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Biomedical subjects

R Garland

Publications and source records attributed to R Garland.

14 recordsLinked to original sources

A retrospective audit of long-term lower limb complications following leg vein harvesting for coronary artery bypass grafting.

OBJECTIVE: To evaluate the prevalence of leg complications following leg-vein harvest for coronary artery bypass grafting. METHOD: A questionnaire was sent to patients who had coronary artery bypass surgery between January 1993 and December 1998. Questions addressed pain, numbness, infection, swelling and general healing. The relationship between the risk factors of diabetes, peripheral vascular disease, previous fractures/injuries to legs, previous deep vein clots and arthritis affecting the legs with post operative symptoms of pain, numbness, swelling and general healing was explored with multivariate analysis. RESULTS: Of 700 questionnaires sent out 497 were returned, of which 422 (60%) were suitable for analysis. Numbness or tingling related to the wound was reported by 256 (61%), of whom 94 (37%) improved within 3 months. However, 105 (41%) had persistent numbness beyond 2 years. Pain in the wound was reported by 193 (46%), of whom 149 (77%) reported that this had improved by 3 months and only 19 (10%) had pain persisting beyond 2 years. A leg wound infection was reported by 126 (32%) patients, with 82 (65%) of these receiving antibiotics. A total of 336 (87% of 387 responses) described their wound as completely healed at 3 months. Unilateral leg swelling was reported by 175 (41%) with 98 of these (56% of those with swelling) improving by 3 months and 41 (23%) with swelling persisting beyond 2 years. There was no relation of wound problems to examined risk factors diabetes (P-values for numbness 0.31, wound healing 0.15, swelling 0.21, pain 0.22) and peripheral vascular disease (P-values for numbness 0.8, wound healing 0.21, swelling 0.18, pain 0.09). There was insufficient data to comment on the influence of fractures/injuries to legs, previous deep vein clots and arthritis affecting the legs. CONCLUSIONS: Wound complications are common following leg vein harvest. Prevalence of infection was higher than has previously been reported. Few people suffer long-term pain from saphenous nerve damage although paraesthesia and swelling were common long-term complications. We did not identify either diabetes or peripheral vascular disease as a risk factor for pain, numbness, swelling or problems with general healing. There is a need for a large multicentre prospective study.

Adult↗

CT fluoroscopy guidance for transbronchial needle aspiration: an experience in 35 patients.

OBJECTIVE: To demonstrate the usefulness of real-time guidance with CT fluoroscopy to improve the yield of transbronchial needle aspiration (TBNA). DESIGN: Prospective, observational. SETTING: A tertiary-care, university-affiliated medical center. METHODS: From December 1998 to April 2000, 35 patients underwent CT fluoroscopy-guided TBNA. Patients with subcarinal and precarinal lymph nodes were only included if a previous attempt was nondiagnostic, as the initial yield in this setting with conventional TBNA is high. TBNA was performed using standard technique in a CT-scan suite. Needle location was confirmed with fluoroscopy without IV contrast being used. Specimens were evaluated on-site for adequacy. RESULTS: The procedure had to be aborted in three patients before TBNA could be performed. Samples were obtained in 32 patients. Samples were nondiagnostic in four patients. Adequate tissue was obtained in 28 of 32 patients (87.5%). Twenty-two patients had a specific benign or malignant diagnosis made, and 6 patients had lymphocytes only on the specimen. In follow-up, only one of these six patients proved to have a malignancy. All procedures were performed within a regular interventional CT time slot of 1 h. No TBNA side effects were noted. CONCLUSION: TBNA under CT fluoroscopic guidance is easy to perform. The yield in all accessible lymph node stations is high.

Adult↗

Safety of bedside percutaneous dilatational tracheostomy in obese patients in the ICU.

STUDY OBJECTIVE: To examine the safety of bedside percutaneous dilatational tracheostomy in obese patients. DESIGN: Case series of consecutive obese patients (body mass index > or = 27 kg/m(2)) with acute respiratory failure in a medical, cardiac, or surgical ICU unit who required tracheostomy for failure to wean and continued mechanical ventilatory support. RESULTS: Thirteen obese patients were identified and consented to the procedure. Bedside percutaneous dilatational tracheostomy was successfully performed in the ICU for all 13 patients. Procedural complications were limited to paratracheal tracheostomy tube placement in one patient, with immediate identification and appropriate correction. Postprocedural complications were limited to a cuff leak in one patient. CONCLUSION: Bedside percutaneous tracheostomy can be safely performed in obese patients.

