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Biomedical subjects

C Martin

Publications and source records attributed to C Martin.

At least 523 records · Page 29Linked to original sources
PubMed1996

Pattern of HIV viraemia and CD4 levels in relation to pregnancy in HIV-1 infected women.

The objective was to study HIV-1 viraemia and CD4 levels during and 6 months after pregnancy. HIV cultures on peripheral blood mononuclear cells (PBMC) and plasma from 225 samples were performed in 90 HIV-1 infected women with 59 continued and 35 terminated pregnancies. P-24 antigen and HIV-DNA were also studied. 34 women originated from European, 44 from African and 10 from other countries while 2 were of unknown origin. HIV was detected in 30% of the plasma cultures from the first trimester and in approximately 50% thereafter. Repeated plasma isolations did not give an indication of HIV activation, nor did the cross-sectional time-to-culture positivity in plasma and in PBMC, PBMC isolation frequencies, HIV-DNA and CD4 levels. The plasma viraemia frequencies were generally higher and the CD4 levels lower in the African women than in the European ones. Six months after delivery there was a significant decrease in the CD4 cell counts compared to delivery, but not when compared to the values during the first or second trimesters. The results showed that HIV activity during pregnancy was relatively stable, followed by indications of resumed activity during the first 6 months after delivery.

Adult↗
PubMed1996

Getting a job in general practice.

Practice nursing is unique in the NHS--one works with and for an employer (the GP) rather than an organisation. Before applying for a post the nurse should gain as much background knowledge as possible about working in a general practice. Both GP and nurse may have misconceptions or uncertainties about each other's role, e.g. the employer may have unrealistic expectations of nursing competencies and potential. The nurse may be unfamiliar with GPs' status as independent contractors, hence their freedom to set terms and conditions of service. Through a process of informal and formal interviews, both parties need to establish clearly what is understood and expected of the other. Study the terms and conditions of service and the final contract carefully before signing. Be open and honest about what the job has to offer and what one can offer the job. Then, once you have accepted, go forward positively!

Family Practice↗
PubMed1996

Meeting the needs of children and families in chronic illness and disease. A greater role for the GP?

BACKGROUND: Care of children with chronic disease is an important part of general practice. While the emphasis of management has traditionally been on the biomedical aspects of ill health categorised by specific medical diagnoses, other dimensions may be important. OBJECTIVE: To define chronic disease and illness. To describe 'non categorical' dimensions or common features of different chronic diseases in childhood and their impact on the child and family involved. To explore needs for care and the role of the general practitioner in providing this care. METHOD: A literature review based on a search of the Medline electronic database. Both quantitative and qualitative articles on the topic of non-categorical or generic approaches to chronic childhood disease were selected on the basis of their quality and relevance to the Australian health care system. RESULTS: Chronic illness disturbs the lives of children, limiting their roles in schools, recreation, and vocational pursuit. Parents and siblings often experience social, economic and personal disadvantage. Care that is orientated to the 'whole child' and facilitates 'family control' in the various stages of illness and disease promotes better coping. Non-categorical management is optimised by continuity of both the setting and provider, with a provider who co-ordinates care. DISCUSSION: Chronic illness management offers a challenge to general practitioners to take on an expanded generalist role. This should complement specialised activities. When technical or specialised disease orientated care bypasses the general practitioner, important elements may be neglected. Proposed case management reforms are a stimulus to reappraise the role of general practitioners in chronic illness and disease care.

Adaptation, Psychological↗
PubMed1996

Gemcitabine: once-weekly schedule active and better tolerated than twice-weekly schedule.

