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Biomedical subjects

A Roman

Publications and source records attributed to A Roman.

At least 19 recordsLinked to original sources

Surgical technique and complications during laparoscopic repair of diaphragmatic hernias.

Diaphragmatic hernias can present as retrocostoxiphoid hernias (RCXH) or diaphragmatic dome hernias. The RCXH include the Larrey hernia (LH), the Morgagni hernia (MH), and the Larrey-Morgagni hernia (LMH). These congenital hernias are usually asymptomatic, and the diagnosis is simplified by two exams: chest X-ray, and thoraco-abdominal computed tomography (CT) scan. The potential risk in this condition is small-bowel incarceration in the hernia defect and subsequent obstruction. We report two cases of LH and one case of LMH treated by laparoscopy between February 2004 and October 2005, with a review of the surgical techniques. Two different laparoscopic techniques were used: the tension-free technique, and resection of the hernia sac with closure of the defect and reinforcement by prosthesis. One patient presented a postoperative cardiac tamponade due to a clip-induced bleeding of an epicardial artery at the inferior surface of the heart. Treatment by laparoscopy is feasible, but a consensus regarding the best laparoscopic repair is needed.

Adolescent↗

Everolimus versus azathioprine in maintenance lung transplant recipients: an international, randomized, double-blind clinical trial.

Everolimus is a proliferation signal inhibitor with immunosuppressive activity that may reduce the rate of progression of chronic rejection, bronchiolitis obliterans syndrome (BOS), after lung transplantation. In a randomized, double-blind clinical trial, 213 BOS-free maintenance patients received everolimus (3 mg/day) or azathioprine (AZA, 1-3 mg/kg/day) in combination with cyclosporine and corticosteroids. The prospectively defined primary endpoint was the incidence of efficacy failure (decline in FEV1 >15%[deltaFEV1 >15%], graft loss, death or loss to follow-up) at 12 months. Incidence of efficacy failure at 12 months was significantly lower in the everolimus group than AZA (21.8% vs. 33.9%; p = 0.046); at 24 months, rates of efficacy failure became similar between the groups. At 12 months, the everolimus group had significantly reduced incidences of deltaFEV1 >15%, deltaFEV1 >15% with BOS, and acute rejection. At 24 months, only incidence of acute rejection remained significantly less in the everolimus group. Treatment discontinuations (particularly due to adverse events), serious adverse events and high serum creatinine values were more common with everolimus. For the first time, a drug has demonstrated significant slowing of loss in lung function, suggesting that patients kept on prolonged maintenance treatment with everolimus may benefit from replacing AZA with everolimus 3 months after lung transplantation.

Adrenal Cortex Hormones↗

Monitoring STI prevalence using telephone surveys and mailed urine specimens: a pilot test.

OBJECTIVES: This pilot test assessed the feasibility of a cost effective population based approach to STI monitoring using automated telephone interviews, urine specimen collection kits sent out and returned by US Postal Service mail, and monetary incentives to motivate participation. METHODS: 100 residents of Baltimore, MD, USA, completed an automated telephone survey and agreed to mail in a urine specimen to be tested for chlamydia and gonorrhoea. Participants were paid dollar 10 for completing the survey and dollar 40 for mailing the specimen. RESULTS: 86% of survey participants mailed in a urine specimen for testing. CONCLUSIONS: Automated telephone surveys linked with testing of mailed-in urine specimens may be a feasible lower cost (relative to household surveys) method of estimating infection prevalences in a population.

Adolescent↗

Ascending aorta syphilitic aneurysm presenting as a dystrophic disease.

A 37-year-old female originating from Central Africa presented with cardiac failure, aortic insufficiency and aortic root dilatation of supposed dystrophic origin. Left coronary ostial dilatation and dense adhesions between the aorta and the pulmonary trunk at operation were the only unusual features. However, pathological examination evoked a syphilitic disease and serology confirmed luetic infection. The diagnosis and the therapeutic approach are discussed. Syphilitic aneurysms belong to the protohistory of vascular surgery, but, in the antibiotherapy era, tracking a syphilitic aneurysm is like fishing for coelacanth. When this pathology mimics a dystrophic aneurysm, diagnosis and therapeutic attitude becomes hazardous and justifies the present report.

Adult↗

Lung transplantation in young infants with interstitial pneumonia.

