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Biomedical subjects

R Clark

Publications and source records attributed to R Clark.

At least 109 records · Page 6Linked to original sources
PubMed1998

Stachybotrys, a mycotoxin-producing fungus of increasing toxicologic importance.

BACKGROUND: Stachybotrys as a fungus has been implicated as a source of mycotoxins. While the toxicity of several well-known mycotoxins (aflatoxins) is well documented, recent studies on Stachybotrys have raised the question that mycotoxins produced by this fungus may be responsible for the health effects of occupants in water-damaged buildings. METHODS: Published articles regarding Stachybotrys-related mycotoxins were reviewed with particular focus on human toxicity. RESULTS: A critical review of papers, reports, and studies on Stachybotrys mycotoxins revealed only descriptive reports of suspected animal and human poisoning secondary to consumption of mold-contaminated food products. No studies of good toxicologic and epidemiologic designs answer whether airborne mycotoxins produced by Stachybotrys could produce specific human toxicity. CONCLUSIONS: Current data on the toxicology of mycotoxins produced by Stachybotrys demonstrate that this group of mycotoxins is capable of producing immunosuppression and inflammatory insults to gastrointestinal and pulmonary systems. Case control study and case reports have suggested a possible association with environmental exposure to Stachybotrys mycotoxins, although a firm causal relationship has not been firmly established. Additional studies are needed to document that humans with sufficient exposure to these mycotoxins develop compatible clinical and pathologic pictures as demonstrated in animal models.

Animals↗
PubMed1998

Small-cell lung cancer: treatment progress and prospects.

Although small-cell lung cancer (SCLC) represents only 20% of all lung cancer cases in the United States, it is the most lethal subtype. Combination chemotherapy unequivocally offers the best chance for improved survival in SCLC. Either PE (platinum plus etoposide) or CAV (cyclophosphamide, Adriamycin, and vincristine) is a reasonable first-line therapy. Alternating PE with CAV does not appear to be significantly superior to PE or CAV alone. Increasing dose intensity, although sometimes associated with higher response rates, does not appear to significantly improve survival and should not be used outside of a clinical study. Several new agents with novel mechanisms of action show promise in treating SCLC. These include: gemcitabine (Gemzar), paclitaxel (Taxol), docetaxel (Taxotere), topotecan (Hycamtin), and irinotecan (Camptosar). Given the poor survival and response rates in relapsed patients and the chemoresponsiveness of SCLC, patients with newly diagnosed extensive disease should be encouraged to enroll in phase I or II trials. Thoracic radiotherapy confers a small survival advantage in limited-stage SCLC patients. Although prophylactic cranial irradiation does not significantly improve survival, it does reduce central nervous system (CNS) recurrences with minimal long-term sequelae. Surgery should be considered only for: (1) resection of a solitary pulmonary nodule, which must be followed by adjuvant chemotherapy; and (2) resection of an unresponsive chest tumor, which may harbor a non-small-cell lung cancer component.

Antineoplastic Agents↗
PubMed1997

Itraconazole maintenance treatment for histoplasmosis in AIDS: a prospective, multicenter trial.

