AIDS debate continues.
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Acquired Immunodeficiency Syndrome↗
Biomedical subjects
B Griffin
Publications and source records attributed to B Griffin.
Percutaneous mitral balloon valvotomy in patients with calcific mitral stenosis: immediate and long-term outcome.
OBJECTIVES: This study analyzed the immediate and long-term outcome of percutaneous balloon mitral valvotomy in patients with and without fluoroscopically visible mitral valve calcification. BACKGROUND: Mitral valve calcification has been shown to be an important factor in determining immediate and long-term outcome of patients undergoing surgical mitral commissurotomy. Patient selection has an important impact on the outcome of percutaneous balloon mitral valvotomy. METHODS: The immediate and long-term results of percutaneous balloon mitral valvotomy were compared in 155 patients with and 173 patients without mitral valve calcification. The patients with calcified valves were assigned to four groups according to severity of calcification. RESULTS: Patients with calcified mitral stenosis more frequently were in New York Heart Association functional class III or IV and more frequently had atrial fibrillation, previous surgical commissurotomy, echocardiographic score > 8, higher pulmonary artery and left atrial pressures, higher pulmonary vascular resistance and mean mitral valve gradient and lower cardiac output and smaller mitral valve area. Mitral valve area after valvotomy was significantly smaller in patients with calcified valves (1.8 +/- 0.06 vs. 2.1 +/- 0.06 cm2) and was > or = 1.5 cm2 in 65% of patients with and 83% of patients without calcified valves (p = 0.004). A successful outcome, defined as mitral valve area > 1.5 cm2 without significant mitral regurgitation and left to right shunting, was achieved in 52% of patients with and 69% of patients without uncalcified valves (p = 0.001). The success rate was 59%, 48%, 35% and 33% in subgroups with 1+, 2+, 3+ and 4+ calcification, respectively. The rates of significant left to right shunting and mitral regurgitation after valvuloplasty were similar in the two groups. Estimated survival rate (80% vs. 99%, respectively, p = 0.0001), survival rate without mitral valve replacement (67% vs. 93%, respectively, p < 0.00005) and event-free survival rate (63% vs. 88%, respectively, p < 0.00005) at 2 years were significantly better in the patients with uncalcified valves. Survival rate curves became progressively worse as the severity of calcification increased. CONCLUSIONS: These findings indicate that immediate and long-term results of mitral valvuloplasty are not as successful in patients with fluoroscopically visible mitral valve calcification as in those without calcification.
Calcinosis↗
Effect of monosaccharides during severe dry heat treatment of coagulation factor VIII concentrates.
During product development of a factor VIII concentrate (Dutch blood banks) the conversion from unsterilized to autoclaved freeze-drying buffer caused impaired product characteristics after severe dry heat treatment (80 degrees C for 72 h). Analysis of the freeze-drying buffers showed the presence of fructose and glucose in heated buffers, resulting from hydrolysis of sucrose. The detrimental effect of glucose and fructose on solubility, yield of factor VIII and color of the heat-treated product was confirmed by freeze-drying and heating products spiked with increasing levels of these monosaccharides. The effect of the use of freeze-drying buffers autoclaved with and without sucrose was examined in two other factors VIII concentrates, S(8) and Z8 (Protein Fractionation Centre, Edinburgh, UK). If sucrose was present during autoclaving of the buffer, a slightly lower yield over freeze-drying and 80 degrees C heat treatment was observed. Since glucose is present as a substrate in the medium for the host cells during cultivation of viruses, its potential effect on the 80 degrees C heated product (Dutch blood banks) was examined during the validation study of the inactivation of HIV-1 and Sindbis. The cultivation cycles for the virus inocula were simulated and residual glucose levels measured. In the supernatant medium of the host cell culture used for the propagation of Sindbis no residual glucose was found. Glucose however was found in the supernatant medium of the host cell culture for propagation of HIV-1, and therefore small molecular weight substances were removed from the actual HIV-1 inoculum by ultrafiltration.(ABSTRACT TRUNCATED AT 250 WORDS)
Buffers↗
Predictors of survival following relapse or progression of small cell lung cancer. Southwest Oncology Group Study 8605 report and analysis of recurrent disease data base.
