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Biomedical subjects

T Andrews

Publications and source records attributed to T Andrews.

At least 37 records · Page 2Linked to original sources

Doctors and substance misuse: types of doctors, types of problems.

The casenotes of 144 doctors who had received treatment for substance misuse were analysed. There were no differences between general practitioners (n = 61) and hospital doctors (n = 58) in terms of their substance misuse histories or the problems they incurred. Differences emerged between the consultant (n = 24) and the non-consultant (n = 34) grades of hospital doctor. The consultants were older at onset of problematic use (42.6 +/- 8.6 vs. 29.9 +/- 9.8 years); they suffered fewer career problems and misused fewer substances. The most frequent pathways into substance use were personality difficulties (76 subjects, 52.8%) and anxiety or depression (46 subjects, 31.9%). A history of depression (n = 36) was associated with perceived stress at work (p = 0.014), and at home (p = 0.06). Past neurotic disturbances (n = 20) were associated with personality difficulties (p = 0.035), anxiety or depression (p = 0.004), and with an earlier onset of problematic substance use (30.2 +/- 8.3 vs. 36.5 +/- 9.8 years, p = 0.014). Principal components of possible antecedents yielded one major component on which all elements loaded; this was labelled the 'disturbance score'. This score showed a reduction with increasing age of onset of problematic substance use.

Adult↗

Glucocorticoids do not affect the induction of a novel calcium-dependent nitric oxide synthase in rabbit chondrocytes.

Incubation of rabbit articular chondrocytes with interleukin-1 beta caused time-dependent expression of NO synthase, determined as nitrite, after a lag period of 6h. The synthesis of nitrite was concentration-dependent and was inhibited by cycloheximide and NG-monomethyl-L-arginine, but not by dexamethasone or hydrocortisone. The synthesis of NO in the 100,000g supernatant of activated chondrocytes was inhibited by EGTA, but not by the calmodulin inhibitors W-13 or trifluoperazine. The synthesis of NO was half-maximal at approximately 20nM free Ca2+. Endotoxin also induced the expression of this NO synthase. Thus, rabbit articular chondrocytes express a novel inducible NO synthase which is Ca(2+)-dependent, and whose induction is not prevented by glucocorticoids.

Amino Acid Oxidoreductases↗

Recurrent Wiedemann-Beckwith syndrome with inversion of chromosome (11)(p11.2p15.5).

A baby with Wiedemann-Beckwith syndrome (WBS) and her phenotypically normal mother carried the same paracentric inversion, inv(11)(p11.2 15.5), in the short arm of chromosome 11. A fetus, sib of the affected baby, had the same inversion and ultrasound scan showed exomphalos. The maternal grandmother is clinically and cytogenetically normal. The pattern of affection in this family is consistent with the suggestion that WBS can be caused by lack of a maternally imprinted gene at 11p15.5, and that in this family the inversion disrupts that gene.

Beckwith-Wiedemann Syndrome↗

De novo ring chromosome 3: a new case with a mild phenotype.

We report an 18 year old female with a de novo ring chromosome 3 found after investigation for short stature. Her karyotype was interpreted as 46,XX, r(3)(p26.2q29). Her phenotype is milder than previously reported cases and illustrates the mild end of the spectrum of the ring chromosome 3 phenotype.

Adolescent↗

Bleeding time prolongation with streptokinase and its reduction with 1-desamino-8-D-arginine vasopressin.

The mechanism by which treatment with thrombolytic agents causes bleeding is not known. Recently, frequency of bleeding events has been shown to correlate with bleeding time, particularly in individuals treated with aspirin. We examined the effects of streptokinase (20,000-60,000 IU/kg) on bleeding time in 40 rabbits pretreated with aspirin, a model for fibrinolytic therapy. We then tested the effects of 1-desamino-8-D-arginine vasopressin (DDAVP) (0.3 microgram/kg), an agent known to reduce bleeding time in a variety of bleeding disorders, in 20 rabbits and compared the results with those of a control group of rabbits receiving normal saline placebo. Aspirin increased the bleeding time from a baseline mean +/- SEM value of 119 +/- 15 to 191 +/- 34 seconds in the control group and from 114 +/- 6 to 188 +/- 18 seconds in the experimental group. The addition of streptokinase increased the bleeding time to 592 +/- 119 seconds in the control group and 810 +/- 114 seconds in the experimental group (p = NS). Subsequent infusion of DDAVP decreased the bleeding time in the experimental group to 302 +/- 29 seconds (p less than 0.01 versus streptokinase) compared with 572 +/- 79 seconds (p = NS versus streptokinase) in the control animals given saline placebo. In a subset of rabbits receiving aspirin and streptokinase (40,000-60,000 IU/kg), samples were obtained for platelet aggregation (n = 16), von Willebrand factor antigen concentration (n = 17), and von Willebrand factor multimer distribution (n = 14). Maximal rates of ADP-induced platelet aggregation were not affected by DDAVP infusion, nor was the plasma concentration of von Willebrand factor antigen, quantified by an immunoradiometric assay, significantly affected by DDAVP infusion. Furthermore, the von Willebrand factor multimer ratio decreased with DDAVP administration. These findings indicate that aspirin and streptokinase combined result in a marked increase in bleeding time that can be reduced by DDAVP. This effect of DDAVP is not accompanied by an increase in platelet aggregation response, plasma von Willebrand factor antigen concentration, or von Willebrand factor multimer ratio.

Animals↗

Pyruvate dehydrogenase activity in osmotically shocked rat brain mitochondria: stimulation by oxaloacetate.

