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HIV incidence and factors associated with HIV acquisition among injection drug users in St Petersburg, Russia.

BACKGROUND: The Russian HIV-1 epidemic has been driven by injection drug use. OBJECTIVE: To determine HIV incidence and identify demographic and behavioral correlates of infection to facilitate the development of longitudinal HIV prevention programs. METHODS: In 2002, a cohort of 520 injection drug users (IDU) in St Petersburg, Russia were recruited and tested and counseled for HIV-1. HIV-seronegative IDU were enrolled and reevaluated at 6 and 12 months. HIV testing was performed and sociodemographic and behavioral data were collected during each study visit. The relationship of sociodemographic and behavioral factors to HIV-1 incidence was assessed. RESULTS: Most enrolled subjects were young, male, living at home, educated, heroin users, and frequently shared needles and other injection paraphernalia. The retention rate at the 12 month follow-up was 80%. The HIV-1 incidence rate was 4.5/100 person-years. In univariate analysis, psychostimulant use, especially frequent use, three or more sex partners in the past 6 months, and females selling sex were associated with HIV seroconversion. In the multivariate analysis, psychostimulant use three or more times per week was the only factor still associated with HIV seroconversion. CONCLUSIONS: The high incidence of HIV infection places St Petersburg among the worst IDU-concentrated epidemics in Europe. Interventions targeting psychostimulant and heroin users and their accompanying behaviors such as frequent injections and increased sexual activity are needed immediately.

Adolescent↗

Hyperoxic ventilation exacerbates lung reperfusion injury.

OBJECTIVE: It is well known that hyperoxia can be potentially harmful to the ventilated patient, although little is known about the potential effects in the setting of lung reperfusion. We hypothesized that hyperoxic ventilation at the time of reperfusion could worsen the effects of lung reperfusion injury. METHODS: Using an ex vivo, blood perfused, isolated rabbit lung system, we evaluated the effects of hyperoxic (fraction of inspired oxygen = 100%, n = 10) versus normoxic (room air, n = 10) ventilation after 18 hours of cold ischemia. Lungs were ventilated and perfused for 2 hours. A control group was immediately perfused and ventilated with a fraction of inspired oxygen of 100%. RESULTS: Lung wet/dry ratios demonstrated lower tissue edema in the normoxic group compared with in the hyperoxic group (6.72 +/- 0.89 vs 7.62 +/- 1.14 [mean +/- standard error of the mean], P = .04). Lung ventilation was also significantly better in the normoxic group versus the hyperoxic group (PCO2 = 28.96 +/- 2.01 vs 36.68 +/- 3.20 mm Hg, P = .04). Conversely, lung oxygenation after 2 hours of reperfusion (normoxic group ventilated for the last 15 minutes on 100% fraction of inspired oxygen) was not significantly different between groups (PO2 = 590.2 +/- 50.1 vs 499.6 +/- 67.5 mm Hg, P = .25). CONCLUSIONS: Ventilating lungs with 100% fraction of inspired oxygen at the time of reperfusion could increase the risk of lung reperfusion injury at the time of transplantation. Thus the patient should be ventilated with as low a fraction of inspired oxygen as possible to achieve adequate oxygen saturations during this critical reperfusion period.

Animals↗

Optimizing quality of outpatient care for patients with inflammatory bowel disease: the importance of specialist clinics.

