Search PubMed⌕ Search

Biomedical subjects

R Matthews

Publications and source records attributed to R Matthews.

At least 55 records · Page 3Linked to original sources
PubMed1997

Cervical cancer as an AIDS-defining illness.

OBJECTIVE: To evaluate the importance of cervical cancer in the spectrum of human immunodeficiency virus (HIV)-related diseases at a single high-risk institution and to compare disease characteristics in HIV-infected women with cervical cancer and those with other AIDS-related malignancies. METHODS: We retrospectively reviewed data on cervical cancer and AIDS in women registered through the New York City Department of Health and institutional tumor registries from 1987 through 1995. RESULTS: During the study period, cervical cancer was diagnosed in 28 HIV-positive women. In 26, cervical cancer was the initial AIDS-defining illness, representing 4% (26 of 725) of the subjects, and it was the sixth most common initial AIDS-defining illness in women. Cervical cancer was the most common AIDS-related malignancy among women, representing 55% of the cases, followed by lymphoma (29%) and Kaposi sarcoma (16%). In 71% of the women with cervical cancer, HIV infection was diagnosed at the time of cancer presentation by routine testing, whereas in women with other malignancies, HIV diagnosis preceded cancer diagnosis (70%) by a mean of 2.7 years. Patients with other malignancies had greater immunosuppression (mean CD4 count 153/microL) than those with cervical cancer (mean CD4 count 312/microL). The recurrence rate for women with cervical cancer was 88%. Although the interval from cancer diagnosis to death was similar in all three groups (9.1-12.4 months), cancer was the cause of death in 95% of HIV-infected women with cervical cancer, compared with 60% of those with other AIDS-related malignancies. CONCLUSION: In urban populations at increased risk for both diseases, cervical cancer is an important AIDS-defining illness and may be the most common AIDS-related malignancy in women.

Acquired Immunodeficiency Syndrome↗
PubMed1997

Crohn's disease presenting with Fournier's gangrene and enterovesical fistula.

Our purpose is to make a case for early operative intervention. A 37-year-old man presented with a large periurethral abscess and Fournier's gangrene. During the ensuing evaluation and treatment, he was found to have previously undiagnosed Crohn's disease with a complex enterovesical fistula. This case stands in contrast to other reports that downplay the morbidity of enterovesical fistula associated with Crohn's disease and advise medical management until gastrointestinal complications require operative intervention.

Abdominal Abscess↗
PubMed1996

Over-expression of Saccharomyces cerevisiae hsp90 enhances the virulence of this yeast in mice.

Saccharomyces cerevisiae, a yeast of low pathogenic potential, is a rare but well-documented cause of invasive infections in humans. The yeast Candida albicans is a much commoner cause of significant and life-threatening infections. In such infections the heat shock protein hsp90 is an immunodominant antigen associated with protective humoral immunity. In this study it was shown that over-expression of S. cerevisiae hsp90, the amino acid sequence of which shows 84% identity to C. albicans hsp90, significantly increased the virulence of a laboratory strain of S. cerevisiae in mice, both in terms of colony counts in the kidney, liver, and spleen, and in terms of mortality. This is the first direct evidence that hsp90 is a virulence factor.

Animals↗
PubMed1996

Epitope mapping the Fim2 and Fim3 proteins of Bordetella pertussis with sera from patients infected with or vaccinated against whooping cough.

Antibody-binding epitopes on the Fim2 and Fim3 proteins of Bordetella pertussis, which have been associated with the induction of protective antibody, were located using sera from 12 patients with whooping cough and 4 vaccinated children. Fifteen epitopes were identified on both Fim2 and Fim3. In each case 9 were recognised by serum antibody from 11 or more infected patients. Epitopes associated with the highest IgG activity were not the same as those associated with the highest IgA activity. None of the vaccinated patients had detectable IgA. Most epitopes showed little or no evidence of serotype-specific responses, suggesting this is largely directed towards conformational epitopes. The reactivity of all but two epitopes was confirmed in an ELISA with patients' sera in which epitopes were re-synthesised as free soluble peptides. The short linear epitopes described may therefore be useful in the development of serodiagnostic assays but are unlikely vaccine candidates.

Amino Acid Sequence↗
PubMed1996

Antibodies against Candida: potential therapeutics?

For many years, there has been controversy over the role of antibodies in immunity to Candida, but recently specific antibodies to mannoproteins and hsp90 have been shown to be protective against murine candidiasis. Combined with technical advances in antibody engineering, this raises the possibility of harnessing such antibodies into a new range of therapeutics.

Animals↗
PubMed1995

Protective effect of vitamin E on lymphocyte growth capacity during incubation in vitro.

