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Biomedical subjects

P Jacobs

Publications and source records attributed to P Jacobs.

At least 451 records · Page 25Linked to original sources
PubMed1983

Cloning and expression in Escherichia coli of full-length complementary DNA coding for human alpha 1-antitrypsin.

A cDNA library prepared from human liver was screened for alpha 1-antitrypsin, a major constituent of plasma which functions as inhibitor of proteolytic enzymes. The library was screened using a 12-base-long synthetic oligodeoxyribonucleotide corresponding to a known DNA fragment of human alpha 1-antitrypsin and by hybrid-selection of alpha 1-antitrypsin mRNA. A plasmid, pULB1523, was identified carrying a cDNA insert of about 1400 bp coding for human alpha 1-antitrypsin. Restriction mapping and DNA sequence analysis indicated that the 1400 bp code for the signal peptide and for the complete mature alpha 1-antitrypsin molecule. In addition, a solid-phase enzyme-linked immunoassay showed that pULB1523 expresses human alpha 1-antitrypsin in bacteria. Fusion of the alpha 1-antitrypsin sequence to the leader sequence of the beta-lactamase gene (plasmid pKT287) resulted also in the expression of the protein in bacteria.

Base Sequence↗
PubMed1983

The effective plasma concentrations of sulmazol (AR-L 115 BS) on haemodynamics in chronic heart failure.

Sulmazol (AR-L 115 BS) is a new inotropic drug which has arterial and venous vasodilating properties. We used it in seven patients with severe refractory heart failure to determine the effective plasma concentration levels and the most effective bolus dose on haemodynamics. The haemodynamic monitoring included a Swan-Ganz catheter in the pulmonary artery and a radial catheter. Haemodynamic measurements and plasma concentration determinations were performed before sulmazol injection and at 5, 10 and 30 min after a bolus 0.25, 0.50, 0.75 mg/kg. We observed a gradual increase in cardiac index and decrease in pulmonary wedge pressure when plasma concentration levels rose but the beneficial effects were mainly observed for sulmazol plasma concentrations above 1 microgram/ml. A bolus injection of 0.75 mg/kg was effective in all cases: a significant increase of cardiac index (1.9 to 2.5 1 min-1 m-2; P less than 0.001) and a significant decrease in pulmonary wedge pressure (30 to 25 mm Hg; P less than 0.005) and right atrial pressure (13 to 10 mm Hg, P less than 0.01) were observed. In these patients sulmazol improved the severely deteriorated left ventricular function without affecting heart rate and blood pressure.

Aged↗
PubMed1983

Treatment of hypertension in acute stage of myocardial infarction. Haemodynamic effects of labetalol.

Labetalol was used to treat systemic hypertension (systolic blood pressure above 150 mmHg) in 11 patients with acute myocardial infarction; its haemodynamic effects and tolerance were studied. Increasing doses of labetalol were infused to lower systolic blood pressure to less than 130 mmHg; the optimal rate was then maintained for one hour (mean rate: 2.3 mg/min). Haemodynamic variables were measured before, during, and after labetalol infusion. Labetalol lowered blood pressure in all patients; this effect was related to a decrease both in total systemic resistance (17.7 to 14 IU) and in cardiac index (3.1 to 2.7 1/min per m2); the stroke index remained unchanged and the heart rate was reduced (94 to 81 beats/min). There was no significant change in the mean pulmonary wedge pressure; it was decreased, however, in the six patients with an initial pressure greater than 15 mmHg. The double product was greatly decreased (16 497 to 8598 mmHg x beats per min), which is favourable in acute myocardial infarction. We conclude that labetalol is a drug of choice to treat hypertension in acute myocardial infarction because it is very effective; its haemodynamic effects are likely to reduce myocardial oxygen requirements and suggest that labetalol administration does not worsen moderate left sided heart failure. The drug, however, may reduce the cardiac output.

Adolescent↗
PubMed1983

Pathogenesis of the postphlebitic syndrome.

The dependent edema, skin pigmentation, local inflammation associated with subcutaneous fibrosis, chronic ulceration, and current infection are the hallmarks of postphlebitic syndrome. In one fifth of the patients there is no evidence of antecedent deep venous occlusion. Current emphasis is therefore on improvement in investigation and the use of treatment programs designed to return venous patency and valve function to normal. Modern management must also take into account local changes in capillary permeability and fibrinolytic activity in the pathogenesis of the venous ulceration.

Edema↗
PubMed1983

Iron binding proteins of iron-absorbing rat intestinal mucosa.