BACKGROUND: Most patients with inflammatory bowel disease (IBD) undergo long-term outpatient follow up. However, quality of care provided by specialist and non-specialist IBD clinics is rarely critically audited. OBJECTIVE: To compare the standard of outpatient care provided by general gastroenterology and specialist IBD clinics within a single hospital using defined quality criteria. METHODS: The case notes of 60 consecutive patients with IBD attending general gastroenterology clinics and of 100 patients attending the specialist IBD clinic were reviewed for fulfillment of six quality criteria over the preceding 18 months. RESULTS: The proportion of patients fulfilling all six criteria was higher in the specialist IBD clinic. In the specialist IBD clinic, compared with the general gastroenterology clinics, blood tests were performed with appropriate frequency during the initiation of immunosuppressive treatment in 7/11 versus 2/12 patients (P=0.04) and during maintenance in 24/31 versus 6/21 patients (P=0.001); bone protection with oral steroids were given to 25/53 versus 4/24 patients (P=0.01); a screening colonoscopy at 8-10 years was performed in 25/27 versus 11/20 patients with ulcerative colitis (P=0.004); annual serum urea and creatinine concentrations were measured in 82/89 versus 31/45 patients prescribed 5-aminosalicylates (P=0.001); annual liver function tests were performed in 96/100 versus 38/60 patients (P=0.001); and annual haematinics were measured in 37/47 versus 18/33 patients with Crohn's disease (P=0.03). CONCLUSION: By these criteria, the specialist IBD clinic provided better care than the non-specialist general gastroenterology clinics. Even in the specialist clinic, however, the care of a minority of patients did not fulfil certain criteria, emphasizing the need for a critical audit of outpatient management of IBD.

Ambulatory Care↗

Serum Nestorone and ethinyl estradiol levels, and ovulation inhibition in women using three different dosage combinations of a Nestorone progestogen-ethinyl estradiol contraceptive vaginal ring on a bleeding-signaled regimen.

OBJECTIVES: This trial tested the hypothesis that menstrually signaled use of contraceptive vaginal rings ("rings") releasing low-dose combinations of Nestorone (NES) and ethinyl estradiol (EE) would reliably suppress luteal activity and ovulation, and prevent unintended pregnancy, while controlling the incidence of menstrual bleeding episodes and bleeding days. METHODS: Nestorone/ethinyl estradiol rings releasing 50/10, 50/20 and 150/15 mug/day were studied through 6 months. A ring was to be used continuously, until its removal was signaled by menstrual bleeding. Reinsertion was required 96 h after removal. Serum for NES, EE and progesterone were collected and assayed, and vaginal ultrasound scans were performed in three 5-week periods to examine luteal activity, follicular growth, ovulation and their correlates. In 10 subjects using the 150/15 ring, six samples were drawn in the 24-h period after ring removal to examine serum levels of NES and EE. RESULTS: One hundred sixty subjects at three doses provided blood samples. Median serum concentrations of NES and EE demonstrated dose ratios slightly below the nominal dose ratios expected. Serum NES concentrations declined 19-22% from weeks 3 to 25. Changes in EE levels depended on dose. Nestorone levels fell 81% by 24 h after ring removal and EE levels fell by 50%. Luteal activity was completely suppressed in 94-95% of cycles and in 90% of subjects. Three pregnancies occurred in subjects participating in this serum sampling study. CONCLUSION: Satisfactory serum levels of NES and EE, and a high level of ovulation suppression were achieved. Irregular ring use, however, permitted pregnancies to occur.

Contraceptive Agents, Female↗

Simvastatin normalizes autonomic neural control in experimental heart failure.

BACKGROUND: HMG-CoA reductase inhibitors (statins) have been shown to beneficially affect outcomes in chronic heart failure (CHF). We hypothesized that statins exert effects on autonomic function, as assessed by plasma norepinephrine levels, direct recordings of renal sympathetic nerve activity (RSNA), and baroreflex function. METHODS AND RESULTS: Normolipidemic CHF rabbits were treated with simvastatin or vehicle. CHF was induced by continuous ventricular pacing at 320 to 340 bpm for 3 weeks. Two to 3 days after instrumentation of the rabbits with renal nerve electrodes and arterial and venous catheters, blood samples and RSNA recordings were obtained in the conscious state. Baroreflex function was assessed after administration of sodium nitroprusside and phenylephrine. Mean baseline RSNA (+/-SEM) in normal rabbits was 19.3+/-3.8%; in CHF rabbits, 39.4+/-2.9% (P<0.05); in CHF rabbits on low-dose (0.3 mg x kg(-1) x d(-1)) simvastatin, 39.8+/-8.3% (P<0.05); and in CHF rabbits on high-dose simvastatin (3 mg x kg(-1) x d(-1)), 21.1+/-4.5% (P=NS). Similar data were observed for plasma norepinephrine. In CHF rabbits treated with 3 mg x kg(-1) x d(-1) simvastatin, baroreflex regulation of heart rate to transient hypotension with sodium nitroprusside was normalized by 66% compared with CHF controls. CONCLUSIONS: These are the first data showing that non-lipid-lowering statin effects include a normalization of sympathetic outflow and reflex regulation in CHF. The precise neural and cellular pathways involved in these responses need further clarification. This finding may have important implications for the treatment of CHF and progression of the disease process.