Vitamin E, an essential lipid-soluble micronutrient, plays an important role in the immune system and serves as an immunostimulant in geriatric subjects. Using an in vitro incubation to simulate aging processes, we find that vitamin E mitigates loss of growth capacity in lymphocytes. Vitamin E presence during in vitro incubation did not affect significantly the level of peroxidation, the effects of exogenous IL-2, PGE2, or indomethacin, nor levels of IL-2 production. Thus, the preservative effect on lymphocyte growth by vitamin E is not due primarily to its antioxidant function or to interleukin-2 or prostaglandin effects. The decreased growth capacity generated by in vitro incubation is accompanied by a variety of cellular alterations, including decreased CD5 surface antigen, enhanced suppression by adherent cells, and impaired communication between lymphocytes and adherent cells. The decrease in CD5 surface antigen correlates inversely with the cell density required for maximal cell proliferation, and the diminished CD5 levels were unaltered by vitamin E presence during the aging process. In contrast, protection of T-cell proliferative capacity by vitamin E in vitro correlates with diminished suppression by adherent cells and normalized interaction between lymphocytes and adherent cells.

Adult↗
PubMed1995

Human lymphocytes incubated in vitro share multiple characteristics with geriatric-derived lymphocytes: a potential in vitro model for aging?

Aging involves a complicated set of parallel reactions that result in multiple cellular and organismic changes and may eventuate in chronic illness. In the immune system, several alterations that correlate with age have been established. In the present study, we report the results of incubating lymphocytes in vitro in whole blood and, employing measures known to be age-dependent, compare these cells 'aged' in vitro with cells from geriatric patients aged in vivo. Cells from blood aged in vivo and incubated in vitro share a number of common characteristics that include decreased growth capacity, shifted growth patterns, increased suppression by adherent cells, decrease in CD5 surface antigen, similar responses to addition of exogenous IL-1, IL-2, PGE2, or indomethacin, and similar production of PGE2. Differences found between in vivo aging and in vitro incubation are IL-2 plasma levels and IL-2 production by activated cells monitored in conditioned minimal medium. Based on these observations, this in vitro system provides a simple method to generate cells that exhibit a very significant subset, but not all, of the characteristics associated with in vivo aging in lymphocytes.

Adult↗
PubMed1995

Glycerol-3-phosphate dehydrogenase activity in human lymphocytes: effects of insulin, obesity and weight loss.

Insulin exposure stimulates an increase in glycerol-3-phosphate dehydrogenase (G3PDH) activity in isolated human lymphocytes that correlates to an increase in G3PDH mRNA and requires new protein synthesis. Synthetic diacylglycerol or phorbol ester can mimic the effect of insulin on G3PDH activity, suggesting that protein kinase C may be involved in regulation of G3PDH levels. In addition, lithium chloride, an inositol phosphate phosphatase inhibitor, and calcium uptake inhibitors can abolish insulin stimulation of G3PDH activity. For obese subjects in whom insulin resistance in vitro can be demonstrated, the extent of insulin stimulation of G3PDH activity is decreased compared to normal weight individuals, and treatment by a very low calorie diet restores insulin stimulation of G3PDH activity. Thus, insulin stimulation of G3PDH activity is dependent upon the metabolic state of the subject from whom the cells are obtained.

Diet, Reducing↗
PubMed1995

Preliminary assessment of a human recombinant antibody fragment to hsp90 in murine invasive candidiasis.

Seroconversion to hsp90 is associated with recovery from systemic candidiasis in humans, and a murine monoclonal antibody to this hsp90 antigen (LKVIRK epitope) was protective in mice. A human recombinant antibody to the same epitope was assessed in acute and chronic models of murine invasive candidiasis. Lethal intravenous challenge with fluconazole-susceptible (strain 4) or fluconazole-resistant (strain 019) Candida albicans, followed 2 h later by a single dose of recombinant antibody, was associated with a statistically significant drop in mortality of > or = 40% (two experiments in BALB/c mice given strain 4; one experiment in CD-1 mice given strain 019) or 23% (BALB/c mice, strain 019). In mice sublethally infected with strain 4, treatment with recombinant antibody was associated with improved renal clearance of infection. Antibody-mediated protection may involve neutralization of the protein-binding properties of circulating candidal hsp90, since LKVIRK strongly bound dexamethasone in vitro.

Amino Acid Sequence↗
PubMed1995

Short stature in homozygous beta-thalassaemia is due to disproportionate truncal shortening.