This paper reviews the toxicity profile of gemcitabine, a novel anticancer drug. Gemcitabine has been administered using two different treatment schedules: once weekly or twice weekly for 3 weeks followed by a week of rest (one cycle). It was well tolerated and alopecia was not a problem. Toxicity was greater in the twice-weekly schedule. Comparing the once-weekly with the twice-weekly schedule, WHO grade 3 or 4 thrombocytopenia was reported in 4.7 and 25.6% of patients, respectively. Other hematological toxicity was minimal. Transient WHO grade 3 or 4 elevations of ALT and AST occurred in 9.2 and 7.2% of patients, respectively, in the once-weekly schedule. For the twice-weekly schedule the corresponding percentages were 12.2 and 13.8%. Symptomatic toxicity was greater in patients who received twice-weekly gemcitabine. Nausea and vomiting was mild and generally well controlled without 5HT3 antagonists. However, there was a greater incidence of nausea and vomiting on the twice-weekly schedule. Flu-like symptoms were documented in 19.8% of patients receiving once-weekly and 63.3% of patients receiving twice-weekly gemcitabine. Peripheral edema, not related to cardiac, hepatic or renal failure, was seen more often in patients on twice-weekly treatment. As the efficacy of gemcitabine in non-small cell lung cancer was equivalent when using both regimens, the better tolerated and more easily administered once-weekly schedule is recommended.

Antimetabolites, Antineoplastic↗
PubMed1996

Inhibition of apoptotic cell death in B-CLL by interferon gamma correlates with clinical stage.

Apoptosis was evaluated in B cells from 41 patients with B-CLL and 20 healthy aged-matched controls. B cells were cultured with and without gamma-IFN and other cytokines; apoptosis was quantified at regular intervals throughout a 5-day culture period. According to Rai's criteria, 17 patients were classified as good risk, 16 as intermediate and eight as high risk. In vitro, purified B cells from B-CLL patients were evaluated for apoptosis. Maximal apoptosis (44.12%) was observed at day 5 in cells from patients with poor prognosis. The addition of gamma-IFN to the culture media prevented apoptosis in a dose-dependent manner. Maximal inhibition of apoptosis was achieved with 100 IU/ml of gamma-IFN. The degree of inhibition of apoptosis by gamma-IFN was greater in cells from the high-risk group patients than in those from the intermediate and good prognosis group (P < 0.0001). The expression of gamma-IFN receptors in B-CLL cells was evaluated using a MnAb against the extracellular domain of gamma-IFN receptor. After 4 days in culture with gamma-IFN, only cells from the intermediate- and high-risk groups showed an increase in the density of gamma-IFN receptors (P < 0.001). gamma-IFN was not detected in the sera of our study patients. However gamma-IFN was detectable in the media from both normal B cells and B-CLL cells in culture; there was no difference in the amount of gamma-IFN released by cells from the three groups of patients studied. Our results show that in vivo gamma-IFN inhibits apoptosis of B cells from B-CLL patients. The inhibitory effect of gamma-IFN on apoptosis correlates directly with the severity of the disease and this is likely explained by a marked upregulation of gamma-IFN receptors in cells from patients in the high-risk group.

Aged↗
PubMed1996

Economic value of gemcitabine in non-small cell lung cancer.

Although cost considerations traditionally have not been important in cancer treatment decision making, there is increasing concern worldwide about the economic impact of therapeutic alternatives in the field of oncology. In particular, there is greater pressure for pharmaceutical companies to assess the economic value of new products. We have investigated and compared the clinical outcomes and corresponding cost savings of a novel nucleoside analog, gemcitabine, with other chemotherapy options in three different health care settings: Germany, the United States, and Spain. To date, most of the work with gemcitabine has been done in non-small cell lung cancer. Most non-small cell lung cancer patients present with advanced disease that is unsuitable for surgery and, in many cases, unsuitable for potentially curative chemotherapy. Chemotherapy for the majority of patients is therefore administered with palliative intent. For this reason, the comparative agents chosen for the economic models were palliative treatments (cisplatin/etoposide and ifosfamide/etoposide). As is customary with oncolytics, gemcitabine was investigated first as a single agent in noncomparative trials. Since data were not available from a comparator trial, we estimated comparative data from the literature sources and expert opinion (German and Spanish cost models) and from retrospective chart reviews (US cost model). In all three models, the efficacy was assumed to be equal, so a cost-minimization approach was used. Gemcitabine monotherapy showed cost savings compared with both cisplatin/etoposide and ifosfamide/etoposide in all treatment settings. The majority of these savings were due to differences in hospitalization for drug administration, and the incidence and treatment of nausea and vomiting and febrile neutropenia.