Action Potentials↗

Stimulation of MMP-11 (stromelysin-3) expression in mouse fibroblasts by cytokines, collagen and co-culture with human breast cancer cell lines.

BACKGROUND: Matrix metalloproteinases (MMPs) are central to degradation of the extracellular matrix and basement membrane during both normal and carcinogenic tissue remodeling. MT1-MMP (MMP-14) and stromelysin-3 (MMP-11) are two members of the MMP family of proteolytic enzymes that have been specifically implicated in breast cancer progression. Expressed in stromal fibroblasts adjacent to epithelial tumour cells, the mechanism of MT1-MMP and MMP-11 induction remains unknown. METHODS: To investigate possible mechanisms of induction, we examined the effects of a number of plausible regulatory agents and treatments that may physiologically influence MMP expression during tumour progression. Thus NIH3T3 and primary mouse embryonic fibroblasts (MEFs) were: a) treated with the cytokines IL-1beta, IL-2, IL-6, IL-8 and TGF-beta for 3, 6, 12, 24, and 48 hours; b) grown on collagens I, IV and V; c) treated with fibronectin, con-A and matrigel; and d) co-cultured with a range of HBC (human breast cancer) cell lines of varied invasive and metastatic potential. RESULTS: Competitive quantitative RT-PCR indicated that MMP-11 expression was stimulated to a level greater than 100%, by 48 hour treatments of IL-1beta, IL-2, TGF-beta, fibronectin and collagen V. No other substantial changes in expression of MMP-11 or MT1-MMP in either tested fibroblast culture, under any treatment conditions, were observed. CONCLUSION: We have demonstrated significant MMP-11 stimulation in mouse fibroblasts using cytokines, matrix constituents and HBC cell lines, and also some inhibition of MT1-MMP. Our data suggest that the regulation of these genes in the complex stromal-epithelial interactions that occur in human breast carcinoma, is influenced by several mechanisms.

3T3 Cells↗

Interobserver agreement in the interpretation of anal intraepithelial neoplasia.

BACKGROUND: Anal carcinoma incidence is increasing, and is highest among men with human immunodeficiency virus (HIV) infection who have sex with men. Anal carcinoma and anal intraepithelial neoplasia (AIN) are ascertained on tissue histology, but requires invasive procedures. Screening for AIN using anal cytology was suggested. The authors evaluated agreement on cytologic and biopsy specimens from HIV-positive men undergoing anal carcinoma screening. METHODS: One hundred twenty-nine HIV-positive men with a history of anal-receptive intercourse underwent anal cytology, anoscopy, and biopsy. Four pathologists independently assessed cytology and biopsy specimens and reached consensus for discordant cases. RESULTS: Each pathologist evaluated 120 cytology and 155 biopsy specimens. The weighted kappa value for overall agreement was 0.54 (95% confidence interval [CI], 0.49-0.59) for cytology specimens and 0.59 (95%CI, 0.55-0.63) for biopsy specimens. The median kappa values for pairwise agreement among pathologists and for agreement with consensus were, respectively, 0.69 and 0.77 for cytology and 0.66 and 0.75 for biopsy. At least 3 pathologists were in agreement for 92 (76.7%) cytology and 134 (86.5%) biopsy specimens. Reliability for the Bethesda classification system was at least moderate, except for the cytologic category of atypical squamous cells of undetermined significance (kappa = 0.12). Fourteen of 29 (48.3%) cytology specimens and 36 of 47 (76.6%) biopsy specimens with consensus interpretation of high-grade squamous intraepithelial lesions (HSIL) were interpreted originally as HSIL by > or = 3 pathologists. The kappa value for agreement with consensus distinguishing HSIL from non-HSIL ranged from 0.55 to 0.88 for cytology specimens and from 0.76 to 0.94 for biopsy specimens. CONCLUSIONS: Agreement for cytologic and biopsy interpretations was generally at least moderate. Nevertheless, these results supported the need for disease indicators with greater reliability.

