Extra-abdominal infections due to Gemella species.

OBJECTIVES: To understand the role of Gemella species as a pathogen causing extra-abdominal infections in the Hospital General Universitario Gregorio Mara?ón. MATERIALS AND METHODS: Between 1994 and 1998, one or more isolates of Gemella sp. were found in 128 patients. The 113 patients with isolates from nonsignificant specimens or representing intra-abdominal infections were excluded. The clinical records of the remaining 15 patients were reviewed as well as the more recent literature. RESULTS: Mean age of patients was 41 years. The underlying conditions most frequently noted were intravenous drug users (n=6; 3 positive for human immunodeficiency virus), alcoholism (n=2), cardiovascular disease (n=2), chronic lung disease (n=2), diabetes (n=1), kidney transplant (n=1). The extra-abdominal infections were skin and soft tissue abscess (n=5), empyema (n=4), brain abscess (n=2), primary bacteremia (n=1), lung abscess (n=1), septic thrombophlebitis (n=1), complicated urinary tract infection (n=1). The infection was monomicrobial in six and polymicrobial in nine cases. Surgical drainage and betalactam antibiotics were used. The outcome was favorable in almost all cases. CONCLUSIONS: Gemella sp. should be included as a cause of localized soft-tissue abscesses, empyema, and bloodstream infection. No case of infective endocarditis was found. Although it is susceptible to several antibiotics, Gemella sp. requires a careful microbiologic diagnosis and a subtle clinical interpretation.     

Prevalence of rheumatoid arthritis in Tucumán,Argentina

OBJECTIVE: To ascertain the prevalence of rheumatoid arthritis (RA) in Tucumán, Argentina. METHODS: The study was conducted between January 1, 1998, and December 31, 1999, in Tucumán province in northwest Argentina. Outpatient and hospitalization medical records for all patients with RA aged > or = 16 years were reviewed. Diagnosis was by 1987 American College of Rheumatology (ACR) criteria for RA and the population data were based on the 1991 national census. Prevalence rates, with 95% CI, were calculated using the number of San Miguel de Tucumán residents who fulfilled the 1987 ACR criteria for RA as numerator, and the city population aged > or = 16 as denominator. Crude and age-specific prevalence rates were calculated as number of cases/1,000 inhabitants. RESULTS: We identified 695 cases of RA. Sex-specific and overall prevalence rates (per 1,000) were 1.97 (95% CI 1.8-2) for all, 0.6 (95% CI 0.49-0.73) for men, 3.2 (95% CI 2.9-3.5) for women. CONCLUSION: Prevalence of RA is low in residents of Tucumán, Argentina, and comparable with rates observed in epidemiological surveys from Southern European countries.     

Effect of tetanus toxin on the accumulation of the permeant lipophilic cation tetraphenylphosphonium by guinea pig brain synaptosomes

Accumulation of the permeant lipophilic cation [(3)H]tetraphenylphosphonium (TPP(+)) by synaptosome preparations from guinea pig brain cerebral cortex is inhibited 1:10 by medium containing 193 mM K(+) and by veratridine. A further 1:10 to 1:15 decrease in TPP(+) uptake occurs under nitrogen and in the presence of mitochondrial inhibitors such as oligomycin, whereas starvation and succinate supplementation have no effect. These data indicate that, in analogy to intact neurons, there is an electrical potential (DeltaPsi, interior negative) of -60 to -80 mV across the synaptosomal membrane that is due primarily to a K(+) diffusion gradient (K(+) (in)-->K(+) (out)). The data also indicate that mitochondria entrapped within the synaptosome but not free mitochondria make a large contribution to the TPP(+) concentration gradients observed.Conditions are defined in which tetanus toxin binds specifically and immediately to synaptosomes in media used to measure TPP(+) uptake. Under these conditions tetanus toxin induces dose-dependent changes in TPP(+) uptake that are blocked by antitoxin and not mimicked by biologically inactivated toxin preparations. The effect of tetanus toxin on TPP(+) uptake is not evident in the presence of 193 mM K(+) or veratridine but remains under conditions known to abolish the mitochondrial DeltaPsi. Moreover, tetanus toxin has no effect on TPP(+) uptake by isolated synaptosomal mitochondria. The results thus define an in vitro action of tetanus toxin on the synaptosomal membrane that can be correlated with biological potency in vivo and is consistent with the in vivo effects of tetanus toxin on neuronal transmission.     

