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Biomedical subjects

D Smith

Publications and source records attributed to D Smith.

At least 469 records · Page 26Linked to original sources
PubMed1997

High-dose chemotherapy with autologous transplantation for persistent/relapsed ovarian cancer: a multivariate analysis of survival for 100 consecutively treated patients.

PURPOSE: To examine the prognostic factors associated with prolonged progression-free survival (PFS) and overall survival (OS) in 100 consecutively treated women undergoing autologous stem-cell transplant for advanced ovarian cancer. PATIENTS AND METHODS: From October 1989 to February 1996, we transplanted 100 patients with ovarian cancer following chemotherapy with high-dose carboplatin, mitoxantrone, and cyclophosphamide with or without cyclosporine (n = 70); melphalan and mitoxantrone with or without paclitaxel (n = 25); or other regimens (n = 5). Their median age was 48 years (range, 23 to 65), 70% had papillary serous histology, 72% had grade III tumors, 66% were platinum-resistant, and 61% had > or = 1 cm bulk. The median number of prior regimens was two (range, one to six). Univariate and multivariate analyses were performed to examine age (< v > or = mean), stage, initial bulk, histology, grade, response to initial therapy, number of prior regimens, time from diagnosis to transplant, transplant regimen, platinum sensitivity, and bulk (< v > or = 1 cm) at transplant. RESULTS: The median PFS and OS times for the 100 patients were 7 and 13 months. A stepwise Cox proportional hazards model identified tumor bulk (P = .0001), and cisplatin sensitivity (P = .0249) as the best predictors of PFS. Age (P = .0017), bulk at transplant (P = .0175), and platinum sensitivity (P = .0330) provided the best prediction of OS. The median PFS and OS times for the 20 patients with platinum-sensitive, < or = 1-cm disease were 19 and 30 months. No differences in OS were seen when chemotherapy or surgery was used to achieve a minimal disease state. CONCLUSION: Before consideration of high-dose therapy for recurrent/persistent advanced ovarian cancer, patients should undergo debulking surgery or chemotherapy to achieve a minimal disease state. Patients with platinum-resistant, bulky disease should not be transplanted. The optimal patients for this therapy may be those with minimal disease responsive to initial chemotherapy.

Adult↗
PubMed1997

Benztropine versus clozapine for the treatment of tremor in Parkinson's disease.

Four open-label studies have reported beneficial effects of clozapine on the tremor of idiopathic Parkinson's disease (PD). We performed a double-blind crossover trial with a 2-week washout, comparing low-dose clozapine to benztropine for the treatment of tremor in PD. Twenty-two subjects enrolled and 19 completed the study. Benztropine and clozapine were equally effective in improving tremor and the motor score of the United Parkinson's Disease Rating Scale at mean doses of 3.0 and 39 mg/day, respectively. Significant adverse events were experienced with each drug, but leukopenia was not encountered. We conclude that the atypical antipsychotic drug clozapine is helpful in the treatment of tremor in PD and should be considered when all other drug therapies fail.

Adult↗
PubMed1997

High-frequency stimulation of the globus pallidus for the treatment of Parkinson's disease.

Long-term treatment of Parkinson's disease (PD) with levodopa is complicated by the development of motor fluctuations and dyskinesias. Posteroventral pallidotomy can improve tremor, bradykinesia, rigidity, and dyskinesias in PD. We performed chronic stimulation of the globus pallidus (CSGP) to duplicate the positive results of pallidotomy with reduced risk of permanent neurologic deficit in patients with advanced PD. The lead for CSGP was stereotactically implanted with the aid of microelectrode recordings in the globus pallidus pars interna. An electrical pulse generator was implanted in the subclavicular region. Stimulation settings were adjusted by computer. Five PD patients (four men, one woman) with disabling symptoms were enrolled. Three of the patients had bilateral implants. At 3 months following the last implant, four patients rated themselves as markedly improved, and one patient was moderately improved. The amount of time in the "on" state increased from 21% at baseline to 65% at 3-month follow-up (p < 0.05). There was a significant improvement in all subscales of the UPDRS (p < 0.05). One patient had an asymptomatic intracranial bleed, one patient had transient hemiparesis during surgery with stimulation, and one patient required surgical repositioning of the lead. Adverse effects caused by stimulation were minimal. CSGP is a safe and effective procedure in PD patients with motor fluctuations and dyskinesias.