Adolescent↗

Surgical ventricular restoration in the treatment of congestive heart failure due to post-infarction ventricular dilation.

OBJECTIVES: The purpose of this study was to test how surgical ventricular restoration (SVR) affects early and late survival in a registry of 1,198 post-anterior infarction congestive heart failure (CHF) patients treated by the international Reconstructive Endoventricular Surgery returning Torsion Original Radius Elliptical shape to the left ventricle (RESTORE)team. BACKGROUND: Congestive heart failure may be caused by late left ventricular (LV) dilation after anterior infarction. The infarcted segment is often akinetic rather than dyskinetic because early reperfusion prevents transmural necrosis. Previously, only dyskinetic areas were treated by operation. Surgical ventricular restoration reduces LV volume and creates a more elliptical chamber by excluding scar in either akinetic or dyskinetic segments. METHODS: The RESTORE group applied SVR to 1,198 post-infarction patients between 1998 and 2003. Early and late outcomes were examined, and risk factors were identified. RESULTS: Concomitant procedures included coronary artery bypass grafting in 95%, mitral valve repair in 22%, and mitral valve replacement in 1%. Overall 30-day mortality after SVR was 5.3% (8.7% with mitral repair vs. 4.0% without repair; p < 0.001). Perioperative mechanical support was uncommon (<9%). Global systolic function improved postoperatively. Ejection fraction (EF) increased from 29.6 +/- 11.0% preoperatively to 39.5 +/- 12.3% postoperatively (p < 0.001). The left ventricular end-systolic volume index (LVESVI) decreased from 80.4 +/- 51.4 ml/m(2) preoperatively to 56.6 +/- 34.3 ml/m(2) postoperatively (p < 0.001). Overall five-year survival was 68.6 +/- 2.8%. Logistic regression analysis identified EF or=80 ml/m(2), advanced New York Heart Association (NYHA) functional class, and age >or=75 years as risk factors for death. Five-year freedom from hospital readmission for CHF was 78%. Preoperatively, 67% of patients were NYHA functional class III or IV and postoperatively, 85% were class I or II. CONCLUSIONS: Surgical ventricular restoration improves ventricular function and is highly effective therapy in the treatment of ischemic cardiomyopathy with excellent five-year outcome.

Aged↗

Impact of inadequate initial antimicrobial therapy on mortality in infections due to extended-spectrum beta-lactamase-producing enterobacteriaceae: variability by site of infection.

BACKGROUND: Infections due to extended-spectrum beta-lactamase-producing Escherichia coli and Klebsiella species (ESBL-EK) have increased markedly in recent years. Risk factors for mortality among ESBL-EK infections have not been studied. METHODS: This retrospective cohort study was conducted in a 625-bed tertiary care medical center and a 344-bed urban community hospital to determine whether inadequate initial antimicrobial therapy (IIAT) (>48 hours between the time a culture was obtained and initiation of an agent to which the infecting organism was susceptible) is associated with mortality in ESBL-EK infections. All hospitalized patients with an ESBL-EK infection between June 1, 1997, and December 31, 2002, were eligible for inclusion. Subsequently, we conducted a nested case-control study to identify risk factors for IIAT. RESULTS: Of 187 subjects, 32 (17.1%) died while in the hospital. Clinical site of infection was a significant effect modifier in the association between IIAT and mortality. The presence of IIAT was an independent risk factor for mortality, but only for nonurinary ESBL-EK infections (adjusted odds ratio [95% confidence interval], 10.04 [1.90-52.96]). Independent risk factors for IIAT were (1) infection with a multidrug-resistant ESBL-EK (ie, resistant to sulfamethoxazole-trimethoprim, aminoglycosides, and quinolones) (14.58 [1.91-111.36]) and (2) health care-acquired ESBL-EK infection (4.32 [1.49-12.54]). CONCLUSIONS: Inadequate initial antimicrobial therapy is an independent risk factor for mortality in ESBL-EK infections, but only among nonurinary infections. Multidrug resistance was a strong risk factor for IIAT.

