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Biomedical subjects

M V Williams

Publications and source records attributed to M V Williams.

At least 73 records · Page 4Linked to original sources
PubMed1996

Short-course adjuvant chemotherapy in high-risk stage I nonseminomatous germ cell tumors of the testis: a Medical Research Council report.

PURPOSE: This United Kingdom Medical Research Council (UK-MRC) study prospectively evaluated efficacy and long-term toxicity of adjuvant chemotherapy in high-risk stage I nonseminomatous germ cell tumors of the testis (NSGCTT). PATIENTS AND METHODS: Eligible patients were those identified by the local histopathologist as having features confirmed in MRC surveillance studies to indicate an approximate 50% risk of relapse. Central histopathology review was undertaken. Chemotherapy consisted of two courses of cisplatin 100 mg/m2, bleomycin 30 mg weekly x 3, and etoposide 120 mg/m2 x 3, every 21 days (BEP). RESULTS: One hundred fourteen eligible cases were enrolled. Median time of follow-up was 4 years, with 93 patients followed-up for at least 2 years. There have been two relapses, including one patient who did not have a germ cell tumor (GCT), according to the reference histopathologist. This patient is alive with active disease, the other has died. There was one death after a cerebrovascular accident during treatment. Assessment of fertility, lung function, and audiometry pretreatment and more than 9 months posttreatment indicated no clinically significant changes. A mean decrease in transfer factor coefficient (KCO) of 15% of the predicted value was noted, but no patient had symptomatic respiratory dysfunction. CONCLUSION: There have been only two relapses among 114 cases of high-risk stage I NSGCTT treated with two courses of adjuvant BEP chemotherapy. The 95% confidence interval (CI) excludes a true relapse rate of more than 5%. Of 104 patients confirmed on histopathology review to have GCT, there has been only one relapse. Adjuvant chemotherapy is free from significant long-term toxicity, offering an effective alternative to surveillance or retroperitoneal lymph node dissection (RPLND) followed by surveillance, and may be preferred by some patients.

Adult↗
PubMed1995

Inadequate functional health literacy among patients at two public hospitals.

OBJECTIVE: To determine the ability of patients to complete successfully basic reading and numeracy tasks required to function adequately in the health care setting. DESIGN: Cross-sectional survey. SETTING: Two urban, public hospitals. PATIENTS: A total of 2659 predominantly indigent and minority patients, 1892 English-speaking and 767 Spanish-speaking, presenting for acute care. MAIN OUTCOME MEASURE: Functional health literacy as measured by the Test of Functional Health Literacy in Adults (TOFHLA), an instrument that measures ability to read and understand medical instructions and health care information presented in prose passages and passages containing numerical information (eg, prescription bottle labels and appointment slips). RESULTS: A high proportion of patients were unable to read and understand written basic medical instructions. Of 2659 patients, 1106 (41.6%) were unable to comprehend directions for taking medication on an empty stomach, 691 (26%) were unable to understand information regarding when a next appointment is scheduled, and 1582 (59.5%) could not understand a standard informed consent document. A total of 665 (35.1%) of 1892 English-speaking patients and 473 (61.7%) of 767 Spanish-speaking patients had inadequate or marginal functional health literacy. The prevalence of inadequate or marginal functional health literacy among the elderly (age > or = 60 years) was 81.3% (187/230) for English-speaking patients and 82.6% (57/69) for Spanish-speaking patients, and was significantly higher (P < .001) than in younger patients. CONCLUSIONS: Many patients at our institutions cannot perform the basic reading tasks required to function in the health care environment. Inadequate health literacy may be an important barrier to patients' understanding of their diagnoses and treatments, and to receiving high-quality care.

Adolescent↗
PubMed1995

The test of functional health literacy in adults: a new instrument for measuring patients' literacy skills.

