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Biomedical subjects

J Thompson

Publications and source records attributed to J Thompson.

At least 613 records · Page 34Linked to original sources

Metabolic changes in the non-insulin-dependent diabetic undergoing minor surgery: effect of glucose-insulin-potassium infusion.

We have compared the metabolic response to minor surgery in the non-insulin dependent diabetic patient with that in the non-diabetic, using transurethral surgery under general anaesthesia as a model. Preoperative blood glucose and 3-hydroxybutyrate concentrations were higher in the diabetic patients, but the response to surgery did not differ. The postoperative cortisol response was lower in the diabetic patients. Glucose insulin potassium infusion (GIK) resulted in lower plasma nonesterified fatty acid, and blood 3-hydroxybutyrate and glycerol concentrations, with markedly higher serum insulin levels compared to patients managed with a 'no insulin' regimen. Blood glucose however was not significantly different except at 2 h postoperatively. Blood metabolite and serum insulin concentrations in the diabetic patients were closer to those in non-diabetic patients in the group not given insulin, than in those given GIK. Rather than rendering the diabetic patient the same as the non-diabetic, GIK produces a further abnormal state which is probably of little benefit. We conclude that there is no indication for the use of insulin in the well or moderately well-controlled non-insulin dependent diabetic patient undergoing minor surgery, provided that glucose containing fluids are not given.

Aged↗

A 133-xenon inhalation system for cerebral blood-flow measurements in ventilated premature babies.

We constructed a Xenon-133 inhalation and trapping system in order to measure cerebral blood flow of ventilated premature babies by means of the noninvasive 133Xe clearance method. The completely lead-shielded inhalation device is a closed system driven by the baby's own respirator and can thus be safely used at the patients bedside in the intensive care unit. Reproducible proximal airway concentrations of 133Xe (with or without leaks around the endotracheal tube) were obtained by in vitro simulation.

Cerebrovascular Circulation↗

Osteoporosis in hypogonadal men: role of decreased plasma 1,25-dihydroxyvitamin D, calcium malabsorption, and low bone formation.

To investigate the pathogenesis of osteoporosis in male hypogonadism we have investigated a heterogeneous group of 13 men with hypogonadism: 7 men (median age 60, range 31-79) with two or more vertebral crush fractures and 6 men (median age 61.5, range 28-76) without vertebral fractures. The group with crush fractures had trabecular and cortical osteoporosis as assessed by Singh grade, iliac crest trabecular bone volume, and metacarpal cortical area/total area. This was accompanied by an altered trabecular architecture with a reduction in number of trabeculae but no change in trabecular width, which contrasts with age-related bone loss in men where there is no reduction in trabecular number but thinning of trabeculae. The fracture group had significantly lower plasma 1,25-dihydroxyvitamin D [1,25(OH)2D] concentrations than the nonfracture group, and this was associated with malabsorption of calcium. Irrespective of the presence or absence of osteoporosis, treatment with testosterone led to a significant increase in total and free plasma 1,25(OH)2D and an improvement in calcium absorption measured with radiocalcium and by balance techniques. In addition, urine biochemistry, metabolic balance studies, and bone biopsy suggest that skeletal retention of calcium and bone formation are increased by testosterone treatment. We conclude that male hypogonadism causes both cortical and trabecular osteoporosis and altered trabecular architecture. A major risk factor for the development of osteoporosis is reduction in plasma 1,25(OH)2D, leading to malabsorption of calcium and reduced bone formation.

Adult↗

Esters and lactones of phenolic amino carboxylic acids: prodrugs for iron chelation.

The new iron chelator N,N'-bis(2-hydroxyphenyl)ethylenediamine-N,N'-diacetic acid (1), its dilactone 2, N,N'-bis(2-hydroxybenzyl)-2-hydroxypropylene-1,3-diamine-N,N'- diacetic acid (3), and its methyl ester lactone 4 and a series of esters of N,N'-bis(2-hydroxybenzyl)ethylenediamine-N,N'-diacetic acid (5) were prepared and their iron chelating efficacy and toxicity determined by using the hypertransfused mouse model of iron overload. The biological activities were compared with results obtained with use of the hypertransfused rat. Esterification enhanced the oral iron chelating activity but also increased toxicity. The diisopropyl ester of 5 exhibited the highest therapeutic index. In vitro measurements showed that the rate of ester hydrolysis at pH 7.5 increased by a factor of 10(4) in the presence of 5 X 10(-4) M ferric ion, which may account for the utility of esters and lactones as prodrugs. Seventeen other chelating agents were screened but showed no intraperitoneal or oral activity.

Animals↗

N5-(1-carboxyethyl)-ornithine, a new amino acid from the intracellular pool of Streptococcus lactis.