Aged↗

Developmental origin of interferon-alpha-producing dendritic cells from hematopoietic precursors.

OBJECTIVE: The aim of this study was to determine the lineage origin of interferon-alpha-producing cells (IPCs), also called plasmacytoid dendritic cells, in mice by evaluating the ability of common lymphoid (CLP) and myeloid (CMP) progenitors to give rise to IPCs. MATERIALS AND METHODS: Sublethally irradiated C57Bl/6 mice were intravenously transplanted with rigorously purified lymphoid and myeloid progenitors from a congenic mouse strain. At various time points posttransplantation mice were analyzed for donor-derived cells by flow cytometry. The developmental potential of all progenitor populations was also tested in in vitro cultures. In addition, in vitro and in vivo derived IPCs were functionally assessed for their interferon-alpha production after virus challenge. RESULTS: Transplantation of 1 x 10(4) common myeloid progenitors, 1 x 10(4) common lymphoid progenitors or 2.5 x 10(4) granulocyte/macrophage progenitors all led to the generation of IPCs within 2 to 3 weeks. In general, IPC reconstitution in spleen and liver by CMPs was more efficient than by CLP. Adding Flt3L alone to in vitro cultures was sufficient to support the development of IPCs from myeloid progenitors whereas CLPs required additional survival factors provided either by stroma cells or by introduction of transgenic Bcl-2. Both myeloid- and lymphoid-derived IPC were indistinguishable by function, gene expression, and morphology. CONCLUSION: Surprisingly, our results clearly show that murine IPCs differentiate from both lineages but are mainly of myeloid origin. These results extend to IPCs the observation made originally in classical dendritic cells that cellular expression of so called lineage markers does not correlate with lineal origin.

Animals↗

Adenosine A2A receptor agonist improves cardiac dysfunction from pulmonary ischemia-reperfusion injury.

BACKGROUND: Ischemia-reperfusion (IR) injury negatively impacts patient outcome in lung transplantation. Clinically, we observed that lung transplant patients with ischemia-reperfusion injury tend to have cardiac dysfunction. Previous studies have shown that ATL-146e (4-{3-[6-amino-9-(5-ethylcarbamoyl-3,4-dihydroxy-tetrahydro-furan-2-yl)-9H-purin-2-yl]-prop-2-ynyl}-cyclohexanecarboxylic acid methyl ester), a selective adenosine A2A receptor agonist, reduces lung inflammation after ischemia-reperfusion. We hypothesized that pulmonary ischemia-reperfusion causes secondary heart dysfunction and ATL-146e will improve this dysfunction. METHODS: We utilized an in vivo rabbit lung ischemia-reperfusion model. The Sham group underwent 120 minutes single lung ventilation. The IR and ATL groups underwent 90 minutes right lung ischemia with 30 minutes right lung reperfusion. The ATL-146e was given intravenously to the ATL group during reperfusion. Cardiac output and arterial blood gases were monitored, and neutrophil sequestration was measured by myeloperoxidase activity. RESULTS: Upon reperfusion, cardiac output (mL/min) significantly dropped in the IR and ATL groups. By 15 minutes reperfusion, cardiac output in the ATL group improved significantly over the IR group and remained significant thereafter. Lung myeloperoxidase activity was significantly reduced by ATL-146e. Although never hypoxemic, arterial oxygenation was lower in the IR and ATL groups while central venous pressures and mean arterial pressures were similar among groups. A separate experiment demonstrated that reperfusion with the antioxidant N-(2-mercaptopropionyl)glycine prevented cardiac dysfunction. CONCLUSIONS: Pulmonary ischemia-reperfusion causes cardiac dysfunction independent of preload, afterload, and oxygenation. The ATL-146e improves this dysfunction presumably by the antiinflammatory effects of adenosine A2A receptor activation on neutrophils. One likely mechanism involves the release of oxidants from the ischemic lung upon reperfusion, which has immediate negative effects on the heart.

