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Biomedical subjects

D Williams

Publications and source records attributed to D Williams.

At least 415 records · Page 23Linked to original sources
PubMed1989

A phase I clinical trial of combined fluoropyrimidines with leucovorin in a 14-day infusion. Demonstration of biochemical modulation.

Two consecutive Phase I trials of continuous infusion 5-fluorouracil (5-FU) or floxuridine (5-FUdR) admixed with leucovorin (LCV) were performed and involved 19 and 24 patients, respectively. The studies were carried out to identify the optimal dose rate of delivery for the two admixtures (5-FU + LCV and 5-FUdR + LCV) administered for 14 days, and to determine if biochemical modulation could be identified. The optimal dose rates for 5-FU plus LCV were 200 mg/m2/d and 5 mg/m2/d, respectively. The optimal dose rates for 5-FUdR plus LCV were 0.075 mg/kg/d and 5 mg/m2/d, respectively. The dose rate limiting toxicity for 5-FU plus LCV was stomatitis and for 5-FUdR plus LCV it was diarrhea. LCV administered as an admixture with either 5-FU or 5-FUdR on an infusion schedule decreases the optimally tolerated dose rates for these two agents to 83% and 60%, respectively. This is achieved with low-dose LCV infusions.

Adult↗
PubMed1989

Molecular cloning of the translocation breakpoint in T-ALL 11;14 (p13;q11): genomic map of TCR alpha and delta region on chromosome 14q11 and long-range map of region 11p13.

Using chromosome walking techniques, overlapping lambda and cosmid clones from the T cell receptor alpha (TCR alpha) region have been isolated; these span the entire J alpha region and parts of the TCR delta gene. Molecular analysis of the acute childhood leukemia cells (T-ALL) 8511 revealed a rearrangement on one chromosome 14 in J alpha 58 kb 5' of C alpha; this does not result in production of alpha message. The translocation was identified 90 kb 5' of C alpha at the previously identified J delta 2 element. A probe derived from the 5' region of the translocation breakpoint hybridized to DNA from a mouse-human cell hybrid containing chromosome 11 as the only human chromosome. This probe was used to isolate cosmid clones from chromosome 11. Several rare cutting restriction enzyme sites were found in close vicinity to the translocation breakpoint, and a long-range map spanning 1000 kb of chromosome region 11p13 was established. Analysis of the DNA from 15 cases of sporadic and familial Wilms' tumor did not reveal any changes, indicating that the translocation breakpoint does not reside in this gene.

Blotting, Southern↗
PubMed1989

The influence of racial factors on psychiatric diagnosis: a review and suggestions for research.

Research on race and diagnosis initially focused on black-white differences in depression and schizophrenia. Statistics showing a higher treated prevalence of schizophrenia and a lower prevalence of depression for blacks seemed to support the claim that blacks did not suffer from depression. Others argued, however, that clinicians were misdiagnosing depression in blacks. This article reviews empirical studies of racial differences in individual symptoms and summarizes the evidence on misdiagnosis. It argues that more attention must be paid to resolving two contradictory assumptions made by researchers working in the area of race and diagnostic inference: (1) blacks and whites exhibit symptomatology similarly but diagnosticians mistakenly assume that they are different; (2) blacks and whites display psychopathology in different ways but diagnosticians are unaware of or insensitive to such cultural differences. The article concludes with suggested research directions and a discussion of critical research issues.

Black or African American↗
PubMed1989

Early identification of high-risk patients using the "estimated" injury severity score and age.

A prospective study was undertaken over a 2 1/2 year period (July 1, 1985-December 31, 1987) to determine the value of a prospective anatomical severity score ["Estimated" Injury Severity Score (EISS)], in combination with age, for early risk assessment. Five hundred ninety-two blunt trauma patients were used to develop a predictive model of mortality through a logistic regression. The model was validated using 216 patients; a high degree of agreement (Kappa 0.73) was found. When isolated head injuries were removed from the model and validation groups, the Kappa increased to 0.80. Prospective anatomical scoring in combination with age may help to identify high-risk trauma patients early during their care.

Adolescent↗
PubMed1989

Effects of etching time on surface morphology and adhesion of a posterior resin to glass-ionomer cement.

This study examined the effects of etching time on surface morphology and adhesion of posterior composite resin to glass-ionomer cement. Three glass-ionomer cements and four etch times were studied. Bond shear strength results revealed significant differences by both cement and etch time. Glass-ionomer surfaces etched for 30 seconds produced the strongest bond to resin. Ketac-Silver cement provided greater shear resistance than either Ketac-Bond cement or GC lining cement. Scanning electron microscopy revealed greater surface roughness for etched versus unetched glass ionomer. However, no subsurface differences were noted with increased etch times. These findings indicate that 30 seconds is the optimal etch time for glass-ionomer cement and that Ketac-Silver cement provides the strongest bond to resin of any of the materials tested. Etched glass-ionomer subsurfaces did not reveal marked differentiation in morphology, suggesting that an alternative method is necessary to detect these differences.

Acid Etching, Dental↗
PubMed1989

Serial angiographic findings during the development of a saccular aneurysm of the coronary artery in association with unstable angina.

