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Biomedical subjects

P Jacobs

Publications and source records attributed to P Jacobs.

At least 271 records · Page 15Linked to original sources
PubMed1990

BiP expression is not increased by the accumulation of PiZ alpha 1-antitrypsin in the endoplasmic reticulum.

PiZ, a mutant human alpha 1-antitrypsin, is associated with liver and pulmonary disease and is characterized by defective secretion and accumulation of the protein in the endoplasmic reticulum. We tested the hypothesis that BiP (a protein that binds newly synthesized protein in the endoplasmic reticulum, prevents secretion of incorrectly folded protein, and solubilizes protein aggregates), could play a part in the retention of PiZ alpha 1-antitrypsin in the endoplasmic reticulum. Subcellular fractions from PiM (normal) and PiZ livers were prepared and analyzed by immunoblotting. No increase of BiP was detected in the PiZ liver. In addition, when total RNA from the same livers were analyzed by slot and Northern blot hybridization, no difference was found in the level of BiP mRNA between PiM and PiZ livers. Similar results were found in clones of CHO and MDCK cells transfected with PiM of PiZ alpha 1-antitrypsin cDNAs. These results indicate that BiP does not play a part in the retention of PiZ alpha 1-antitrypsin and suggest that PiZ protein is not misfolded.

Animals↗
PubMed1990

Enhanced natural killer cell activity and long survival in acute non-lymphoblastic leukaemia. A case report.

Natural killer (NK) cell activity is capable of mediating an antileukaemic effect. Accordingly this phenomenon was studied during the course of the 13-year disease-free survival of a patient after treatment for acute non-lymphoblastic leukaemia in order to test the hypothesis that concurrent tuberculosis may have induced this cell population and thereby modulated clinical and haematological course of the disease. An unusually high spontaneous cytotoxicity was demonstrated, which may have played a role in the prolonged survival. This latter finding is consistent with the theoretical possibility that chronic inflammation may enhance the activity of this particular cell population and supports the concept that therapeutic modulation of NK activity remains an achievable goal in clinical medicine.

Adolescent↗
PubMed1990

Methyldopa, intravascular haemolysis and renal disease. A case report.

A 74-year-old man, who was receiving methyldopa to control systemic hypertension, presented to hospital in biventricular cardiac failure. He was found to be severely anaemic and jaundiced as a result of acute intravascular haemolysis with prominent haemoglobinuria. The cardiac failure and anaemia were initially refractory to fluid restriction and diuretics, but responded to red cell transfusion. Renal failure supervened, probably on the basis of hypoperfusion as a consequence of diuresis and hypotension. The patient died suddenly, possibly from myocardial infarction. Acute intravascular destruction of red cells in association with methyldopa appears not to have been previously reported.

Acute Kidney Injury↗
PubMed1990

A prospective analysis of prognostic factors in the myelodysplastic syndromes.

In view of the uncertainty regarding the natural history and management of individuals with the myelodysplastic syndromes, a prospective study of 43 consecutive and previously untreated patients was undertaken in order to identify haematological features that could predict for poor prognosis. A significant correlation between percentage of blasts in the bone marrow, maturity index and the number of cell lineages involved was demonstrated with both the risk of leukaemic transformation and survival. It remains to be determined whether further accumulation of data will result in similar predictive values for karyotypic analysis, in vitro bone marrow culture and the species of plasminogen activator secreted by the cells. Since treatment ranges from red cell transfusion and administration of maturation-inducing agents to aggressive cytotoxic chemotherapy or bone marrow transplantation, the development of predictive models, based on relevant prognostic factors, remains the most rational basis for choices between these various options.

Age Factors↗
PubMed1990

Treatment of adult acute lymphoblastic leukaemia.