Adenosine A2 Receptor Agonists↗

Mitral repair is superior to replacement when associated with coronary artery disease.

OBJECTIVE: To compare the outcomes of mitral repair and replacement in revascularized patients with ischemic mitral regurgitation. SUMMARY BACKGROUND DATA: Combined coronary bypass (CABG) and mitral procedures have been associated with the highest mortality (>10%) in cardiac surgery. Recent studies have suggested that mitral valve replacement (MVR) with sparing of the subvalvular apparatus had comparable results to mitral repair when associated with CABG. METHODS: Over the past 7 years, 54 patients had CABG/mitral repair versus 56 who had CABG/MVR with preservation of the subvalvular apparatus. The groups were similar in age at 69.2 years in the replacement group versus 67.0 in the repair group. We compared these 2 groups based on hospital mortality, incidence of complications including nosocomial infection, neurologic decompensation (stroke), pulmonary complication (pneumonia, atelectasis, and prolonged ventilation), and renal complications (acute renal failure or insufficiency). RESULTS: The mitral repair group had a hospital mortality of 1.9% versus 10.7% in the replacement group (P = 0.05). Infection occurred in 9% of repairs compared with 13% of replacements (P = 0.59). The incidence of stroke was no different between groups (2 of 54 repairs vs. 2 of 56 replacements, P = 1.00). Pulmonary complication rate was 39% in repairs versus 32% in replacements (P = 0.59). Worsening renal function occurred in 15% of repairs versus 18% of replacements (P = 0.67). CONCLUSIONS: Mitral repair is superior to mitral replacement when associated with coronary artery disease in terms of perioperative morbidity and hospital mortality. Although preservation of the subvalvular apparatus with MVR has a theoretical advantage in terms of ventricular function, mitral repair clearly adds a survival benefit in patients with concomitant ischemic cardiac disease.

Adult↗

Social regulation, medicalisation and the nurse's role: insights from an analysis of nursing documentation.

BACKGROUND: Medicine is recognised as a dominant source of governmentality and social regulation, and although nursing has been implicated in the same process, analytical work in this area has been sparse. OBJECTIVES: The article aims to present an analysis of nursing records in order to understand the structural and social processes that mediate the texts. METHODS: 45 sets of nursing records drawn from four clinical sites in Ireland were subjected to a discourse analysis. RESULTS: This article focuses on two main themes that were derived from data: (i) the manner in which nurses controlled, regulated and invigilated patients' activities of daily living and (ii) the way in which activities of daily living were mediated by a biomedical worldview in the clinical settings. Through the organising framework of Activities of Daily Living (ADLs), normative social practices relating to hygiene, eating and drinking, sleeping and so forth were surveyed and monitored within clinical settings. We construct qualitative categories around a range of ways that nurses assessed and judged patients' capacities at ADLs. Furthermore, it is argued that the framework of ADLs epitomises the medicalisation of normative social practices, whereupon the most mundane of normal functions become redefined as an actual or potential clinical pathology, legitimating nursing interventions. According to the nursing documentation, biochemical interventions in the form of various medications were the most dominant means through which nurses attempted to restore or improve the functional capacity of an ADL. CONCLUSION: We conclude by proposing that nurses' invigilation of patients' ADLs is not necessarily a repressive feature of nursing practice, but rather has the potential to be used to advocate on patients' behalf in certain circumstances.

Activities of Daily Living↗

Effects of alcohol on verbal processing: an event-related potential study.