A 60 year old man presented with unstable angina and electrocardiographic features suggestive of disease of the left anterior descending coronary artery. Angiography showed slight proximal narrowing in this artery with reduced density of contrast that suggested an associated thrombus. Repeat angiography after 24 hours of heparin administration showed the development of a small saccular aneurysm. Three weeks later, after a further episode of unstable angina, angiography showed enlargement of the aneurysm. Although there were no further episodes of angina, repeat angiography three months after the initial event showed further slight enlargement of the aneurysm. It is suggested that the episodes of angina at rest were secondary to embolisation of thrombotic or atheromatous material or both.

Angina Pectoris↗
PubMed1989

Efficacy of barbiturates in the treatment of resistant intracranial hypertension in severely head-injured children.

Cerebral perfusion pressures (CPP) of less than 50 torr are associated with marginal cerebral blood flow and poor outcome. We report our experience with a group of 7 children who survived long period with CPP of less than 50 torr during treatment with pentobarbital. The study group was identified through a retrospective review of all head-injured patients admitted to Cardinal Glennon Memorial Hospital for Children between 1984 and 1986. All of the patients presented had sustained intracranial pressure of greater than 20 torr which was resistant to conventional therapy. All patients received pentobarbital for at least 24 h and all had documented CPP of less than 50 torr for more than 30 min during that time. Of these 7 children: 3 made good recoveries; 2 are moderately disabled, and 2 are vegetative. Neither the CPP nor the length of pentobarbital coma was an accurate predictor of outcome. It seems likely that these children are a subset of those previously defined as having resistant intracranial hypertension and that, as a group, they may have benefited from pentobarbital administration. It is also apparent that, in this group, low CPP was not indicative of irreversible brain damage or brain death.

Adolescent↗
PubMed1989

One-year follow-up results of the 1985-1986 National Heart, Lung, and Blood Institute's Percutaneous Transluminal Coronary Angioplasty Registry.

In 1,801 patients in the 1985-1986 Percutaneous Transluminal Coronary Angioplasty Registry, overall 1-year mortality was 3.2%, the 1-year myocardial infarction rate was 7.2%, and the 1-year coronary artery bypass surgery rate was 13.2%. In the 78% of the cohort with all lesions successfully dilated and without major procedural complications (successful patients), the corresponding rates were 1.9%, 2.6%, and 6.4%. Nearly 20% of all deaths, 40% of all infarctions, and 25% of all bypass operations occurred in the small subset of patients (6.8%) who sustained periprocedural occlusion. Event rates were higher in patients with multivessel disease than in those with one-vessel disease. At 1 year, angina-free status was reported by approximately three fourths of all surviving patients, regardless of initial success. However, compared with successful patients, unsuccessful patients underwent intervening bypass surgery (42% vs. 6%) to achieve asymptomatic status more frequently. Comparison of the 1-year event rates in the 1985-1986 registry with those in the 1977-1981 registry indicated reductions in all major untoward events. These reductions became apparent after controlling for the more extensive disease of the 1985-1986 registry patients. In contrast, use of repeat angioplasty has increased by 50%. We conclude that the improved initial results reported in the 1985-1986 registry cohort were maintained at 1-year follow-up.

Angina Pectoris↗
PubMed1989

Translocations and rearrangements in T-cell acute leukemias with the t(11;14) (p13;q11) chromosomal translocations.

Chromosomal translocations involving the T-cell receptor alpha and delta genes at q11 on chromosome 14 are the most common cytogenetic abnormalities in patients with T-cell tumors. We have demonstrated that the t(11;14)(p13;q11) translocation in two T-ALL patients involves the J delta region suggesting that the translocation proceeds or coincides with delta gene rearrangement. Additional rearrangements on both normal and translocated chromosomes 14 are described including rearrangement of both Tcr-alpha and Tcr-delta genes, and deletions within the J alpha region. The polyclonality of rearrangements on the normal chromosome 14 in one of the patient samples demonstrates that T-cell receptor rearrangement continues after the translocation event. The identification of clonally expanded rearrangements involving both the Tcr-delta and the Tcr-alpha genes in a single patient suggests a cascade model for delta----alpha expression may be a viable pathway for T-cell maturation.

Base Sequence↗
PubMed1989

The clonal origin of thyroid nodules and adenomas.

The clonal origin of thyroid tumors in female mice heterozygous for a deficiency of the X-linked enzyme glucose-6-phosphate dehydrogenase (G6PD) was studied. Tumor phenotype was demonstrated by enzyme histochemistry. Because monophenotypia is not synonymous with monoclonality, a method to estimate the degree of mingling of the two cellular phenotypes in normal tissue was devised. Twenty-five point three percent of 624 randomly chosen pairs of adjacent follicular cells were of unlike phenotype, suggesting that if tumors were derived from 2 or more cells at least a quarter would express polyphenotypia. Four hundred fifty-three thyroid lesions induced in 20 GPDX (enzyme-deficient) mice, 20 C3H (normal) mice, and 48 heterozygous (C3HxGPDX) mice by radiation and long-term goitrogen treatment were studied. One hundred twenty-eight adenomas (sharply defined or encapsulated hypercellular lesions) were found in heterozygotes; 108 (84%) were monophenotypic, and 20 (16%) were largely monophenotypic with degenerate areas or included normal cells. None were clearly polyphenotypic. Seventy-five nodules (circumscribed but not encapsulated, largely normocellular lesion with prominent stroma) were found in heterozygotes; 25 (33%) only were monophenotypic. It is concluded that thyroid adenomas are monoclonal and nodules polyclonal. The variegated pattern of polyphenotypia in the nodules together with their prominent stromal component leads to the suggestion that there is a causative role for the stroma in their generation.