The distribution and quantitation of the iron-binding proteins of rat small intestinal mucosa was studied, in iron-deficient and replete animals, to explore their role in the absorption of iron. Adsorption (mucosal uptake) of iron in in situ ligated loops of small intestinal mucosa was found to be uniform throughout the length of the small intestine whereas absorption (carcass uptake) showed a steep decreasing gradient from the duodenum to the ileum. The disrupted, in vivo labeled mucosal cells were fractionated by isopycnic centrifugation and transferrin and ferritin were quantitated by radioimmunoassay. Transferrin derived from mucosal cells was shown to have a higher affinity for the antibody than transferrin in serum. Of the transferrin present in the mucosal extract, only a portion could be accounted for by contamination from the serum; the proteolysis resistant and intrinsic transferrin may be mucosal cell specific. Transferrin was found in similar amounts in all regions of the small intestine, was not affected by iron loading but doubled in response to iron deficiency. Mucosal ferritin was found in greater amounts in the iron-absorbing areas of the intestine, increased in the duodenum of iron-loaded animals, and decreased in iron-deficient animals. The incorporation of newly absorbed radioiron into ferritin was only found in iron absorbing regions and was completely inhibited by colchicine and cytochalasin-B, suggesting that ferritin was loaded with iron at the point of iron absorption and that the process is associated with vesicle movement and not simple diffusion. Transferrin and ferritin-specific immunoabsorption and also gel filtration established that no other soluble iron binding proteins were involved in absorption.

Animals↗
PubMed1983

Hemodynamic and clinical response to three-day infusion of sulmazol (AR-L 115 BS) in severe congestive heart failure.

Sulmazol (AR-L 115 BS) is a new positively inotropic drug with arterial and venous vasodilating properties. We studied the effects of sulmazol (three-day infusion) on clinical tolerance, hemodynamics, and blood gas levels in ten patients with severe chronic heart failure. The hemodynamic monitoring included a Swan-Ganz catheter in the pulmonary artery and a radial catheter. Blood gas levels were determined on samples of arterial and mixed venous blood. After 24 hours of infusion, there was a significant increase in cardiac index (2 to 2.5 L/min/sq m; p less than 0.005) and a significant decrease in pulmonary wedge pressure (28 to 19 mm Hg; p less than 0.001) and in right atrial pressure (7 to 4 mm Hg; p less than 0.001) without significant changes in heart rate and systolic blood pressure. These beneficial effects lasted during the three days of infusion. Oxygen delivery was significantly increased (350 to 443 ml/min/sq m; p less than 0.005) without significant change in arterial oxygen tension. The side effects included nausea, vomiting, anorexia, and mild thrombocytopenia. We conclude that sulmazol is a potent drug which may improve severely deteriorated left and right ventricular function in patients with chronic refractory heart failure without affecting the heart rate and the systolic blood pressure.

Aged↗
PubMed1983

Economic evaluation of corporate medical programs.

The cost of corporate medical programs is receiving increasing attention in times of financial austerity. This article reviews the published data on economic evaluations of such programs. It develops a framework within which profitability and cost-effectiveness can be assessed. Critical evaluation of the available data confirms the probable cost benefit of preemployment examinations, and absenteeism and alcohol abuse control programs. It is noted that the data are limited to a small and unrepresentative sample of industry.

Absenteeism↗
PubMed1983

The effects of dexamethasone and tetradecanoyl phorbol acetate on plasminogen activator release by human acute myeloid leukemia cells.

This investigation was undertaken to examine the extent to which leukemic cell functions are susceptible to regulation in vitro and to investigate their heterogeneity in this regard. Since plasminogen activator release is known to be a modulatable cellular function that can be influenced by antiinflammatory steroids and tetradecanoyl phorbol acetate (TPA), the effect of these two compounds on the secretion of urokinase- or tissue-type enzymes by leukemic cells was studied. The release of both enzyme species could be stimulated or suppressed by these substances by mechanisms that were inhibitable by actinomycin-D and hence required transcription of new mRNA. Plasminogen activator release by cells from 41/45 patients with AML was either stimulated or inhibited by 10(-7) M dexamethasone, implying that most AML cells possess glucocorticoid receptors. In 26/45 cases, the enzyme was inhibited by this steroid to less than 25% of control values. Pronounced inhibition of this degree was not encountered with normal polymorphonuclear leukocytes. Plasminogen activator secretion by AML cells was profoundly inhibited in 20/41 cases by 1 ng/ml TPA and stimulated in 8/41 cases. Leukemic blasts varied considerably in their response to dexamethasone and TPA. Plasminogen activator release should prove a sensitive means of monitoring the responses of AML cells to biologically active compounds.

Cell Survival↗
PubMed1983

The secretion of plasminogen activators by human myeloid leukemic cells in vitro.

Peripheral blood cell preparation from 23 normal subjects and 72 patients with acute and 32 patients with chronic myeloid leukemia were cultured in vitro and released plasminogen activators were analyzed. The quantity of plasminogen activator secreted by leukemic cells varied widely and could not be correlated with the clinical severity of the disease. Immunochemical and electrophoretic techniques have been used to show that normal peripheral blood granulocytes released exclusively urokinase-like plasminogen activator, whereas leukemic cells secreted either urokinase or a tissue activator-like enzyme. The molecular species of enzyme released by acute myeloid leukemic cells may serve as a diagnostic marker of relevance to the management of this disease, since patients with acute myeloid leukemia whose cells released only tissue plasminogen activator did not respond to combination chemotherapy. Tissue plasminogen activators released by leukemic cells may display an unusual electrophoretic pattern that resembles that shown by urokinase. Immunochemical procedures are therefore essential for the correct identification of these enzymes.

