Detoxification with phenobarbital of alprazolam-dependent polysubstance abusers

Alprazolam appears to have an abuse liability among opiate addicts, and detoxification can be prolonged. The authors describe experience with five methadone maintenance patients who were polysubstance abusers and were admitted specifically for detoxification from alprazolam dependence. Phenobarbital in tapering doses adequately suppressed withdrawal symptoms and shortened hospitalization.     

Vagal stimulation rapidly increases leptin secretion in human stomach

BACKGROUND & AIMS: Leptin production has been reported in the rat and in human stomach. It initiates intestinal nutrient absorption. In this study, we analyzed the effect of vagal stimulation on leptin release in the human stomach. METHODS: We studied the secretion of gastric acid and leptin on stimulation with insulin (a stimulant of vagal pathways via hypoglycemia) and pentagastrin in 11 healthy men (normal endoscopy and normal histological gastric mucosa), 5 with previous highly selective vagotomy (HSV), and 6 without HSV. Fundic biopsies were performed for immunostaining of leptin. RESULTS: There was no difference between the 2 groups with respect to age, body mass index, basal leptin (4.8 +/- 1.2 ng/15 minutes) and gastric acid (0.7 +/- 0.2 mmol/15 minutes) outputs. Leptin-immunoreactivity was found in the fundic glands, and its distribution and density were similar in 2 groups. Insulin caused a rapid (15-minute) increase in leptin output in men without HSV (31 +/- 9 ng/15 minutes), but not in those with HSV (7.7 +/- 3.2 ng/15 minutes). Insulin-stimulated gastric leptin was biphasic, with a rapid increase (15 minutes after injection) followed by a second steady and sustained increase (39.9 +/- 7.6 ng/15 minutes at 120 minutes after injection). Pentagastrin increased gastric leptin output in individuals with (30 +/- 4.9 ng/15 minutes) and without (26 +/- 3.2 ng/15 minutes) HSV. Insulin and pentagastrin did not modify plasma leptin, whatever HSV status. CONCLUSIONS: Vagal stimulation of leptin release in the human stomach suggests that leptin is released during the cephalic phase of gastric secretion. Luminal leptin may be involved in vagus-mediated intestinal functions.     

Anal carcinoma: incidence and effect of cumulative infections

INTRODUCTION: Human papilloma virus (HPV) causes anal condyloma that is a risk factor for anal carcinoma. The incidence and mechanism of invasive anal carcinoma in patients with anal condyloma are prospectively determined. PATIENTS AND METHODS: From 1993 to 2002, 228 consecutive patients (164 HIV positive) with anal canal condylomas were included in the study, after curing of their lesions. They were asked to attend follow-up visits at 3- or 6-month intervals. We checked for anal co-infection with syphilis, gonococci, viruses (Epstein-Barr virus, cytomegalovirus, herpes simplex, HPV types), and quantified Langerhans' cells (LC) in anal mucosa at baseline and during follow up. We cured and analysed relapsed condylomas during follow up (3-112 months; median 26). Serum HIV loads and CD4 T-lymphocyte counts were determined at each visit and the densities of LC in consecutive specimens from patients with cancers were compared with that for a matched control group (n = 23). RESULTS: Analysis of 199 patients showed high-grade dysplasia (HGD) in 13.6% of patients, more in HIV-positive (16%) than in HIV-negative (6%) patients at baseline. During follow up, 3.5% (7/199; six HIV positive) patients developed invasive carcinoma after 13-108 months and 112 (56%) patients relapsed condylomas. HIV and anal co-infection were identified as independent risk factors (P < 0.01) for HGD and cancer: odd ratio (95% confidence interval) of 9.4 (2.4-37.4) and 3.67 (0.95-14.2), respectively. LC densities in anal mucosa were lower in patients with invasive carcinoma than in controls. CONCLUSION: The risk of invasive carcinoma in HPV-infected patients is increased by HIV and anal co-infection. Decreases in LC numbers in anal mucosa may favour this outcome.     

Effects of ursodeoxycholic acid (ursodiol) treatment on chronic viral hepatitis in heart transplant patients: results of a prospective,double-blind,placebo-randomized study

BACKGROUND: Chronic viral hepatitis averages 15% to 20% in heart transplant patients. Several studies have shown that ursodiol may improve liver biochemistry in patients with chronic hepatitis. We used a double-blind randomized controlled trial to evaluate the effect of ursodiol in heart transplant patients with chronic viral hepatitis. METHODS: Thirty heart patients with chronic viral hepatitis B, C, or non-A-G received ursodiol, 800 mg per day (group 1), and 30 received placebo (group 2) for 12 months. Endpoints were improvement in liver biochemical tests and in total Knodell score. Intent-to-treat and per-protocol analyses were performed. RESULTS: At entry, both groups were comparable for all of the studied parameters. During the study period, serum alanine aminotransferase, aspartate aminotransferase, and gamma-glutamyl transpeptidase variations were not different between group 1 and group 2 patients. Knodell score improved in 20% of group 1 patients and in 43% of group 2 patients (NS). Adverse events or mortality were not different in the two groups during the study period. Similar results were observed by intent-to-treat and per-protocol analyses. CONCLUSIONS: A 12-month course of ursodiol therapy had no effect on liver enzymes or liver histology in heart transplant patients with chronic hepatitis.     