Acute Disease↗

Management and outcome patterns for adult Pneumocystis carinii pneumonia, 1985 to 1995: comparison of HIV-associated cases to other immunocompromised states.

STUDY OBJECTIVES: Encompassing periods preceding and following major advances in the diagnosis and management of HIV-related Pneumocystis carinii pneumonia (PCP), the purpose of this study was to determine whether management and outcome patterns of non-HIV PCP parallel the management and outcomes of AIDS-related PCP. DESIGN: Retrospective review of medical records. SETTING: A 375-bed tertiary-care urban teaching hospital and referral center. PATIENTS: All adult patients with morphologically confirmed PCP from 1985 to 1995. MEASUREMENTS AND RESULTS: From 1985 to 1995, 638 confirmed cases of PCP were identified, including 605 cases in 442 HIV-positive persons (HIV + PCP), and 33 cases in 33 non-HIV patients (non-HIV PCP). For HIV + PCP cases, a peak of 104 cases occurred in 1987, with a gradual decline to 23 in 1995. The proportion of cases requiring hospitalization declined from a peak of 91.6% in 1987 to a low of 51.6% in 1992. ICU admission was required for 6.3 to 8.2%, and mechanical ventilation for 4.7 to 5.7%. Overall mortality improved from 11.7 to 6.6%, although mortality for intubated patients remained at 50 to 60%. For the non-HIV PCP cases, 97% occurred from 1989 to 1995 with similar annual frequency, 97% required hospitalization, 69% required ICU admission, and 66% required intubation. Overall mortality was 39%, and mortality for intubated patients was 59%. CONCLUSIONS: Despite major advances in diagnosis and management, PCP remains a significant problem in non-HIV-infected patients, and respiratory failure remains associated with a high mortality rate for patients with both HIV + PCP and non-HIV PCP.

AIDS-Related Opportunistic Infections↗

Peripheral blood CD4 + T-lymphocyte counts during Pneumocystis carinii pneumonia in immunocompromised patients without HIV infection.

STUDY OBJECTIVES: To assess the potential use of peripheral blood CD4 + T-lymphocyte counts (CD4 + counts) as a clinically useful biological marker to identify specific immunocompromised patients (without HIV infection) at high risk for Pneumocystis carinii pneumonia (PCP). DESIGN: Prospective observational study. SETTING: Three hundred seventy-five-bed tertiary-care urban referral teaching hospital, and 250-bed community-based referral hospital. PATIENTS: One hundred seventy-one consecutive confirmed HIV-seronegative hospitalized and ambulatory adults, including 22 patients with active PCP, 8 patients with bacterial pneumonia, 24 persons in two groups considered at high clinical risk, 38 persons in two groups considered at low or undefined risk, and 79 persons in four groups considered not at risk for PCP (including healthy individuals). MEASUREMENTS AND RESULTS: Compared to counts in healthy individuals, median CD4 + counts were significantly decreased in patients with active PCP (61 cells/microL vs 832 cells/microL; p = 0.001) where 91% of patients had a CD4 + count < 300 cells/microL at the time of PCP diagnosis. Median CD4 + counts were also reduced in the high clinical risk groups of recent organ transplant recipients (117 cells/microL; p = 0.007), 64% with < 300 cells/microL, and patients receiving chemotherapy (221 cells/microL; p<0.01), 80% with < 300 cells/microL. For the low or undefined clinical risk groups, the median CD4 + counts were not significantly reduced, although 39 to 46% of individuals receiving long-term corticosteroid therapy (alone or in combination with other agents) had CD4 + counts < 300 cells/microL. Median CD4 + counts in individuals considered not at risk for PCP were similar to those in healthy subjects. Compared to counts in patients with active PCP, median CD4 + counts were significantly higher in bacterial pneumonia patients (486 cells/microL; p<0.05), but similar to those in healthy subjects. CONCLUSIONS: These data suggest that for immunosuppressed persons without HIV infection (especially in low or undefined PCP risk groups), CD4 + counts may be a useful clinical marker to identify specific individuals at particularly high clinical risk for PCP and may help to guide chemoprophylaxis.

Adult↗

Enhanced in vivo human immunodeficiency virus-1 replication in the lungs of human immunodeficiency virus-infected persons with Pneumocystis carinii pneumonia.