Eighty-five consecutive patients with acute lymphoblastic leukaemia (ALL), having a median age of 24 years (range 10-69 years), underwent induction and consolidation chemotherapy with weekly parenteral vincristine, Adriamycin, l-asparaginase and daily oral prednisone (VAAP), followed by standard (CNS) prophylaxis. Maintenance therapy was given for 3 years and consisted of daily 6-mercaptopurine, weekly methotrexate and monthly intrathecal therapy, with drug intensification comprising either vincristine, Adriamycin and l-asparaginase (VAA) or cyclophosphamide, vincristine, cytosine arabinoside and prednisone (COAP). Complete remission (CR) was obtained in 59 patients (69%) and only the French-American-British (FAB) L1 morphology was a significant predictive factor (P = 0.048). Twenty-three patients failed to achieve CR and of these 12 had primary drug resistance. Median follow-up is currently 260 weeks, median predicted survival of all patients is 58 weeks and for those who achieved CR it is 104 weeks. Median duration of CR is 70 weeks. Of the prognostic factors for survival, only FAB L1 subtype was significant. Bone marrow relapses occurred in 29 patients, and of these 9 (31%) achieved CR. There has been CNS relapse in two patients and both have died. Eleven patients continue in CR off therapy, with a median of 152 weeks. This regimen is effective, with acceptable toxicity, and a number of patients are potentially cured. The incidence of resistant and relapsing disease is an argument for further intensifying both induction and postinduction therapy.

Adolescent↗
PubMed1990

Leukaemia and transient leukaemia in Down syndrome.

We have reviewed 215 published cases of leukaemia and transient leukaemia in Down syndrome. There is an over-representation of mosaic trisomy 21, possibly the result, at least in part, of a survival effect. The most intriguing observation is a bimodal distribution of maternal age, produced largely because cases with true leukaemia have a significantly higher maternal age than cases with transient leukaemia (33.5 versus 29.5 years). In conjunction with evidence that meiosis I nondisjunction is infrequent in transient leukaemia, this suggests different mechanisms for the etiology of leukaemia and transient leukaemia, and favours a locus predisposing to transient leukaemia proximal to the centromere on the long arm of chromosome 21.

Adolescent↗
PubMed1990

Three different schedules of low-density lipoprotein apheresis compared with plasmapheresis in patients with homozygous familial hypercholesterolemia.

PURPOSE: To determine the biochemical and clinical response of two patients with homozygous familial hypercholesterolemia to three different schedules of low-density lipoprotein apheresis compared with plasmapheresis. PATIENTS AND METHODS: Two female patients aged 17 years, both affected by homozygous familial hypercholesterolemia, underwent low-density lipoprotein apheresis using a dextran-sulfate/cellulose affinity column on successive twice-weekly, weekly, and biweekly schedules. Plasmapheresis was carried out only at biweekly intervals. Plasma lipids and apolipoproteins A1 and B were assayed before and after each procedure. Cardiac status was assessed before and after the study. RESULTS: On schedule 1 of apheresis, the immediate post-procedure low-density lipoprotein cholesterol levels declined to 60 mg/100 dL plasma. Quasi-steady-state values of low-density lipoprotein cholesterol and apolipoprotein B were also markedly reduced, with levels approaching the upper limits of normal for age and sex. This response was attenuated as the intervals between procedures were prolonged. No advantage of low-density lipoprotein apheresis over plasmapheresis was observed during the biweekly protocol except that after plasmapheresis high-density lipoprotein cholesterol levels declined by 50% or more compared with less than 10% after apheresis. The latter procedure, especially on schedules 1 and 2, caused an increase in the quasi-steady-state concentrations of both high-density lipoprotein cholesterol and apolipoprotein A1. Thus, mean low-density lipoprotein cholesterol/high-density lipoprotein cholesterol and apolipoprotein B/apo A1 ratios were reduced by more than three- to four-fold during twice-weekly apheresis. Other laboratory parameters remained stable throughout except for iron and hemoglobin levels, which were reduced with both plasmapheresis and apheresis. Xanthomas regressed significantly in the one patient who had not been treated prior to the current trial. Cardiac changes were minor in both patients. CONCLUSION: Low-density lipoprotein apheresis proved safe and effective on an accelerated protocol as well as during more conventional schedules. Owing to its simplicity, selectivity, and safety, apheresis using a dextran-sulfate/cellulose column is possibly the optimum means currently available for the extracorporeal removal of low-density lipoprotein cholesterol.

