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Biomedical subjects

H White

Publications and source records attributed to H White.

At least 19 recordsLinked to original sources
PubMed1992

The risk of stroke in patients with acute myocardial infarction after thrombolytic and antithrombotic treatment. Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto Miocardico II (GISSI-2), and The International Study Group.

BACKGROUND: Many trials in patients with acute myocardial infarction have demonstrated that thrombolytic therapy is not associated with an excessive risk of stroke, as compared with conventional treatment. However, the incidence of various forms of stroke in patients treated with different thrombolytic and antithrombotic regimens and the associated effect of risk factors for stroke are largely unknown. METHODS: Strokes occurring in patients hospitalized with acute myocardial infarction who were enrolled in either of two large trials were analyzed. The patients were randomly assigned to receive streptokinase (1.5 million units) or recombinant tissue plasminogen activator (t-PA) (100 mg) and also randomly assigned to receive subcutaneous heparin or no heparin. Ninety-one percent of the patients also received aspirin. RESULTS: Complete data were available on 20,768 patients. A total of 236 (1.14 percent) had strokes in the hospital; 0.36 percent had hemorrhagic strokes, 0.48 percent ischemic strokes, and 0.30 percent strokes of undefined cause. Patients treated with t-PA had a small but significant excess of stroke as compared with those who received streptokinase (1.33 vs. 0.94 percent; adjusted odds ratio, 1.42; 95 percent confidence interval, 1.09 to 1.84). The administration of subcutaneous heparin in addition to a thrombolytic agent did not increase the risk of stroke (risk with heparin, 1.13 percent; without heparin, 1.14 percent). Older age, a higher Killip class, and the occurrence of anterior infarction significantly increased the risk of stroke, whereas a higher body-mass index or a history of hypertension, diabetes, or smoking did not. CONCLUSIONS: Patients with acute myocardial infarction who receive thrombolytic therapy have a small risk of stroke. Treatment with t-PA as compared with streptokinase resulted in a small but significant excess of stroke. Subcutaneous heparin, given together with t-PA or streptokinase and aspirin, did not result in an increased risk of stroke.

Aged↗
PubMed1992

The role of tungstate and/or molybdate in the formation of aldehyde oxidoreductase in Clostridium thermoaceticum and other acetogens; immunological distances of such enzymes.

Besides Clostridium thermoaceticum and C. formicoaceticum other resting acetogenic clostridia such as C. aceticum and C. thermoautotrophicum and to a lesser extent non-clostridial acetogens such as Butyribacterium methylotrophicum and Eubacterium limosum were able to reduce propionate to propanol at the expense of carbon monoxide or formate. Methylviologen usually increased the reduction rate. Ten microM molybdate in the growth medium decreased this capability for C. thermoaceticum but increased it or had no effect for the other organisms. Ten microM tungstate in the growth medium increased the aldehyde oxidoreductase activity in all organisms. Crude extracts of C. thermoaceticum cells grown in the presence of 10 microM or 1 mM molybdate showed by ELISA the same or even a 4 fold concentration of aldehyde oxidoreductase in the latter case. However, the enzymic activity was very low in both cases. Omission of dithionite in the growth medium diminished the antigen by a factor of about 8. The immunological distance between the enzyme from C. thermoaceticum and C. thermoautotrophicum was rather low but very large to C. formicoaceticum and undeterminably large to the other organisms.

Aldehyde Oxidoreductases↗
PubMed1992

Confronting the issues of patient safety and investigator conflict of interest in an international clinical trial of myocardial reperfusion. Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries (GUSTO) Steering Committee.

The Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries (GUSTO) trial is a large scale international trial of new myocardial reperfusion strategies. The primary hypothesis is that early and sustained coronary artery recanalization will be associated with a significant reduction in mortality. The four regimens that are being tested are 1) streptokinase with subcutaneous heparin; 2) streptokinase with intravenous heparin; 3) accelerated recombinant tissue-type plasminogen activator (rt-PA) with intravenous heparin; and 4) combination streptokinase, rt-PA and intravenous heparin. The planned recruitment of 41,600 patients in 1,500 sites from 15 countries is expected to be completed by December 1992 and will enable detection of a 15% reduction or 1% absolute difference in mortality compared with that associated with standard therapy (streptokinase and subcutaneous heparin). In designing the trial, two important issues were directly addressed. First, a strategy was developed to provide assurance of patient safety during large scale investigational use of an aggressive thrombolytic regimen. This includes fascimile transmission of a one-page safety summary form to the Data Coordinating Center within 24 h of death or discharge, acceptance of the concept of "net clinical benefit" and close surveillance of the trial's progress by the independent Data and Safety Monitoring Committee. Second, to avoid potential conflict of interest beyond elimination of any position of financial equity, the Steering Committee unanimously voted to prohibit any honoraria for speaking engagements, payment for consultancy or travel or reimbursement of any kind from any of the five corporate sponsors until 1 year after publication of the results. Incorporation of these approaches may facilitate the design of future large scale randomized trials in cardiovascular medicine.