Aged↗
PubMed1997

Biological monitoring for mercury within a community with soil and fish contamination.

To assess the impact of elevated levels of inorganic mercury in soil and dust and organic mercury in fish, biological monitoring was conducted among Native Americans living next to an inactive mercury mine in Clear Lake, California. Of resident tribal members, 46% (n = 56) participated in biomonitoring. Urine mercury levels are equivalent to background, indicating that soil and dust exposures among study participants are not substantial. The average blood organic mercury level among study participants is 15.6 +/- 8.8 micrograms/l (n = 44), which is higher than levels reported by others among those who do not consume fish (2 micrograms/l). Consistent with results from other studies, a correlation between fish consumption and blood organic mercury is observed (p = 0.03). The margin between observed and established adverse effect levels for adults is examined for blood organic mercury and found to be less than 10-fold for 20% of the study population. Protective public health efforts for the study population and other similarly exposed populations, notably those who consume commercial fish products, are considered.

Adult↗
PubMed1997

Rice burning and asthma hospitalizations, Butte County, California, 1983-1992.

We investigated the association between rice burning and daily asthma hospitalizations in Butte County, California, from 1983 to 1992. Eighty-two percent of planted rice was burned, with a mean of 555 acres burned on days when burning was permitted. For 60% of the days during this period, no rice burning occurred. Peak burning occurred in fall and spring but was not correlated with criteria pollutants. Asthma admissions averaged 0.65/day and peaked in March. In the basic Poisson model with daily asthma hospitalizations as the outcome of interest, burn acreage showed a small but statistically significant elevation of risk for hospitalization per acre of rice burned [relative risk (RR) = 1.0001; 95% confidence interval (CI), 1. 00004-1.0002], after adjusting for maximum daily temperature, seasonal factors, and yearly population. In this model, burn acreage showed a dose-response effect as acreage burned increased. Days with the greatest acreage burned (>499 acres) had the largest risk of hospitalization (RR = 1.23; CI, 1.09-1.39), and days with moderate burning (between 100 and 499 acres) had a slightly lower risk of admission (RR = 1.2; CI, 1.05-1.37). Elevations of air pollutants were not associated with days of increased rice burning; however, rice burn acreage was shown to have a small but statistically significant effect on asthma morbidity in Butte County. This evidence suggests that further limitations on the daily amount of rice straw permitted to be burned should be considered to reduce pulmonary morbidity related to asthma.

Adolescent↗
PubMed1997

School-related issues among HIV-infected children.

OBJECTIVE: Many children with human immunodeficiency virus (HIV) infection are surviving long enough to reach school age. This study describes issues related to school attendance and disclosure of HIV infection in a population of HIV-infected children. METHODS: A statewide pediatric HIV surveillance system was used to collect data on school-age (>/=5 years old) HIV-infected children. In addition, HIV clinic nurses familiar with the child's history participated in a cross-sectional survey that collected information on school-related issues during the 1993-1994 school year. RESULTS: Of the 92 school-age children, only 3 were too ill to attend school. Another 5 children were home-schooled. Of the 84 who attended school outside the home, 25% had severe symptoms of HIV infection (Centers for Disease Control and Prevention [CDC] clinical category C). Absence from school ranged from less than 2 weeks during the year for half of the children (51%) to more than 8 weeks for 9 children (12%). Twenty-nine percent of the children received medication in school, usually administered by the school nurse. Over two thirds of the 50 children ages 5 to 10 years had not been told that they had HIV infection. Only 1 of the 20 children more than 10 years of age was not aware of her HIV infection. For 53% of the children attending school, no school personnel had been informed of the child's HIV infection. Administration of HIV medications at school, age of child, and treatment at one particular HIV clinic were associated with the parents' decision to inform school personnel. In the 47% of cases where the school had been informed, school nurses were most frequently notified, followed by principals and teachers. CONCLUSION: Only 3% of school-age children were too ill to attend school, and almost all were enrolled in public schools. The number of HIV-infected children reaching school age will continue to grow, and public schools will bear the responsibility for educating these children. Health care providers will increasingly be called upon for guidance by both educators and families to assure that HIV-infected children receive the best education possible.