Intracellular concentrations of amino acids were determined in cells of Streptococcus lactis 133 during growth in complex, spent, and chemically defined media. Glutamic and aspartic acids represented the major constituents of the amino acid pool. However, organisms grown in spent medium or in defined medium supplemented with ornithine also contained unusually high levels of two additional amino acids. One of these amino acids was ornithine. The second compound exhibited properties of a neutral amino acid by coelution with valine from the amino acid analyzer. The compound did not, however, comigrate with valine or any other standard amino acid by two-dimensional thin-layer chromatography. The unknown amino acid was purified by paper and thin-layer chromatography, and its molecular structure was determined by 1H and 13C nuclear magnetic resonance spectroscopy. This new amino acid was shown to be N5-(1-carboxyethyl)-ornithine. The 14C-labeled compound was formed by cells of S. lactis 133 during growth in spent medium or defined medium containing [14C]ornithine. Formation of the derivative by resting cells required ornithine and the presence of a metabolizable sugar. N5-(1-Carboxyethyl)-ornithine was synthesized chemically from both poly-S-ornithine and (2S)-N2-carbobenzyloxy-ornithine as a 1:1 mixture of two diastereomers. The physical and chemical properties of the amino acid purified from S. lactis 133 were identical to those of one of the synthetic diastereomers. The bis-N-trifluoroacetyl-di-n-butyl esters of the natural and synthetic compounds generated identical gas chromatography-mass spectrometry spectra. A mechanism is suggested for the in vivo synthesis of N5-(1-carboxyethyl)-ornithine, and the possible functions of this new amino acid are discussed.

Gas Chromatography-Mass Spectrometry↗

Acute myelocytic leukemia with acute aortic occlusion as presenting symptom.

In a 42-year-old Caucasian female, acute myelocytic leukemia (M2) presented as occlusion of the distal aorta and right iliac artery. She died after 10 days of respiratory failure. At postmortem examination the aortic wall contained multiple thrombi composed of fibrin and leukemic cells. There was no evidence of diffuse intravascular coagulation. Thromboplastic activity of the blast cells could have played a role in the formation of thrombi in the large vessels of this patient.

Acute Disease↗

Correlation of nasopharyngeal and conjunctival cultures with middle ear fluid cultures in otitis media. A prospective study.

Eighty children with acute otitis media (AOM) were prospectively studied to determine the correlation and clinical usefulness of nasopharyngeal (NP), conjunctival (CONJ), and middle ear fluid (MEF) cultures. NP cultures correlated more accurately with MEF (p less than 0.01) than did CONJ cultures (p less than 0.05) for both Streptococcus pneumoniae and Haemophilus influenzae (H. flu). The positive predictive value of NP cultures for positive MEF was only 47%, but the negative predictive value was 87 percent. NP cultures, therefore, appear to have significant predictive clinical value only when negative in identifying children likely to have sterile MEF. High correlation of NP, CONJ, and MEF in children with H. flu conjunctivitis (p less than 0.01) suggests that early systemic rather than topical antibiotic treatment for H. flu conjunctivitis in small children may avert subsequent occurrence of the "conjunctivitis-otitis" syndrome.

Administration, Oral↗

Alpha-2 interferon therapy of hairy-cell leukemia: a multicenter study of 64 patients.

Sixty-four patients with hairy-cell leukemia (HCL) (61 had undergone prior splenectomy) were treated with alpha-2 interferon (Intron A, Schering Corp, Kenilworth, NJ) subcutaneously three times per week at a dosage of 2 X 10(6) U/m2. Three patients (5%) demonstrated a complete response (CR) with apparent eradication of hairy cells from the bone marrow, 45 patients (70%) showed a partial response (PR) defined as normalization of all three blood counts associated with decreased involvement in the bone marrow, and nine patients (14%) showed a minor response that included improvement in at least one blood count. Three patients had no response, three patients died before completing 1 month of therapy, and one patient refused further therapy after 1 month of therapy. The median platelet count returned to normal by the second month of treatment. The median hemoglobin returned to greater than 12 mg/dL by the fourth month of treatment, and the median granulocyte count to greater than 1,500/mu by the fifth month of treatment. Bone marrow biopsy analysis during interferon therapy demonstrated a decrease in median hairy-cell index by more than half. Transfusion of both RBCs and platelets were decreased within 4 months of initiating treatment. Serious infections, which averaged four per month in 16 of the 64 patients before interferon therapy, were rarely observed after the first month of treatment. Treatment-induced toxicity was mild, consisting primarily of influenza-like symptoms, fatigue, and minor skin disorders. Alpha-2 interferon therapy is highly effective in reversing the course of progressive HCL and should be considered the treatment of choice for a minimum of 12 months in patients who have progressive disease post-splenectomy.

Adult↗

Indices of injury. Development and status.

Each of the indices of injury provides a systematic method by which to collect and report data about the trauma victim. Since the 1960s, researchers and physicians have tried to develop predictive tools which are capable of evaluating the current status of the victim as well as determining morbidity and mortality. This article traces the development of indices of injury and provides their current status.

Adolescent↗

Alpha-2-interferon/melphalan/prednisone in previously untreated patients with multiple myeloma: a phase I-II trial.