BACKGROUND AND OBJECTIVE: Growth failure in homozygous beta-thalassaemia has been recognized for many years, and has persisted despite major treatment advances. In this cross-sectional study, sitting and standing height were measured to determine whether growth failure was disproportionate. DESIGN: Patient data were analysed in three age groups, 2-10 years, 11-18 years and 19 and over. Sitting height and subischial leg length were also determined in a cohort of parents (n = 19) and normal Greek adolescents (n = 32). PATIENTS AND MEASUREMENTS: Of the known 156 patients with homozygous beta-thalassaemia in the State of Victoria, 154 (98.7%) attend our institution. Sitting and standing heights were measured, using Harpenden stadiometers, in 57 of 60 (95%) patients aged 2-18 years and in a random selection of 51 of 89 patients aged 19 and over (57%). Measurements are expressed as mean +/- SDS. Other data analysed included serum concentrations of ferritin, zinc, copper, FSH, LH, oestradiol and testosterone, according to standard laboratory assays, together with pubertal status and bone age in patients aged less than 19 years. RESULTS: Standing height standard deviation scores in the 2-10 age group were -0.687 +/- 0.861 (n = 9), in the 11-18 age group were -1.838 +/- 1.413 (n = 48) and in the age group 19 and over were -1.175 +/- 1.126. In individuals aged 2-10 years, sitting height standard deviation scores (SDS) were -1.56 +/- 1.02, in individuals 11-18 years were -3.76 +/- 1.51 (n = 48), and in individuals 19 years and over were -2.77 +/- 1.20 (n = 51), compared with subischial leg length SDS which were, in individuals aged 2-10 years 0.214 +/- 0.91; in 11-18 years, -0.063 +/- 1.347, and in individuals 19 and over, 0.37 +/- 1.18. These data show that the reduction in standing height was the result of truncal shortening. Mean sitting height SDS was significantly lower in children with homozygous beta-thalassaemia, compared with their parents (P < 0.001), and in a subgroup of Greek adolescents with homozygous beta-thalassaemia compared with age and sex matched normal Greek adolescents (P < 0.001). No correlation was found between truncal shortening and other clinical and biochemical variables measured. CONCLUSIONS: Short stature in our patients with homozygous beta-thalassaemia is due to disproportionate truncal shortening. The aetiology of truncal shortening in this patient group is likely to be multifactorial, although hypogonadism and chelation therapy may be contributory factors.

Adolescent↗
PubMed1995

Effect of enalapril in dogs with pacing-induced heart failure.

A repeated-measures study was conducted on 5 dogs to clinically, radiographically, and echocardiographically characterize the actions of the angiotensin-converting enzyme inhibitor, enalapril, before and after development of experimentally induced heart failure. Heart failure was artificially induced, using a surgically implanted programmable ventricular pacemaker, which stimulated the heart at a rate of 245 beats/min until a low-output cardiomyopathic state developed. This condition was then stabilized by decreasing the pacing rate to 190 beats/min. Pacing-induced heart failure was successfully induced in a mean +/- SD 4.2 +/- 1.95 weeks. The condition closely resembled the clinical, radiographic, and echocardiographic features of naturally acquired idiopathic dilated cardiomyopathy in dogs. Enalapril was well tolerated by dogs, and clinical adverse reactions did not develop. Results of echocardiographic studies indicated that enalapril treatment during the control period resulted in a significant (P < 0.05) increase in velocity of circumferential fiber shortening and a significant (P < 0.05) decrease in left ventricular ejection time. Therapeutic responses to enalapril were evident after development of heart failure. These included reduced severity of clinical signs of disease, evidence of decreased radiographically determined cardiac size (2 of 5 dogs), radiographic evidence of a reduction in pulmonary edema and congestion (4 of 5 dogs), significant (P < 0.05) reductions in left atrial and ventricular chamber dimensions (left atrial dimension, diastolic left ventricular internal dimension as determined echocardiographically), and improvement in some echocardiographic indices of left ventricular performance (velocity of circumferential fiber shortening and left ventricular ejection time).

Analysis of Variance↗
PubMed1994

Glucose and insulin responses in isolated human lymphocytes reflect in vivo status: effects of VLCD treatment.

Human lymphocyte growth response to mitogen was examined in vitro under different conditions to monitor aspects of carbohydrate utilization in three groups: obese nondiabetic, obese/NIDDM, and normal-weight individuals. Although lymphocyte growth capacity in minimal medium for these three groups was found to be similar at a glucose concentration of 72 micrograms/ml in the absence of insulin or glycerol, differences in mitogen-stimulated growth were observed at lower glucose concentrations or in the presence of insulin or glycerol. Interestingly, these metabolic alterations in lymphocytes can be normalized by treating obese and obese/NIDDM subjects with a very low calorie diet (VLCD) regimen. The results of this study indicate that lymphocyte culture in a defined medium may provide a mechanism to examine different metabolic states and to evaluate treatment regimens (diet, exercise, etc.) for obese and NIDDM subjects.

