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Biomedical subjects

P Jacobs

Publications and source records attributed to P Jacobs.

At least 433 records · Page 24Linked to original sources

Dobutamine effects on blood gases and hemodynamics in acute myocardial infarction with heart failure.

We studied the effects of dobutamine on blood gases, venous admixture and hemodynamics in ten patients suffering an acute myocardial infarction (AMI) with left heart failure. After one hour infusion of dobutamine (mean dose: 6.3 micrograms/kg X min) there was an increase in cardiac index (27%, P less than 0.005), and a decrease in pulmonary wedge pressure (13%, P less than 0.025) and right atrial pressure (25%, P less than 0.025). The increase in oxygen delivery (23%, P less than 0.005) and mixed venous oxygen tension (10%, P less than 0.01) were neither accompanied by significant change in low arterial oxygen tension nor in high venous admixture. We conclude that dobutamine improves hemodynamics and oxygen delivery in AMI without affecting existant intrapulmonary shunting.

Aged↗

Oral iron therapy in human subjects, comparative absorption between ferrous salts and iron polymaltose.

Iron absorption was directly compared between equivalent doses of ferrous salts and a polymaltose complex using a twin-isotope technique in which each individual acts as his own control. In the first study, bioavailability of iron from ferrous sulfate and the complex was defined at physiologic doses of 5 mg (Group 1: n = 14) and therapeutic doses of 50 mg (Group 2: n = 13). In Group 1, mean absorption from salt was 47.77% (SD 14.58%) and from polymaltose, 46.56% SD 17.07%). In Group 2, mean absorption from salt was 32.92% (SD 13.42%) and from polymaltose, 27.07% (SD 6.50%). In a second study, 100 mg of iron in a chewable formulation was used to compare absorption between equal doses of ferrous fumarate and the polymaltose complex. Mean absorption from salt was 10.25% (SD 6.89%) and from polymaltose 10.68% (SD 4.68%). At all three dosage levels, iron is equally available from salt or polymaltose for hemoglobin synthesis (p greater than 0.20), and absorption negatively correlated with plasma ferritin (p less than 0.01). These two materials may be used interchangeably in the treatment of patients with absolute iron deficiency.

Absorption↗

Rapidly fatal bronchiolitis obliterans with circulating antinuclear and rheumatoid factors.

A 57-year-old woman developed severe bronchiolitis obliterans and presented circulating antinuclear and rheumatoid factors without any evidence of connective tissue disease. The evolution was rapidly fatal despite corticosteroid therapy and immunosuppressive treatment. The post-mortem study disclosed no connective tissue disease lesions. We suggest that the serologic abnormalities could be secondary to the inflammation of the bronchioles.

Antibodies, Antinuclear↗

Mechanism of acute anthracycline cardiotoxicity in isolated rat hearts: carminomycin versus daunomycin.

Cardiotoxicity limits the use of anthracyclines which are potent anticancer agents. In the isolated rat heart, we investigated the mechanism of acute anthracycline cardiotoxicity and compared a new anthracycline, carminomycin, with daunomycin which is in established use. Daunomycin 1.75 X 10(-5) M produced a fall in cardiac output (36 +/- 2 versus 58 +/- 1 ml/min; p less than 0.01), left ventricular power production (9 +/- 0.7 versus 16 +/- 0.3 mJ/sec/g; p less than 0.01), and efficiency of heart work (3.3 +/- 0.2 versus 6.3 +/- 0.2 mJ/sec/ml O2; p less than 0.01; mean +/- S.E. 40 min after daunomycin). Carminomycin (1.75 X 10(-5) M) produced a greater fall in cardiac output than equimolar daunomycin (26 +/- 2 versus 36 +/- 2 ml/min; p less than 0.01). Daunomycin did not reduce coronary flow rate, heart rate, or oxygen consumption. From the preceding data, we inferred that, since afterload and preload were constant in this model, heart failure was due to a depressed inotropic state. Procedures that increased cytosolic calcium relieved heart failure namely, pretreatment with digoxin (62.4 micrograms), isoproterenol (10(-6) M), and increased perfusate Ca2+ (5 mM versus 2.5 mM) all prevented carminomycin-induced fall in cardiac output (41 +/- 1, 47 +/- 5, and 52 +/- 1, respectively, versus 26 +/- 2 ml/min; p less than 0.01). Acute anthracycline contractile failure was also associated with a fall in high-energy phosphate compounds which could also have contributed to the decreased inotropic state. We conclude that carminomycin is more cardiotoxic than daunomycin in equimolar concentrations and that a lowered cytosolic calcium and decreased energy stores might cause the contractile failure. The cytosolic calcium and high-energy phosphate compounds were lowered by separate mechanisms.