Biomedical Research↗
PubMed1992

Estimates of the frequency of chromosome abnormalities detectable in unselected newborns using moderate levels of banding.

Data on structural chromosome abnormalities identified during prenatal diagnosis were used to estimate the number of such abnormalities that would be detectable in an unselected series of newborns using moderate levels of banding (400 to 500 bands). These estimates were compared with the rates detected in nonbanded surveys of newborns. Between 1976 and 1990 prenatal diagnosis using banding techniques was carried out in our laboratory on 14,677 women aged 35 and over. Among these, we detected 112 structural rearrangements, 32 unbalanced and 80 balanced. These figures were adjusted by two methods to give an estimate of the frequency of structural abnormalities in the newborn. Our data suggest that the use of moderate levels of banding increases the frequency of unbalanced structural abnormalities from 0.052 to 0.061% and of balanced structural abnormalities from 0.212 to 0.522%. Thus, the total number of chromosome abnormalities detectable in the newborn is increased from 0.60% in unbanded preparations to 0.92% in banded preparations.

Adult↗
PubMed1992

The tungsten-containing aldehyde oxidoreductase from Clostridium thermoaceticum and its complex with a viologen-accepting NADPH oxidoreductase.

Purification of aldehyde oxidoreductase from C. thermoaceticum, the first detected enzyme able to reduce reversibly non-activated carboxylic acids to the corresponding aldehydes (White, H., Strobl, G., Feicht, R. & Simon, H. (1989) Eur. J. Biochem. 184, 89-96), results in the generation of multiple forms of the enzyme. The specific activities for the viologen-mediated dehydrogenation of butyraldehyde for the two main forms of the purification procedure are 530 and 450 U/mg. Two forms of the enzyme composed of alpha,beta- and alpha,beta,gamma-subunits, can be differentiated. The latter binds to red-Sepharose and can be eluted very specifically with NADPH. In contrast to the alpha,beta-types the trimeric forms also catalyse the reversible reduction of oxidised viologen with NADPH (VAPOR activity). The dimer alpha,beta can oligomerize and the alpha,beta,gamma-trimer can easily form various oligomers or split off the gamma-subunit. The apparent molecular masses of the subunits alpha,beta and gamma are 64, 14 and 43 kDa. The alpha,beta-form reveals an apparent molecular mass of 86 kDa containing about 29 iron, 25 acid-labile sulphur, 0.8 tungsten and forms about 1 mol pterine-6-carboxylic acid by permanganate oxidation. The corresponding values of the trimer showing a mass of 300 kDa, are about 82 Fe, 54 S, 3.4 W and 2.5 pterine-6-carboxylic acid. In addition, 1.7 mol of FAD could be found which seems to be a component of the gamma-subunit. The aldehyde oxidoreductase from C. thermoaceticum and that from C. formicoaceticum (White, H., Feicht, R., Huber, C., Lottspeich, F. & Simon, H. (1991) Biol. Chem. Hoppe-Seyler 372, 999-1005) show qualitative similarities as far as the Fe, S, W and pterin content and the broad substrate specificity are concerned. However, there are also surprisingly marked differences with respect to composition and amino-acid sequence.

Aldehyde Oxidoreductases↗
PubMed1991

Comparison of effects of thrombolytic therapy on left ventricular function in patients over with those under 60 years of age.

This study examined the effect of age on left ventricular (LV) function, assessed by contrast ventriculography 3 weeks after a first acute myocardial infarction in 312 patients who received thrombolytic therapy within 4 hours of the onset of infarction and in 83 patients who received placebo. Streptokinase was given to 188 patients and recombinant tissue-type plasminogen activator (rt-PA) to 124. Patients were divided into 2 age groups: less than 60 years (n = 244) and greater than or equal to 60 years (n = 151). Thrombolytic therapy improved ejection fraction in both age groups: from 54 +/- 13 to 59 +/- 11% (p = 0.021) in the younger group and from 50 +/- 14 to 57 +/- 13% (p = 0.004) in the older group. Ejection fraction was identical in streptokinase- and rt-PA-treated patients. Multifactor analysis of variance revealed that younger age and thrombolytic therapy were independently associated with improved ejection fraction. Thrombolytic therapy also reduced end-systolic volume (p = 0.001) by 14 ml in the elderly and 9 ml in the younger group. Minor bleeding complications were more frequent in the elderly and 3 serious hemorrhages occurred in patients greater than or equal to 60 years. These findings reveal that thrombolysis improves LV function in all age groups studied. Because increasing age is independently associated with a lower ejection fraction after acute myocardial infarction, thrombolytic therapy may confer greater benefits in older patients.