Absenteeism↗
PubMed1997

Cost effectiveness of treatment to National Cholesterol Education Panel (NCEP) targets with HMG-CoA reductase inhibitors. Trial design.

HMG-CoA reductase inhibitors effectively reduce cholesterol levels, and this is associated with a lower rate of cardiovascular events. Some HMG-CoA reductase inhibitors are more effective than others in reducing low density lipoprotein (LDL) cholesterol, and such drugs should help patients achieve LDL cholesterol targets prescribed by the National Cholesterol Education Panel (NCEP). This paper describes the design of a trial comparing the clinical efficacy and cost effectiveness of four HMG-CoA reductase inhibitors in reducing LDL cholesterol to specified targets. This trial is being conducted in 30 physicians' practices in the USA. Its primary aim is to assess the resource use required to achieve and maintain NCEP targets by all patients randomised and followed up for one year.

Anticholesteremic Agents↗
PubMed1997

Clostridial vaccination efficacy on stimulating and maintaining an immune response in beef cows and calves.

Experiments were conducted to determine the efficacy in stimulating and maintaining an immune response in the presence of maternal antibodies, compare the extent of the anamnestic responses to revaccination, and compare the maternal antibody response of 2- or 5-mL clostridial vaccination. In Exp. 1, 118 nursing calves were randomly assigned to receive a 2-mL (Alpha-7, A7) or a 5-mL clostridial vaccine (Ultrabac 7; UB7) at 50.4 +/- 15.30 (X +/- SD) d of age (d 0 = date of calving). Calves were revaccinated with the same treatment on d 170. Blood samples were collected from 10 calves of each treatment group on d 50, 170, and 191 to determine antitoxin units for Clostridium perfringens type C (PC) and D (PD) and agglutination titers for Cl. chauvoei (CC). The A7-treated calves tended (P < .10) to have higher PC units on d 170, an increased rate of change in PD units from d 170 to d 191 (P < .06), and a tendency (P < .10) for enhanced CC titers on d 191 compared with UB7-treated calves. In Exp. 2, 109 pregnant cows and 83 pregnant heifers were randomly assigned within a 2 x 2 x 2 factorial design. The main effects were dam age (cow or heifer), dam treatment (A7 or UB7), and calf treatment (A7 or UB7). Dams were vaccinated with A7 or UB7 d 124 prepartum (d -124) and d 53 after birth. At d 53.4 +/- 12.88, calves were vaccinated with A7 or UB7 (d 53). Calves were revaccinated with the same treatment on d 173. Blood samples were collected from 10 dams per treatment group on d -124, 53, and 173 and from their calves on d 53, 173, and 194. Cows had higher antitoxin levels for PC (P < .01) and PD (P < .05) than heifers. The A7-treated dams had higher (P < .01) PD units on d 53 and d 173 and CC on d 173 than did UB7-treated dams. Calves from A7-treated cows had higher (P < .03) PD units on d 53 than calves from UB7-treated cows. The A7-treated calves had higher titers for CC (P < .01) on d 173 than did UB7-treated calves, and this enhanced level seemed to continue to d 194 (P < .08). In conclusion, titers for clostridial diseases in 50- to 53-d-old calves can be enhanced if dams are vaccinated approximately 4 mo before calving, and 120 d between clostridial vaccinations seems to be too long for adequate protection.

Agglutination Tests↗
PubMed1997

Ocular abnormalities in chronic schizophrenia: clinical implications.