Antimetabolites, Antineoplastic↗
PubMed1996

Gemcitabine: safety profile unaffected by starting dose.

Gemcitabine, a novel anticancer agent, has been shown to be active in several human solid tumours, including non-small cell lung cancer and pancreatic cancer. In addition, gemcitabine has been noted to have a particularly mild safety profile for such an active agent and is lacking some of the classical toxicities of oncolytics, i.e. alopecia, severe nausea and vomiting, and mucositis. Therefore, the safety data from 790 patients in 18 completed clinical studies were integrated to study its toxicity profile in more detail. In all of these studies gemcitabine was administered as a 30-minute intravenous infusion every week for three weeks followed by a week of rest (one cycle). This integrated database confirmed that gemcitabine is well tolerated. Its haematological toxicity was mild and short lasting. The low incidence of infection was correspondingly low. Transaminase elevations occurred frequently, but they were usually mild and rarely dose-limiting. Mild proteinuria and haematuria were seen but were rarely clinically significant. There was no evidence of cumulative hepatic or renal toxicity. Nausea and vomiting were mild, rarely dose-limiting and generally well controlled with standard antiemetics. Flu-like symptoms were experienced in a proportion of patients but were short-lasting. Where oedema or peripheral oedema were experienced, there was no evidence of any association with cardiac, hepatic or renal failure. Hair loss was rare. The integrated database was also analysed according to starting dose (800, 1000 or 1250 mg/m2) in a subset of 665 chemonaive patients to see whether an increased dose resulted in increased toxicity. In general, only small, clinically insignificant differences in toxicity were seen between the three dose groups. Although segmented neutrophil count appeared to increase as starting dose increased (grade 3 or 4, 19.4%, 23.2%, 28.3% respectively), this was not associated with an increased incidence of infection. In some cases, toxicity decreased with increasing dose but this may have been because of imbalances between the patient groups. These findings indicate that not only is gemcitabine well tolerated, but it also has a broad therapeutic index and the use of higher doses may be possible.

Antimetabolites, Antineoplastic↗
PubMed1996

[Intrapetrous cholesteatoma].

Intrapetrous cholesteatomas correspond to lesions extending beyond the classical limits of impairment at the level of the middle ear. This paper analyzes 31 cases of which only 2 are definitely primary, the other 29 probably being secondary. In 5 cases, a cholesteatoma had been previously removed by an open or semi-open technique. Such cholesteatomas, that are found at all ages (from 12 to 74), affect both sexes equally. They are easy to diagnose when the symptomatology combines a history of otitis, damage to facial motoricity, mixed deafness or anacusis and a tympanic aspect of cholesteatoma. They are much more difficult to diagnose in the absence of any facial deficit, of major deafness, and even more so if the tympanum is closed. CT-scanning and MRI now enable a precise study of the nature of the complaint and its extension. Surgical treatment requires full mastery of all the techniques of otoneurosurgery, the procedure depending very much upon the seat and extent of the intrapetrous cholesteatoma.

Adolescent↗
PubMed1995

Microfocus X-ray Diffraction of Spherulites of Poly-3-hydroxybutyrate.

The microfocus X-ray beamline at the European Synchrotron Radiation Facility has been used to investigate the variation in molecular orientation and crystallinity in spherulites of the organic polymer poly-3-hydroxybutyrate (PHB). This is the first report of the correlation of optical and X-ray measurements on spherulitic polymer films where X-ray diffraction patterns have been recorded and displayed continuously in real time while the specimen was tracked in steps of 10 mum across an incident X-ray beam with a diameter as small as 10 mum.

