Progressive bulbar palsy and gammopathy.
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Bulbar Palsy, Progressive↗
Biomedical subjects
D B Smith
Publications and source records attributed to D B Smith.
A model clinical neuroscience curriculum.
We have attempted to identify those attitudes, skills, and competencies in the clinical neurosciences that every graduating medical student should possess. Curricular guidelines are provided that may act as a model educational outline, to be adapted and utilized as individual circumstances dictate and resources permit. A universal, although not lockstep, curriculum emerges from these considerations.
Curriculum↗
Vigabatrin for refractory complex partial seizures: multicenter single-blind study with long-term follow-up.
The irreversible GABA transaminase inhibitor vigabatrin (VGB) was given in a single-blind fashion to 89 patients with complex partial seizures (CPS) refractory to conventional drugs. The median number of CPS per month decreased from 11.0 to 5.0 after addition of VGB, and 51% of patients had a 50% or greater decrease in CPS frequency (p less than 0.001). Side effects (principally drowsiness, ataxia, and headache) occurred mainly during the initiation of therapy and decreased during therapy. After 12 weeks on VGB, side effects significantly interfered with functioning in only 13% of patients, and the efficacy:toxicity ratio warranted continued administration in 74% of patients. Coadministration of VGB resulted in a mean decrease of 20% in phenytoin serum concentration (p less than 0.001). Sixty-six patients with a favorable response to VGB during the single-blind study have been followed for a median of 16.7 months on VGB. No serious systemic or neurologic toxicity has been detected, and most patients have retained their initial favorable CPS control.
Aminocaproates↗
Quantitative measurement of plasma gelsolin and its incorporation into fibrin clots.
Gelsolin is a newly recognized actin-binding protein of plasma that severs actin filaments. The concentration of plasma gelsolin was measured by three independent methods: an enzyme-linked immunosorbent assay (ELISA) and two functional assays based on the ability of gelsolin to accelerate the polymerization of actin (a "nucleating" assay) or to sever preformed actin filaments (a "cutting" assay). The gelsolin level in 56 samples of human plasma ranged between 100 and 330 micrograms/ml. The mean plasma concentrations measured by the different assays were ELISA, 207 micrograms/ml; nucleating assay, 233 micrograms/ml; cutting assay, 247 micrograms/ml. The mean serum level of gelsolin was found to be 24% lower than that of plasma when paired samples were examined (183 micrograms/ml). The difference between plasma and serum gelsolin concentrations can be accounted for by a direct interaction between gelsolin and fibrin as shown by the binding of radiolabeled gelsolin to clots made from purified fibrinogen. Further, unlabeled gelsolin inhibits the binding of the labeled species to fibrin, but hemoglobin and albumin do not. Fibrin oligomers, but not fibrinogen, alter the sedimentation characteristics of radiolabeled gelsolin in sucrose gradients. The amount of gelsolin incorporated into the clot is increased if the clots are made in the presence of actin filaments or fibronectin. Thus, serum levels of gelsolin are lower than plasma levels because of an interaction between gelsolin and fibrin clots.
Actins↗
Phase I clinical trial of methylene dimethane sulfonate.
Methylene dimethane sulfonate is the first member of the homologous series of straight-chain diol sulfonates. It was selected for phase I testing because of high activity in the rat Yoshida sarcoma system and a possible novel site of alkylation due to its small molecular size. Methylene dimethane sulfonate was administered as a rapid iv bolus infusion to 39 patients at doses ranging from 14 to 225 mg/m2. Nausea and vomiting were not severe but total alopecia occurred in the majority of patients at doses greater than 100 mg/m2. The dose-limiting toxic effect was thrombocytopenia, which was cumulative with lower, more prolonged nadirs following successive courses. The median time to platelet count nadir was 21 days, with recovery by 35 days. A minor response was seen in one patient with an adenocarcinoma of the lung. The recommended dose for phase II studies is 125 mg/m2 for patients who have received prior chemotherapy and 150 mg/m2 for those who have not, in an every 35-day schedule.
Adult↗
Phase II trial of rDNA alfa 2b interferon in patients with malignant carcinoid tumor.
