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Biomedical subjects

A Gardner

Publications and source records attributed to A Gardner.

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

Volvulus of the small bowel: an uncommon complication after laparoscopic cholecystectomy.

We report here two patients with volvulus of the small bowel after laparoscopic cholecystectomy (LC). There has been only one case report of a similar condition after LC in the English literature; the patient had malrotation of the midgut. Both patients we are reporting had previous pelvic surgery resulting in intraabdominal adhesions. Volvulus had occurred along an axis between the mesenteric attachment and the adhesion to the parietal peritoneum of the involved loop of small bowel. The creation of pneumoperitoneum could conceivably allow rotation to occur. One patient presented with signs of peritonitis from a gangrenous segment of small bowel. The other presented with continued abdominal pain after surgery. Definitive diagnosis was made only at laparotomy. Previous surgery is considered a relative contraindication to LC, although the incidence of morbidity and conversion to open procedure appear not to be influenced by previous surgery. Surgeons should be aware of volvulus as a complication after LC in patients who had previous abdominal surgery.

Adult↗
PubMed1997

Insulin-induced hypertension in rats depends on an intact renin-angiotensin system.

This study tested the dependence of insulin-induced hypertension in rats on a functional renin-angiotensin system. Rats were instrumented with chronic artery and vein catheters and housed in metabolic cages. After acclimation, 10 rats began receiving the angiotensin-converting enzyme inhibitor (ACEI) benazepril at 1.8 mg.kg-1.d-1 via a continuous intravenous infusion that was maintained throughout the study; 8 control rats received vehicle. Four days after starting ACEI or vehicle, all rats entered a 5-day control period that was followed by a 7-day insulin infusion at 1.5 mU.kg-1.min-1. Glucose was coinfused at 22 mg.kg-1.min-1 to prevent hypoglycemia. Insulin infusion in control rats increased mean arterial pressure (MAP; measured 24 h/d) from an average of 101 +/- 1 to 113 +/- 2 mm Hg on day 1; MAP averaged 110 +/- 1 mm Hg for the 7-day infusion period. Glomerular filtration rate decreased, although not significantly, from 2.7 +/- 0.1 to 2.1 +/- 0.2 mL/min on day 3. Chronic ACEI decreased baseline MAP from an average of 97 +/- 1 to 79 +/- 1 mm Hg and markedly attenuated the increase in MAP during insulin. MAP averaged 81 +/- 1 mm Hg for the 7-day period and increased significantly, to 85 +/- 2 mm Hg, only on day 3. Likewise, the tendency for glomerular filtration rate to decrease was blunted. These results indicate that insulin-induced hypertension in rats depends on angiotensin II and suggest that a reduction in glomerular filtration rate contributes to the shift in pressure natriuresis.

Angiotensin II↗
PubMed1997

Exercise testing and exercise rehabilitation for patients with peripheral arterial disease: status in 1997.

Intermittent claudication is a common manifestation of peripheral arterial occlusive disease (PAOD). Patients with claudication are limited in terms of work, housework and leisure activities so that functional status is very impaired. Therefore, the goals for treatment should focus on improving the functional impairment as well as on modifying risk factors. Evaluation of the functional status is of critical importance before beginning any therapy so that any resultant changes can be assessed. A validated graded treadmill protocol and validated questionnaires are used for this purpose. Three questionnaires that are currently used include the Walking Impairment Questionnaire, the PAOD Physical Activity Recall and the Medical Outcomes Study SF-36. Exercise rehabilitation is a method that has been particularly efficacious for treating the functional impairment associated with intermittent claudication. Exercise rehabilitation has been shown to improve pain-free treadmill walking distance by 44% to 300% and absolute walking distance by 25% to 442%. In addition, improvements have also been reported (using questionnaire data) in the ability to walk distances and speeds, in amount of habitual physical activity and in physical functioning. Thus, exercise rehabilitation has caused improvements not only in exercise capacity but also in community-based functional status. Because of the benefits of this treatment, in addition to the low associated morbidity, exercise therapy is recommended as an important treatment option for people with intermittent claudication due to PAOD.

Animals↗
PubMed1996

Fluconazole versus amphotericin B in the treatment of hematogenous candidiasis: a matched cohort study.