OBJECTIVE: To develop a valid, reliable instrument to measure the functional health literacy of patients. DESIGN: The Test of Functional Health Literacy in Adults (TOFHLA) was developed using actual hospital materials. The TOFHLA consists of a 50-item reading comprehension and 17-item numerical ability test, taking up to 22 minutes to administer. The TOFHLA, the Wide Range Achievement Test--Revised (WRAT-R), and the Rapid Estimate of Adult Literacy in Medicine (REALM) were administered for comparison. A Spanish version was also developed (TOFHLA-S). SETTING: Outpatient settings in two public teaching hospitals. PATIENTS: 256 English- and 249 Spanish-speaking patients were approached. 78% of the English- and 82% of the Spanish-speaking patients gave informed consent, completed a demographic survey, and took the TOFHLA or TOFHLA-S. RESULTS: The TOFHLA showed good correlation with the WRAT-R and the REALM (correlation coefficients 0.74 and 0.84, respectively). Only 52% of the English speakers completed more than 80% of the questions correctly. 15% of the patients could not read and interpret a prescription bottle with instructions to take one pill by mouth four times daily, 37% did not understand instructions to take a medication on an empty stomach, and 48% could not determine whether they were eligible for free care. CONCLUSIONS: The TOFHLA is a valid, reliable indicator of patient ability to read health-related materials. Data suggest that a high proportion of patients cannot perform basic reading tasks. Additional work is needed to determine the prevalence of functional health illiteracy and its effect on the health care experience.

Adult↗
PubMed1994

Pilot studies of 2 and 1 course carboplatin as adjuvant for stage I seminoma: should it be tested in a randomized trial against radiotherapy?

PURPOSE: Underpinned by increased confidence in cure of metastatic seminoma by chemotherapy during the past 12 years, three management strategies for Stage I seminoma have been evaluated by six collaborating centers within the Anglian Germ Cell Tumor Group. This paper evaluates the efficacy of surveillance, prophylactic radiotherapy and adjuvant chemotherapy, and discusses these differing management approaches. METHODS AND MATERIALS: Patients were recruited into the study between 1982 and 1992. There was no randomization between treatment groups. Seventy-nine patients received prophylactic radiotherapy (median follow-up = 51 months), 67 patients had surveillance alone (median follow-up = 61 months) and 78 patients were treated with adjuvant single agent platinum (median follow-up = 44 months). Fifty-three of these patients received two courses of platinum (median follow-up = 51 months) and 25 patients received one course (median follow-up = 29 months, range 22-72 months). RESULTS: There were 18 (27%) recurrences on surveillance, five (6%) after radiotherapy, one (1%) after two courses of adjuvant single agent platinum and none after one course of carboplatin. There was one death from testis cancer after radiotherapy and none after adjuvant chemotherapy treatments. Two patients died with drug resistant disease after relapse on surveillance. There was one death from a myocardial infarction after prophylactic radiotherapy and one death from suicide in the surveillance group. A retrospective quality of life questionnaire reviewing the incidence of early and late toxicity revealed no major differences though they suggest that those treated with one course adjuvant carboplatin had somewhat less sickness and an earlier return to work. CONCLUSION: Single agent carboplatin appears well tolerated and is an effective adjuvant treatment for Stage I seminoma. A multicenter randomized trial of the different treatment modalities is required to further evaluate its use.

Adult↗
PubMed1994

Chemotherapy for germ cell tumours: prophylactic ciprofloxacin reduces the incidence of neutropenic fever.

To assess the value of prophylactic ciprofloxacin in reducing the incidence of neutropenic fever in men receiving intensive chemotherapy for germ cell tumours, we reviewed the case notes of 88 consecutive patients treated between January 1986 and December 1992. Nadir blood counts were performed in all patients on day 14. From 1989, prophylactic ciprofloxacin 250 mg b.d. was started when the neutrophil count was less than 1 x 10(9)/l and then prescribed for all subsequent courses of chemotherapy from day 7 to day 21. In total, 88 men received 429 courses of chemotherapy. Prophylactic ciprofloxacin was prescribed for 168 courses. This was associated with a trend towards reducing the risk of admission per course of chemotherapy from 8% (20/261) to 4% (6/168) (P = 0.08). WHO grade 3/4 neutropenia (< 1 x 10(9)/l) was documented for 240 (56%) courses of chemotherapy. The incidence of fever in these patients was significantly reduced from 15% (20/131) to 5% (6/109) (P = 0.02) with prophylactic ciprofloxacin. Two patients, one of whom had received prophylactic ciprofloxacin, died of chest infection confirmed on post-mortem. The results of this non-randomized, retrospective study suggest that prophylactic ciprofloxacin 250 mg b.d. is effective in reducing the incidence of fever complicating neutropenia during chemotherapy for germ cell tumours. To be cost effective, it should be given only to neutropenic patients.