Fourteen patients with malignant carcinoid tumors were treated with rDNA alfa 2b interferon by sc injection three times per week. Treatment was started at a dose of 2 milliunits/m2, with escalations to 3, 5, 7, and 10 milliunits/m2 at 2-week intervals depending on toxicity. No objective tumor regressions were seen, but five of 14 patients (36%) had 50% reduction in 24-hour 5-hydroxyindoleacetic acid excretion and six of nine (67%) with carcinoid syndrome had a good symptomatic response. Biochemical responses occurred during the first 8 weeks of treatment, and escalation of the dose of interferon did not increase the response rate. The rDNA alfa 2b interferon has activity in patients with the carcinoid syndrome and should be used at a low dose (2-3 milliunits/m2) until symptoms recur.
Adult↗
Ifosfamide by bolus as treatment for advanced non-small cell lung cancer.
Ifosfamide at 5 g/m2 was given as a bolus to 48 patients with advanced progressing non-small cell lung cancer. Mesna (5 g/m2) was also given with the ifosfamide, both over 30 min. Further mesna was then given p.o. (3 g/m2) at 4, 8, and 12 h. If oral mesna was not acceptable then one or, if necessary, two 4-h to 6-h infusions (3 g/m2) were administered. A maximum of six courses at 3-weekly intervals was prescribed. A total of 174 courses was administered, and oral mesna was given during 64 courses: discharge was considered possible within 8-10 h after 55% of courses. Haematological toxicity was mild and no renal dysfunction was noted. Two patients became drowsy shortly after ifosfamide, but recovered 24-36 h later. The objective response rate was 29%, with one complete responder. A further 31% of patients (symptomatic responders) with stable disease symptomatically improved after the chemotherapy, by 20 or more points on the Karnofsky scale. The median survival was 5 months for the whole group, and 8 months each for the objective and symptomatic responder groups. Most patients' Karnofsky and respiratory scores improved with the chemotherapy. Ifosfamide with mesna can be given by short infusions, and the mesna given p.o. prevents any urothelial toxicity. Further exploration of short-infusion ifosfamide and mesna therapy would reduce hospitalization and allow for day-case regimens.
Adult↗
A phase II study of cyclophosphamide as a 24-hr infusion in advanced non-small cell lung cancer.
Twenty patients with progressive non-small cell lung cancer who had received no prior chemotherapy were treated with 24-hr infusions of cyclophosphamide at a dose of 2.5 g/m2. The median number of courses administered was three (range one to six). There was one PR and one CR, an overall response rate of 10% (95% confidence limits 2-32%). A further six patients experienced excellent relief of distressing symptoms, unresponsive to other measures, as a result of the chemotherapy. The median survival for the 20 patients was 18.5 weeks (range 4-75 weeks). The median leukocyte nadir count was 1.1 X 10(9)/1 and median platelet nadir count 226 X 10(9)/1. There were no episodes of cystitis and gastrointestinal toxicity was moderate. This study has not shown any advantage for the infusion schedule over conventional bolus regimens, but further dose escalation or more prolonged infusion times may improve results.
Adult↗
Gynecological cancers: etiology and pathophysiology.
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Adolescent↗
Resistance of 129/J mice to Schistosoma mansoni infection.
Mice of the strain 129/J bred at this Institute (WEHI 129/J) were exposed once or repeatedly to cercariae of Schistosoma mansoni and worm burdens determined. In keeping with reports of S. japonicum infection in these mice, a high level of resistance was recorded. Radio-labelled extracted antigens of S. mansoni adult worms were reacted with sera from exposed 129/J mice and infected BALB/c mice. Immunoprecipitated antigens preferentially recognized by antibodies in 129/J mice include proteins of Mr 99,000 and 21,000. Whether responses to these antigens are a cause or a consequence of resistance remains to be established.
Animals↗
Mr 26,000 antigen of Schistosoma japonicum recognized by resistant WEHI 129/J mice is a parasite glutathione S-transferase.