BACKGROUND: Survival after relapse or progression of small cell lung cancer (SCLC) is poor. The Southwest Oncology Group (SWOG) initiated a study of modulation of cyclophosphamide (Cy) resistance in this population. At study closure, the value of testing new regimens in previously treated patients was being debated nationally: Is there an independent impact of treatment over favorable prognostic factors? Thus, the authors analyzed the SWOG recurrent SCLC data base. METHODS: A 12-hour infusion of cytosine arabinoside (ara-C) was used as a potential repair inhibitor of Cy-induced DNA damage in patients with relapsed SCLC. A data base of successive SWOG studies in recurrent SCLC was formed. The independent contribution to survival of prognostic factors, type of prior chemotherapy (CT), time from diagnosis, and type of CT on relapse were then assessed. RESULTS: There were 3 partial responses observed in 67 patients, with substantial myelotoxicity. The median survival was 2.5 months, and 16% lived beyond 6 months. The multivariate analysis of the recurrent SCLC data base found that a normal lactate dehydrogenase (LDH) and second-line treatment with etoposide plus cisplatin (EP), if not initially treated with either alternating or complex multidrug regimens, were the only independent predictors of improved survival. The 2-year survival of this subset was 20%. CONCLUSIONS: The Cy/ara-C program cannot be recommended for patients with recurrent SCLC. However, EP independently contributed to improved survival in patients without complex prior CT and a normal LDH. This finding supports future trials of new approaches in certain subsets of SCLC patients with limited prior treatment.
Adult↗
Response of plasma low density lipoprotein subfractions to oestrogen replacement therapy following surgical menopause.
OBJECTIVE: Epidemiological studies suggest that postmenopausal oestrogen replacement reduces the incidence of cardiovascular disease. The purpose of this study was to establish the effects of oestrogen replacement therapy on subfractions of plasma low density lipoprotein in bilaterally oophorectomized women. DESIGN: In a placebo controlled, double-blind study, patients were randomized on a two to one basis to receive either oestradiol valerate (2 mg/day) or placebo respectively for a period of 16 weeks. PATIENTS: Seventeen women aged 28-51 years who had all had hysterectomy and bilateral oophorectomy at least 2 months before recruitment were assigned to either the active (n = 12) or placebo (n = 5) group. MEASUREMENTS: Plasma lipids, lipoproteins, apolipoproteins and LDL subfractions were determined immediately before and after the treatment period. LDL subfractions were isolated directly from plasma by density gradient ultracentrifugation within 24 hours. Non-parametric statistical analysis was carried out within each group using Wilcoxon's signed rank test for matched pairs. RESULTS: After 16 weeks of treatment, HDL cholesterol, apo A-I and HDL-2 were increased in the group receiving oestrogen (HDL cholesterol +12%, P < 0.01; apo A-I +14%, P < 0.01; HDL-2 +24% P < 0.01). While there were no significant changes in serum cholesterol, LDL cholesterol or triglycerides, the proportion and concentration of the least dense LDL-I subfraction was decreased significantly (-27%, P < 0.05). The LDL subfraction of intermediate density (LDL-II) was decreased in eight subjects, while small, dense LDL-III was unaffected. Overall, these changes resulted in an apparent shift in the distribution of LDL subfractions towards small, dense LDL-III, although there was no net increase in the latter. CONCLUSION: In view of a similar and characteristic response of LDL subfractions to hypolipidaemic drugs that enhance the clearance of LDL via the LDL receptor, the present findings suggest that oestrogen promotes the preferential removal of LDL-I and II by activating LDL receptors. As this effect is normally associated with a reduction in the circulating level of LDL, it should not be regarded as an unfavourable response to oestrogen replacement therapy.
Adult↗
Comparative effects of fenoldopam mesylate and nitroprusside on left ventricular performance in severe systemic hypertension.
To compare the effects of fenoldopam (n = 15), a selective dopamine-1 agonist, and nitroprusside (n = 14) on left ventricular (LV) function in severely hypertensive subjects (diastolic blood pressure (BP) greater than 120 mm Hg), both agents were infused to reduce diastolic BP by 40 mm Hg (or less than 110 mm Hg). Indexes of LV systolic and diastolic functions were obtained using gated radionuclide angiography before the initiation of treatment and after targeted BP was achieved. Both fenoldopam and nitroprusside effectively reduced systolic and diastolic BP to target levels. Changes in heart rate, peak filling rate and relative end-diastolic volume were similar with both agents. Baseline ejection fraction increased after infusion of both drugs. The magnitude of the increase in ejection fraction was far greater with fenoldopam than with nitroprusside (+22% vs +8%; p = 0.04), despite a lesser reduction in systolic BP (-12 vs -22%, p = 0.002). Furthermore, the reduction in relative end-systolic volume (-35 vs -20%; p = 0.04), and increase in the ratio of peak systolic pressure to relative end-systolic volume (+43 vs +6%; p = 0.007) were greater after fenoldopam than after nitroprusside. The greater increment in parameters of LV systolic function produced by fenoldopam than by nitroprusside suggests an effect on LV performance that is independent of afterload reduction.
