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Biomedical subjects

B McDonald

Publications and source records attributed to B McDonald.

At least 109 records · Page 6Linked to original sources
PubMed1984

Cisplatin. An active drug in the treatment of disseminated gastric cancer.

Cis-diamminedichloroplatinum (DDP) was administered at 100 mg/m2 intravenously bolus with every 3-week schedule in patients with measurable and nonmeasurable incurable gastric cancer. Twenty patients were treated, 12 with measurable and 8 with nonmeasurable disease. Four of the 12 (33%) patients with measurable lesions had objective remissions. One remission was complete, lasting 60+ weeks. Patients with nonmeasurable disease were not eligible for response evaluation; they were followed for toxicity and survival. Hematologic, renal, and gastrointestinal toxicities were similar to those reported in other patient populations receiving DDP. Neurotoxicity proved to be dose limiting in two patients. The median survival was 38+ weeks for responders, 24 weeks for all patients, and 13 weeks for those 8 patients with nonmeasurable disease. DDP should be considered an active drug against gastric cancer. A better understanding of the dose response relationship for DDP in gastric cancer is necessary before the best dose and schedule can be chosen for DDP in combination with other active agents.

Adenocarcinoma↗
PubMed1984

C-II anapolipoproteinemia and severe hypertriglyceridemia. Report of a rare case with absence of C-II apolipoprotein isoforms and review of the literature.

A new case of C-II anapolipoproteinemia (complete apolipoprotein C-II deficiency) as the cause of severe hypertriglyceridemia with chylomicronemia (type I lipoprotein phenotype) is described. The patient was a five-year-old boy living in Connecticut. He had splenomegaly, episodic abdominal pain, and bloody stools. Absence of apolipoprotein C-II (and its isoforms C-II1 and C-II2) was documented by a sensitive and specific radioimmunoassay, analytical isoelectric focusing, and in vitro lipolytic assay. Decreased levels of high- and low-density lipoprotein cholesterol and apolipoproteins A-I and A-II and increased levels of plasma triglycerides and apolipoprotein E were found. Post-heparin extra-hepatic lipoprotein lipase activity was within normal range. Incorporation of exogenous purified human apolipoprotein C-II to an incubation mixture of purified lipoprotein lipase and the patient's triglyceride-rich lipoproteins resulted in a dramatic increase in the catabolic rate of the defective triglyceride-rich lipoproteins. The absence of the isoforms of apolipoprotein C-II in this patient indicates that a common gene exists for the C-II isoproteins, which appear to be necessary for normal triglyceride transport in humans. A literature review of 23 reported cases indicates that xanthomas and hepatosplenomegaly are less common in C-II anapolipoproteinemia than in lipoprotein lipase deficiency, the other major etiologic cause of genetic chylomicronemia.

Adolescent↗
PubMed1984

Drug combinations in the treatment of gastric adenocarcinoma: a randomized Southwest Oncology Group study.

The FAM combination with the simultaneous administration of 5-fluorouracil, doxorubicin, and mitomycin C is considered standard chemotherapy for gastric adenocarcinoma. This study was initiated to determine whether a kinetically designed sequential administration of these three drugs would be superior and whether the presence or absence of easily measurable tumor would imply differences in survival. To do so, the Southwest Oncology Group tested two schedules in a randomized study of 239 patients. Independent judgments of response were made by two authors with the same results. Equivalent response rates (23% of all eligible sequential and 30% simultaneous) and median survival durations (22 and 23 weeks, respectively) were seen. Patients with and without readily measurable tumors each lived a median of 22 weeks. Higher degrees of hematologic toxicity were associated with prolonged survival (median 27 weeks versus 20 weeks, p = 0.04). Patients treated by community oncologists were described as having higher response rates than those treated in major medical centers (64% versus 31%, p = 0.03). The meaning of this is questionable in that there were no statistical differences in survival or toxicity. Those with prior exposure to 5-fluorouracil had only a tendency, without statistical significance, for a slightly inferior response and survival.

Adenocarcinoma↗
PubMed1983

Randomized comparisons of radiotherapy and CCNU versus radiotherapy, CCNU plus procarbazine for the treatment of malignant gliomas following surgery. A Southwest Oncology Group Report.