Adolescent↗
PubMed1994

Appraisal of a glycopeptide cloaking strategy for a therapeutic oligopeptide: glycopeptide analogs of the renin inhibitor ditekiren.

Among the limitations to the practical therapeutic oligopeptide are low oral availability, indifferent aqueous solubility, and an astonishing efficient sequestration and biliary elimination by a multi-capacity liver transporter. Given the purposed use of N- and O- linked saccharides as functional appendages of eukaryotic peptides and proteins, a strategy of glycopeptide mimicry was examined for the oligopeptide renin inhibitor, ditekiren. The anticipation was that the saccharide would impart significant aqueous solubility, and might impact beneficially on the remaining two limitations. Execution of this approach was achieved by the removal of the (dimethylethoxy)carbonyl amino terminus of ditekiren, and its substitution by Boc-L-asparagine N-linked mono- and disaccharides. Potent hypotensive activity, as measured by a human renin-infused rat assay, is observed for virtually all of these structures (N-linked beta-pyranose D-N-acetyglucosaminyl, D-glucosaminyl, D-N-acetylgalactosaminyl, D-mannosyl, D-galactosyl, D-maltosyl, D-cellobiosyl, D-chitobiosyl, but not L-fucosyl). The basis for this dramatic improvement (relative to ditekiren in the same assay) is the diversion of the peptide clearance from rapid liver biliary clearance to slower urinary clearance (Fisher, J. F.; Harrison, A. W.; Wilkinson, K. F.; Rush, B. R.; Ruwart, M. J. J. Med. Chem. 1991, 34, 3140). Guided by the human renin-infused rat hypertension assay, an evaluation of the linker-saccharide pairing was made. Loss of hypotensive activity is observed upon substitution of the Boc-L-asn by Boc-D-asn, and by removal of the Boc amino terminus of the glycopeptide. Potent hypotensive activity is preserved by replacement of the Boc-L-asn linker by succinate, malate, tartrate, and adipate linkers. With the longer adipate spacer, attachment of the saccharide to the P-3 phenylalanine--with omission of the P-4 proline--retains activity. These data suggest value to the glycopeptide guise for preserving the in vivo activity, and for the beneficial manipulation of pharmacodynamics, of this renin inhibitory oligopeptide. This strategy may have general applicability.

Amino Acid Sequence↗
PubMed1994

Efficacy and toxicity of vinblastine, bleomycin, and methotrexate with involved-field radiotherapy in clinical stage IA and IIA Hodgkin's disease: a British National Lymphoma Investigation pilot study.

PURPOSE: To assess the efficacy and toxicity of vinblastine, bleomycin, and methotrexate (VBM) chemotherapy with involved-field radiotherapy in clinical stage IA and IIA Hodgkin's disease. PATIENTS AND METHODS: Thirty eligible patients with clinical stage IA or IIA Hodgkin's disease, at intermediate risk of relapse, were enrolled into a prospective multicenter pilot study. They received two cycles of VBM chemotherapy, followed by involved-field radiotherapy and then four further cycles of VBM. The median follow-up duration from the start of treatment is 30 months. RESULTS: All 26 patients with assessable disease showed an objective response after two cycles of VBM (nine complete responses, 17 partial responses). By the completion of treatment, 27 patients were in complete remission; two had stable residual masses, which have not progressed at 26 and 34 months of follow-up; and one patient who died of treatment-related sepsis was in complete remission at that time. Two relapses have occurred, 19 and 28 months after starting VBM. Cough and dyspnea developed in 14 of 30 patients, and were associated with impairment of pulmonary function tests. Three episodes of neutropenic sepsis were recorded. CONCLUSION: VBM with involved-field radiotherapy is an effective treatment for early Hodgkin's disease. However, the associated toxicity, both pulmonary and hematologic, is severe, making the regimen unsuitable for routine use.

Adolescent↗
PubMed1994

Case report: the pulmonary lesions of chickenpox pneumonia--revisited.