Animals↗

Gaucher's disease in the black population of South Africa. A case report.

The diagnosis of the non-neuropathic form of Gaucher's disease was confirmed by haematological and enzymatic investigations in a Black girl. The aetiological relationship of this condition with Gaucher's disease in other populations is uncertain, but lack of expression of the enzyme defect in the white blood cells in our patient might be significant in this context. This case serves to emphasize that Gaucher's disease enters into the differential diagnosis of unexplained splenomegaly, irrespective of the ethnic background of the affected person.

Adolescent↗

Epsilon-aminocaproic acid-induced myopathy. A case report.

The prolonged administration of epsilon-aminocaproic acid (EACA) resulted in the development of severe proximal myopathy associated with high plasma creatine kinase values, rhabdomyolysis, myoglobinuria, and mild hyperbilirubinaemia. Withdrawal of the drug led to spontaneous resolution of the clinical and biochemical syndrome. Structural and enzyme studies of a biopsy specimen of the involved skeletal muscle supported the presence of subclinical myopathy. The mechanism whereby EACA produces its toxicity in muscle may in part be due to inhibition of cathepsin D, but the possibility that other proteases are involved has not been excluded. The fact that this clinical syndrome is rare despite the widespread use of EACA may be because it only occurs in subjects with a subclinical skeletal muscle disorder which is unmasked by the drug.

Adult↗

Trephine biopsy of the bone marrow.

We present a review of trephine biopsy of the bone marrow based on an experience of approximately 10 000 examinations. It is our view that, in adults, examination of material obtained by aspiration combined with a trephine biopsy allows for the most thorough morphological assessment of the marrow. Morbidity is limited to transient discomfort to the patient, and even bilateral procedures are conveniently performed on outpatients. There is no absolute contraindication to combining aspiration and trephine biopsy, but in severe bleeding disorders due to acquired or congenital coagulation factor deficiencies replacement therapy is indicated and the patient should be observed in hospital for 24 hours following the procedure. Thrombocytopenia is not associated with significant bleeding from the biopsy site in our experience. The advantages of the trephine biopsy are that it allows better overall assessment of cellularity and morphology and is indispensable in cases where aspiration has failed or where infiltration due to the myeloproliferative syndrome or to haematological and non-haematological malignancies has occurred. With marrow hypoplasia and granulomatous disorders involving the marrow, the trephine biopsy is indispensable for diagnosis.

Biopsy, Needle↗

Jaundice following bone marrow transplantation. The problem of diagnosis.

Jaundice presented a major diagnostic and therapeutic problem in 6 out of 20 patients undergoing allogeneic bone marrow transplantation for severe acute aplastic anaemia or leukaemia in relapse. In the first 2 cases histological features of graft-versus-host disease were demonstrable in the skin but absent in the liver. In the 3rd case B-virus hepatitis was the most likely diagnosis, in the 4th cumulative cytotoxic chemotherapy was incriminated, and in the last 2 cases the jaundice was obstructive. These 6 cases illustrate the varied causation of jaundice in patients undergoing bone marrow transplantation, and emphasize that correct diagnosis is essential for rational management.

Adolescent↗

Diagnostic value of trephine biopsy in bone disease.

A clinical diagnosis of myeloma was made in a 44-year-old woman with anaemia, a markedly raised erythrocyte sedimentation rate, osteolytic lesions in the pelvis, and a pathological fracture of the femur. Confirmatory trephine biopsy showed, instead of plasma cell infiltration, destruction of the normal micro-anatomy of the marrow with bridging fibrosis, gross osteoclastic proliferation, and areas of new bone formation. These are the features of hyperparathyroidism. Subsequently, a solitary adenoma of the parathyroid glands was demonstrated and resected. This case illustrates the value of examination of the trabeculae in trephine biopsy specimens in the diagnosis of bone disease.

Adult↗

The antithrombic drugs in clinical practice.