One hundred and fifteen eligible patients with histologically verified malignant gliomas (astrocytoma grade III-IV) were randomized to receive either radiotherapy 6 000 rads/7 week plus CCNU 130 mg/M2 every 6 weeks (treatment 1) or radiotherapy 6 000 rads/7 weeks plus CCNU 75 mg/M2 day 1 plus procarbazine 100 Mg/m2 days 1-14 every 6 weeks (treatment 2) within 4 weeks following surgical resection. The response rates showed no statistically significant differences between treatment 1 CR/PR - 24/17% and treatment 2 CR/PR - 14/14% (P-value = 0.31). The median survival was also not significantly different: 55 and 50 weeks for treatments 1 and 2, respectively. The most important prognostic parameter identified was age with younger patients showing higher response rates and longer survival. Patients' performance status was also a useful prognostic parameter for response and survival. Neither the extent of surgical resection nor the tumor grade correlated significantly with the outcome. Further studies are needed to identify active chemotherapeutic agents for the treatment of brain tumors.

Brain Neoplasms↗
PubMed1982

Clinical trial of chlorozotocin, DTIC, and dactinomycin in metastatic malignant melanoma.

Thirty evaluable patients with metastatic malignant melanoma were treated with a combination of chlorozotocin, DTIC, and dactinomycin. One complete and four partial responses were achieved, for an overall response rate of 17%. Cumulative myelotoxicity was noted, as well as universal gastrointestinal intolerance. One patient developed probable drug-related nephrotoxicity. A survival advantage was noted for responding patients. We conclude that the addition of chlorozotocin did not improve response rate or response duration and that further trials with this drug combination cannot be recommended.

Adolescent↗
PubMed1978

Phase I--II study of intermittent bolus administration of DTIC and actinomycin D in metastatic malignant melanoma.

Twenty-six patients with disseminated malignant melanoma were treated with intermittent bolus DTIC and actinomycin D in an escalating dose schedule, starting at 650 and 1 mg/m2 respectively. Courses were repeated at 3--4-week intervals. Twenty four patients were evaluable for toxicity and 22 were evaluable for response. Two patients (9%) had a complete remission lasting 7+ and 14 months, and three patients (14%) had a partial remission lasting 2+, 5+, and 14+ months. Nausea and vomiting, lasting 24 hours, was observed in 88% of patients, while diarrhea was noted in 17%. Stomatitis and alopecia were less frequently observed. All responses occurred at nonmyelosuppressive doses and in patients with visceral-predominant metastases. This schedule offers the patient the convenience of single-day treatment and less prolonged gastrointestinal intolerance. Further evaluation of this drug combination and schedule would appear to be indicated.

Adult↗
PubMedDate not supplied

Accuracy of clinical operational diagnostic criteria for Alzheimer's disease in relation to different pathological diagnostic protocols.

In this study we analysed the accuracy of two sets of clinical diagnostic criteria, the NINCDS/ADRDA and DSM-III-R, in relation to the currently used pathological diagnostic criteria for Alzheimer's disease (AD), the Khachaturian criteria, the Tierney A3 criteria and the CERAD protocol. The sensitivity of the individual clinical diagnostic criteria, NINCDS/ADRDA and DSM-III-R, is poor (34-58%) irrespective of the pathological diagnostic criteria applied for the definite diagnosis of AD. The combination of the NINCDS/ ADRDA 'possible' and 'probable dementia of the Alzheimer type' (DAT) categories has a high sensitivity (91-98%). However the combination resulted in very poor specificity (40-61 %). Thus, none of the clinical diagnostic criteria is satisfactory. We found similar results when we analysed the predictive value of these clinical diagnostic criteria. The positive predictive value of NINCDS 'probable DAT' category and that of the DAT diagnosis by DSM-III-R is very high (89-100%). This makes the use of these categories suitable for research purposes. However, the negative predictive value of both diagnoses is poor (33-63%), making these criteria unsuitable for diagnostic purposes in clinical practice.

Aged↗
PubMedDate not supplied

Clustering of pathological features in Alzheimer's disease: clinical and neuroanatomical aspects.