Infection with the varicella zoster virus can include pulmonary complications. These may cause such minor symptomatology as to go unrecognized and unimaged. We describe a case of active chickenpox pneumonia that mimicked pulmonary metastases and was detected incidentally by means of computed tomography in a man with a past history of testicular teratoma.

Adult↗
PubMed1993

Purification and characterization of the herpes simplex virus type 2-encoded uracil-DNA glycosylase.

The herpes simplex virus type 2 (HSV-2) uracil-DNA glycosylase (UNG) was from the nuclei of infected KB cells using ion exchange, affinity, and chromatofocusing chromatography techniques. Chromatography on DNA cellulose revealed two distinct HSV-2-encoded UNGs. One species, designated A, was purified approximately 324-fold, while the second species, designated B, was purified approximately 130-fold. The HSV UNG species B was observed to unidirectionally convert to the A species, suggesting that the B species binding to DNA cellulose may be the result of an association with other DNA binding proteins. SDS-PAGE demonstrated that both species A and B had molecular weights of 32,000. The HSV-2-encoded UNGs could be distinguished from the cellular nuclear UNG based upon differences in their behavior on the chromatography matrixes and by their molecular weights. There were no significant differences in the biochemical properties of the HSV-2-encoded or nuclear UNGs. Furthermore, all of these UNGs reacted with a monoclonal antibody produced against the human placental UNG. These data support recent studies, at both the DNA and the amino acid levels, which have demonstrated that this enzyme is highly conserved between species.

Blotting, Western↗
PubMed1993

Audit reduces the reluctance to use single fractions for painful bone metastases.

We have conducted three audits of the number of fractions used within our department to treat symptomatic bone metastases. The initial audit identified 133 patients treated for bone metastases in a 3-month period using 538 fractions (mean number of fraction = 4.1, range 1-14). These figures were presented at our audit meeting along with a literature review which provided no evidence of any advantage of multiple fractions over single fractions. Departmental guidelines recommending the use of single fractions were established. A subsequent audit identified 149 patients treated with 520 fractions (mean number of fractions = 3.5, range 1-11). A third audit identified 148 patients treated with 335 fractions (mean number of fractions = 2.3, range 1-10). Audit has resulted in a reduction in the number of fractions used to treat bone metastases in our department. The major effect was seen after the second audit.

Bone Neoplasms↗
PubMed1993

The metabolism of AIDS-associated mycoplasmas.

Mycoplasma fermentans and Mycoplasma pirum have been recovered from human immunodeficiency virus (HIV)-positive persons. M. fermentans has been isolated with much higher frequency from HIV-positive than from HIV-negative persons. Mycoplasma genitalium has been detected by polymerase chain reaction in the blood of a patient with AIDS. Little is known about the biology of these mycoplasmas, especially their physiology, biochemistry, and growth response to inhibitors of essential metabolic loci or transport. Metabolically, they resemble other Mycoplasma species. Those studied lack cytochromes, the tricarboxylic acid cycle, and portions of the hexose monophosphate shunt. According to limited data, they fix CO2, use ATP to phosphorylate fructose-6-phosphate, have substrate phosphorylation and transaminase(s), and interconvert most purines and pyrimidines. The synthesis of thymidine may be limited. They may require a variety of essential small molecules for optimal growth (e.g., pyridoxal phosphate, ribose-1-phosphate). Their pathogenic potential and cultural lability may involve the production of the superoxide anion and the hydroxyl radical. We hypothesize that the mycoplasmas generate toxic oxygenated products that damage the host cell, probably membrane, permitting the mycoplasmas to gain easier access to the interior of the cell. The mycoplasma-damaged host cell membrane may also effect the maturation or release of HIV particles from the cell.

AIDS-Related Opportunistic Infections↗
PubMed1992

Bleomycin lung: the effect of different chemotherapeutic regimens.