The relationship of serum human immunodeficiency virus-1 (HIV-1) RNA levels to HIV-1 RNA levels in other compartments, such as the lungs, is not well characterized. The purpose of this study was to determine the viral burden of HIV-1 in the lungs by comparing HIV-1 RNA in cell-free bronchoalveolar lavage fluid (BALF) with that in serum. Specimens were examined from 77 HIV-seropositive adults (CD4(+) cell counts: 0 to 700 cells/mm(3); 48% receiving prescribed antiretroviral agents), comprising 43 asymptomatic individuals who were compared with 34 persons with active lung disease caused by Pneumocystis carinii (n = 26), bacteria (n = 3), Mycobacterium avium complex (n = 2), Nocardia sp. (n = 1), Aspergillus sp. (n = 1), or pulmonary Kaposi's sarcoma (n = 1). For serum HIV-1 RNA, the proportion of subjects with detectable levels and the mean values were similar for asymptomatic individuals and persons with active lung disease (85% versus 86%, respectively) (6.64 x 10(4) versus 1. 81 x 10(5) HIV-1 RNA copies/ml; p = 0.13). In contrast, HIV-1 RNA in BALF was more often detected (16% versus 62%; p = 0.001), and mean values were higher (1.04 x 10(5) versus 3.31 x 10(6) HIV-1 RNA copies/ml; p = 0.032), in subjects with active lung disease than in asymptomatic subjects, independent of early or advanced clinical stages of HIV-related disease. For both study groups, HIV-1 RNA levels in BALF exceeded those in serum in 56% of cases by up to 66-fold, and did not correlate with local levels of tumor necrosis factor-alpha, granulocyte-macrophage colony-stimulating factor, or interleukin-16. HIV-1 proviral DNA in cells from BALF was detected in up to 86% of subjects, more frequently in persons with advanced HIV disease (p = 0.0496), and often involved > 10% of BALF cells, but did not correlate with HIV-1 RNA detected in BALF. These data provide evidence for active HIV-1 replication in the lungs. HIV-1 replication is compartmentalized relative to serum, may be restricted, is independent of HIV-1 proviral DNA and clinical stage of HIV, and may be influenced by pulmonary disease such as P. carinii pneumonia or by other local or lung-specific factors. The lungs represent a large reservoir for HIV-1, and may present a source of persistent HIV-1 replication even during periods of apparent clinical latency of HIV-1 infection.

AIDS-Related Opportunistic Infections↗

Suppression of hypoxia-associated vascular endothelial growth factor gene expression by nitric oxide via cGMP.

PURPOSE: To investigate the suppressive effect of nitric oxide (NO) on vascular endothelial growth factor (VEGF) gene expression and to elucidate its mechanism of action. METHODS: Immortalized human retinal epithelial (RPE) cells, H-ras-transfected murine capillary endothelial cells, and nuclear factor-kappaB (NF-kappaB) RelA knockout 3T3 fibroblasts had VEGF gene expression stimulated by hypoxia, TPA (phorbol ester 12-O-tetradecanoylphorbol-13 acetate), and ras-transfection. The dose response and time course of inhibition of VEGF gene expression by NO were characterized by northern blot analysis, ribonuclease protection assay, and enzyme-linked immunosorbent assay. The effects of NF-kappaB and cGMP in the NO-induced suppression of VEGF gene expression were quantitated. cGMP production was inhibited by LY 83583 (6-anilino-5,8-quinolinedione), a specific inhibitor of guanylate cyclase production, and cGMP accumulation was quantitated by immunoassay. RelA knockout 3T3 fibroblasts were used to assess the contribution of NF-kappaB to the downregulation of VEGF by NO. RESULTS: The NO donor sodium nitroprusside (SNP) decreased hypoxia-induced VEGF gene expression in a dose- and time-dependent manner. One hundred fifty micromolar SNP completely suppressed hypoxia-induced VEGF mRNA levels for at least 24 hours. Constitutive VEGF expression was not altered by SNP. The SNP-mediated decreases in VEGF expression were associated with increases in intracellular cGMP and were blocked by LY 83583. Sodium nitroprusside was able to decrease hypoxia-induced VEGF mRNA increases in fibroblasts deficient in the RelA subunit of NF-kappaB. Nitric oxide was also effective at suppressing increased VEGF expression secondan, to mutant ras and TPA. CONCLUSIONS: These data indicate that NO decreases hypoxia-induced VEGF via a cGMP-dependent mechanism and suggest that NO may serve as an endogenous inhibitor of both hypoxia- and non- hypoxia-enhanced VEGF expression in vivo.