Adolescent↗
PubMed1990

Myeloma.

Myeloma is a malignancy of plasma cells that are terminally differentiated B-lymphocytes. The clinical spectrum varies from the incidental discovery of a pathologically raised monoclonal immunoglobulin on routine electrophoresis in asymptomatic patients to widespread skeletal involvement with incapacitating bone pain. Symptoms may result from a solitary tumor mass, described as an extramedullary plasmacytoma, in virtually any part of the body. Metabolic abnormalities commonly include hypercalcemia, elevated plasma urate levels, or the development of amyloidosis, all of which may disturb renal function. High paraprotein levels cause hyperviscosity, resulting in generalized debility and varying degrees of disturbed mental function. The natural history is determined by the mass of the tumor coupled with its unique biologic features. Median survival of unselected patients, without effective treatment but once symptoms are evident, is approximately 7 months; this period can be significantly prolonged with appropriate therapy. As a first step, urgent medical management is often necessary, centering on rehydration, correction of hyperviscosity, and reversal of metabolic defects, each of which may improve renal function. Over the longer term, specific antitumor drugs have extended median survival to approximately 30 months, and most regimens include a combination of melphalan and prednisone, with or without other cytotoxic drugs. Alternative forms of treatment include sequential hemibody irradiation, recombinant alpha interferon, and in suitably selected patients, high-dose chemoradiotherapy followed by bone marrow transplantation. The latter approaches offer promising management options and are currently the subject of evaluation in controlled clinical trials.

Animals↗
PubMed1990

Effect of intraluminal antibiotics on translocation of Candida albicans in burned guinea-pigs.

Guinea-pigs were pretreated orally with various antibiotics and given 3 x 10(10) Candida albicans by gastric lavage followed by a 40 per cent TBSA full skin thickness burn. The mesenteric lymph nodes, liver and spleen were cultured for the presence of viable organisms. Caecal contents were quantitatively cultured for aerobic bacteria and C. albicans. Clindamycin and penicillin G were the greatest promoters of translocation followed by the combination streptomycin/bacitracin. The mechanism for antibiotic-induced translocation is multifactorial centering on intestinal flora, anaerobic spectrum of the antibiotic and host defense as well as microbe virulence. The systemic use of broad-spectrum antibiotics, particularly those with strong anaerobic activity, should not be taken too lightly. A severely immunocompromised patient on this type of therapy may be prone to a severe fungal infection. This study reaffirms the concept that translocation from the gastrointestinal barrier is a potential source of life-threatening nosocomial infection.

Animals↗
PubMed1990

Economic and ethical consideration in the intensive care unit.

Intensive care units (ICUs) sustain life but, in certain cases, this resource becomes a means to prolong dying, with great physical, emotional and financial impact. The cost to care for patients in the ICU is at least three times more than general ward care; thus, ICUs have become one of the largest cost centres in the hospital. Economic pressures require us to be mindful of whom the ICU treats and for how long. Health professionals working in the ICU must critically appraise the ethical basis for their behaviour and actions. In so doing, many are likely to appeal to the patient's right to self-determination and the physician's reliance on the principles of beneficence and non-maleficence as the underpinnings of morality in medicine. One approach is to examine the issues and rights pertinent to an individual case using a circular model. Decisions are based on medical facts and prognosis, a patient's right to self-determination, a patient's best interests and external factors. Health personnel would be compelled to consider all of these issues. Within this framework, prevention or resolution of moral dilemma can take place within the clinical rather than the legal forum.

Adult↗
PubMed1990

National estimates of intensive care utilization and costs: Canada and the United States.