PURPOSE: To study the efficacy and safety of maintenance treatment with itraconazole for disseminated histoplasmosis in patients with AIDS. PATIENTS AND METHODS: This was a prospective, multicenter, open-label study conducted at university-based hospitals participating in the AIDS Clinical Trial Group (ACTG). Forty-six AIDS patients with mild to moderate disseminated histoplasmosis who had successfully completed 12 weeks of induction treatment with itraconazole were treated with itraconazole, 200 mg once daily (42 patients) or 400 mg once daily (4 patients). Patients were followed at monthly intervals with clinical and laboratory assessment for relapse or toxicity. Primary outcome measures were relapse of histoplasmosis and survival. Secondary outcome measures included drug-limiting toxicity and changes in serum and urine Histoplasma polysaccharide antigen (HPA) levels. RESULTS: Two patients relapsed during a median follow-up period of 87 weeks. The 1-year relapse-free rate was estimated to be 95.3% (95% CI, 85.3%-99.7%). One relapse may have been related to poor adherence to treatment and the second to concurrent administration of rifampin. From the start of maintenance treatment, the estimated 1-year survival rate was 73.0% (95% CI, 67.5%-77.9%). Five patients discontinued treatment because of suspected drug toxicity, three of whom had possible or probable hepatotoxicity. Median serum and urine HPA levels declined significantly during treatment. The only patient in whom antigen levels rose >2 U developed clinical relapse 1 week later; antigen levels were unavailable in the other relapsing patient. CONCLUSIONS: Itraconazole, 200 mg daily, is effective in preventing relapse of disseminated histoplasmosis in patients with AIDS. It is generally well tolerated, but clinicians should be alert for drug interactions and possible hepatotoxicity.

AIDS-Related Opportunistic Infections↗
PubMed1997

Terminology of developmental abnormalities in common laboratory mammals (version 1).

This paper presents the first version of an internationally-developed glossary of terms for structural developmental abnormalities in common laboratory animals. The glossary is put forward by the International Federation of Teratology Societies (IFTS) Committee on International Harmonization of Nomenclature in Developmental Toxicology, and represents considerable progress toward harmonization of terminology in this area. The purpose of this effort is to provide a common vocabulary that will reduce confusion and ambiguity in the description of developmental effects, particularly in submissions to regulatory agencies worldwide. The glossary contains a primary term or phrase, a definition of the abnormality, and notes, where appropriate. Selected synonyms or related terms, which reflect a similar or closely related concept, are noted. Nonpreferred terms are indicated where their usage may be incorrect. Modifying terms used repeatedly in the glossary (e.g., absent, branched) are listed and defined separately, instead of repeating their definitions for each observation. Syndrome names are generally excluded from the glossary, but are listed separately in an appendix. The glossary is organized into broad sections for external, visceral, and skeletal observations, then subdivided into regions, structures, or organs in a general overall head to tail sequence. Numbering is sequential, and not in any regional or hierarchical order. Uses and misuses of the glossary are discussed. Comments, questions, suggestions, and additions from practitioners in the field of developmental toxicology are welcomed on the organization of the glossary as well as on the specific terms and definitions. Updates of the glossary are planned based on the comments received.

Animals↗
PubMed1997

The early relationship of drug abusing mothers and their infants: an assessment at eight to twelve months of age.

Ten mother-infant dyads in which the mother abused drugs during pregnancy were compared to 10 matched drug-free dyads using a short form of the Parent-Child Early Relational Assessment to analyze videotaped mother-infant interactions. Interactions consisted of two five-minute segments: structured and unstructured play. Infants were 8-12 months of age. There was a consistent tendency for the drug abusing group mean scores to separate from the controls. Drug abusing dyads had significantly more (r = .71, Fisher's Exact Probability) ratings below 3.0 in the unstructured play situation for items that measured enthusiasm, responsivity to infant cues, and infant happiness. These categories provide preliminary evidence for those characteristics which may be most problematic in the relationship between drug abusing mothers and their infants, especially in situations in which mother is responsible for providing structure.

Adult↗
PubMed1997

Capillary electrophoresis as a clinical tool for the analysis of protein in serum and other body fluids.

Most electrophoretic analyses of proteins in the clinical laboratory are currently carried out by electrophoresis in acrylamide or agarose gels. This labor-intensive method is now being challenged by capillary electrophoresis (CE) because of its potential for automated, rapid, high efficiency separations. The automatability of CE itself, combined with its amenability to interfacing with other robotized functions, positions this technology perfectly for the analysis of proteins in physiological matrices, such as serum, urine, and cerebrospinal fluid. The focus of this overview is to familiarize the clinical scientist with the research demonstrating the applicability of the technology to the clinical protein laboratory.