OBJECTIVES: We describe our experience with infants suffering from interstitial pneumonia referred for lung transplantation. METHODS: From April 1998 to December 2000, three infants were admitted to our lung transplantation program: a 9-month-old girl (patient 1) suffering from surfactant protein C deficiency who had high oxygen requirements (fraction of inspired oxygen: 70% to 90%), and two boys, ages 2 (patient 2) and 9 months (patient 3), who were ventilator-dependent due to chronic pneumonitis of infancy. RESULTS: Patients were transplanted at the age of 5 months (patient 2) and 13 months (patients 1 and 3) at 87 to 105 days after being accepted for lung transplantation. All cases underwent a sequential double lung transplant on cardiopulmonary bypass. The immunosuppressive regime included tacrolimus, prednisone, and azathioprine. Patients 2 and 3 also received basiliximab. Two cases suffered a mild rejection episode that responded to high-dose steroids. Patient 2 was ventilator-dependent for 8 months after transplant, owing to severe bronchomalacia and left main bronchus stenosis. Bronchial stenosis resolved after pneumatic dilatation and endobronchial stenting. This patient also presented with a pulmonary artery anastomosis stricture that required percutaneous balloon dilatation. All three patients are at home, carrying out normal activities for their age, with no respiratory symptoms after a period of 8 to 29 months of follow-up. CONCLUSIONS: Interstitial pneumonia of infancy is a rare disease with a bad prognosis and no specific treatment; therefore, lung transplantation represents a good therapeutic option for these infants.

Female↗

Blood cyclosporine C0 and C2 concentrations and cytomegalovirus infections following lung transplantation.

The aim of this study was to determine whether cyclosporine levels predose (C0) and at two hours postdose (C2) were higher among patients presenting with cytomegalovirus (CMV) infection or disease. Between days 40 and 365 posttransplantation serial C0 and C2 levels were measured in 15 lung transplant recipients. Nine developed 13 episodes of CMV infection or disease. Both C0 and C2 levels were higher during CMV infection or disease episodes. Eleven of the 13 CMV episodes (84%) displayed C0 >220 ng/mL and none had C0 <200 ng/mL. For C2, 11 of 13 CMV episodes (84%) showed C2 >1200 ng/mL and none had C2 <1000 ng/mL. Among determinations that did not coincide with a CMV episode, 7 of 21 (33%) showed C0 >220 and 9 of 21 (42%) showed C2 >1200, respectively (P<.05). In conclusion, cyclosporine blood levels are higher among patients presenting with CMV infection or disease.

Adult↗

Prolonged desipramine treatment increases the production of interleukin-10, an anti-inflammatory cytokine, in C57BL/6 mice subjected to the chronic mild stress model of depression.

BACKGROUND: Depression is associated with activation of the inflammatory response system (IRS). In humans, antidepressants significantly increase the production of interleukin-10 (IL-10), a negative immunoregulatory cytokine. The aims of the present study were to examine the effects of desipramine, a tricyclic antidepressant, on the IRS in C57BL/6 mice with and without exposure to chronic mild stress (CMS). METHODS: We examined the effects of desipramine on the cytotoxic activity of natural killer (NK) cells, the proliferative responses of lymphocytes after stimulation with IL-1, IL-2, lipopolysaccharide (LPS), concanavaline-A (Con-A), phytohaemagglutinin-P (PHA), pokeweed mitogen (PWM), and anti-CD3 monoclonal antibodies, the production of IL-2, IL-4, IL-10 and interferon-gamma (IFNgamma) by T lymphocytes and the ability of B cells to proliferate after stimulation by lipopolysaccharide (LPS). RESULTS: Prolonged treatment of C57BL/6 mice subjected to CMS with desipramine increases the ability of T cells to produce IL-10 and the ability of B cells to proliferate after stimulation with LPS; and significantly decreases the cytotoxic activity of NK cells and the proliferative responses of lymphocytes after stimulation with Con-A, PHA and anti-CD3 monoclonal antibodies. Repeated administration of desipramine to non-stressed mice increases the activity of T lymphocytes, lowers that of B lymphocytes, increases the production of IL-10 by T cells and has no significant effect on the activity of NK cells. CONCLUSION: Prolonged desipramine treatment of stressed and non-stressed C57BL/6 mice induces an increase in the production of IL-10, an anti-inflammatory cytokine.

Animals↗

Nebulized amphotericin B prophylaxis for Aspergillus infection in lung transplantation: study of risk factors.