Alpha-2-interferon (IFN) has demonstrable activity in advanced, relapsing, or refractory multiple myeloma. Because of the in vitro synergism between the IFNs and cytotoxic agents, we conducted a trial of 30 previously untreated patients with multiple myeloma utilizing various doses of alpha-2-IFN in combination with standard oral doses of melphalan and prednisone. The combination was well-tolerated without unusual or unexpected toxic effects. The limiting toxicity included dose-related myelosuppression, and alpha-2-IFN induced flu-like symptoms and fatigue. Response was seen in at least as many patients as would be expected with melphalan and prednisone alone. The maximal tolerated dose for a phase II-III trial was 5.0 X 10(6) IU/m2 of alpha-2-IFN in combination with standard doses of melphalan and prednisone. Future trials should utilize this dose of alpha-2-IFN with dose de-escalation according to tolerance.

Adult↗

Involvement of the central nervous system by non-Hodgkin's lymphoma in adults. A review of 36 cases.

Thirty-six (10.1 per cent) of a total of 355 adult patients with non-Hodgkin's lymphoma seen over a seven and a half year period developed compression or infiltration of the central nervous system (CNS). In nine patients (2.5 per cent) extradural tumour masses compressed the spinal cord or brain. Five of these patients, all previously untreated, responded well to treatment, with excellent recovery of CNS function and survival in the long term. The prognosis for the four patients with advancing drug-resistant systemic disease at the time of CNS compression was poor. In 27 patients (7.6 per cent) a clinical or cytological diagnosis of meningeal infiltration was made (on cerebrospinal fluid). Meningeal disease was seen most frequently in patients with high-grade lymphoma, either at presentation or during subsequent progression of systemic disease. All of these patients have died of systemic and/or CNS disease less than 20 (median 3) months from diagnosis of meningeal disease. Meningeal infiltration represents a significant clinical problem for which new approaches to prophylaxis and treatment are required.

Adolescent↗

Detection of B-cell lymphoma in peripheral blood by DNA hybridisation.

As an alternative to morphological identification of circulating neoplastic lymphocytes in the blood of patients with non-Hodgkin's lymphoma, DNA of peripheral blood lymphocytes was analysed for clonal immunoglobulin gene rearrangements in 29 patients with low-grade B-cell lymphomas. 76% of the patients showed clonal rearrangements of immunoglobulin genes in their blood, including 58% of those with no other evidence of disease. In seven patients from whom paired samples were available the rearranged bands found in the blood and in lymph-node biopsy specimens containing histologically confirmed lymphoma were identical. Detection of circulating lymphoma cells by use of tumour-specific anti-idiotype antibodies and cytofluorimetry showed complete agreement with the results of DNA analysis.

B-Lymphocytes↗

Evidence for the early prenatal development of cortical cholinergic afferents from the nucleus of Meynert in the human foetus.

A combined histochemical and biochemical approach has shown that the cholinergic system in the nucleus of Meynert region of the substantia innominata is well defined both histochemically and neurochemically within the first 3 months of gestation in the human foetus. Thus, at between 12 and 22 weeks of development the most intense acetylcholinesterase (AChE) histochemical reactivity was observed in the neuropil, cell bodies and processes in the nucleus of Meynert. AChE-stained fibres were observed which coursed from the nucleus of Meynert towards the cortical mantle and within the mantle AChE-stained fibres were also present. Micropunch samples from within the nucleus of Meynert contained higher levels of choline acetyltransferase (ChAT) activity than any other area examined including the striatum, while in the cortical mantle the level of ChAT activity was comparable to that found in the adult cerebral cortex. These observations suggest that the cholinergic innervation from the nucleus of Meynert--considered to be the major source of cholinergic afferents in the adult cerebral cortex--may play a key role in the early development of the human neocortex.

Acetylcholinesterase↗

Epidemic of prosthetic valve endocarditis caused by Staphylococcus epidermidis.

In an epidemic of prosthetic valve endocarditis caused by Staphylococcus epidermidis the surgeon was found to be the source of contamination. The probable route was accidental puncture of gloves during operation. During the epidemiological investigation a second cluster of patients contaminated with Staph epidermidis during open heart surgery was found also related to one surgeon. This strain caused no detectable signs or symptoms of infection. Carriage of virulent staph epidermidis has rarely been recognised as a hazard but may have serious consequences.

Carrier State↗

Effect of probenecid on the disposition of captopril and captopril dimer in the rat.

The urinary excretion of captopril has been studied in a bladder-cannulated rat model and compared with that obtained after co-administration with probenecid. Probenecid reduced significantly the urinary excretion of captopril from 41% to 21% of the administered dose over a 3-hr period and significantly lowered urine flow rates. In addition, the effect of probenecid on plasma levels of captopril and total captopril (captopril plus disulfides) after oral administration of the disulfide prodrug captopril dimer (10 mg/kg) has been studied in a conscious rat preparation. Co-administration of probenecid (20 mg/kg) given either orally or intravenously increased both the plasma levels of captopril and total captopril (captopril plus captopril disulfides) over a 4-hr period. A prolonged significant inhibition of plasma ACE after co-administration of probenecid and captopril dimer suggests that probenecid may be useful to prolong the action of captopril or the prodrug captopril dimer.

Animals↗