Mice of the inbred strain 129/J bred at this Institute (WEHI 129/J) are relatively resistant to chronic infection with the parasitic helminth Schistosoma japonicum. In contrast to more permissive mouse strains such as BALB/c, the WEHI 129/J mice are high responders to a Mr 26,000 adult worm antigen designated Sj26. Cloned cDNAs corresponding to Sj26 have been identified in a S. japonicum phage lambda gt11 amp3 expression library, and their nucleotide sequences have been deduced. The predicted amino acid sequence of the antigen specified by these cDNAs shows striking homology with class mu isozymes of mammalian glutathione S-transferases (RX:glutathione R-transferase, EC 2.5.1.18). Extracts of adult worms contain glutathione S-transferase activity, and affinity chromatography of enzyme activity on glutathione columns leads to the purification of a Mr 26,000 molecule that comigrates with Sj26. Although vaccination studies in mice with a beta-galactosidase-Sj26 fusion protein from Escherichia coli are encouraging, more immunogenic preparations of the antigen are likely to be required to establish the utility of Sj26 as a model vaccine.
Amino Acid Sequence↗
Does ovarian sex cord tumour with annular tubules produce progesterone?
Probable progesterone production was identified by an immunoperoxidase assay in a case of an ovarian sex cord tumour with annular tubules. The tumour was associated with a serous cystadenofibroma in the opposite ovary and with adenoma malignum (adenocarcinoma) of the cervix.
Adenocarcinoma↗
Role of plasma gelsolin and the vitamin D-binding protein in clearing actin from the circulation.
We determined the plasma kinetics of both actin and complexes of actin with the two high affinity actin-binding proteins of plasma, gelsolin, and vitamin D-binding protein (DBP). Actin is cleared rapidly from the plasma by the liver (half-disappearance time, 0.5 h). Using radiolabeled actin-binding proteins, we found that actin accelerated the clearance of both plasma gelsolin and the vitamin D-binding protein. In separate experiments we found that DBP-actin complexes were cleared more quickly than gelsolin-actin complexes, at a rate comparable to the clearance of actin from the blood. A low affinity interaction (dissociation constant, 2.9 X 10(-4) M) between actin and fibronectin was found, suggesting that little actin will bind to fibronectin in plasma. We conclude that while plasma gelsolin and DBP may both clear actin from the circulation, DBP appears to play a more important role. By so doing, DBP may conserve the filament-severing activity of plasma gelsolin.
Actins↗
Temporal lobectomy for partial complex seizures: evaluation, results, and 1-year follow-up.
Twenty-six patients were evaluated for temporal lobectomy. Fourteen underwent initial monitoring with electrodes in the amygdala and hippocampus bilaterally. Twelve had initial monitoring with scalp and sphenoidal electrodes. Four had conclusive localization without depth electrodes. Twenty-three patients underwent lobectomy. At 1-year minimum follow-up, 15 were seizure free. Five had greater than 90% reduction in seizure frequency. Complications of depth electrodes were one hemorrhage and one abscess. One patient developed impaired memory following surgery. Temporal lobectomy is effective in well-selected patients. Depth electrodes localize seizure onset from mesial temporal structures. Scalp and sphenoidal recording may be sufficient in some cases.
Adolescent↗
Mother love and infant death, 1750-1920.
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Child Welfare↗
Evaluation of the impact of Medicare and Medicaid prospective payment on utilization of Philadelphia area hospitals.
The article evaluates the impact of Medicare and Medicaid DRG prospective payment on utilization in Philadelphia area hospitals. These hospitals began a combined Medicare-Medicaid DRG prospective payment at the same time after a common cost-based reimbursement history. Particular attention is paid to the hospital-driven as opposed to physician-driven explanations of declining inpatient utilization. The evaluation of the Tax Equity and Fiscal Responsibility Act (TEFRA) and Diagnosis-Related Group (DRG) interventions uses an ARIMA model that removes both seasonal and autoregressive effects. Both TEFRA and the DRG payment system produced significant reductions in average length of stay, total hospital days, and hospital occupancy rates. Neither, however, had a significant effect on admissions. Hospitals with a higher proportion of Medicare and Medicaid discharges reduced their average length of stay more than other facilities. Hospitals with a higher proportion of outpatient visits to inpatient admissions also reduced inpatient length of stay more. Hospitals with higher than expected overall admissions after the introduction of the DRG program tended to have lower than expected average lengths of stay. The results lend support to the "hospital-driven" interpretation of declines in average length of stay. They fail to support the contention that the DRG system will produce automatic counteracting increases in admissions in the system as a whole.
Bed Occupancy↗