PURPOSE: To compare the efficacy and toxicity of fluconazole and amphotericin B in the treatment of hematogenous candidiasis in cancer patients. PATIENTS AND METHODS: A matched cohort study of cancer patients with hematogenous candidiasis was conducted. Forty-five patients with hematogenous candidiasis who received fluconazole (200 to 600 mg/day) in an open-label trial at the University of Texas M. D. Anderson Cancer Center, Houston, Texas, between February 1990 and June 1992 were matched to 45 patients treated with amphotericin B (0.3 to 1.2 mg/kg/day) for the same diagnosis. Criteria for matching included the following prognostic variables at the initiation of therapy: pneumonia, neutropenia (< 1,000 cells/mm3), number of positive blood cultures before therapy, infecting Candida species, underlying disease, and the simplified acute physiology score. Response and survival at 48 hours, after 5 days of therapy, and at the end of therapy, as well as toxicity rates were obtained. Other post hoc analyses were performed. Differences in outcomes were assessed by the McNemar, the sign, and the log rank tests. RESULTS: Patients were similar with respect to the matching criteria, age, sex, status of underlying disease, use of antibiotics and growth factors, duration of treatment, presence and removal of central venous catheters, disseminated disease, and concomitant infections. Response rates at 48 hours and 5 days were similar between the two study groups. Overall response rates at the end of therapy were 73% for patients treated with fluconazole and 71% for patients treated with amphotericin B (P = 0.78). There were no differences in survival rates or causes of death. Toxicity was observed in 9% of patients treated with fluconazole and in 67% of patients treated with amphotericin B (P < 0.0001). Toxic effects of amphotericin B included nephrotoxicity, hypokaliemia, and fever and chills. CONCLUSION: Fluconazole is effective and better tolerated than amphotericin B for the treatment of hematogenous candidiasis in cancer patients.

Adult↗
PubMed1995

Differential inhibition by iodonium compounds of induced erythropoietin expression.

Diphenylene iodonium chloride suppresses the cobaltous chloride-induced expression of erythropoietin by Hep3B cells to about 50% at a concentration of 30 nM. At that concentration, it has no effect on the response to low oxygen. The related compound iodonium diphenyl chloride acts similarly but is a much less effective inhibitor. If, as reported, diphenylene iodonium chloride is a specific inhibitor of cytochrome b, it follows that the response to CoCl2 is dependent on that enzyme but the response to hypoxia is not.

Biphenyl Compounds↗
PubMed1995

Cystic fibrosis mutation analysis: report from 22 U.K. regional genetics laboratories.

We have collated the results of cystic fibrosis (CF) mutation analysis conducted in 22 laboratories in the United Kingdom. A total of 9,807 CF chromosomes have been analysed, demonstrating 56 different mutations so far observed and accounting for 86% of CF genes in the native Caucasian population of the United Kingdom. delta F508 is the most common at 75.3% of CF mutations (range 56.5-83.7%), followed by G551D (3.08%; range 0.71-7.60%), G542X (1.68%; range 0.85-3.66%), 621 + 1 (G > T) (0.93%; range 0.41-3.16%), 1717-1(G > A) (0.57%; range 0.17-1.14%), 1898 + 1)(G > A) (0.46%), R117H (0.46%), N1303K (0.46%), and R553X (0.46%). The data show a clear geographical variation in the distribution of some of the mutations, most notably a marked regional variation in the distribution of 621 + 1 (G > T) and 1989 + 1(G > A), which are both apparently more frequent in Wales. R560T and R117H appear to be more frequent in Ireland and Scotland, and G551D more frequent in Scotland. In summary, these data illustrate that the mutations present within a particular population need to be defined in order to provide meaningful carrier screening and testing for rare mutations in affected individuals. Furthermore, it is apparent that the ethnic origin of a patient, even within a small country such as the United Kingdom, should be taken into account.

Cystic Fibrosis↗
PubMed1995

Atypical apoptotic cell death induced in L929 targets by exposure to tumor necrosis factor.