Journal Article↗
PubMed1995

Transfusion requirements in critical care. A pilot study. Canadian Critical Care Trials Group.

OBJECTIVE: To evaluate the effects of a restrictive and a liberal red blood cell (RBC) transfusion strategy on mortality and morbidity in critically ill patients. STUDY DESIGN: Multicenter, prospective, randomized clinical trial. PATIENT POPULATION: Sixty-nine normovolemic critically ill patients admitted to one of five tertiary level intensive care units with hemoglobin values less than 90 g/L within 72 hours of admission. INTERVENTIONS: Patients were randomly allocated to one of two RBC transfusion strategies. Hemoglobin values were maintained between 100 and 120 g/L in the liberal transfusion group and between 70 and 90 g/L in the restrictive group. RESULTS: Primary diagnosis and mean +/- SD age (58.6 +/- 15 vs 59.0 +/- 21 years and Acute Physiology and Chronic Health Evaluation II score (20 +/- 6.2 vs 21 +/- 7.2) were similar in the restrictive and liberal groups, respectively. Daily hemoglobin values averaged 90 g/L in the restrictive group vs 109 g/L in the liberal group (P < .001). The restrictive group received 2.5 U per patient compared with 4.8 U per patient in the liberal group. This represents a 48% relative decrease (P < .001) in RBC units transfused per patient. The 30-day mortality rate was 24% in the restrictive group compared with 25% in the liberal group; the 95% confidence interval around the absolute difference was -19% to 21%. Similar observations were noted for intensive care unit mortality (P = .76) and 120-day mortality (P > .99). In addition, survival analysis comparing time until death in both groups did not reveal any significant difference (P = .93) between groups. Organ dysfunction scores were also similar (P = .44). CONCLUSION: In this small randomized trial, neither mortality nor the development of organ dysfunction was affected by the transfusion strategy, which suggests that a more restrictive approach to the transfusion of RBCs may be safe in critically ill patients. However, the study lacked power to detect small but clinically significant differences. Therefore, further investigations of RBC transfusion strategies are warranted.

APACHE↗
PubMed1995

Alternative splicing of MLH1 messenger RNA in human normal cells.

The hMLH1 protein, composed of 756 amino acids, is the human homologue of the bacterial DNA mismatch repair protein MutL, and germ line mutations of the hMLH1 gene have been identified in kindreds with hereditary nonpolyposis colorectal cancer. We have detected three alternatively spliced forms of hMLH1 mRNA in normal lymphocytes and tissues. One of the spliced forms lacks the coding region of hMLH1 from codons 227 to 295 and the two other transcripts are predicted to encode two truncated proteins retaining the 264 and 226 N-terminal amino acids of hMLH1, respectively. The biological significance of this alternative splicing remains to be established.

Adaptor Proteins, Signal Transducing↗
PubMed1995

A simple p53 functional assay for screening cell lines, blood, and tumors.

Mutations in the p53 gene are implicated in the pathogenesis of half of all human tumors. We have developed a simple functional assay for p53 mutation in which human p53 expressed in Saccharomyces cerevisiae activates transcription of the ADE2 gene. Consequently, yeast colonies containing wild-type p53 are white and colonies containing mutant p53 are red. Since this assay tests the critical biological function of p53, it can distinguish inactivating mutations from functionally silent mutations. By combining this approach with gap repair techniques in which unpurified p53 reverse transcription-PCR products are cloned by homologous recombination in vivo it is possible to screen large numbers of samples and multiple clones per sample for biologically important mutations. This means that mutations can be detected in tumor specimens contaminated with large amounts of normal tissue. In addition, the assay detects temperature-sensitive mutants, which give pink colonies. We show here that this form of p53 functional assay can be used rapidly to detect germline mutations in blood samples, somatic mutations in tumors, and mutations in cell lines.

Adolescent↗