The rational use of antithrombic drugs centres on the fundamental differences in the pathogenesis of arterial or venous thrombosis. The major role of platelets in the development of occlusion in arteries contrasts with prominent fibrin deposition in the slower moving venous blood. Logically, antiplatelet agents are used to treat patients at high risk from arterial disease and anticoagulants for those with venous thrombo-embolism. These sound theoretical principles have been linked to steady improvement in diagnostic techniques, and there now exists an extensive literature on available drugs and their clinical evaluation. It is therefore surprising how little agreement exists on the practical use of the antithrombic drugs. In patients with coronary artery disease, secondary prevention of myocardial infarction is favourably influenced by administration of aspirin, dipyridamole or sulphinpyrazone. However, differences are not statistically significant so that confident recommendations for their use cannot yet be made. In mitral valve disease, anticoagulants are effective in reducing systemic thrombo-embolism; in patients with cardiac prostheses, dipyridamole should be added. In the cerebral circulation, vertebrobasilar and carotid ischaemia need to be distinguished and suitable lesions surgically corrected. Patients not undergoing endarterectomy are divided into two groups. In those with symptoms stable for more than 3 months, aspirin alone is sufficient; patients with recent deterioration or a shorter history are best treated with conventional anticoagulants followed by the addition of aspirin. In venous thrombo-embolic disease, heparin prophylaxis should be combined with reversal of identifiable risk factors. In treating the acute event, anticoagulation, with or without preceding thrombolytic therapy, is preferred. In addition, the clinician must select an antithrombic regimen o take into account the possibility of drug interaction, the need for and feasibility of laboratory monitoring, and the total number of medicines prescribed for the patient. Failure to restrict tablets to manageable numbers will lead to poor compliance and unpredictable therapeutic response.

Anticoagulants↗

Chronic granulocytic leukaemia. A 10-year experience in the Black, Coloured and White populations of the south-western Cape Province.

In a 10-year retrospective analysis of 92 patients in the stable phase of chronic granulocytic leukaemia, the three major race groups (White, Coloured and Black) in the south-western Cape were compared. There were consistent differences in respect of age, sex distribution, and the presence of the Philadelphia chromosome. Despite these differences the clinical presentation, haematological features, response to treatment and survival rates did not vary significantly.

Adolescent↗

Large-cell lymphocytic lymphoma.

Progress in the treatment of large-cell lymphocytic lymphoma during the last decade has been such that cure has replaced palliation as the objective of treatment. In pathologically proven stage I or II disease appropriate radiotherapy is adequate. It is of major importance to recognize that even in stage III or IV disease cure is possible, and it is therefore in the patient's best interests that initial assessment take into account the morphological and immunobiological features of the tumour as well as other prognostic factors, and that a chemotherapeutic regimen of established efficacy be prescribed. Newer challenges are a need to define optimum chemotherapy and explore the roles of bone marrow transplantation and immunological manipulation of the tumour with monoclonal antibodies.

Humans↗

Molecular cloning of human haptoglobin cDNA: evidence for a single mRNA coding for alpha 2 and beta chains.

Human haptoglobin (Hp) is a plasma glycoprotein composed of alpha and beta polypeptide chains that are covalently associated by disulfide bonds. It had been suggested that alpha and beta polypeptides could be synthesized via a common precursor polypeptide. We report the molecular cloning of DNA complementary to human Hp mRNA. One of the clones, pULB1148, carries a full length copy coding for both alpha 2 and beta polypeptides. In vitro translation of human liver mRNA hybridizing with this cDNA gives a protein mol. wt. of 49000 daltons. The sequence of the alpha 2 beta cDNA shows the presence of a single Arg residue between Gln 142 of the alpha 2 chain and Ileu 1 of the beta chain. With a few minor exceptions, the DNA sequence fits the previously published amino acid sequences. The differences are the presence of an Asp residue at position 52 of alpha 2 instead of Asn, the existence in beta of only one Lys residue between Gly 65 and the following Gln, the presence of Ser and Cys at positions 218-219 instead of Cys-Ser, and of Asp residues at positions 205 and 235 instead of Asn.

Amino Acid Sequence↗

Body weight, static and dynamic skinfold thickness in small premature infants during the first month of life.

The growth of prematurely born infants is different from the growth of fetuses of the same age remaining in utero. This is in part due to changes in body composition that occur after birth. In search for a practical and reliable method to assess the growth of small prematures, we analyzed data obtained in two anthropometric studies that included 180 premature infants of 750-1750 g weight at birth, and we studied the relationships between weight, static skinfold thickness (SSFT) and dynamic skinfold thickness (delta SFT, i.e. the percentage of change in skinfold thickness between 15 and 60 s after application of the Harpenden caliper). The results show that the SSFT increases steadily after birth in spite of a significant decrease in weight and delta SFT. Whether it contains fat or not, the fold of the skin is increasing in thickness at a time when by weight alone, one would have considered that there was no growth. The nutritional implication of this finding remains to be studied. Serial correlations of measures obtained at each period indicate that weight and SSFT have a good correlation to same measures in subsequent weeks (P less than 0.01). delta SFT, however, showed only a weak correlation (P = 0.05). The delta SFT follows the general pattern of known changes in total body water, but it is not accurate enough to determine changes in individual infants; further studies are thus needed to find a practical method to evaluate changes of body composition and its relevance in the measurement of growth of premature infants.

Body Composition↗