Dipeptidyl peptidase-4 expression in pancreatic tissue from patients with congenital hyperinsulinism

Congenital hyperinsulinism (CHI) is caused by unregulated insulin release and leads to hyperinsulinaemic-hypoglycaemia (HH). Glucagon like peptide-1 (GLP-1), glucose-dependent insulinotropic peptide (GIP), peptide YY (PYY) and the enzyme; dipeptidyl peptidase-4 (DPP-4) all regulate appetite and glucose homeostasis. These proteins have been identified as possible contributors to HH but the mechanism remains poorly understood. We aimed to look at the expression pattern of pancreatic DPP-4 in children with focal and diffuse CHI (FCHI and DCHI, respectively). Using immunohistochemistry; we determined DPP-4 expression patterns in the pancreas of CHI patients. DPP-4 was found to be expressed in the pancreatic β, α and δ-cells in and around the focal area. However, it was predominantly co-localised with β-cells in the paediatric tissue samples. Additionally, proliferating β-cells expressed DPP-4 in DCHI, which was absent in the FCHI pancreas. Insulin was found to be present in the exocrine acini and duct cells of the DCHI pancreas suggestive of exocrine to endocrine transdifferentiation. Furthermore, 6 medically-unresponsive DCHI pancreatic samples showed an up-regulation of total pancreatic DPP-4 expression. In conclusion; the expression studies have shown DPP-4 to be altered in HH, however, further work is required to understand the underlying role for this enzyme.     

Management of painful temporomandibular joint clicking with different intraoral devices and counseling: a controlled study

Objective

The benefit of the use of some intraoral devices in arthrogenous temporomandibular disorders (TMD) patients is still unknown. This study assessed the effectiveness of the partial use of intraoral devices and counseling in the management of patients with disc displacement with reduction (DDWR) and arthralgia.

Materials and Methods

A total of 60 DDWR and arthralgia patients were randomly divided into three groups: group I (n=20) wore anterior repositioning occlusal splints (ARS); group II (n=20) wore the Nociceptive Trigeminal Inhibition Clenching Suppression System devices (NTI-tss); and group III (n=20) only received counseling for behavioral changes and self-care (the control group). The first two groups also received counseling. Follow-ups were performed after 2 weeks, 6 weeks and 3 months. In these sessions, patients were evaluated by means of a visual analogue scale, pressure pain threshold (PPT) of the temporomandibular joint (TMJ), maximum range of motion and TMJ sounds. Possible adverse effects were also recorded, such as discomfort while using the device and occlusal changes. The results were analyzed with ANOVA, Tukey’s and Fisher Exact Test, with a significance level of 5%.

Results

Groups I and II showed improvement in pain intensity at the first follow-up. This progress was recorded only after 3 months in Group III. Group II showed an increased in joint sounds frequency. The PPT values, mandibular range of motion and the number of occlusal contacts did not change significantly.

Conclusion

The simultaneous use of intraoral devices (partial time) plus behavioral modifications seems to produce a more rapid pain improvement in patients with painful DDWR. The use of NTI-tss could increase TMJ sounds. Although intraoral devices with additional counseling should be considered for the management of painful DDWR, dentists should be aware of the possible side effects of the intraoral device’s design.     