2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
Late (two-year) follow-up after percutaneous balloon mitral valvotomy.
Percutaneous balloon mitral valvotomy (PBMV) compares well with surgical commissurotomy, showing comparable improvement in symptoms and catheterization-proven valve area early after the procedure. This study reports the New York Heart Association class, mitral valve area calculated by echocardiography, and the results of transseptal cardiac catheterization 2 years after PBMV. The data are compared with the status immediately before and after PBMV. Forty-one patients returned to enter the study (mean follow-up time 24 +/- 3 months). All patients were evaluated clinically by the same investigator who had seen them at the time of PBMV. Transseptal cardiac catheterization and echocardiographic analysis (2-dimensional and Doppler echocardiography) were performed on the same day. At follow-up, 17 patients were class I, 20 were class II, and 4 were class III. Although the mitral valve area calculated by cardiac catheterization increased significantly from immediately before to immediately after PBMV there was a decrease in the calculated mitral valve area at 2-year follow-up. Echocardiographic analysis did not show as large an increase in mitral area, immediately after PBMV, and no significant decrease in mitral valve area at 2 years (before PBMV planimetry 1.1 +/- 0.1 cm2; immediately after 1.8 +/- 0.1 [p less than 0.05]; follow-up 1.6 +/- 0.1 [p = not significant compared with immediately after PBMV]). Doppler halftime measurements were similar. PBMV is effective therapy with good midterm results for selected patients with mitral stenosis.
Adult↗
The prognostic significance of postoperative residual contrast enhancement on CT scan in pediatric patients with medulloblastoma.
The clinical and therapeutic features of 20 patients with medulloblastoma treated at Children's Hospital and Medical Center, Seattle, from 1980 to 1987, were retrospectively analyzed with regard to prognosis. The overall actuarial 5-year survival rate was 63%, with 57% of patients free from recurrence at 5 years. Residual contrast enhancement on CT scans taken immediately postoperatively was associated with a significantly decreased 5-year recurrence-free survival rate; the 5-year recurrence-free survival rate was 100% for those patients without post-operative residual enhancement compared to 41% for those patients with residual enhancement. A high risk group of patients with residual contrast enhancement persisting one year following diagnosis was identified. No patient in this group survived without disease progression. Other factors, including sex, age at diagnosis, evidence of tumor dissemination, or extent of surgical resection as reported by the neurosurgeon, did not significantly influence prognosis.
Adolescent↗
Phase II evaluation of high-dose intravenous cisplatin for treatment of adult malignant gliomas recurrent after chloroethylnitrosourea failure.
Twenty-one patients with recurrent malignant glioma who had failed prior chemotherapy with nitrosoureas were treated with high-dose intravenous cisplatin on days 1 and 8 of successive 4 week cycles. Fourteen patients were evaluable for response. Four patients showed partial responses; mean time to tumor progression (MTP) was 8 weeks. Six patients stabilized; MTP was 11 weeks. Four patients showed no response. There were no infectious or hemorrhagic complications, but partial hearing loss occurred in 7 patients and severe vomiting in 8 patients. High-dose intravenous cisplatin demonstrates substantial activity against malignant gliomas recurrent after chloroethylnitrosourea (CENU) failure.
Adult↗
Left atrial V waves following mitral valve replacement are not specific for significant mitral regurgitation.