OBJECTIVE: As part of a randomised double-blind study of a new atypical antipsychotic we sought to determine both the levels of visual acuity and the occurrence of toxic side-effects in a group of patients treated for many years on a variety of antipsychotics. METHODS: Twenty-three inpatients with a DSM-III-R diagnosis of chronic schizophrenia from two separate hospital locations who met the criteria for the double-blind trial were examined for ocular abnormalities at both baseline and at trial completion. RESULTS: At baseline a high prevalence of abnormalities was identified: 19 patients (82.6%) were found to have one or more ocular abnormalities, including lens opacities/cataracts and corneal pigmentation; three patients, with delusions related to the sun, were noted to have solar burns; a high proportion (almost 70%) of patients had untreated visual acuity problems. No further changes were observed at the follow-up examinations. CONCLUSIONS: The possible causes of ocular disturbance in schizophrenia and the reasons for the relatively high ocular morbidity in this group are thought to result from both illness-related factors and the effects of antipsychotic medication. Causality is confounded by a number of issues such as the high prevalence of smoking, poor general health and the variety of antipsychotic medications used in the treatment of psychosis as well as substance abuse. The clinical implications are considered in this paper in relation to the move towards community-based psychiatric services.

Adult↗
PubMed1997

Zidovudine monotherapy versus zidovudine plus zalcitabine combination therapy in HIV-positive persons with CD4 cell counts 300-500 cells/mm3: a double-blind controlled trial. The M50003 Study Group Coordinating and Writing Committee.

OBJECTIVE: To assess the safety and clinical and immunological activity of zalcitabine/zidovudine combination therapy compared with zidovudine monotherapy in persons with no or limited antiretroviral experience and CD4 counts of 300-500 cells/mm3. DESIGN AND SETTING: A double-blind controlled multi-centre study conducted in specialist human immunodeficiency virus (HIV) care centres in Spain, Portugal and Australia. Participants were randomized at study entry to zidovudine (200 mg three times daily) plus zalcitabine (0.75 mg three times daily) or matched placebo. The primary end point was the proportion of patients with CD4 above baseline value at 24 months. The secondary end points were time to AIDS/death, quality of life (by MOS-30) and safety. RESULTS: The study was terminated prematurely following the results of the Delta and ACTG 175 studies. Two-hundred and fifty-six patients entered the protocol of whom all but 15 were treatment naive. One hundred and twenty-seven patients commenced zidovudine and 129 commenced a combination of zidovudine/zalcitabine. The median duration of follow-up was 634 days with a median time on blinded therapy of 500 days. Using the last available CD4 count data, 32.4% randomized to zidovudine and 65.1% randomized to zidovudine/zalcitabine remained above baseline at study close (P < 0.001). No significant differences were observed in the time taken for CD4 count to return to baseline. Over 104 weeks, median CD4 counts rose in the combination group from 399 to 509 cells/mm3 whereas those randomized to zidovudine fell from 410 to 374 cells/mm3. Only 12 AIDS events and two deaths (both accidental) occurred during the study with no differences between groups. No differences in quality of life were observed. Adverse events were the cause of treatment discontinuation in 8.6% of patients with no differences between treatment arms. A further 8.2% of patients were lost to follow-up. At least one adverse event (all severities, all relationships) was experienced by 80.3% of patients randomized to zidovudine and 79.8% of patients on combination. Peripheral neuropathy (all grades) was reported in 10.1% of patients randomized to the combination and 3. 1% in the zidovudine arm (P = 0.026). Oral ulcers were reported in 7.8% and 4.7% of combination and zidovudine monotherapy arms, respectively. Neutropenia was more common in the zidovudine group (22%) than the combination group (14%). CONCLUSIONS: Combination of zidovudine/zalcitabine as initial therapy maintains CD4 count above commencement levels in a significantly greater proportion of patients than zidovudine monotherapy. In persons with CD4 counts > or = 300 cells/mm3 inclusion of zalcitabine with zidovudine does not increase the incidence of adverse events or adversely affect quality of life.

Adult↗
PubMed1997

Giant pseudocyst formation associated with chronic corneal edema.

A 39-year-old man with a 3-week history of an enlarging mass protruding from his right cornea is presented. Clinical and pathologic findings were compatible with a large corneal pseudocyst. Causes of corneal cyst and pseudocyst formation, as well as a proposed mechanism for the giant pseudocyst formation presented here, are discussed.

Adult↗
PubMed1997

Sporadic medullary thyroid carcinoma associated with toxic multinodular goitre.

