Cytidine deaminase in rheumatoid arthritis

Cytidine deaminase (CD) is an cytoplasmic enzyme found in high concentrations in polymorphonuclear leucocytes (polymorphs). In rheumatoid arthritis (RA) huge numbers of polymorphs are attracted to inflamed joints where they lyse releasing their contents into synovial fluid. The thesis describes a series of experiments designed to test the hypothesis that, in RA, CD drains from synovial fluid to blood where serum levels represent an integrated measure of 'acute' inflammation. An assay was established and evaluated. Studies of CD in joint tissues and body fluids showed that serum levels of CD were raised in RA patients with a gradient running from synovial polymorphs to synovial fluid, across the synovium to blood. The mean synovial fluid CD level was very close to the value predicted using a mathematical model of synovial fluid solute kinetics. Studies of a variety of other enzymes and a selective inhibitor of CD supported the joint polymorph as the source of origin for serum CD in RA. Clinical evaluation revealed a small diurnal variation in serum CD in RA patients probably related to exercise increasing lymphatic drainage from joints. Serum CD was shown to correlate cross-sectionally and longitudinally with other clinical and biochemical measures of joint inflammation in RA, and levels were able to detect the flare produced by the withdrawal of non-steroidal anti-inflammatory drugs from RA patients. The results were discussed according to the principles of measurement theory. In conclusion, serum CD is a simple, cheap, reproducible and sensitive measure of joint inflammation in RA that reflects polymorph lysis known to be at the centre of the inflammatory process. It supplies the clinician with a serological tool for patient monitoring which is a direct assessment of one aspect of inflammation

An investigation into folate deficiency in healthy underprivileged infants with special emphasis on the interpretation of the Figlu test after oral histidine

In South Africa, as: in other countries with a large underprivileged population group, the problem of malnutrition and its- associations and complications assumes considerable importance. Until the socioeconomic problems involved are solved, attention must be directed to early diagnosis, treatment and prophylaxis of malnutrition and its associations. At the Red Cross Children's Hospital, Cape Town, a considerable percentage of admissions are for marasmus and kwashiorkor. Anemia is a frequent association, (Walt, I.959) sometimes contributing to the mortality (Walt, Holman and Naidoo, 1957)

A study of non infective jaundice in pregnancy

INTRODUCTION: Pregnancy with jaundice is considered as high risk pregnancy. Jaundice affects a small percentage of pregnant women, yet it takes a major toll on health of both mother and fetus especially in developing countries like India. It complicates 3-5% of pregnancies and is one of the important causes of maternal and neonatal morbidity and mortality worldwide. Throughout the pregnancy there exists alteration in normal physiological and hormonal profiles. Incidence of jaundice in pregnancy is 0.4-0.9/1000 in India. It could be peculiar to the pregnancy such as acute fatty liver of pregnancy, recurrent cholestatic jaundice in pregnancy and jaundice complicating preeclampsia of pregnancy. It can be concurrent with pregnancy such as due to infective pathology like viral hepatitis and also due to preeclampsia, HELLP, Acute fatty liver in pregnancy, intrahepatic cholestasis in pregnancy, hyperemesis gravidorum, Wilson disease, cirrhosis with portal hypertension or it could be due to drugs administered during pregnancy. The present study analyses the cause of the disease, altered liver function, maternal and fetal morbidity and mortality and preventive measures in jaundice complicating pregnancy. This study will be helpful in better understanding and improving the maternal and perinatal outcome in jaundice complicating pregnancy. AIM OF THE STUDY: 1. Studying the incidence of non infective jaundice in pregnant women in this tertiary care centre. 2. To enumerate the various causes of non infective jaundice in pregnancy. 3. To follow the course of the disease and the numerous complications it Ensues. 4. To form a preplanned algorithm of investigations to diagnose non infective jaundice in pregnancy. 5. To study the best protocol for the management of non infective jaundice in pregnancy. 6. To follow maternal and fetal outcomes in non infective jaundice in pregnancy. MATERIALS AND METHODS: The study was a single institution prospective randomized study conducted in Madurai Medical College over a period of six months. A total of 40 patients were included in the study. All the patients were thoroughly examined and case sheets were written in the same fashion to facilitate comparison. All of them underwent clinical examination and an algorithm of investigations required to approach the diagnosis of non infective jaundice. The patients were subjected to various forms of treatment available in the tertiary care centre. The protocol was approved by the Ethical Review Board of the institute and an informed consent was obtained from all patients. The patients were followed through the course of the disease taking into account the complications of the disease, the management protocols including the obstetric management and blood product transfusion, the maternal and fetal outcomes and the recovery time. The maternal outcome was derived from the rate of complications, ICU stay, recovery interval and maternal mortality. The fetal outcome was studied by the number of live births, NICU admission and perinatal mortality. The patients were followed up for the duration of hospital stay and the recovery time was recorded. PARTICIPANTS: The patients were selected from those attending the obstetric department at the hospital with no specific limitation imposed on age and gestational age. All the patients were diagnosed to have jaundice clinically with the exclusion criteria being infective hepatitis in pregnancy. METHODS: All the patients satisfying the inclusion criteria were carefully evaluated in terms of clinical examination, recording of BP, obstetric examination, laboratory investigations including Hb, platelet, urine albumin, clotting time, renal function test, liver function test, serum uric acid, LDH, viral markers, ultrasonogram. CONCLUSION: HELLP constitutes most of the causes of non infective jaundice, it leads to increased maternal morbidity than mortality. Hence mortality is preventable with early diagnosis. Higher blood pressure reading showed higher risk of complications. Higher bilirubin values and altered LFT were more prone for severe manifestations of the disease. Advanced maternal age at gestation are higher risk of complication. Cirrhosis with portal hypertension was found to be the cause of maternal mortality among all causes of non infective jaundice in a tertiary care centre. Early intervention and delivery of the fetus within 24hrs reduces the incidence of complications and improved prognosis and reduce delivery recovery time. Patients presented with lower BP recovered earlier Preterm babies of affected mothers ran a higher risk of complications