The mechanism by which tumor necrosis factor (TNF) induces cytotoxicity of murine fibroblasts was investigated. Electrophoresis of DNA extracted from TNF-treated L929 targets showed fragmentation of DNA into a ladder-like pattern, typical of cells dying by apoptosis. Morphologic analysis also indicated apoptotic cell death, demonstrating clumping and crescentic condensation of chromatin. In contrast, chromatin condensation and ladder-like DNA fragmentation were not detected in L929 targets dying by necrosis from exposure to heat, repeated cycles of freeze-thaw, and sodium azide. Chromatin condensation was an early event, detected as early as 6 h of incubation. However, DNA fragmentation (assayed by double-stranded fragmentation assay and gel electrophoresis), as well as the apoptotic changes detected by Hoechst fluorescence, both occurred later and did not precede TNF cytotoxicity (membrane permeabilization detected by trypan blue or propidium iodide staining). This atypical pattern of apoptosis was a characteristic of L929 target cells rather than a generalized cytotoxic response to TNF because TNF-treated squamous cancer cells showed typical features of apoptosis (DNA fragmentation before cytotoxicity) and etoposide-treated L929 cells demonstrated the same atypical kinetics as TNF-treated cells. Zinc significantly inhibited TNF cytotoxicity as well as DNA fragmentation of L929. However, because DNA fragmentation occurred belatedly in TNF-treated targets, lagging behind cytotoxicity, the protection by zinc against TNF appears mediated by events that occur before the ultimate endonuclease-induced cleavage of DNA into small fragments.

Animals↗
PubMed1993

Inhibition of DNA repair with aphidicolin enhances sensitivity of targets to tumor necrosis factor.

To test whether DNA injury contributes to TNF-induced cytotoxicity, we attempted to enhance DNA injury by inhibiting its repair and then assessing effects on cytotoxicity. DNA repair, assayed as unscheduled DNA synthesis, was first detected in TNF-sensitive targets by 2-3 h of incubation with TNF. Targets resistant to TNF cytotoxicity did not demonstrate significant repair replication. Repair preceded the detection of TNF-induced DNA injury, which was subsequently demonstrated by a double-stranded DNA fragmentation assay, sedimentation of DNA in neutral and alkaline sucrose gradients, and gel electrophoresis of extracted DNA. This suggested that early during exposure to TNF, DNA repair proceeds more rapidly than strand breakage. To inhibit repair, nontoxic concentrations of aphidicolin (inhibitor of DNA polymerase-alpha) and dideoxythymidine (inhibitor of DNA polymerase-beta and gamma) were used. Aphidicolin inhibited repair and consistently sensitized to TNF cytotoxicity, decreasing the ID50 for TNF at least 10- to 50-fold. In contrast, dideoxythymidine had no effect on repair or cytotoxicity. Deoxycytidine, which competitively inhibits binding of aphidicolin to DNA polymerase, blocked the sensitization in a concentration-dependent fashion. In targets sensitized with aphidicolin, TNF-induced strand breakage was accelerated, being detected by 4 h of culture in the sucrose gradient assay. Sensitization to TNF was not due to a heightened activation of poly (ADP-ribose) polymerase. These results indicate that TNF-induced strand breakage participates in TNF-induced cytotoxicity and that the level of DNA repair plays a role in determining relative sensitivity of targets.

Aphidicolin↗
PubMed1993

Involvement of Ras and Raf in the Gi-coupled acetylcholine muscarinic m2 receptor activation of mitogen-activated protein (MAP) kinase kinase and MAP kinase.

Stimulation of the acetylcholine muscarinic m2 receptor (m2R) expressed in Rat 1a fibroblasts results in the activation of the cytoplasmic mitogen-activated protein kinase (MAPK). Concomitant with carbachol stimulation of the m2R was the activation of MEK (MAPK kinase) and Raf. MEK is the dual function kinase that phosphorylates and activates MAPK. Raf is a serine/threonine kinase capable of phosphorylating and activating MEK. Carbachol stimulation of the m2R also activated Ras. Pertussis toxin treatment of Rat 1a cells inhibited the m2R-mediated activation of Ras, Raf, MEK and MAPK. In contrast, epidermal growth factor receptor-mediated activation of Ras, Raf, MEK and MAPK was pertussis toxin-insensitive. m2R activation of Ras, Raf, and MAPK was insensitive to inhibition by genistein, while the epidermal growth factor receptor-induced responses were inhibited by genistein. The findings demonstrate that both Ras and Raf can be regulated by seven-membrane-spanning receptors that selectively couple to Gi proteins.

Adenosine Triphosphate↗
PubMed1993

Consistent chromosomal anomalies in keratinocyte cell lines derived from untreated malignant lesions of the oral cavity.