A review of hard-copy computed tomography (CT) images of patients who had undergone chemotherapy for testicular teratoma revealed that the incidence of lung toxicity appeared to be lower in those who had received bleomycin by slow infusion [EBCi (3) regimen, etoposide/bleomycin/cisplatin] rather than by intravenous bolus [PVB regimen, cisplatin/vinblastine/bleomycin; BEP (5) regimen, bleomycin/etoposide/cisplatin]. This difference reached statistical significance only for PVB vs EBCi (3) (t = 2.63, P less than 0.01). Nevertheless, in view of continuing reports of mortality resulting from bleomycin-induced pulmonary fibrosis in patients receiving the drug by i.v. bolus, further exploration of these results is clearly justified.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1991

Preservation of natural endothelial cytopathogenicity of cytomegalovirus by propagation in endothelial cells.

Cytomegalovirus (CMV) is a source of major complications in immunosuppressed individuals, and endothelial involvement in CMV infection is well documented. Traditionally the virus has been propagated in fibroblasts, however this process may alter CMV's characteristics, thereby limiting the fibroblast model's utility as a research tool. In our efforts to develop a more accurate in vitro model of CMV/endothelial cell interaction, we have propagated a recent isolate (CMV VHL) through multiple passages in human umbilical vein endothelial cells (HUVE) and, collaterally in neonatal human dermal fibroblasts (NHDF). Infection of HUVE inoculated with either sub-strain of the virus was confirmed by CMV-specific in situ hybridization and by immunocytochemical staining for CMV antigens. Whereas infection of HUVE by substrain VHL/E (endothelial-raised) was accompanied by dramatic cytopathology resembling that observed clinically, the endothelial cytopathic potential of VHL/F (fibroblast-raised) was lost by its 20th passage in NHDF. Similarly, the ability of VHL/F to initiate sustained productive infection in HUVE was severely attenuated; plaque assay of culture supernatants and infected cell fractions, as well as virus-specific DNA polymerase assay of cell lysates, demonstrated progressive viral reproductive activity in VHL/E-inoculated HUVE, whereas VHL/F reproduction was barely detectable. Since properties of VHL/F bear strong resemblance to those of the fibroblast-raised AD169, these studies suggest that while the fibroblast adaptation process commonly employed in the propagation of CMV restricts the host range of the virus and attenuates its spectrum of cytopathic potential, endothelial-based propagation preserves the natural endothelial cytopathogenicity of the original isolate.

Antigens, Viral↗
PubMed1991

Characterization of two monoclonal antibodies to Epstein-Barr virus diffuse early antigen which react to two different epitopes and have different biological function.

Five monoclonal antibodies (mAbs) were identified using immunofluorescence that were specific for the Epstein-Barr virus (EBV) encoded 52/50 kDa early antigen (EA-D) protein complex. Evidence to suggest that these mAbs react with the same 52/50 kDa EA-D protein was obtained by Western blotting, immunoprecipitation and ELISA. Two of the mAbs, 90E2 and 214A9, neutralized EBV DNA polymerase activity. The 214A9 mAb also inhibited the activity of bacteriophage T4 DNA polymerase while the 90E2 mAb did not. These data suggest that the 90E2 and 214A9 mAbs recognize two different epitopes on the 52/50 kDa EA-D protein. The high frequency of recovery of hybridomas producing anti 52/50 kDa EA-D mAbs suggest that this protein may have an important role in EBV pathogenesis/replication.

Animals↗
PubMed1991

Inhibition of herpes simplex virus types 1 and 2 replication in vitro by mercurithio analogs of deoxyuridine.

The in vitro antiviral activity of several 5-mercurithio analogs of 2'-deoxyuridine (dUrd) on the replication of herpes simplex virus types 1 (HSV-1) and 2 (HSV-2) were examined. Of those compounds tested, the thioglycerol analog of 5-mercuri-2'-deoxyuridine (HgdUrd) was most effective in inhibiting the replication of HSV-1 in KB cells with a 50% inhibitory dose (ID50) of 0.001 micrograms/ml while the glutathione analog of HgdUrd was the most effective in inhibiting the replication of HSV-2 with a ID50 of 0.075 micrograms/ml. Conversely in HeLa TK- cells, the mercaptoguanosine analog of HgdUrd was the most effective compound in inhibiting virus replication with ID50S of 0.098 and 0.001 micrograms/ml for HSV-1 and HSV-2 respectively. These results suggest that these mercurithio analogs of dUrd are as effective as acyclovir in preventing the replication of these herpesviruses.

Antiviral Agents↗