Age Factors↗
PubMed1991

Retrospective postmortem dementia assessment. Validation of a new clinical interview to assist neuropathologic study.

Neuropathologic studies of dementia and normal aging suffer from a lack of individuals examined for the presence and severity of dementia before death. To increase clinical information in such cases, a retrospective collateral interview was developed. Thirty-nine individuals were studied; 27 had autopsies. In all cases, the autopsy confirmed the Retrospective Collateral Dementia Interview (RCDI) diagnosis of the presence or absence of dementia; the RCDI had a sensitivity of 88% and a specificity of 80% for specifically detecting probable Alzheimer's disease. Agreement between the RCDI and premortem diagnosis was 96%; between RCDI and medical records, 100%. Agreement between RCDI staging of dementia severity and the last assessment of the living subject was 70%; between the RCDI and a brief staging at death, 86%. This validation confirms the value of postmortem interviews with close informants to assess dementia presence and severity.

Aged↗
PubMed1991

Purification and some properties of the tungsten-containing carboxylic acid reductase from Clostridium formicoaceticum.

Judged by properties observed during the purification and based on the sequence of the first 25 amino acids, the enzyme from Clostridium formicoaceticum catalysing the reversible reduction of non-activated carboxylic acids to aldehydes at the expense of reduced viologens, is astonishingly different from that found by us in C. thermoaceticum. According to native and SDS gel electrophoresis the reductase is nearly homogeneous after only 26-fold purification. The specificity for various substrates and artificial electron carriers is also broad, but V of the purified aldehyde dehydrogenase activity (54 U/mg enzyme for butanal) is about 1 order of magnitude lower than that of the enzyme from C. thermoaceticum. The reductase is a dimer of two identical subunits with an Mr of 67,000 each. Increased enzyme concentrations seem to lead to higher oligomers. Per dimer 11 +/- 1 iron, 16 +/- 1 acid labile sulphur, 1.4 tungsten and after permanganate oxidation 1.6 mol pterin-6-carboxylic acid have been found.

Aldehyde Dehydrogenase↗
PubMed1991

Transposition of the greater omentum in the prevention and treatment of radiation injury.

The greater omentum provides a tissue flap that can readily be transposed for surgical reconstruction both inside and outside the abdominal cavity. To prevent radiation enteritis, an omental sling or envelope can be constructed at the end of an abdominal operation to displace small bowel from the pelvis prior to radiotherapy. The immunological and angiogenic properties of the omentum are particularly useful when reconstruction is required in a region of late radiation injury. Indications for omental transposition in this context include reinforcement of anastomoses, pelvic fistula repair, chest wall and axillary reconstruction, vascular cover, pharyngostoma, bronchopleural fistula and possibly lymphoedema.

Enteritis↗
PubMed1991

Fulminant hepatic failure after repeated exposure to isoflurane anesthesia: a case report.

A previously healthy but obese 26-yr-old woman was diagnosed as having hepatic dysfunction 17 days after the third of three consecutive exposures to isoflurane anesthesia for paranasal sinus surgery. Serum laboratory findings included elevated aminotransferases and bilirubin. Radiographical evaluations showed no evidence of extrahepatic disease. Serological studies were negative for acute viral infections, and serum copper was normal. The patient's condition deteriorated over the ensuing 17 days, with hyperreflexia, hypoglycemia and a rapid fall in serum aminotransferases with a concomitant rise in bilirubin level and prothrombin time despite maximal medical support. The liver volume as shown by computed tomography fell from 1,290 cm3 to 680 cm3 over 6 days. The patient underwent successful orthotopic liver transplantation 25 days after onset of symptoms. Histopathological examination of the resected liver showed submassive and massive necrosis, with a few foci of microvesicular steatosis and ultrastructural evidence of mitochondrial abnormalities. Although we found insufficient evidence to prove that this case was caused by isoflurane anesthesia, the clinical course and histopathological findings are similar to those in hepatic injury caused by halothane anesthesia. Therefore we report this as a possible case of fulminant hepatic failure resulting from isoflurane anesthesia.

Adult↗