Blood Glucose↗
PubMed1994

Dietary deprivation of B-vitamins reflected in murine splenocyte proliferation in vitro.

The effect of murine dietary deprivation of specific B-vitamins on in vitro splenocyte proliferative response in short-term tissue culture was examined in serum-free, protein-free, minimal medium. Using different media formulations, incorporation of [3H]thymidine was used to monitor the relative growth capacity of phytohemagglutinin-stimulated splenocytes from mice exposed to different diets. The results demonstrate that the growth deficit observed in vitro in the absence of specific vitamin(s) in the medium correlates only to those specific vitamin(s) eliminated from the diet. Dietary repletion is followed by restoration of a normalized response in vitro. The finding that murine dietary experience is reflected in vitro in splenocyte proliferative response monitored by [3H]thymidine incorporation suggests that human dietary experience might be monitored by similar analysis of human peripheral blood lymphocyte response.

Animals↗
PubMed1994

Glutamine protects Chinese hamster ovary cells from radiation killing.

Chinese Hamster Ovary (CHO) cells were propagated in vitro and exposed to varying doses of ionizing radiation. The surviving fraction of cells was determined, being found to be a function of the radiation dose. The cell survival curves obtained as a function of radiation dose were modified by the inclusion of varying doses of glutamine in the medium with glutamine demonstrating a radioprotective effect. The radioprotectant effect of glutamine for CHO cells was more pronounced at higher radiation doses. Glutamine has been categorized as a non-essential amino acid in that it can be synthesized in some tissues; however, a number of cell lines require glutamine to survive and grow in vitro and supplementation of glutamine has been found to ameliorate the stress of surgery or irradiation to the gastrointestinal tract. It may be appropriate to consider glutamine as a conditionally essential amino acid.

Animals↗
PubMed1994

TQM brings collaboration to patient transport process.

Total quality management (TQM) principles can be utilized to achieve successful outcomes of an interdepartmental problem-solving process prior to implementation of a TQM formal structure within an organization. Prior to implementation of the new process, patient transport time from nursing units to lab destination was calculated at 17.6 minutes; postimplementation, an institutional benchmark of 15.4 minutes has been set. The mechanisms utilized for development, implementation, and evaluation of a process improvement team is the focus of the article. The reader will be taken on a journey through an interdepartmental problem-solving process utilizing the TQM principles.

Cooperative Behavior↗
PubMed1994

Cardiovascular actions of dopexamine in anaesthetized and conscious dogs.

1. Arterial blood pressure, heart rate and cardiac contractility were measured in pentobarbitone-anaesthetized mongrel dogs and in conscious, instrumented dogs. 2. In anaesthetized dogs (n = 5), dose-response curves were obtained by intravenous infusion of increasing doses of dopexamine (5-20 micrograms kg-1 min-1). Infusions were administered three times to each animal to determine whether the responses were reproducible. Dopexamine increased heart rate and myocardial contractility and decreased blood pressure. The dose-response curves for dopexamine did not differ significantly over time. 3. In a second group of dogs (n = 6), dose-response curves (5-20 mg kg-1 min-1) were obtained as above and repeated after the administration of amitriptyline (2 mg kg-1, i.v.). Amitriptyline caused a non-significant reduction in the inotropic and chronotropic responses to dopexamine. 4. Control dose-response curves for dopexamine (5-50 micrograms kg-1 min-1) were similarly obtained in a third group of dogs (n = 6), and repeated after bilateral vagotomy and sympathetic denervation of the heart. In these animals, a third dose-response curve for dopexamine was obtained after the administration of ICI 118551 (0.2 mg kg-1, followed by 0.2 mg kg-1 h-1). The chronotropic response to dopexamine was significantly reduced after cardiac denervation. There was a small, non-significant reduction in the inotropic and depressor responses after denervation. Administration of ICI 115881 significantly reduced both the inotropic and chronotropic response to dopexamine and caused a non-significant reduction in the depressor response. 5. The effect of raclopride (0.2 mumol kg-1, p.o.) was investigated by comparison of the dose-response curves for dopexamine in a control group of dogs (n = 6) to those obtained in dogs which had been pretreated with raclopride (n = 5). Raclopride had no significant effect on the cardiovascular responses to dopexamine. 6. In conscious, instrumented dogs (n = 5), pretreated with raclopride, dose-related positive inotropic and chronotropic and depressor responses to dopexamine infusions were recorded. The chronotropic responses in conscious animals were significantly greater than those in the anaesthetized animals.7. The results of this study indicate that both the positive inotropic and chronotropic actions of dopamine are due to a combination of direct, Beta2-adrenoceptor-mediated effects and the baroreceptor reflex response to the depressor action of the drug.

Adrenergic beta-Antagonists↗