Although ICUs generate attention as consumers of resources, no national data on utilization and costs were available in Canada. U.S. estimates are too old for current comparison. Based on national hospital survey data from Statistics Canada, we calculated the utilization of ICUs in all Canadian general hospitals from 1969 to 1986 and estimated costs for 1986. Using the American Hospital Association's Annual Survey, we estimated comparable trend data from U.S. hospitals for the period of 1979 to 1986, and national ICU costs for 1986. The results demonstrated steady growth in Canadian utilization from 1969 to 1986, with increased ICU patient days (17 to 42 days/1000 population). National costs for 1986 were estimated at $1.03 billion (Canadian), which was roughly 8% of total inpatient costs and 0.2% of Canada's gross national product (GNP). Utilization trend data for the United States showed a rapid increase from 1979 through 1982 with slower growth after that. In the United States, ICU utilization in 1986 was estimated at 108 patient days/1000 population. Total ICU costs were estimated at $33.9 billion (U.S.), which is 20% of all inpatient hospital costs and accounts for 0.8% of the GNP. ICU utilization in the United States is 2.5 times that of Canada.

Canada↗
PubMed1990

Phenotypic expression of the HLA linked iron-loading gene in males over the age of 40 years: a population study using serial serum ferritin estimations.

The frequency of the HLA linked iron-loading gene was assessed in 1783 Afrikaner men over the age of 40 years living in the South Western Cape. Measurements, made on three occasions over a 4.5 year period, included the serum ferritin concentration, a screening test for reduced unsaturated iron-binding capacity and the percentage transferrin saturation. The serum gamma-glutamyl transferase concentration was used as a marker of alcohol abuse. The diagnosis of homozygosity was based on a serum ferritin concentration that was persistently greater than 400 micrograms l-1 and a percentage transferrin saturation greater than 55%. Using these criteria, 17 subjects were diagnosed as homozygous, corresponding to a disease frequency of 0.0095, a gene frequency of 0.0976 and a heterozygote frequency of 0.176 (95% confidence limits: 0.135-0.213). None of the subjects had overt clinical haemochromatosis. Typing for the HLA-A, -B, -C and -DR loci showed that the HLA-A3 allele (frequency 0.6471 and relative risk 4.4) was the only independent marker for the iron-loading gene in this asymptomatic population. Using the present approach it was not possible to distinguish between heterozygotes, alcohol abusers and normal subjects with serum ferritin concentrations at the upper end of the normal range.

Adult↗
PubMed1990

Combination chemotherapy for advanced diffuse large cell lymphoma. The adverse effects of bone marrow invasion, gastrointestinal tract involvement or high bulk disease.

Thirty-nine adults with clinical stage III or IV diffuse large cell lymphoma were prospectively randomised to receive etoposide with doxorubicin (Group 1: n = 17), the same schedule of etoposide with carminomycin (Group 2: n = 8), or BACOP (Group 3: n = 14). The complete remission rates were respectively 24%, 25% and 28%, and further good partial remissions were 41%, 25% and 14%. The incidence of adverse prognostic factors was examined with the first two groups combined for comparison to patients receiving BACOP. The low complete remission rates were attributable to bone marrow invasion in 64% (16/25) of patients in groups 1 and 2, and 64% (9/14) in group 3; to extensive gastrointestinal tract involvement in 24% (6/25) of patients in groups 1 and 2, and 36% (5/14) in group 3; and to high bulk disease in 24% (6/25) of patients in groups 1 and 2, and 36% (5/14) in group 3. Actuarially predicted survival has not been reached for group 1, is 12 months for group 2, and 8 months for group 3; these different trends are not statistically significant. The trial was discontinued when it became clear that there was no difference between the two- and five-drug treatment regimens and that unacceptably low remission rates were obtained in patients having a high incidence of these poor prognostic factors, particularly when compared with results being reported in regimens that contain high or intermediate doses of methotrexate.

Adolescent↗