Blood Proteins↗
PubMed1997

Identification of monoclonal proteins in serum: a quantitative comparison of acetate, agarose gel, and capillary electrophoresis.

A selected group of 308 sera were analyzed by capillary electrophoresis (CE), agarose gel electrophoresis (AGE), and cellulose acetate electrophoresis (CAE) and evaluated for abnormalities that would suggest the presence of a monoclonal protein. The sensitivity (an electrophoretic abnormality in sera that contained a monoclonal protein) and specificity (a normal electrophoretic pattern in sera that did not contain a monoclonal protein) was determined for each electrophoretic procedure. CAE was the most specific procedure and CE was the most sensitive. The increase in sensitivity of CE was primarily due to increased detection of cryoglobulins and free light chains. The quantitation of the gamma region and/or monoclonal antibody peaks by CE was similar to results obtained by AGE. Quantitation of very large monoclonal protein peaks (> 3.0 g/dL) by on-line absorption detection (CE) yielded higher results than quantitation by dye-binding (AGE).

Acetic Acid↗
PubMed1997

A pilot study of eye movement during mammography interpretation: eyetracker results and workstation design implications.

Digital mammography can potentially improve mammography image and interpretation quality. On-line interpretation from a workstation may improve interpretation logistics and increase availability of comparison images. Interpretation of eight 4k- x 5k-pixel mammograms on two to four 2k- x 2.5k-pixel monitors is problematic because of the time spent in choosing which images display on which monitors, and zooming and roaming on individual images that are too large to display completely at full resolution. The authors used an eyetracker to measure radiologists viewing behavior during mammography interpretation with film on a viewbox. It was observed that a significant portion of the mammographers' time is spent viewing "comparison pairs" (typically two or more comparisons per case), such as the left mediolateral and craniocaudal images or old and new images. From the eyetracker measurements, we estimated that the number of image display, roam, and zoom operations decreases from an average of 64 for one monitor to 31 for four monitors, with the largest change going from one to two monitors. We also show that fewer monitors with a faster response time is superior to more monitors with a slower response time. Finally, the authors demonstrate the applicability of time-motion analysis to mammographic workstation design.

Adult↗
PubMed1997

Growth hormone attenuates early left ventricular remodeling and improves cardiac function in rats with large myocardial infarction.

OBJECTIVES: We sought to investigate the cardiac effects of growth hormone (GH) administration during the early phase of pathologic remodeling in a rat model of large myocardial infarction (MI). BACKGROUND: Recent evidence suggests that exogenous administration of GH evokes a hypertrophic response and increases left ventricular (LV) function in vivo in rats with normal or chronically failing hearts. We hypothesized that these effects would attenuate ventricular remodeling early after MI. METHODS: Fifty-eight male rats underwent sham operation (n = 19) or had induced MI (n = 39). The day after the operation, the infarcted rats were randomized to receive 3 weeks of treatment with GH, 3 mg/kg body weight per day (n = 19) or placebo (n = 20). Echocardiography, catheterization and isolated whole heart preparations were used to define cardiac structure and function. RESULTS: Growth hormone caused hypertrophy of the noninfarcted myocardium in a concentric pattern, as noted by higher echocardiographic relative wall thickness at 3 weeks and by morphometric histologic examination. Left ventricular dilation was reduced in the GH-treated versus placebo group (echocardiographic LV diastolic diameter to body weight ratio 2.9 +/- 0.1 vs. 3.5 +/- 0.2 cm/kg; p < 0.05). In vivo and in vitro cardiac function was improved after GH treatment. Despite elevated insulin-like growth factor-1 (IGF-1) serum levels in GH-treated rats, myocardial IGF-I messenger ribonucleic acid was not different among the three groups, suggesting that an increase in its local expression does not appear necessary to yield the observed effects. CONCLUSIONS: These data demonstrate that early treatment of large MI with GH attenuates the early pathologic LV remodeling and improves LV function.