First described in 1959, medullary thyroid carcinoma (MTC) arises from parafollicular C cells distributed throughout the thyroid, and may occur in one of two clinical forms, sporadic (80%) or familial. Familial MTC may present as a palpable thyroid nodule, but may also be diagnosed by screening relatives of an index case for a raised basal serum calcitonin or a rise in calcitonin following a stimulated pentagastric test. Both tests are highly sensitive for C-cell hyperplasia and MTC. Sporadic cases of MTC most commonly present as asymptomatic thyroid nodules with normal thyroid function tests. In this note, the history of a patient is presented in which a sporadic MTC was associated with goitre and both symptoms and biochemical evidence of thyrotoxicosis.

Adult↗
PubMed1997

Physiological and neuroendocrine correlates of social position in normotensive and hypertensive rat colonies.

The hypothesis to be tested was that socially dominant (D) males in a mixed gender rat colony will have: higher blood pressure (BP) decreased hypothalamic pituitary axis (HPA) activity measured by plasma corticosterone (C) and increased sympathetic activity measured by plasma noradrenaline (NA) as compared to socially subordinate (S) males. BP was measured continuously by implanted aortic telemetry (Data Sciences, MN), plasma noradrenaline measured by HPLC with electrochemical detection and plasma C by RIA. Colonies were established using 8 of each sex of 4 strains: SHR, WKY, and our two Y chromosome congenic strains, SHR/y and SHR/a. Social ranking was determined by physical scarring scores, overall locomotor activity and patrol behaviour. D males had higher BP (active dark cycle) across strains compared to subordinates S: SHR-180 vs 148 mmHg, WKY-145 vs 142 mmHg, SHR/y-185 vs 145 mmHg, SHR/a-180 vs 160 mmHg. Using an acute stressor, BP responsiveness was higher in D than in S SHR and SHR/y males. D males had higher NA levels than S males across strains: (SHR-76% increase, WKY-31% increase, SHR/y-29% increase, SHR/a-40% increase). S males had significantly higher C levels than D males across strains (SHR-29% increase, WKY-123% increase, SHR/y-25% increase, SHR/a-61% increase). The hypertensive Y chromosome (SHR or SHR/y) produced higher SBP during the active dark cycle in D males than in D males with a normotensive Y chromosome (WKY or SHR/a). In conclusion, D males from related hypertensive strains showed elevated sympathetic activity measured by plasma NA and reduced HPA activity measured by plasma C as compared to S males. (Supported by HL-48072-04).

Animals↗
PubMed1997

Analysis of urinary progesterone metabolites with behavioral correlation in Guenther's dik-dik (Madoqua guentheri).

Urine samples and behavioral data were collected from nine adult female Guenther's dik-dik (Madoqua guentheri) from September 1989-November 1992. The durations of predefined individual behaviors were recorded during focal sampling periods and ad libitum. Immunoreactive pregnanediol-3-glucuronide (PdG) concentration in dik-dik urine was determined by radioimmunoassay. The immunoreactive PdG radioimmunoassay was validated for use with dik-dik by determining parallelism [F(alpha=0.05,1,4) = 0.04) between a serially diluted PdG standard and serially diluted dik-dik urine. Behavioral estrus was manifested by lordosis. Eighty-nine percent of the estrous behavior occurred during or within 2 days of the interluteal phase period, as delineated by immunoreactive PdG concentrations; thus, a high degree of correlation between hormone concentrations and behavioral data was observed. The mean (+/-SD) luteal phase, interluteal phase, and estrous cycle lengths were 14.4+/-5.5 days (range, 6-29 days; n = 50), 6.6+/-5.1 days (range, 2-33 days; n = 50), and 20.2+/-6.6 days (range, 10-43 days; n = 48), respectively. During the collection period, one animal conceived, with a gestation period of 170 days. Estrous cyclicity occurred throughout the year, with no evidence of seasonality. Cochromatography of pooled urine samples with radiolabeled PdG indicated that the major progesterone metabolite detected by the immunoreactive PdG antibody during luteal phase and pregnancy was not PdG. This is the first detailed description of female dik-dik reproductive endocrine activity.

Animals↗