We have analyzed the tendency of amyloid load, neuritic plaques and neurofibrillary tangles (NFT) in the hippocampus and neocortex to occur in clusters in 49 consecutive cases of Alzheimer's disease (AD). This clustering tendency of the pathology was analysed in relation to severity of clinical disease assessed within 6 months before death, duration and age at onset of disease and at death. Amyloid plaques showed only a slight tendency to cluster together while neuritic plaques and, even more, NFT were clearly clustered. A greater clustering tendency was associated with more severe clinical impairment with particularly strong correlations being found between the clustering tendency of NFT in the hippocampus and clinical memory deficit, and between the clustering tendency of NFT in the parietal neocortex and overall cognitive deficit. Neuritic plaques showed similar but less pronounced and robust correlations between clustering and cognitive status. In the hippocampus NFT clustering was also negatively correlated with age at death, but not duration of disease nor age of disease onset. We conclude that clustering characterises neuritic pathology but not diffuse amyloid deposits and significantly affects cognition. The discrepancies between the group diagnosed as AD-only and the patient group that contained all patients, including the ones with mixed pathology, lead us to believe that any additional pathology might have a significant effect on the cognitive status of AD patients.

Alzheimer Disease↗
PubMedDate not supplied

Relative roles of plaques and tangles in the dementia of Alzheimer's disease: correlations using three sets of neuropathological criteria.

We have performed a quantitative analysis of the amyloid load (plaques), neuritic plaques and neurofibrillary tangles (NFT) in the frontal, temporal and parietal association cortices of autopsied brains from 49 prospectively evaluated patients with Alzheimer's disease (AD) diagnosed according to three sets of published pathological criteria. These patients had been assessed clinically with psychological testing of cognitive abilities within 6 months of death. Correlations were sought between severity of pathological change and cognitive status before death, duration of disease and age at death. Using Khachaturian and CERAD criteria highly positive correlations were obtained between the extent of cognitive deficit and the density of NFT in frontal and parietal lobes. The percentage area of cortex occupied by amyloid in the parietal lobe was correlated to the cognitive deficit only in the CERAD-diagnosed cases. The density of all amyloid plaques (AP) showed no correlation with the extent of cognitive deficit, but the densities of neuritic plaques did correlate with cognitive deficit. Both amyloid load and tangle densities were positively correlated with disease duration. All these correlations were reduced or absent in a subgroup of cases fulfilling the Tierney et al. A3 diagnostic criteria for AD. We found no pathological measure that correlated with the age of patients at death. Amyloid loads and NFT densities showed highly significant but selective positive correlations, the most striking being between temporal lobe NFT density and frontal and parietal lobe amyloid load and between temporal lobe NFT density and frontal and parietal lobe NFT densities. Correlations involving AP density as a measure of amyloid load were almost always less significant than those involving the percentage area of cortex occupied by amyloid, suggesting that the latter measures amyloid load more accurately. However, the highest correlations of NFT densities were with neuritic plaque densities. Overall this study highlights the relevance of neuritic changes (revealed by NFT and neuritic plaques) and the irrelevance of amyloid plaques to the dementia of AD.

Aged↗
PubMedDate not supplied

Microanalysis of senile plaques using nuclear microscopy.

Silver-staining "senile" plaques occurring in the brain are a major part of the pathology of Alzheimer's disease. The elemental composition of these structures, and the possible presence of aluminum and silicon in these structures, has been the subject of an increasing research effort over the last decade. However, the results have often been contradictory. Using a scanning proton microprobe, the elemental composition of senile plaques has been determined. This instrument, similar to an electron probe, uses a focused beam of protons scanned across a sample to map the elements. The technique is absolutely quantitative and is sensitive down to the parts per million level. Tissue from six cases of clinically and pathologically characterized cases of Alzheimer's disease and two aged neurologically normal controls was scanned. It was found that aluminum and silicon occur at a level of 50 ppm or greater in the cores of 20% of senile plaques and that the total occurrence of aluminum or silicon in scans containing plaques was not above background. The major uncertainties affecting interpretation of results of this kind are discussed, and it is suggested that the least controllable factor is contamination in the reagents used to prepare and stain the tissue. This indicates that until plaques can be unambiguously identified and analyzed in untreated tissue, no conclusion can be reached on whether senile plaques contain aluminum and silicon.

Aged↗