Left atrial or pulmonary capillary wedge pressure V waves are used immediately after mitral valve replacement to evaluate valve competence. However, their correlation with hemodynamically significant regurgitation has not been established. Transesophageal echocardiography (TEE) was used to prospectively examine whether left atrial V waves represented significant mitral regurgitation in 11 patients undergoing mitral valve replacement. Left atrial pressure V waves were measured in the immediate postcardiopulmonary bypass period by direct cannulation of the right superior pulmonary vein and recorded on a paper chart recorder. In each patient, three evaluations of mitral regurgitation by Doppler TEE were made at 15-minute intervals. In 22 of 33 evaluations, left atrial V waves with peak V wave height more than 5 mm Hg above the mean left atrial pressure were present. However, only in 3 of these periods did transesophageal echocardiography show evidence of more than trace mitral regurgitation by pulsed Doppler and color flow mapping. As indicators of mild-to-severe mitral regurgitation diagnosed by TEE, left atrial V waves had a specificity for the three evaluation periods of 40%, 30%, and 40%. Left atrial V waves with peak height greater than 5 mm Hg above mean left atrial pressure frequently appear following mitral valve replacement, but these V waves are nonspecific signs of mitral regurgitation.
Aged↗
Pharmacokinetics and efficacy of structurally related spirohydantoin and spirosuccinimide aldose reductase inhibitors.
1. Six potent aldose reductase inhibitors (ARI), three spirohydantoin (I to III) and three spirosuccinimide (IV to VI) compounds, showed similar IC50 activities in vitro for the inhibition of rat lens aldose reductase, but their ED50 values in diabetic rats varied as much as 20-fold in the lens and 50-fold in the sciatic nerve tissue. Pharmacokinetic studies were undertaken to investigate these findings. Structure-pharmacokinetic relationships were studied following i.v. administration to cynomolgus monkeys. 2. The clearance (CL) of each spirosuccinimide ARI was faster (greater than 5 times) than that of the corresponding spirohydantoin compound. In both series the CL values of the C(4) methyl and methoxy analogues were 4-fold greater than those for the unsubstituted compounds, although the CL values of the methoxy and methyl derivatives in the same series were not significantly different. 3. The volumes of distribution (Vss) of the spirohydantoins were about one-half those of the corresponding spirosuccinimides, and the Vss values of the parent compounds of both ARI series did not differ dramatically from those of their methyl and methoxy analogues. 4. All six compounds were eliminated from plasma in a biexponential fashion. The half-lives (lambda 1 and lambda 2) of the spirohydantoin compounds were much longer than those of the corresponding spirosuccinimide compounds, and the unsubstituted compounds had longer half-lives than their methyl and methoxy derivatives. The longest lambda 1 and lambda 2 half-lives were observed for imirestat, while two of the spirosuccinimides had the shortest half-lives. 5. These results indicate that the relationships observed between the in vitro and in vivo activities of the six ARI can be attributed to structurally dependent differences in metabolic clearance.
Administration, Oral↗
Prevalence of unsuspected mitral regurgitation and left ventricular diastolic dysfunction in patients with coronary artery disease and acute pulmonary edema associated with normal or depressed left ventricular systolic function.
To define the prevalence and role of left ventricular (LV) systolic dysfunction, LV diastolic dysfunction and mitral regurgitation (MR) in patients with acute pulmonary edema, 40 patients with coronary artery disease and acute pulmonary edema were prospectively evaluated within 36 hours of presentation. LV ejection fraction and 3 parameters of LV diastolic function were measured with radionuclide ventriculography, whereas MR was assessed with Doppler echocardiography. LV ejection fraction was normal in 11 (27%) and depressed in 29 (73%) patients. Moderate or severe MR without LV diastolic dysfunction was common and equally prevalent in patients with and without LV systolic dysfunction (33 vs 38%; difference not significant). Diastolic dysfunction without MR was less frequent but equally prevalent in patients with and without systolic dysfunction (17 vs 27%; difference not significant). Two (18%) of 11 patients without and 12 (33%) of 36 patients with LV systolic dysfunction had both MR and LV diastolic dysfunction. Furthermore, MR was clinically silent and unsuspected in two-thirds of all patients with MR, regardless of a normal or depressed systolic function. These data show that there is a high prevalence of unrecognized moderate to severe MR in patients with acute pulmonary edema, regardless of the presence or absence of LV systolic dysfunction. Furthermore, the prevalence of LV diastolic dysfunction without MR is relatively low even in patients with normal LV systolic function and pulmonary edema. Thus, unrecognized MR may be an important contributor to the syndrome of acute pulmonary edema in patients with normal or depressed LV systolic function.
Aged↗
Results of neutron radiosurgery for inoperable arteriovenous malformations of the brain.