Adenoma↗
PubMed1988

Combined floxuridine and cisplatin in a fourteen day infusion. Phase I study.

Twenty patients received 28 courses of 5FUDR (floxuridine) admixed with Cisplatin (CDDP) and administered as a continuous infusion for 24 hours for 14 consecutive days. Pharmaceutical studies of the admixture of 5FU with CDDP and 5FUDR with CDDP demonstrated that only 5FUDR was compatible with CDDP and that the admixture was stable for 7 days. This Phase I study established the optimal dose rate for the individual components of the admixture and demonstrated that CDDP decreases the maximum tolerated dose rate for 5FUDR. The optimal dose rate for 5FUDR is 0.075 mg/Kg/d, and for CDDP the optimal dose rate is 7.5 mg/M2/d. Dose rate limiting toxicity is an enteritis which is radiographically similar to regional enteritis and is related to the 5FUDR. An ancillary finding was a significant decrease in serum magnesium levels in 11 of 13 monitored courses presumably related to the platinum.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1988

Demonstration of somatic mutation and colonic crypt clonality by X-linked enzyme histochemistry.

Cellular mosaicism resulting from X-chromosome inactivation in heterozygous females can be shown histochemically; using this approach we have demonstrated age-related gene reactivation and tumour clonality. We now show in female mice heterozygous for reduced expression of glucose-6-phosphate dehydrogenase (G6PD) activity that colonic epithelial cells express either normal or low enzyme activity, and form patches composed of multiple crypts of uniform phenotype. We also show that a low-enzyme colonic epithelial cell phenotype can be induced in normal mice by carcinogen treatment, these cells again occur in patches, but are restricted to scattered single crypts, the frequency of which is related to treatment. A small proportion of colonic tumours in carcinogen treated normal mice are also of low-enzyme phenotype. We conclude that we have visualized the effects of a sporadic carcinogen induced somatic mutation in the G6PD gene of crypt stem cells and that a single stem cell maintains each colonic crypt. This inducible defective activity of a ubiquitous 'housekeeping' enzyme provides a somatic clonal marker system of wide potential application.

Animals↗
PubMed1988

Colposcopic assessment of the accuracy of cervical cytology screening.

Two hundred asymptomatic women in a general practice were screened both cytologically and colposcopically for evidence of cervical intraepithelial neoplasia. The prevalence detected by cytology alone was 5%, but the prevalence detected by cytology and colposcopy together was 11%. None of the larger lesions of cervical intraepithelial neoplasia (affecting more than two quadrants of the cervix) was associated with negative cytology. The false negative cytology rate for smaller lesions was 58%. The clinical importance of the smaller lesions that were not accurately detected by cytology screening is unknown. As these lesions affected 6% of the screened population further studies of their clinical course are urgently required. Local destructive treatment in such cases may represent considerable overtreatment. If these lesions prove to be clinically important, however, the results of this study predict an increasing epidemic of preinvasive and invasive disease of the cervix.

Adolescent↗
PubMed1988

Percutaneous transluminal coronary angioplasty in 1985-1986 and 1977-1981. The National Heart, Lung, and Blood Institute Registry.

In August 1985, the Percutaneous Transluminal Coronary Angioplasty Registry of the National Heart, Lung, and Blood Institute reopened at its previous sites to document changes in angioplasty strategy and outcome. The new registry entered 1802 consecutive patients who had not had a myocardial infarction in the 10 days before angioplasty. Patient selection, technical outcome, and short-term major complications were compared with those of the 1977 to 1981 registry cohort. The new-registry patients were older and had a significantly higher proportion of multivessel disease (53 vs. 25 percent, P less than 0.001), poor left ventricular function (19 vs. 8 percent, P less than 0.001), previous myocardial infarction (37 vs. 21 percent, P less than 0.001), and previous coronary bypass surgery (13 vs. 9 percent, P less than 0.01). The new-registry cohort also had more complex coronary lesions, and angioplasty attempts in these patients involved more multivessel procedures. Despite these differences, the in-hospital outcome in the new cohort was better. Angiographic success rates according to lesion increased from 67 to 88 percent (P less than 0.001), and overall success rates (measured as a reduction of at least 20 percent in all lesions attempted, without death, myocardial infarction, or coronary bypass surgery) increased from 61 to 78 percent (P less than 0.001). In-hospital mortality for the new cohort was 1 percent, and the nonfatal myocardial infarction rate was 4.3 percent. Both rates are similar to those for the old registry. The long-term efficacy of current angioplasty remains to be determined.

Age Factors↗