3T3 Cells↗

Insulin-induced vascular endothelial growth factor expression in retina.

PURPOSE: Clinical studies have demonstrated that intensive insulin therapy causes a transient worsening of retinopathy. The mechanisms underlying the initial insulin-induced deterioration of retinal status in patients with diabetes remain unknown. Vascular endothelial growth factor (VEGF) is known to be operative in the pathogenesis of diabetic retinopathy. The current study was conducted to characterize the effect of insulin on retinal VEGF gene expression in vitro and in vivo. METHODS: The effect of insulin on VEGF expression in vivo was examined by in situ hybridization studies of rat retinal VEGF transcripts. To examine the mechanisms by which insulin regulates VEGF expression, human retinal pigment epithelial (RPE) cells were exposed to insulin, and VEGF mRNA levels were quantified with RNase protection assays (RPAs). Conditioned media from insulin-treated RPE cells were assayed for VEGF protein and capillary endothelial cell proliferation. The capacity of insulin to stimulate the VEGF promoter linked to a luciferase reporter gene was characterized in transient transfection assays. RESULTS: Insulin increased VEGF mRNA levels in the ganglion, inner nuclear, and RPE cell layers. In vitro, insulin increased VEGF mRNA levels in human RPE cells and enhanced VEGF promoter activity without affecting transcript stability. Insulin treatment also increased VEGF protein levels in conditioned RPE cell media in a dose-dependent manner with a median effective concentration of 5 nM. The insulin-conditioned RPE cell media stimulated capillary endothelial cell proliferation, an effect that was completely blocked by anti-VEGF neutralizing antibody. CONCLUSIONS: Insulin increases VEGF mRNA and secreted protein levels in RPE cells through enhanced transcription of the VEGF gene. Intensive insulin therapy may cause a transient worsening of retinopathy in patients with diabetes through increased retinal VEGF gene expression.

Animals↗

Use of adjunctive corticosteroids in severe adult non-HIV Pneumocystis carinii pneumonia.

STUDY OBJECTIVE: To examine the use of adjunctive corticosteroids in cases of severe Pneumocystis carinii pneumonia (PCP) in non-HIV-infected adult patients. DESIGN: Retrospective review of medical records. SETTING: Tertiary care urban teaching hospital. PATIENTS: Review identified 31 consecutive histologically confirmed primary cases of adult non-HIV-related PCP. Complete records were available for 30 patients, including 20 male and 10 female patients with a mean age of 58.3+/-15 years (+/-SD). Underlying conditions included organ transplantation (n=13), long-term immunosuppressive therapy (n=9), and chemotherapy for malignancy (n=8). All patients had documented PO2 <65 mm Hg or arterial oxygen saturation <90% on room air. INTERVENTIONS: Following the identification of P carinii, in addition to trimethoprim-sulfamethoxazole or pentamidine therapy, 16 patients received increased steroids (> or =60 mg prednisone daily equivalent; increased high-dose steroid group), whereas 14 patients were maintained on a regimen of low doses (< or =30 mg prednisone equivalent daily) or had steroid therapy tapered (low-dose steroid group). RESULTS: The increased high-dose steroid group demonstrated a shorter required duration for mechanical ventilation (6.3+/-6 days vs 18.0+/-21 days; p=0.047), a shorter duration of ICU admission (8.5+/-7 days vs 15.8+/-8 days; p=0.025), and a shorter duration of supplemental oxygen use (10.0+/-4 vs 32.2+/-33; p=0.05). The hospital duration to discharge for the nine survivors in each group favored the use of corticosteroids (15.4+/-5 days vs 36.3+/-33 days; p=0.077). Similar rates were observed for intubation (75% vs 57%; p=0.442) and in-hospital mortality (44% vs 36%; p=0.722). CONCLUSIONS: These preliminary data suggest that high-dose adjunctive corticosteroids may accelerate recovery in cases of severe adult non-HIV PCP.

Anti-Infective Agents↗

Aerosolized pentamidine as alternative primary prophylaxis against Pneumocystis carinii pneumonia in adult hepatic and renal transplant recipients.