Pyruvate dehydrogenase complex activity (PDHC) measured by CO2 release isotopic assay has generally been much lower than activity measured by the spectrophotometric arylamine acetyltransferase assay (ArAT). Decarboxylation of [1-14C]pyruvate was measured in osmotically shocked rat brain cortical mitochondria. Activity is dependent on the concentration of the substrate pyruvate. Activity of 74.6 units +/- 12.3 SD (n = 22) was observed at 4 mM pyruvate (1 unit = 1 nmol pyruvate decarboxylated/min/mg protein). Activity was dependent on added NAD, CoA, and thiamine pyrophosphate, implying increased mitochondrial permeability after osmotic shock. Freeze/thaw with sonication of the mitochondrial preparation reduced PDHC activity to 11.5 units +/- 3.0 SD (n = 4). Oxaloacetate produced a marked stimulation of activity. The optimal assay contained 3 mM oxaloacetate, and without oxaloacetate activity fell to 15.4 units +/- 9.9 SD (n = 8). These studies highlight the importance of optimal substrate concentrations in the CO2 release isotopic PDHC method. Higher PDHC activity is found with intact mitochondria and thus activity values should be interpreted in the light of the presence or absence of intact mitochondria in individual preparations.

Animals↗

Hypomelanosis of Ito: a manifestation of mosaicism or chimerism.

We describe three patients with the cutaneous manifestations of hypomelanosis of Ito. Two, with unusual abnormalities of their toes, had a mixture of diploid and triploid cells in cultured skin fibroblasts. The published clinical descriptions of hypomelanosis of Ito and diploid-triploid mosaicism are reviewed. Chromosome heteromorphisms, HLA types, and DNA fingerprints were studied in an attempt to elucidate the origin of the disease in our patients. We conclude that hypomelanosis of Ito is a manifestation of a heterogeneous group of disorders, the common factor being the presence of two genetically different cell lines. It can result from chromosomal mosaicism or chimerism, from a postzygotic mutation, or from X inactivation. The risk of recurrence is negligible if the proband is a male; if the proband is female the risk is also low but an X linked mutation must be considered.

Chimera↗

Efficacy of computerized tomography in the preoperative staging of pancreatic carcinoma.

The increasing use of nonoperative methods for the diagnosis and palliative treatment of pancreatic cancer has placed greater emphasis on computerized tomography (CT) in staging of this malignancy. The present study was done to review our experience with CT in staging pancreatic cancer, specifically its efficacy in predicting lesions amenable to curative versus noncurative surgical treatment. Sixty six consecutive patients with pancreatic cancer who were considered potential candidates for surgical resection and who had preoperative CT scans over the 4-year period from 1982 through 1986 were studied. Preoperative CT scans were reviewed by a radiologist without knowledge of patients' surgical management. CT criteria for unresectable disease include hepatic and distant metastasis as well as evidence of locally advanced disease, including peripancreatic fascial extension, extension of tumor to locally contiguous structures, vascular encasement/invasion, and local lymphadenopathy. CT predicted resectability with a sensitivity of 75 per cent and a positive predictive value of 38 per cent. Unresectability was predicted with a sensitivity of 72 per cent and positive predictive value of 93 per cent. CT incorrectly predicted unresectable disease in three patients who had a curative resection. CT was most reliable when it predicted unresectability due to the presence of hepatic and/or distant metastasis. CT predicted unresectability with least sensitivity using criteria for locally advanced disease. Therapeutic decisions for nonoperative management of patients with pancreatic cancer based upon CT predictions of unresectable disease, especially predictions of unresectability solely on the basis of locally advanced disease, can not be recommended at this time.

Adenocarcinoma↗

Nonmedical costs to patients and their families associated with outpatient chemotherapy.

One hundred thirty-nine patients receiving outpatient chemotherapy kept diaries of nonmedical expenses resulting from their disease and its treatment. Diaries were kept for both treatment and nontreatment weeks. Results showed that the mean cost to patients and their families for treatment weeks was $72.81, and for nontreatment weeks it was $45.88. Approximately 45% of these costs were out-of-pocket expenses, and 55% were wages lost. Transportation and food were the largest out-of-pocket expenses. Patients living at greater distance from treatment had higher out-of-pocket costs, and younger patients reported more wages lost. Fourteen percent of the patients were estimated to be spending more than 50% of their weekly incomes on nonmedical expenses, and these patients were found largely in the lower-income categories. A method is proposed for using these data to estimate total nonmedical expenses for different treatment regimens, and also for estimating cancer patients' total nonmedical costs nationally.

Adolescent↗

Cytogenetic studies in spontaneous abortuses.

In a series of 450 products of conception received for cytogenetic analysis, tissue culture was attempted on 309, and karyotypes were established using banding techniques in 154 singleton specimens. Abnormalities of karyotype were identified in 19%; of these abnormalities, 48% were autosomal trisomies. Gestational age was decreased in the abnormal specimens, and their developmental age was retarded by comparison with their gestational age. Factors contributing to the relatively low incidence of abnormality are examined. The major factor appears to be the clinical interest of collaborating staff, leading to selection, either intentional or unintentional, of particular phenotypes and hence a non-random series. A negative relationship is suggested between frequency of monosomy X and autosomal trisomy, both being associated with maternal age.

Abortion, Spontaneous↗

Recombinant chromosome 18 in two offspring of a chromosome 18 inversion heterozygote.

A case of partial trisomy of chromosome 18 due to a recombinant pericentric inversion is described. Prenatal diagnosis in a subsequent pregnancy identified a foetus with the recombinant chromosome 18, and the pregnancy was terminated. A comparison is made between the risks reported in the relevant literature where recombinant offspring have resulted from chromosome 18 inversion heterozygotes and those observed in this case.

Abnormalities, Multiple↗