Aspects of structure-activity relationships and physiology of gastrin and related peptides

When, in 1973, I embarked upon this study, the hormone gastrin seemed a suitable hormone to study with regard to investigation of structure-activity relationships and physiology of a peptide hormone. Gastrin was best known at that stage as a linear peptide comprising 17 amino acids, which was stable at room temperature and was resistant to degradation by vigorous treatments such as boiling {Gregory and Tracy, 1964; Berson and Yalow, 1971; Yalow and Berson, 1972) and pH extremes (Piszkiewicz, 1974). Such a molecule could thus be studied at room temperature, using conventional biochemical techniques, without the need for any special precautions to preserve its integrity

Studies on Fascioliasis with special reference to Fasciola Gigantica in East Africa

Following a general introduction, the extensive literature on fascioliasis is reviewed. The distribution, importance, pathogenesis and pathology of the disease are considered, with special emphasis on Fasciola gigantica infections.Field studies are reported on the epidemiology and control of F. ßiganti.ca in East Africa and a survey described of infections with Fasciola spp. in African wild mammals. This survey was undertaken in order to assess the importance of wild mammals in the epidemiology of this disease, in view of the increasing development of game parks and ranching schemes.The techniques used in the experimental studies are outlined with emphasis on those modified during this work. The techniques described include the cultural methods by which the infective agents were obtained, with special reference to the large scale production of metacercariae of F. gigantica and a detailed discussion of the problems which had to be overcome before this was possible. Other techniques described include those used in haematological examinations, faecal egg counts, liver function tests, serum enzyme assays and other biochemical studies.The difficulties which had to be overcome to obtain and maintain experimental cattle and sheep free of intercurrent diseases in Kenya are discussed.Observations are described which were made in the course of several experiments using a total of 35 sheep and 46 cattle in Edinburgh and in Kenya.In Edinburgh the experiments comprised studies on the pathogenesis of acute and chronic fascioliasis (Fasciola hepatica) in sheep.In Kenya chronic fascioliasis (F. gigantica) was studied in sheep with special emphasis on the economic importance of this condition. It was found that the infected animals gained weight more slowly than the uninfected controls and that this arose mainly from differences in the amount of body fat.Several experiments were carried out in Kenya on cattle infected with single doses of 500, 1000 or 2000 metacercariae of F. gigantica or with two doses of 500 metacercariae ten weeks apart. The pathogenesis of the disease and the parasitological findings in these animals are described in detail. Other studies described include observations on long term chronic fascioliasis in cattle.The gross pathology of P. giçantica infections in cattle from 2 -51 weeks after infection is also described.The main finding from these studies is that F. gigantica appeared to be less pathogenic for cattle than reported by earlier workers.There was no evidence of an "acquired self- cure" under the conditions of these experiments, which would support the suggestion that resistance to F. sigantica infections in cattle may be merely related to the fibrosity of the liver parenchyma. Further support was found for this suggestion from the study of the leucocyte levels and other observations.Evidence was found that F. gigantica has a relatively short life in cattle.The dissertation ends with a discussion of the results from the experimental infections

A record of research directed towards enhancement of the safety of clinical anaesthesia

Clinical Anaesthesia is an indispensable adjunct to the surgical treatment of disease. It directly affects the lives of a great number of people since every year no fewer than one in every twenty-five persons in the population is required to undergo a procedure which necessitates it. Of itself non-therapeutic, clinical anaesthesia must, above all else. be safe for the patient. Any adverse outcome to clinical anaesthesia and factors relevant to its administration results, at best, in postoperative morbidity for the patient and, at worst, his demise. Identification and examination of the factors and circumstances which have a material influence on the safety of anaesthesia for the patient, provided the motivation for and is the central theme of this collection of research publications which was submitted to the University of Cape Town in fulfilment of the requirements for the award of the Degree of Doctor of Science (Medicine). The publications submitted report the results of forty years of endeavour. In terms of their subject matter, these publications may be broadly grouped into the following five fields of interest: - 1) The Epidemiology of Death Attributable to Anaesthesia. 2) Pharmacogenetic States of concern to the Anaesthetist - a) The Malignant Hyperthermia Myopathy. b) The Acute Porphyrias. 3) The Effects of Anaesthetics on the Liver - Studies of Hepatic Drug Metabolism of relevance to post-Halothane Hepatitis and the hepatotoxicity of anaesthetic agents. b) The treatment of Fulminant Liver Failure. 4) Heat Homeostasis during Anaesthesia - a) Inadvertent Hypothermia during anaesthesia. b) Induced Hypothermia during anaesthesia. 5) Miscellaneous. Within these fields of interest, papers have been grouped in terms of related aspects of the main topic they cover. Editorial comment is included where appropriate. The nature and scope of many of the above investigations was such as to require, for their satisfactory conclusion, collaborative interdisciplinary research combining the endeavours of other clinicians and paramedical scientists. Appropriate recognition of such collaboration has resulted in the multiple authorship registered for many of the publications in this collection