S. than in adult controls. Atopic symptoms (particularly hayfever), positive prick tests with grass pollen antigens, and a higher mean serum concentration of IgE antibody to timothy grass pollen were more common in nephrotic children with HLA-B12 than in those without HLA-B12. There was also an increased frequency of the haplotype HLA-A1 and HLA-B8, mainly among the non-atopic patients.


Acute leukaemia after immunosuppressive therapy. Three cases of acute myeloid leukaemia developing after treatment of renal disease with cyclophosphamide have been studied. None of the cases was complicated by additional treatment with irradiation or other cytotoxic agents, or by a pre-existing malignancy. Marrow aplasia as a cause of the leukaemia was ruled out. It is suggested that the immunosuppressive action of cyclophosphamide could predispose to the development of malignancy in two ways: malignant clones of cells could emerge and multiply or oncogenic viruses could invade the cells or escape from immunological control and cause induction and development of malignancy.


An integrated view of the metabolic and genetic basis for obesity. The propensity to obesity in animals and man identifies those individuals who are genetically favoured to survive when food supplies are scarce. Obese subjects are limited in their ability to produce heat, either in a cold environment or after food, because of a reduced activity in skeletal muscle of a "futile" cycle in glucose metabolism. The impaired thermogenesis reduces the maintenance requirement for energy in the pre-obese individual so that a "normal" energy intake can only be balanced by excessive exercise or the expansion of adipocytes. The basal metabolic rate rises as obesity develops and compensates for the impaired thermogenic mechanism.


Mortality and morbidity in Jamaican adults with sickle-cell trait and with normal haemoglobin followed up for twelve years. An epidemiological survey of adults aged 35--64 years living in a rural area of Jamaica was started in 1962--63 and continued until 1975. Information was available on 856 subjects with AA and 119 subjects with AS haemoglobin genotypes. The mortality-rates over 12 or 13 years and the number of clinic attendances in 10 years did not differ significantly between subjects with AA and those with AS haemoglobin. The patterns of disease as well as the life expectancy of the two groups appeared to be the same.


Temporary hypothyroidism after surgical treatment of thyrotoxicosis. Mild clinical hypothyroidism associated with low levels of serum total thyroxine (T4) and tri-iodothyronine (T3) and raised levels of serum thyroid-stimulating hormone (T.S.H.) has been observed in 14 of 40 patients (35%) in the early months after a subtotal thyroidectomy for thyrotoxicosis under cover of propranolol. In 10 of the patients, however, the hypothyroidism was temporary and at 6 months after operation the thyroid hormone levels were normal and the serum T.S.H. levels had fallen. In 4 of the patients in whom clinical and biochemical evidence of hypothyroidism persisted 6 months postoperatively, long-term T4 replacement therapy was instituted. It is concluded that the diagnosis of permanent hypothyroidism should not be made with confidence before 6 months have elapsed after operation and that the incidence of hypothyroidism following the surgical treatment of thyrotoxicosis may have been overestimated in the past.


Amine metabolism and the small bowel in uraemia. Intestinal intubation was carried out in 21 subjects: 9 with end-stage renal failure, 2 with early renal insufficiency, 7 untreated patients with blind-loop syndrome, and 3 normal volunteers. All 9 patients with uraemia had significantly raised duodenal dimethylamine (D.M.A.) concentrations compared with the other groups tested. Alteration of the intestinal bacterial flora with antibiotics markedly reduced serum D.M.A. and trimethylamine concentrations and modified the symptoms. Potentially toxic metabolites in the small bowel might have significant nutritional and toxic sequelae in uraemia and these findings suggest that current therapeutic approaches to the treatment of end-stage kidney disease should be re-examined in relation to bowel flora.


Mucus antibodies in pulmonary tuberculosis and chronic obstructive lung disease. An indirect immunofluorescence technique and an indirect immunoperoxidase technique were used on cryostat sections of human group-O submaxillary salivary gland and rat stomach. Circulating antibodies reacting with mucus antigen(s) were found in sera from 52-7% of patients with active pulmonary tuberculosis and in 21-8% of patients with chronic obstructive lung disease. Among hospital patients with other diseases and healthy controls, mucus antibodies were found in 7-2 and 5.4% respectively. The mucus antibodies were not absorbed by an excess of red blood-cells derived from group AD+ healthy subjects or from the rat donor of the stomach, while the fluorescence and the immunoperoxidase reactions were almost completely abolished after the absorption of positive sera with human dried bronchial secretion. It is postulated that mucus antibody may be a new and important serological marker of disorders accompanied by mucus accumulation in the lung and possibly other organs and/or by severe changes of the anatomical structures which act as a barrier to the reabsorption of abnormal amounts of mucus.