Cytogenetic analysis has been carried out on 8 early passage cell lines derived from 8 untreated human oral squamous cell carcinomas. Clonal aberrations were detected in the karyotypes of each cell line. A high frequency of breakpoints were noted on chromosomes 1, 7, 8, 9, 11, and X. An isochromosome 8 was present in 6 out of 8 cell lines; isochromosome 9 (3 cell lines) and isochromosome 11 (1 cell line) were also found. In 4 out of 8 cell lines X chromosome harboured breakpoints, a novel finding in oral squamous cell carcinomas. Breakpoints were common on chromosome 1, with 1p12-p13 most frequently involved. Tandem duplication of 11q13-q23, which contains a number of growth regulatory genes, was also noted in 2 cases. We correlate the sites of proto-oncogenes and other growth control genes with chromosomal breakpoints and suggest that several of these may play a role in the pathogenesis of oral cancer.

Adult↗
PubMed1993

Interferon-gamma-induced increased sensitivity of HER2/neu-overexpressing tumor cells to lymphokine-activated killer cell lysis: importance of ICAM-1 in binding and post-binding events.

Treatment of HER2/neu-overexpressing target cells with interferon gamma (IFN gamma) (200-2000 U/ml for 3 days) markedly enhances their sensitivity to lymphokine-activated killer (LAK) cell lysis. Increased sensitivity is associated with an up-regulation of intercellular adhesion molecule ICAM-1 determinants and a down-regulation of HER2/neu expression. In the present study, we show that exposure to another cytokine, tumor necrosis factor alpha (200 U/ml for 3 days), also decreased HER2/neu expression but had no effect on LAK cell lysis and ICAM-1 expression. This suggests that down-regulation of oncogene expression is not sufficient by itself to induce an enhanced sensitivity to LAK cell lysis. IFN-induced enhanced lysis was associated with an increased binding between effectors and targets, and antibodies to ICAM-1 as well as its counter-receptor LFA-1, blocked the increased binding and lysis. Treatment with IFN gamma still significantly enhanced lysis even when concanavalin A was added to the assay to induce maximal binding, indicating that a post-binding effect also participated in enhanced cytotoxicity. These post-binding alterations, were also sensitive to blocking with anti-ICAM-1 and anti-LFA-1 antibodies. Treatment with IFN also sensitized targets to lysis by T cells in the presence of lectin but had no effect on the relative resistance of HER2+ cells to lysis mediated by perforin or TNF. Together these data demonstrate the importance of ICAM-1 determinants in binding and post-binding events in the IFN-induced increased lysis of HER2/neu+ targets.

Cell Adhesion Molecules↗
PubMed1993

Resistance of HER2/neu-overexpressing tumor targets to lymphokine-activated-killer-cell-mediated lysis: evidence for deficiency of binding and post-binding events.

HER2/neu-overexpressing tumor cell lines are relatively resistant to lymphokine-activated killer (LAK) cell cytotoxicity when compared to HER2/neu-nonexpressing lines. HER2/neu+ targets were also resistant to binding by LAK large granular lymphocytes (LGL) as shown by visualization at the single-cell level, a target monolayer binding assay and in "cold" target inhibition experiments. HER2/neu+ LAK-resistant ovarian cell lines demonstrated an absence of ICAM-1 expression while expression of LFA-3, N-CAM, laminin and beta 1 integrins was comparable to that of HER2/neu- targets. In contrast, the HER2/neu+ breast cell line, SKBR-3, which was also resistant to lysis and binding by LAK LGL, demonstrated normal expression of ICAM-1. Anti-ICAM-1 antibodies blocked binding and lysis of HER2/neu- carcinoma targets by LAK cells, further supporting the notion that lack of ICAM-1 expression on HER2/neu+ cells contributes to their resistance. The modest binding and lysis of HER2/neu+ targets by LAK cells was significantly inhibited by anti-LFA-1 antibodies, suggesting the existence of another counter-receptor for LFA-1 on HER2/neu+ targets. The following also supported deficiencies in post-binding events when HER2/neu+ cells resisted the lytic activity of LAK cells: (a) when the relative resistance to effector cell binding was overcome by exogenous lectin. HER2/neu+ cell lines were still resistant to LAK cytolysis, and (b) HER2/neu+ targets were resistant to perforin-containing granule extracts obtained from the CTLL-R8 cytotoxic lymphocyte cell line. These results indicate that deficiency in effector binding as well as post-binding events contributes to the resistance of HER2/neu-overexpressing tumor targets to LAK-cell-mediated lysis.