Animals↗
PubMed1997

Cystic fibrosis transmembrane conductance regulator gene mutations in severe nasal polyposis.

A wide range of clinical phenotypes are associated with mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. In some cases, CFTR mutations have been identified in adults presenting with isolated features of cystic fibrosis such as mild lung disease, pancreatic insufficiency or male infertility, with normal sweat duct function. Nasal polyps are also a prominent feature of cystic fibrosis but it is unknown whether they also may represent a monosymptomatic form of the disease. We have screened the CFTR gene of 55 patients with severe nasal polyposis, who had no other features which would suggest a diagnosis of cystic fibrosis. The screening looked for mutations common to 86% of sufferers from cystic fibrosis. Three carriers were detected including one patient with the uncommon R117H mutation and two carriers of the delta F508 mutation. In addition there was one presumed carrier with a cystic fibrosis child, whose mutation we did not detect. This study has identified three CFTR mutation carriers in 55 patients with severe nasal polyposis. This is not significantly higher than the incidence in the general population. We cannot, from these figures, categorically rule out a slight association between CFTR mutations and simple nasal polyposis. However, we have demonstrated that the vast majority of patients with polyposis do not have inactivation of the CFTR gene.

Adult↗
PubMed1997

Length of maternity leave and quality of mother-infant interactions.

The aim of this study was to assess the association between the length of maternity leave and the quality of mother-infant interactions; 198 employed mothers of 4-month-old infants were interviewed and videotaped in their homes during a feeding time. Hierarchical multiple regression analyses indicated a direct association between shorter length of leave and more negative affect and behavior in maternal interactions with their infants. Infant and mother stressor/protective variables added significantly in predicting the quality of the mother-infant relationship. There were also significant interaction effects between the length of leave and these variables. Mothers who either reported more depressive symptoms or who perceived their infant as having a more difficult temperament and who had shorter leaves, compared with mothers who had longer leaves, were observed to express less positive affect, sensitivity, and responsiveness in interactions with their infants. The public policy implications of the relation between length of maternity leave, maternal and infant individual differences, and the quality of mother-infant interactions are discussed.

Adult↗
PubMed1997

Efficacy of trovafloxacin for treatment of experimental Bacteroides infection in young and senescent mice.

We investigated the efficacy of trovafloxacin, a new quinolone, in comparison with that of clindamycin in the treatment of intra-abdominal abscesses caused by Bacteroides fragilis in young and senescent mice. The development of abscess formation, the number of viable organisms, and antibiotic concentrations were measured, and the values for young and old mice were compared. Trovafloxacin was well distributed to the tissues in both young and old animals. Although the pharmacokinetics and concentrations of trovafloxacin in serum were similar between young and old mice, the levels in tissue were higher in senescent mice than in young mice. Trovafloxacin therapy sterilized abscesses in 94% of young mice and in 73% of old mice, but this difference was not significant. This therapeutic response to trovafloxacin was similar to that seen with clindamycin. These results suggest that aging may not have any adverse effect on the therapeutic outcome for intra-abdominal abscesses caused by B. fragilis.

Abdominal Abscess↗
PubMed1997

The Role of Selective Lymphadenectomy in Breast Cancer.

BACKGROUND: Axillary node dissection is considered a standard staging procedure in patients with breast cancer. The procedure is associated with significant morbidity and provides pathologists with many lymph nodes to evaluate. METHODS: A total of 174 women participated in a trial that included preoperative lymphoscintigraphy and intraoperative lymphatic mapping using a combination of a vital blue dye and radiocolloid mapping. RESULTS: The intraoperative lymphatic mapping correctly identified a sentinel lymph node (SLN) in 160 (92%) of 174 patients. One skip metastasis (0.7%) occurred in 136 women who had a subsequent complete node dissection. CONCLUSIONS: Lymphatic mapping and SLN biopsy using a combination of mapping techniques provide accurate nodal staging for women with breast cancer. With this technique, approximately 70% to 80% of women with no axillary metastases could be spared the morbidity of a complete node dissection.