Cells, Cultured↗
PubMed1982

Reducing the incidence of non-A,non-B post-transfusion hepatitis by testing donor blood for alanine aminotransferase: economic considerations.

Recent studies have established a relation between elevated alanine aminotransferase levels in donor blood and the incidence of non-A, non-B hepatitis in recipients of such blood. Routine testing of donor blood for alanine aminotransferase activity in order to reduce hepatitis is not currently supported, largely because the results of such testing are unknown. We assessed the potential economic benefits of screening donor blood for alanine aminotransferase as a means to reduce post-transfusion hepatitis. Benefits, defined as the expected costs of hepatitis potentially avoided, ranged from $898 to $31,629 per 1000 blood units collected. This wide range reflected lack of information about the natural history of non-A, non-B hepatitis. Costs were defined as the direct costs of testing and the indirect costs associated with loss of blood product, additional donor recruitment, and informing donors of their abnormal aminotransferase levels; costs ranged from $3,151 to $4,003 per 1000 units. Our results suggest that if prospective studies demonstrate that exclusion of blood with elevated aminotransferase levels decreases non-A, non-B hepatitis in recipients, the net economic impact may be positive. However, because of major uncertainties about the medical consequences of non-A, non-B hepatitis, the benefit estimates are so broad that they preclude a definitive policy decision.

Alanine Transaminase↗
PubMed1982

Haematology Grand Rounds. Hairy cell leukaemia masquerading as malignant lymphoma.

Pancytopenia with massive splenomegaly, minimal lymphadenopathy and circulating atypical lymphoid cells with cytoplasmic projections characterize the lymphoproliferative disorder known as hairy cell leukemia, or leukaemic reticulo-endotheliosis. Many of the features of hairy cell leukaemia are shared with a malignant lymphoma of the B-cell type, from which it can be distinguished on a number of criteria, including histological examination of bone marrow, lymph nodes, liver and spleen. Recognition that this syndrome is not homogeneous is important, since in the B-cell tumour the clinical course is progressive, requiring chemotherapy which is usually effective; the disease is indolent in leukaemic reticulo-endotheliosis and drug treatment may actually shorten survival. The patient presented illustrates the ease with which this diagnostic error can arise, and the features separating these two unusual entities are reviewed.

Bone Marrow↗
PubMed1982

Is staging laparotomy necessary in Hodgkin's disease? An analysis of 100 operations.

A series of 100 patients with Hodgkin's disease were submitted to staging laparotomy, without mortality and with negligible morbidity. Thirty-one patients were restaged: 23 had occult intra-abdominal disease and 8 false-positive lymphangiograms. Standardized treatment programmes were tested against our clinical and pathological data to determine whether staging laparotomy would alter therapeutic decisions. Programmes based on clinical staging and employing radical radiotherapy would have encompassed all disease without recourse to laparotomy. In contrast, a more conservative programme which employed mantle field irradiation for clinically localized cervical disease, without laparotomy, would have missed disease in 12% of cases. Patients with supradiaphragmatic nodal Hodgkin's disease should either have prophylactic abdominal irradiation (without laparotomy) or more limited radiotherapy determined by laparotomy (without prophylactic irradiation).

Adolescent↗
PubMed1982

Acyclovir therapy in cutaneous herpes simplex following bone marrow transplantation. A case report.

Herpes simplex virus was demonstrated in rapidly progressing cutaneous lesions 7 days after allogeneic bone marrow transplantation in a 14-year-old girl. Extension of the eruption was not controlled by hyperimmune plasma and transfer factor. In contrast, prompt and complete resolution followed administration of acyclovir. The absence of renal insufficiency or damage to the new graft emphasizes the value of this agent in managing progressive herpes simplex infections in immunocompromised patients.

Acyclovir↗
PubMed1982

Angio-immunoblastic lymphadenopathy.

Two patients presented with a short history of constitutional symptoms including fatigue, weight loss, night sweats and pruritus. Both had hepatosplenomegaly and tender lymphadenopathy, and in each case lymph node biopsy revealed prominent vascularization of the interfollicular zones and the presence of an amorphous eosinophilic fibrillar material, together with many epithelioid histiocytes, immunoblasts and plasma cells. In other areas of the same lymph nodes unequivocal lymphocytic lymphoma was present. The first patient was treated with levamisole, to which there was dramatic response. She subsequently died of septicaemia, and at autopsy was shown to be free of lymphoma. The second patient responded completely to the epipodophyllotoxin VP16-213 and is back at work as a heavy labourer without any residual disease. These 2 cases illustrate that complete clinical remission can be obtained in patients with this disease even after lymphomatous transformation has occurred. Levamisole has the additional attraction of being less immunosuppressive in patients whose immune response is already impaired.

Adult↗