Monitoring of human cytomegalovirus infections in heart transplant recipients by pp65 antigenemia

BACKGROUND: Rapid diagnostic techniques offer the opportunity of early diagnosis of human cytomegalovirus (CMV) infection in immunocompromized patients at risk of developing CMV disease and syndrome. The use of CMV pp65 antigenemia as a predictor of CMV syndrome and disease in heart transplant recipient after induction therapy was studied retrospectively. METHODS: One hundred and nineteen consecutive heart transplant recipients treated with induction therapy who survived more then 14 d were monitored for CMV infection. Ninety-four recipients were seropositive for CMV. Twenty-five recipients were seronegative for CMV and received grafts from seropositive donors. Pre-emptive therapy was used in seropositive patients when CMV pp65 antigenemia was greater than 50 antigen-positive cells per 2 x 10(5) peripheral blood leukocytes (PBL); prophylactic therapy was done only in seronegative recipient matched with seropositive donor. RESULTS: High-level CMV pp65 antigenemia (50 antigen-positive cells 2 x 10(5) PBL) occurred in 34% (41 of 119) of patients at a median of 44 d following transplantation. In seropositive recipients, 16% (15 of 94) of patients developed CMV invasive disease or syndrome, and in seronegative recipients 20% (5 of 25) of patients developed CMV disease or syndrome. Sixty-six per cent (62 of 94) of CMV seropositive patients were identified as not requiring pre-emptive therapy. In seropositive and seronegative recipients, the sensibility and negative predictive value of the cut-off level of 50 antigen positive cell for CMV disease and syndrome was 100%. The specificity was 79% and positive predictive value was 49%. CONCLUSION: Because of the excellent sensibility and negative predictive value of the cut-off level of 50 antigen positive cell per 2 x 10(5) PBL, application of pre-emptive therapy guided by high level of CMV pp65 antigenemia in the context of induction therapy allow to omit antiviral therapy in many at risk patients. In the context of pre-emptive and prophylactic therapy, the cut-off level of 50 antigen positive cell do not allow to predict with accuracy the development of CMV disease or syndrome.     

Secretory phospholipase A(2) activity and release kinetics of vascular tissue remodelling biomarkers after coronary artery bypass grafting with and without cardiopulmonary bypass.

BACKGROUND: Cardiopulmonary bypass (CPB) has long been recognised as a main cause of a postoperative complex systemic inflammatory response after coronary artery bypass grafting (CABG). METHODS: We determined the kinetics of peripheral blood release of the novel inflammatory biomarkers secretory phospholipase A(2) (sPLA(2)), matrix metalloproteinase-9 (MMP-9) and tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) during the first 6 days following surgery in 16 patients undergoing CABG with (on-pump, n=9) or without (off-pump, n=7) CPB. Kinetic curves for these markers were compared to those of the well-known inflammatory parameters C-reactive protein (CRP) and fibrinogen. RESULTS: sPLA(2) activity exhibited a maximum value on day 2, then decreased until day 6 for both groups and in a similar manner as CRP levels. On the other hand, elevation of plasma levels of both MMP-9 and TIMP-1 occurred as early as on day 1 and remained at this level until day 6. No significant difference in kinetic characteristics (peak value, area under the curve, initial slope) between CABG with and without CPB was observed. CONCLUSIONS: These data show that the off- and on-pump groups did not show significantly different kinetics for the releases of all biomarkers studied, including sPLA(2) and biomarkers of the MMP-TIMP network. The off-pump procedure may therefore lead to global surgical trauma as important as CPB in terms of the systemic inflammatory process and matrix proteolysis pathway activation.     

Neurochemical monitoring using intracerebral microdialysis during cardiac resuscitation

Objective After cardiac resuscitation, hypoxic encephalopathy often is the limiting factor regarding outcome due to the oxygen sensitivity of the brain. Intracerebral microdialysis is a highly sensitive technique to monitor cerebral energy metabolism and for the early detection of cerebral hypoxia.Patient and interventions A 34-year-old male patient who had to be craniectomized due to a mass demanding middle cerebral artery infarct. A microdialysis catheter was inserted into the left frontal lobe and, as control, into the abdominal subcutaneous adipose tissue. Pulmonary embolism and asystolia leading to cardiac resuscitation occurred.Measurements and results The cerebral chemical markers of energy metabolism glucose, lactate, pyruvate, and the marker of cell membrane damage glycerol were measured. Except for subcutaneous glucose, all markers showed a sudden and significant increase during resuscitation and a prolonged period afterwards. After some hours all values returned to normal.Conclusion This is the first reported case of monitoring neurochemical markers using intracerebral microdialysis during cardiac resuscitation. The findings indicate the importance of early and efficient resuscitation and demonstrate that deviations in cerebral energy metabolism are reversible.     

Tendon calcifications in chondrocalcinosis

Fine linear extraarticular calcium deposits were found in X-rays of 7 of 52 patients with articular chondro-calcinosis (ACC). Seven Achilles tendons, seven quadriceps tendons, and one plantar fascia were affected. In a control group of comparable age and sex, without ACC but with generalized osteoarthritis, no calcifications were found in the tendons. On a biopsy specimen of an Achilles tendon with such calcium deposits, X-ray diffraction showed that they had the characteristics of calcium pyro-phosphate dihydrate. Isolated small foci of crystals were observed on some segments of tendon bundles. The presence of fine linear calcifications on X-rays of the Achilles or quadriceps tendons may be a useful aid in the radiologic diagnosis of so-called articular chondrocalcinosis.