Hypoglycaemic effect of liposome-entrapped insulin administered intragastrically into rats. The possibility of using liposomes as intragastric carriers of insulin was investigated in normal and diabetic rats. 1-3 units of insulin entrapped in dipalmitoylphosphatidylcholine cholesterol liposomes administered to normal rats decreased blood-glucose levels in 4 h to about 77% of those before treatment. Higher doses (4-2 and 8-4 units) extended this effect over 24 h. 1-0 units of insulin entrapped in the same liposomes had an even more pronounced effect in diabetic rats--levels of blood-glucose were reduced to 57% of pretreatment values after 4 h. Insulin entrapped in egg phosphatidylcholine/cholesterol liposomes was less effective. The effectiveness of liposome-entrapped insulin was similar in diabetic rats whether administered intragastrically or intraperitoneally but free insulin was more effective intraperitoneally. Radioimmunoassay of insulin in the serum confirmed that lowering of blood-glucose after the intragastric administration of liposome-entrapped insulin was related to the entry of at least some of the insulin into the circulation.


Pregnancy hepatitis in Libya.

Pregnancy hepatitis in Libya. The death-rate from hepatitis in pregnant women in Libya is high. Of 922 hepatitis patients treated during 1975, 377 were males and 545 were females. The case fatality-rate was 0.53% for males and 7-67% for females. In 293 pregnant women it was 12-97% compared with 1-6% in 252 non-pregnant women. In pregnant women deaths occurred mainly in the last trimester. Although 18-4% of the male patients and 15-2% of the women were hepatitis B surface antigen (HBsAg) positive, no patient shown to be antigen-positive died. The frequency of hepatitis in the second half of the year fell both in pregnant women and in the general population, suggesting a warning hepatitis-A epidemic. The exact cause of the high mortality in pregnant women is not clear, but it may have a nutritional basis.


Oral methionine in the treatment of severe paracetamol (Acetaminophen) overdose. 30 patients at risk of hepatic damage from paracetamol (acetaminophen) ingestion were given 2-5 g oral methionine every four hours up to a total dose of 10 g. The first dose was given within ten hours of the overdose. There were no deaths and no reports of hepatic encephalopathy or other complications. In 21 patients plasma aspartate-aminotransferase remained within normal limits. These results suggest that methionine may be effective in reducing the frequency and severity of paracetamol-induced liver damage and may provide an effective non-toxic alternative to cysteamine.


Integrated concentrations of catecholamines in phaeochromocytoma. The measurement of integrated concentrations of catecholamines has been made possible by a new blood-sampling system. Information about the behaviour of phaeochromocytomas obtained in three patients suffering from this condition suggests that catecholamine crises are caused by active synthesis of hormones, rather than release from a stored pool.


The neurology of vitamin B12 deficiency. Metabolic mechanisms. The widely held view that the neurological and haematological complications of vitamin-B12 deficiency have different metabolic mechanisms appears unsound. It is suggested that the metabolic mechanisms involved are similar and that the neurological manifestations are the result of a secondary disturbance in folate metabolism as has already been postulated for the megaloblastosis.


Measuring partial thromboplastin-time. An international collaborative study. A series of collaborative exercises on the partial thromboplastin-time (P.T.T.) test, involving over three hundred hospital centres in Britain and overseas, were performed in 1975. Lyophilised test plasmas were issued from the World Health Organisation Collaborating Centre for Anticoagulant Control Reagents to participants, together with a standardised reference P.T.T. reagent and a standard technique. Hospitals were asked to test the plasma samples with the standardised reagent and technique in parallel with their customary local P.T.T. reagent and method. The overall success-rate in detecting the intrinsic clotting abnormality in the eight abnormal test samples was higher with the standardised reagent and technique than with all other reagents. Furthermore, fewer hospitals obtained false positive results when the normal plasma sample was tested with the standardised method rather than with their usual routine reagents. An index was used to measure the success-rate of the P.T.T. reagents in correctly identifying the test plasmas as normal or abnormal. The eight test plasmas showed a varying degree of abnormality. A system of "weighting" was therefore introduced as the failure of a P.T.T. method to detect more severe defects was regarded as more serious. Although hospitals were unfamiliar with the standardised method, the results established its superiority over all other P.T.T. reagents included in the trials in sufficient numbers for analysis. Failures with commercial reagents may have been caused by insensitivity of the cephalin extracts or the unreliability of the manufacturers recommended techniques. Since the same laboratories obtained good results with the standardised method technical failure can be excluded.