Twenty patients with inoperable arteriovenous malformations (AVMs) of the brain were treated with neutron radiosurgery. A 50 MeV cyclotron was used to deliver 9 Gy in a single fraction through 7 to 14 isocentric portals. The size and shape of the portals were customized to each treatment site. Nineteen patients have been followed for a median duration of 24 months following neutron radiosurgery. A radiographically demonstrable partial response was seen in 8 patients (42%). No complete responses were observed. There has been one post-treatment hemorrhage, no fatalities, and no evidence of radiation toxicity. The low response rate and absence of toxicity suggest that the appropriate dose for neutron radiosurgical treatment of AVMs is higher than the dose of 9 Gy at isocenter used in this initial study.
Adult↗
Interaction of heparinoids with platelets: comparison with heparin and low molecular weight heparins.
Heparin interacts with platelets to impair collagen-induced aggregation and adhesion to collagen. Low molecular weight heparin and heparinoids have little or no inhibitory activity in these platelet-collagen interactions. Thrombin-induced aggregation of platelets is inhibited by any of the glycosaminoglycans that will block the action of thrombin on fibrinogen. However, heparin is a much more potent inhibitor than low molecular weight heparins or heparinoids at equigravimetric concentrations in these reactions. The inhibition of ristocetin or asialo-von Willebrand factor aggregation of platelets is partially blocked by high dose heparin but not by low molecular weight heparin or heparinoids. The heparin-induced IgG antibody, produced to a heparin-platelet complex, aggregates platelets strongly in the presence of heparin, less strongly in the presence of low molecular weight heparins and pentosan polysulfate and not at all with dermatan sulfate or the pentasaccharide. Heparan sulfate does interact with platelets and this antibody, which is of interest because of the heparan sulfate on endothelial cells. Clinical information to date suggests a low incidence of heparin antibodies in patients receiving only low molecular weight heparin of the depolymerized type. Whether long-term clinical use of low molecular weight heparins, heparan sulfate, and dermatan sulfate will give rise to specific antibodies that would cause a similar problem as heparin remains to be seen.
Autoantibodies↗
Infants with medulloblastoma: a single institution review of survival.
Although the prognoses of children with medulloblastoma have improved dramatically over the last several decades, the reported survival for very young children with this tumor remains poor. We undertook a retrospective review of patients less than 36 months of age at the time of the diagnosis of a medulloblastoma who were treated at our institution during a 36-year period. Of 28 such patients, 10 patients are presently surviving without disease at a median of 150 months from diagnosis. The presence of a metastatic tumor at the time of diagnosis was identified as a significant indicator of a poor prognosis, and all completely staged patients without metastasis are surviving without a recurrence of disease. This report suggests that the survival of very young children with a medulloblastoma may not be as poor as has been previously reported, particularly if a disseminated tumor is not present at the time of diagnosis.
Cerebellar Neoplasms↗
Cerebral mass lesions in patients with AIDS.
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Acquired Immunodeficiency Syndrome↗
Comparative effects of propranolol and diltiazem on systolic and diastolic left ventricular function in essential hypertension.
The effects of propranolol and diltiazem on left ventricular systolic and diastolic function in hypertensive subjects (DBP 90-114 mmHg) were examined with M-mode and 2D echocardiograms in 21 patients in a double-blind fashion prior to and after 4 months of treatment. Systolic function was assessed by measurement of fractional shortening, mean velocity of fibre shortening, peak systolic pressure/end systolic dimension ratio, and end systolic stress/end systolic dimension ratio. To assess diastolic function, maximal rate of change in left ventricular dimension (MAXD), maximal rate of change in posterior wall thinning (MAX PWT) and early diastolic (EDD) and late diastolic dimension changes (LDD) were calculated using digitised M-mode images of mid-wall diameter. Both propranolol and diltiazem reduced systolic and diastolic pressures similarly. No significant changes were observed in any of the parameters of systolic function with either drug. Similarly neither propranolol nor diltiazem altered MAXD or EDD significantly. Although changes in maximal rate of posterior wall thinning (MAX PWT) were not significant with either drug, diltiazem improved MAX PWT in 7 of 8 patients. The results of the study demonstrate that both propranolol and diltiazem reduce blood pressure without significant deleterious effects on systolic or diastolic function. Diastolic functional parameters, which were not abnormal at baseline, showed no consistent change with either propranolol or diltiazem.
Blood Pressure↗