Cell Adhesion Molecules↗
PubMed1993

The comparative costs of care using apnoea monitors and scales in families with a cot death.

This paper reports the findings from a programme, which provided support to families with a subsequent baby following a cot death. One hundred families participated in the study. Fifty families were randomly allocated apnoea monitors, and the remainder provided with scales and weight charts for daily weighing. The results show that the parents in both groups expressed equal satisfaction with their designated method. However, compared with families allocated scales, those using apnoea monitors attended the child health clinics more often, and the number of contacts with the paediatrician was increased. They also had slightly more home and general practitioner contacts and hospital admissions. The capital and running costs of providing monitors was also greater for this group.

Apnea↗
PubMed1992

Effects of beta-2 microglobulin anti-sense oligonucleotides on sensitivity of HER2/neu oncogene-expressing and nonexpressing target cells to lymphocyte-mediated lysis.

The mechanism by which HER2/neu overexpressing tumor cells resist NK, LAK, and LDCC cytotoxic lymphocytes was investigated. Resistance was not explained by a delay in kinetics of lysis, concurrent resistance to TNF, or a diminished expression of the transferrin receptor. HLA-class I expression, however, was markedly elevated compared to HER2 nonexpressing targets suggesting a reason for resistance. To test the role of class I, we selectively decreased expression by incubation of targets with beta-2 microglobulin anti-sense oligonucleotides. Anti-sense-treated HER2+ targets, displaying levels of class I comparable to HER2- targets, were still markedly resistant to cytotoxic effectors. Down-regulation of class I expression in HER2- carcinoma cells also had no effect on sensitivity to cytotoxicity by anti-sense treatment of Raji and U937 targets resulted in enhanced sensitivity to NK and LAK effectors but not to T cells mediating LDCC. These data indicate resistance to cytotoxicity in HER2-expressing targets cannot be solely explained by heightened expression of class I. The data also support the concept that class I expression regulates sensitivity to NK and LAK cells (but not LDCC effectors) in selected targets.

Animals↗
PubMed1992

Effect of calcium on the vasoactive response of arterioles to light during fluorescent intravital microscopy of the tibialis anterior muscle of the hamster.

Arterioles may undergo a transient vasoactive response when exposed to light during fluorescent intravital microscopy. We hypothesized that the type and frequency of the vasoactive responses by arterioles to light is calcium dependent. In order to test this hypothesis we quantitated the type and frequency of vasoactive responses by arterioles to light in the presence and absence of calcium within the suffusate bathing the muscle. In addition, we determined whether the presence or absence of calcium also influenced the reactivity of these arterioles to adenosine and norepinephrine. In separate experiments, we determined the effect of increases in suffusate calcium concentration on the resting diameter of arterioles. The concentration of calcium in the suffusate significantly influenced the frequency of light-induced vasoactivity of the arterioles of the tibialis anterior muscle: a normal suffusate calcium concentration of 2 x 10(-3) M was associated with an incidence of light-induced vasoreactivity of 77% but decreased significantly to 58% when calcium was removed from the suffusate. Although the frequency of the vasoactive response to light was different for the two experimental conditions, the type of vasoactive response, predominately vasomotion, was similar. The vasoactive responses of arterioles to adenosine and norepinephrine were similar in the presence and absence of calcium in the suffusate. However, the concentration of calcium in the suffusate did significantly influence resting arteriolar diameters: 2 x 10(-3) M calcium CaCl2 caused a mean decrease in the arteriolar diameter of 11.6 (+/- 3.0)%, 4 x 10(-3) M CaCl2 caused a mean decrease of 41.2 (+/- 12)%, and 8 x 10(-3) M CaCl2 caused a mean decrease of 55.4 (+/- 14.4)%. These results show that the concentration of calcium in the suffusate bathing the tibialis anterior muscle during fluorescent intravital microscopy significantly influences the vasoactive response of arterioles to light. Further investigation of the mechanisms of light-induced effects on microcirculation during fluorescent intravital microscopy will become important as this technique is used more widely in the study of the microcirculation of solid tissues and organs.

Adenosine↗