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Biomedical subjects

H White

Publications and source records attributed to H White.

At least 91 records · Page 5Linked to original sources
PubMed1993

Hepatitis B virus replication in diverse cell types during chronic hepatitis B virus infection.

Hepatitis B virus-specific nucleic acid sequences and proteins have been detected in extrahepatic tissues of acutely and chronically infected patients. However, apart from peripheral blood mononuclear cells and bone marrow cells, little is known about the specific cell types that permit viral replication. In this study, we assessed the extrahepatic tissues of four patients who died with chronic hepatitis B virus infection and two uninfected controls by means of in situ hybridization and immunohistochemical study. Three of these patients had diffuse extrahepatic distribution of the virus. Hepatitis B virus nucleic acid sequences and proteins were detected in the lymph nodes, spleen, bone marrow, kidney, skin, colon, stomach, testes and periadrenal ganglia. The following cell types were found to be positive for hepatitis B virus: endothelial cells, macrophages/monocytes, hematopoietic precursors, basal keratinocytes, mucosal epithelial cells, stromal fibroblasts and sustentacular and neuronal cells. It is probable that these cells could support viral replication because hepatitis B virus DNA replicative intermediates, viral transcripts and HBsAg and HBcAg proteins were detected in most. These findings may be relevant to the initiation of extrahepatic syndromes associated with chronic hepatitis B virus infection such as vasculitis, glomerulonephropathy, neuropathy and dermatitis.

Adult↗
PubMed1993

Representational-momentum effects in the cerebral hemispheres.

On each trial, after three squares of different sizes (inducing display) were sequentially presented at central fixation, a target square was briefly lateralized to the right or left hemisphere (RH or LH) of 24 normal right-handed males. Subjects determined whether or not the target differed in size from the third inducing square. Half of the targets that differed were consistent with size changes in the inducing display (e.g., a target smaller than the third square in an inducing display presented in a large-to-small order) and half were inconsistent. Three retention intervals (RIs) between offset of third inducing square and onset of target were used. At the shortest RI, error-rate differences in responding to consistent vs. inconsistent targets, i.e., representational-momentum (RM) effects, were larger in the RH than in the LH, and RM effects in the RH, but not in the LH, were affected by RI.

Adult↗
PubMed1993

Fine needle aspiration cytology in maxillofacial surgery--experience in a district general hospital.

101 fine needle aspirations of 82 head and neck masses in 72 patients performed in one maxillofacial unit over a 5-year period were studied retrospectively. Satisfactory reports were obtained for 69 masses. Fifty six (81.2%) were confirmed histologically and 13 (18.8%) by clinical follow up of at least 6 months' duration. The sensitivity was 96.7% and specificity 100% with a positive predictive value of 100%. No complications were recorded. Provided the unsatisfactory specimens are correctly recognised this technique provides a useful aid in the management of head and neck masses.

Adenoma, Pleomorphic↗
PubMed1993

Strokes and net clinical benefit.

The need for careful assessment of stroke incidence in a trial comparing highly effective thrombolytic regimens was recognised in the design of the GUSTO trial. There was a gradation of stroke incidence from 1.22% in the streptokinase (SK) and subcutaneous heparin group, to 1.4% in the SK and intravenous heparin group, 1.55% in the tissue plasminogen activator (t-PA) and intravenous heparin group and 1.64% in the combination t-PA and SK group. The concept of net clinical benefit was developed to balance the adverse effect of stroke with the benefit of mortality reduction. On this analysis, the net clinical benefit favoured the accelerated t-PA regimen over the SK regimens.

Aged↗
PubMed1993

Issues raised by GUSTO.

The GUSTO trial raises several questions including the role of heparin in thrombolysis. The need for intravenous versus subcutaneous heparin with streptokinase (SK) has not been clarified in this trial. It is more likely that the superiority of tissue plasminogen activator (t-PA) was due to its accelerated administration rather than the accompanying heparin. Despite the improvement in survival, much is still to be achieved in obtaining optimal reperfusion rates.

Heparin↗
PubMed1993

Hirudin and Hirulog.

A brief outline is presented of a proposed trial of Hirulog versus heparin after thrombolytic therapy with streptokinase (SK). The lower patency rates achieved with SK compared with tissue plasminogen activator (t-PA) suggest that a potent thrombin specific agent may be more important for SK than for t-PA therapy. This study will involve more than 400 patients with two dose levels of Hirulog. Endpoints will be angiographic patency, and ST segment monitoring showing evidence of coronary reperfusion.

Hirudin Therapy↗
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↗