BACKGROUND: Aspergillus infection remains a major cause of morbidity and mortality after lung transplantation. Therefore, some strategies have been attempted, one of which is nebulized amphotericin B (nAB); however, the efficacy of this prophylaxis has not been shown clearly. The aim is to study whether nAB can protect against Aspergillus infection in lung transplant recipients. PATIENTS AND METHODS: A study of risk factors was conducted in 55 consecutive lung allograft recipients. Twenty-three potential risk factors were analyzed. In 44 (80%) patients, nAB was indicated as prophylaxis. Multivariate analysis using logistic regression was performed. RESULTS: Eighteen of the 55 patients (33%) developed infection due to Aspergillus spp. Multivariate analysis showed nAB to be a preventive factor (odds ratio: 0.13; 95% confidence interval [CI] 0.02-0.69; p < 0.05) and cytomegalovirus (CMV) disease was an independent risk factor for developing Aspergillus infection (odds ratio: 5.1; 95% CI 1.35-19.17; p < 0.05). Only 1 patient required withdrawal of the prophylaxis owing to bronchospasm. nAB was well-tolerated in the remaining patients with only a few, mild, easily controlled side effects. CONCLUSIONS: The present results show that nAB prophylaxis may be efficient and safe in preventing Aspergillus infection in lung-transplanted patients, and CMV disease increases the probability of Aspergillus infection.

Adolescent↗

Mycophenolic acid plasma concentrations: influence of comedication.

Mycophenolate mofetil (MMF) in combination with cyclosporine (CsA) or Tacrolimus (TAC) has been show to be a potent immunosuppressive agent. The authors assessed the mycophenolic acid (MPA) plasma levels achieved in clinical practice and evaluated the effect of concomitant administration of CsA and TAC . One hundred forty transplant patients (kidney: 120 and lung: 20) received a triple immunosuppression regimen of CsA or TAC, prednisone and MMF. Twenty-two renal transplant patients received double therapy with MMF and prednisone. There was no correlation between MMF dose and MPA trough concentrations (r = -0.0657). The medians (range) of the MPA dose-to-concentration ratio (D/C) in the CsA and TAC groups were 0.90 (0.11-8.33) and 0.56 (0.11-14.3), respectively (p < 0.0001). According to the post transplant period (1-3, 4-6 and >6 months), D/C values were significantly lower in patients receiving MMF and TAC than those receiving MMF and CsA in all three periods. MPA levels in patients treated with MMF and CsA were significantly lower than those obtained in double therapy. The D/C ratio in CsA-treated patients, increased significantly (p = 0.0005) when CsA level increased. There was no relationship between D/C ratio and TAC blood concentrations. These results suggest that CsA exerts an influence on MPA trough levels, although further work is required to characterize the mechanism of interaction.

Adult↗

Control of high-dose-cisplatin-induced emesis with an all-oral three-drug antiemetic regimen.

In this pilot trial, the antiemetic efficacy and tolerability of an all-oral antiemetic combination in the prevention of both acute and delayed nausea and vomiting following high-dose cisplatin was evaluated. Fifty-two patients receiving cisplatin (median dose 100 mg/m2) were entered. Patients received (1) 60 min prior to cisplatin: prochlorperazine spansule 15 mg, dexamethasone 20 mg, granisetron 2 mg; (2) 12 h after cisplatin: prochlorperazine spansule 15 mg, dexamethasone 10 mg; (3) on days 2 and 3: prochlorperazine spansule 15 mg b.i.d., dexamethasone 8 mg b.i.d.; (4) on days 4 and 5: dexamethasone 4 mg b.i.d. All antiemetics were administered orally. The study period was the 120 h after cisplatin administration. The primary efficacy end-point was complete control (no vomiting, retching or antiemetic rescue) of delayed emesis (24-120 h after cisplatin). Complete control of delayed emesis was achieved in 26 patients (53%). Nineteen patients (39%) noted no delayed nausea. Complete control of acute emesis (24 h after cisplatin) was attained in 44 patients (86%). The no nausea rate during the first 24 h was 74%. Overall, 39 patients (80%) were satisfied or very satisfied with their outcome. Treatment was well tolerated with infrequent and minor adverse events. In conclusion, an all-oral combination of granisetron, dexamethasone and prochlorperazine is a highly effective and well-tolerated regimen for preventing acute cisplatin-induced emesis. Control of delayed emesis was not better than with current standard treatment, and more effective approaches are needed.

Administration, Oral↗

Isoniazid prophylaxis in lung transplantation.

The incidence of tuberculous disease (TD) is higher in lung-transplant patients than in the general population. During a 7-year period, we included 61 patients who underwent lung transplantation in a prospective isoniazid prophylaxis protocol. Isoniazid was prescribed to infected and anergic patients not previously treated when added to the waiting list. Six of 61 patients (10%) developed tuberculosis. We observed no differences in tuberculous disease incidence between infected-anergic and non-infected patients. In our tuberculous-endemic area, isoniazid prophylaxis is safe and offers protection from TD to infected and anergic patients who must be enrolled in a lung transplantation program.