Unproven stem cell–based interventions and achieving a compromise policy among the multiple stakeholders

Background

In 2004, patient advocate groups were major players in helping pass and implement significant public policy and funding initiatives in stem cells and regenerative medicine. In the following years, advocates were also actively engaged in Washington DC, encouraging policy makers to broaden embryonic stem cell research funding, which was ultimately passed after President Barack Obama came into office. Many advocates did this because they were told stem cell research would lead to cures. After waiting more than 10 years, many of these same patients are now approaching clinics around the world offering experimental stem cell-based interventions instead of waiting for scientists in the US to complete clinical trials. How did the same groups who were once (and often still are) the strongest supporters of stem cell research become stem cell tourists? And how can scientists, clinicians, and regulators work to bring stem cell patients back home to the US and into the clinical trial process?

Discussion

In this paper, we argue that the continued marketing and use of experimental stem cell-based interventions is problematic and unsustainable. Central problems include the lack of patient protection, US liability standards, regulation of clinical sites, and clinician licensing. These interventions have insufficient evidence of safety and efficacy; patients may be wasting money and time, and they may be forgoing other opportunities for an intervention that has not been shown to be safe and effective. Current practices do not contribute to scientific progress because the data from the procedures are unsuitable for follow-up research to measure outcomes. In addition, there is no assurance for patients that they are receiving the interventions promised or of what dosage they are receiving. Furthermore, there is inconsistent or non-existent follow-up care. Public policy should be developed to correct the current situation.

Conclusion

The current landscape of stem cell tourism should prompt a re-evaluation of current approaches to study cell-based interventions with respect to the design, initiation, and conduct of US clinical trials. Stakeholders, including scientists, clinicians, regulators and patient advocates, need to work together to find a compromise to keep patients in the US and within the clinical trial process. Using HIV/AIDS and breast cancer advocate cases as examples, we identify key priorities and goals for this policy effort.

     

A Synthetic Influenza Virus Vaccine Induces a Cellular Immune Response That Correlates with Reduction in Symptomatology and Virus Shedding in a Randomized Phase Ib Live-Virus Challenge in Humans

Current influenza vaccines elicit primarily antibody-based immunity. They require yearly revaccination and cannot be manufactured until the identification of the circulating viral strain(s). These issues remain to be addressed. Here we report a phase Ib trial of a vaccine candidate (FLU-v) eliciting cellular immunity. Thirty-two males seronegative for the challenge virus by hemagglutination inhibition assay participated in this single-center, randomized, double-blind study. Volunteers received one dose of either the adjuvant alone (placebo, n = 16) or FLU-v (500 μg) and the adjuvant (n = 16), both in saline. Twenty-one days later, FLU-v (n = 15) and placebo (n = 13) volunteers were challenged with influenza virus A/Wisconsin/67/2005 (H3N2) and monitored for 7 days. Safety, tolerability, and cellular responses were assessed pre- and postvaccination. Virus shedding and clinical signs were assessed postchallenge. FLU-v was safe and well tolerated. No difference in the prevaccination FLU-v-specific gamma interferon (IFN-γ) response was seen between groups (average ± the standard error of the mean [SEM] for the placebo and FLU-v, respectively, 1.4-fold ± 0.2-fold and 1.6-fold ± 0.5-fold higher than the negative-control value). Nineteen days postvaccination, the FLU-v group, but not the placebo group, developed FLU-v-specific IFN-γ responses (8.2-fold ± 3.9-fold versus 1.3-fold ± 0.1-fold higher than the negative-control value [average ± SEM] for FLU-v versus the placebo [P = 0.0005]). FLU-v-specific cellular responses also correlated with reductions in both viral titers (P = 0.01) and symptom scores (P = 0.02) postchallenge. Increased cellular immunity specific to FLU-v correlates with reductions in both symptom scores and virus loads. (This study has been registered at ClinicalTrials.gov under registration no. {"type":"clinical-trial","attrs":{"text":"NCT01226758","term_id":"NCT01226758"}}NCT01226758 and at hra.nhs.uk under EudraCT no. 2009-014716-35.)