STUDY OBJECTIVE: To examine the safety and efficacy of aerosolized pentamidine (AP) as alternative primary prophylaxis against Pneumocystis carinii pneumonia (PCP) in adult liver and kidney transplant recipients. DESIGN: Retrospective review of medical records. SETTING: Tertiary care urban teaching hospital with active liver and kidney transplant programs. PATIENTS: Adult liver and kidney transplant recipients intolerant of trimethoprim-sulfamethoxazole (TMP-SMX) therapy and referred to the AP clinic between June 1991 and December 1994. INTERVENTIONS: Each patient received monthly AP, 300 mg, delivered by a nebulizer (Respirgard-II), preceded by inhaled albuterol, 180 micrograms. During the period of follow-up, information related to side effects of AP and incidence of PCP was recorded. RESULTS: A total of 35 patients were identified, 18 liver and 17 kidney transplant recipients. Fourteen patients received AP as initial prophylaxis because of prior sensitivity to TMP-SMX. In another 19 patients, initial TMP-SMX therapy was discontinued for leukopenia (5), elevated liver function test values (4), rash (3), nausea (2), renal failure (2), seizure (2), and thrombocytopenia (1). In addition, two patients received AP in the setting of organ rejection. Liver transplant recipients received AP for an average of 4.28 +/- 1.6 months, and renal transplant recipients received AP for an average of 5.71 +/- 4.3 months. Adverse effects of AP included bronchospasm (two), dyspnea (one), cough (one), and nausea (one). AP therapy was discontinued in only one patient due to severe bronchospasm. There were no cases of PCP in the 35 patients receiving AP. CONCLUSIONS: These observations suggest that AP is well tolerated and may be an effective alternative for PCP prophylaxis in adult liver and kidney transplant recipients intolerant to TMP-SMX therapy.

Adult↗

Quantitative culture of HIV-1 from bronchoalveolar lavage cells.

Determination of the infectious virus burden at the organ level is critical for understanding the pathophysiology of human immunodeficiency virus type 1 (HIV-1) infection. To evaluate the burden of HIV-1 in the lung, quantitative cultures were performed on bronchoalveolar lavage (BAL) cells from 11 HIV-1 seropositive subjects without respiratory infections and compared with peripheral blood mononuclear cells (PBMC) obtained from the same subjects. Fifty percent (50%) of subjects had positive BAL cell cultures while 82% had positive PBMC cultures. There was much less virus cultured from BAL cells than from PBMCs, whether using phytohemagglutinin (PHA)-stimulated peripheral blood lymphocyte (PBL) targets (p < 0.05) or adherent monocyte targets (p < 0.02). There was no significant difference between the HIV-1 titers obtained for BAL cells whether using PHA-stimulated PBL or adherent monocyte targets (p = 0.13). These studies demonstrate that BAL cell cultures for HIV-1 in subjects without respiratory infections are less frequently positive than PBMC cultures, that less virus can be recovered from BAL cells than from PBMC, and that HIV-1 isolates from BAL cells replicate in both PHA-stimulated PBL targets and adherent monocyte targets. Quantitative assessment of virus burden in the lung is important for future studies of HIV-1 pathogenesis and for evaluating potential antiretroviral therapies aimed at altering the natural history of organ dysfunction associated with retroviral replication.

Adult↗

The effects of covert sensitization on preference for sexual stimuli: a preliminary analogue experiment.

Although covert sensitization is a widely and diversely employed clinical technique, there is no generally accepted conceptual guideline for its implementation. Consequently, there is considerable variability in the way covert sensitization procedures are employed, which may account for the reported inconsistency in its clinical effectiveness. The present study is an analogue experimental test of a conceptual account of covert sensitization that is based upon classical conditioning. The classical conditioning procedure is viewed as affecting operant target behaviors by altering the reinforcer effectiveness of target stimuli. This was explicitly tested by examining the effects of covert sensitization on subjects' preference for sexual stimuli in an operant choice paradigm. The results support the conceptual account.

Adult↗

Images of health and medical science conveyed by television.

Content analysis was carried out on medical programmes on BBC television over a three-month period. Television medical programmes were shown to concentrate on hospital-based, technological and expert-dependent issues at the expense of primary care and community health. Images of technology, the hospital and the hospital specialist were found to predominate. Issues such as the family, preventive care, housing and the environment were rarely raised. Doctors appeared and spoke in 94 per cent of programmes, whereas nurses were seen (although not necessarily heard) in 30 per cent. Of 70 doctors interviewed on television, nearly three quarters were hospital doctors or scientists. Only one doctor was explicitly referred to as a general practitioner.

Health↗