BACKGROUND: Behavioral studies suggest that alcohol intoxication impairs the speed and accuracy of word recognition and categorization, but alcohol's effects on the brain during verbal cognitive processing are not adequately understood. Using event-related potentials (ERP) and a word-recognition paradigm, this study investigated the effects of alcohol intoxication on prelexical, semantic, and mnemonic aspects of verbal processing. METHODS: Concurrent measures of ERPs and skin conductance responses were obtained in a word-repetition priming task and permitted a comparison of the effects of alcohol on the central and autonomic physiologic systems. Social drinkers participated in all four cells of the within-subjects balanced placebo design, in which the effects of alcohol and information as to the beverage content (expectancy) were manipulated. The average peak blood alcohol level peaked at 0.045%. RESULTS: None of the manipulations affected behavioral performance, and expectancy had no effect on any of the measures. In contrast, alcohol ingestion attenuated the temporoparietal N180, suggesting an impairment in prelexical pattern-recognition processes. Alcohol significantly increased the amplitude of N450 and the latency of P580, particularly on trials evoking sympathetic arousal as measured with skin conductance responses. CONCLUSIONS: Although behavioral measures were unaffected, ERPs showed that a moderately low alcohol dose affected verbal processing during both early, prelexical and late, semantic stages. Alcohol significantly increased the difficulty of semantic access and integration, as reflected in larger N450 amplitude and longer P580 latency. This effect was particularly prominent on arousal-related trials, suggesting that alcohol impairs processes that modulate cognitive functioning. The lack of an interaction between the factors of repetition and beverage suggests that a moderately low alcohol dose exerts these effects via the semantic and integration systems rather than via memory processes.

Adult↗

Assessment of ultrasound guided percutaneous ethanol injection and parathyroidectomy in patients with tertiary hyperparathyroidism.

BACKGROUND: Tertiary hyperparathyroidism continues to cause significant morbidity in patients with chronic renal failure. This is frequently resistant to medical management and may ultimately require a surgical parathyroidectomy. Recent studies have reported upon the technique of percutaneous ethanol ablation for both primary and tertiary hyperparathyroidism. In this study we report on a 5 year experience using ethanol injection and compare the results with surgical parathyroidectomy. METHODS: A prospective study in 39 patients with tertiary hyperparathyroidism, 25 were dialysis dependent and 14 had a functioning renal allograft. Twenty-two patients underwent percutaneous fine needle ethanol injection (PFNEI) and 17 underwent surgical parathyroidectomy. RESULTS: A > 30% reduction in intact parathyroid hormone (iPTH) was achieved in 11 of 22 patients undergoing PFNEI after a mean of 1.8 +/- 1.4 injections per gland. In four patients, symptomatic hyperparathyroidism recurred and they required further PFNEI or surgical parathyroidectomy at 17, 28, 46, and 48 months later. There was no significant reduction in iPTH in 11 patients following PFNEI after a mean of 2.5 +/- 1.3 injections per gland. They all required a subsequent surgical parathyroidectomy for symptomatic hyperparathyroidism. Four patients developed a laryngeal nerve palsy following PFNEI, two of which were permanent. Seventeen patients underwent successful surgical parathyroidectomy as a primary procedure. CONCLUSION: Whilst PFNEI is successful in primary hyperparathyroidism, when typically only one adenoma is present, the effectiveness of PFNEI is unpredictable and the long term results are poor compared with those of surgical parathyroidectomy in tertiary hyperparathyroidism. The procedure is not without complications and makes subsequent surgery more difficult. Therefore it can only be recommended for patients with a known single parathyroid gland such as patients in whom hyperparathyroidism has recurred following a previous surgical subtotal parathyroidectomy and who are unsuitable for further surgery.

Administration, Cutaneous↗

A comprehensive study of the association between hepatitis C virus and glomerulopathy.