Adolescent↗

Mycophenolate mofetil pharmacokinetics in transplant patients receiving cyclosporine or tacrolimus in combination therapy.

Mycophenolate mofetil is a highly effective immunosuppressant drug used in the prophylaxis of organ rejection in combination with cyclosporine or tacrolimus and corticosteroids. The present study is a retrospective data analysis of the routinely estimated mycophenolic acid plasma trough levels in 60 transplant patients (kidney, n = 49; lung, n = 11) receiving mycophenolate mofetil in combination with prednisone and cyclosporine (n = 45) or tacrolimus (n = 15). Coadministration of cyclosporine instead of tacrolimus resulted in a significant increase of median (range) of the ratio of dose-to-concentration 0.92 (0.11-8.33) (n=167) versus 0.38 (0.11-14.28) (n = 66); P < 0.0001. No correlation was seen between mycophenolate mofetil dose and mycophenolic acid trough concentrations. The dose-to-concentration in cyclosporine-treated patients increased significantly (P<0.0001) as the cyclosporine level increased, suggesting a possible interaction between mycophenolate mofetil and cyclosporine. No correlation was seen between dose-to-concentration and tacrolimus blood levels (P x 0.215). Further studies are necessary to investigate this issue.

Adult↗

Yin yang 1 negatively regulates the differentiation-specific E1 promoter of human papillomavirus type 6.

Human papillomavirus type 6 (HPV-6) is a low-risk HPV whose replication cycle, like that of all HPVs, is differentiation dependent. We have previously shown that CCAAT displacement protein (CDP) binds the differentiation-induced HPV-6 E1 promoter and negatively regulates its activity in undifferentiated cells (W. Ai, E. Toussaint, and A. Roman, J. Virol. 73:4220-4229, 1999). Using electrophoretic mobility shift assays (EMSAs), we now report that Yin Yang 1 (YY1), a multifunctional protein that can act as a transcriptional activator or repressor and that can also inhibit HPV replication in vitro, binds the HPV-6 E1 promoter. EMSAs, using subfragments of the promoter as competitors, showed that the YY1 binding site is located at the 5' end of the E1 promoter. When a putative YY1 site was mutated, the ability of YY1 to bind was greatly decreased. The activity of the mutated E1 promoter, monitored with the reporter gene luciferase, was threefold greater than that of the wild-type promoter, suggesting that YY1 negatively regulates HPV-6 E1 promoter activity. Nuclear extracts from differentiated keratinocytes showed decreased binding of YY1 to the wild-type promoter. Consistent with this, in differentiated keratinocytes, the activity of the transfected luciferase gene transcribed from the mutated promoter was comparable to that of the wild-type promoter; both promoters were up-regulated in differentiated keratinocytes compared to undifferentiated cells. These data suggest that YY1 functions in undifferentiated keratinocytes but not in differentiated keratinocytes. Both the wild-type and mutated promoters could be negatively regulated by overexpression of a plasmid encoding CDP. Thus, both YY1 and CDP appear to be negative regulators of the differentiation-induced HPV-6 E1 promoter and thereby the HPV life cycle. In contrast, only binding of CDP was detected using the E1 promoter of the high-risk HPV-31.

3T3 Cells↗

Effect of ibuprofen and diethylcarbamazine on the hemodynamic and inflammatory response to endotoxin in the dog.

We studied the effects of pretreatment with either ibuprofen (15 mg/kg), diethylcarbamazine (DEC, 15 mg/kg), or vehicle, on the hemodynamic, hematologic, and serum tumor necrosis factor-alpha (TNF-alpha) and interleukin (IL)-6 responses to a bolus Escherichia coli endotoxin infusion (2 mg/kg) in 21 pentobarbital-anesthetized dogs (n = 7 each group). Hematologic and cytokine data were collected before and 0.5, 1, and 3 h after endotoxin infusion. Endotoxin decreased arterial pressure (P(a)), cardiac output (CO), total leukocyte (WBC) and platelet counts, and increased lactate, TNF-alpha, and IL-6. TNF-alpha levels peaked at 1 h and decreased by 3 h, whereas IL-6 remained elevated. Ibuprofen abolished the endotoxin-induced changes in P(a) and lactate, but did not alter the initial decrease in CO, WBC, and platelets or the increase in TNF-alpha and IL-6. DEC did not alter the response to endotoxin, although the DEC group had higher TNF-alpha and IL-6 levels before endotoxin infusion compared to controls. We conclude that the cardiovascular effects of ibuprofen in the canine model of acute endotoxemia are not due to suppression of the systemic inflammatory response.

Animals↗