Journal Article↗
PubMed1997

Consequences of growth hormone deficiency on cardiac structure, function, and beta-adrenergic pathway: studies in mutant dwarf rats.

To evaluate GH's role in cardiac physiology and its interrelationship with the beta-adrenergic system, we studied GH-deficient dwarf (dw/dw) and control rats in 4 groups of 20 each: dwarf group receiving placebo, dwarf-GH group receiving 2 mg/kg GH, dwarf-GH-propranolol group receiving 2 mg/kg GH and 750 mg/liter propranolol, and a control group of Lewis rats receiving placebo. Dwarf rats showed reduced left ventricular weight and myocyte cross-sectional area, and impaired cardiac performance in vitro. Left ventricular pressure-volume curves showed a shift upward and leftward, indicating reduced distensibility. These abnormalities reversed after GH treatment regardless of concomitant propranolol administration. Although isoproterenol responsiveness was reduced in dwarf rats, there were no differences in beta-adrenergic receptor density, affinity, Na+,K+-adenosine triphosphatase activity, or adenylyl cyclase activity. In summary, myocyte size, cardiac structure, myocardial contractility, and distensibility are abnormal in GH deficiency. The effects of GH are not mediated by the beta-adrenergic pathway, which, in turn, is unaffected by changes in the GH-insulin-like growth factor I axis. Thus, GH plays a regulatory role in normal cardiac physiology that is independent of the beta-adrenergic system.

Adrenergic beta-Agonists↗
PubMed1997

Screening Childhood Cancer Survivors for Breast Cancer.

The development of second primary solid tumors, especially breast neoplasms, is increased among patients who have survived childhood or adolescent malignancies. With the increased long-term survival of patients with pediatric cancer, questions regarding breast cancer screening in this group have been raised. At this time, there are no established guidelines for breast cancer surveillance in this high-risk population. The objective of this review is to summarize the incidence, list additional risk factors for the development of breast cancer, and discuss the benefits of early detection of second primary breast cancers in pediatric cancer survivors. We have devised an algorithm for breast cancer screening in survivors of childhood malignancy. Implications of treatment with radiation and chemotherapy and the influence on prognosis of genetic abnormalities such as p53 mutations are debated.

Journal Article↗
PubMed1997

Lymphoedema: a study of Otago women treated for breast cancer.

Lymphoedema, the swollen arm that can follow treatment for breast cancer, is the build up of lymph fluid which is unable to flow normally due to the surgical removal of axillary lymph nodes or the scarring of these nodes from radiotherapy. Previous studies indicate a lack of recognition of preventative measures and treatment of lymphoedema amongst health professionals and women treated for breast cancer. There also appears to be a lack of acknowledgement of the effects that lymphoedema can have on those who develop it. Of 181 women surveyed 68 (38%) reported having developed arm swelling at some stage since their treatment, 56 (31%) of whom met the study criteria for lymphoedema. Of those with lymphoedema 21 (37%) women had not consulted anyone regarding their swollen arm; a further 10 (18%) sought advice, but were offered no treatment. Therefore, in total, 31 (55%) of the women with lymphoedema received no treatment. The remaining 25 (45%) were offered a variety of treatments. In the group of women with lymphoedema, most arm swelling occurred within the first year. For a smaller number, swelling occurred up to 25 years later. Twenty-one percent of those affected, recalled advice about its prevention, compared with 36% in the group who had not experienced lymphoedema. Lifestyles were affected in many ways, with 21 (37.5%) of the women reporting pain of varying intensity and frequency. Other effects were on dress/choice of clothing, household duties, sleep, employment and sports.

Breast Neoplasms↗