BACKGROUND: Hepatitis C virus (HCV)-related infection is commonly associated with a wide range of glomerulonephritides (GN) including membranoproliferative glomerulonephritis (MPGN). The causal link between HCV infection and renal disease has been postulated through the induction of cryoglobulinaemia and secondary GN. However, the detection of viral particles or genomes within the kidneys of HCV-infected patients has proved to be difficult. With that in mind, we have studied a population of Egyptian HCV-positive patients with associated GN in an attempt to detect viral particles, antigens or RNA within their kidneys. METHODS: Fifty patients were found to be HCV positive out of 303 who presented with a glomerulopathy between 1998 and 1999 at the Mansoura Urology and Nephrology Center, Egypt. Comprehensive investigations of these 50 patients were undertaken including an evaluation of their clinical, biochemical, histological, virological and immunological parameters. In addition, their kidney biopsy material was analysed by electron microscopy (EM) to detect viral particles, by immunohistochemistry to detect a viral core antigen and by RT-PCR to detect RNA. This was compared with 50 HCV-negative controls. RESULTS: Positivity for HCV antibodies was higher among patients with GN (38%) compared with healthy blood donors (16%). Genotype 4 was sequenced in 70% of the HCV-positive samples examined. MPGN was the most common type of GN accounting for 54% of patients. Extrarenal manifestations were absent in the majority (80%) of patients even though 54% had cryoglobulinaemia. EM revealed virus-like particles in 50% of biopsies. Immunohistochemistry failed to reveal HCV-related antigens in kidney sections. HCV RNA was detected in the cryoprecipitates in 66% of patients and 22% of frozen renal sections. Control sections were negative. CONCLUSION: Our findings suggest a causal link between HCV and GN based on the observation of virus-like particles as well as viral RNA within the kidney sections of patients with HCV-associated glomerulopathies.

Antibodies, Viral↗

Reversibility of androgen deprivation therapy in patients with prostate cancer.

PURPOSE: We determined the duration of testosterone suppression and recovery in patients with prostate cancer treated with a hydrogel implant releasing the gonadotropin releasing hormone (GnRH) agonist histrelin or treated with a depot GnRH agonist. MATERIALS AND METHODS: Luteinizing hormone (LH) and testosterone (T) responses were monitored in 3 groups. Group 1 comprised 7 patients treated with histrelin implant, which is inserted into the arm of the patient while under local anesthesia, and suppresses LH and testosterone. Following implant removal antiandrogens (flutamide or bicalutamide) were administered. Group 2 comprised 8 patients treated with long-term depot GnRH super agonists which were later withheld and patients were given bicalutamide. Group 3 consisted of 7 patients treated with bicalutamide. RESULTS: In group 1 LH and T were in the castration range while implants were in place. LH increased 1 to 6 weeks after implant removal followed by an increase in T. In 7 of 8 patients in group 2, LH, T and prostate specific antigen remained suppressed for 9 months. In 6 of 7 group 3 patients LH and T increased with a decrease in prostate specific antigen. CONCLUSIONS: Despite continuous prolonged T suppression for up to 3 years due to histrelin implant, LH and T increased rapidly following implant removal, indicating that suppression is reversible. In view of the 9-month suppression of LH and T after the last depot GnRH injection in 7 of 8 patients, it is possible to space GnRH agonist administration at longer intervals. However, T must be monitored to determine that suppression is maintained.

Aged↗

Finasteride and flutamide therapy in patients with advanced prostate cancer: response to subsequent castration and long-term follow-up.

OBJECTIVES: To report the efficacy of castration after progression on finasteride and flutamide. Standard androgen deprivation strategies for prostate cancer typically lead to castrate levels of testosterone. One alternative is the use of finasteride and flutamide. METHODS: A Phase II trial evaluated the combination of finasteride (5 mg/day) and flutamide (250 mg three times daily) in patients with rising prostate-specific antigen levels after local treatment for prostate cancer or with newly discovered metastatic disease. Patients were followed up for subsequent events, including castration-free, androgen-independent prostate cancer (AIPC)-free, and overall survival. RESULTS: With a median follow-up of 88 months, 5 patients (25%) continued on finasteride and flutamide, and 12 had stopped this combination and subsequently underwent medical or surgical castration. No patients experienced a flutamide withdrawal effect. All patients experienced more than a 50% decline in prostate-specific antigen after castration (mean 89%). The median protocol treatment failure-free survival was 29.9 months, the median castration-free survival was 37 months, and the median AIPC-free survival was 48.6 months. At 5 years, the overall survival rate was 65% (95% confidence interval 47% to 90%); 29% were alive and have not required castration, and 35% were alive and free of AIPC. CONCLUSIONS: Finasteride and flutamide have a durable effect in suppressing prostate-specific antigen progression in some men with advanced prostate cancer. Furthermore, castration induces secondary responses that may be of shorter duration than if started initially, although the overall period of hormonally responsive prostate cancer is more than 4 years.

Adenocarcinoma↗