Increase and plateau of CD4 T-cell counts in the 3(1/2) years after initiation of potent antiretroviral therapy

We evaluated CD4 cell counts over a 3(1/2) year period following the initiation of potent antiretroviral therapy (ART) in the Multicenter AIDS Cohort Study. The study population included 314 HIV-infected gay men who provided CD4 cell counts for at least 2 years after the initiation of potent ART. Trends in CD4 cell counts and plasma HIV-RNA were analyzed by regression methods that incorporated the statistical dependencies of outcomes measured over time within individuals. Regardless of CD4 cell count at initiation of potent ART, CD4 cell counts increased significantly (p <.05) in the first 2 years after initiation. However, between 2 and 3(1/2) years after initiation, these counts neither increased nor decreased. The pattern of the proportion with plasma HIV-RNA <400 copies/ml was similar to CD4 cell count (i.e., increased significantly after initiation and plateau in the subsequent 1(1/2) years). The single most important predictor of the steady state CD4 cell count that was maintained between 2 and 3(1/2) years after initiation was the change in plasma HIV-RNA in the first year after initiation of potent ART.     

Comparative effect of an essential oil mouthrinse on plaque,gingivitis and salivary Streptococcus mutans levels: a double blind randomized study

An open, randomized, controlled study with two parallel treatment groups was done to evaluate the efficacy of a Lippia sidoides essential oil (EO) 1% mouthrinse compared with chlorhexidine 0.12% mouthrinse, applied two times daily for 1 week, in the treatment of dental plaque and gingivitis. Fifty‐five patients were included in the study. The efficacy variables were the colony count of Streptococcus mutans from the stimulated saliva and periodontal indices on days 0, 7 and 30 after commencement of therapy. Twenty eight patients received chlorhexidine mouthrinse (Periogard^®) and 27 Lippia sidoides essential oil mouthrinse (Cepakill^®). The clinical and microbiological parameters were significantly reduced by both mouthrinses. No significant difference was seen between the two groups (p > 0.05). There was a significant reduction in the colony count of S. mutans in both groups (p < 0.05). Chlorhexidine treatment reduced more efficiently than L. sidoides, however, no statistical difference was seen, the efficacy of both groups was similar (p = 0.3). The results indicate that Chlorhexidine mouthrinse reduced plaque index, gingival bleeding and the number of CFU (colonies forming units) more efficiently than L. sidoides but did not reach statistical significance. This study demonstrated that Lippia sidoides EO mouthrinse is effective in reducing microbial plaque and gingival inflammation. Copyright © 2009 John Wiley & Sons, Ltd.     

Acute renal failure in the critically I11: Management by continuous veno-venous hemodiafiltration

The consequences of newer techniques of continuous renal replacement therapy in critically ill patients are not yet fully known. The clinical and biochemical impact of continuous veno-venous hemodiafiltration (CVVHD) was, therefore, prospectively studied in 60 critically ill patients with acute renal failure. Prospective clinical, biochemical, and hematological data were collected from patients receiving CVVHD. Over the initial 24 hours of therapy, CVVHD resulted in a decrease in mean plasma urea from 34.5 mmol/L (95% confidence interval [CI], 29.4 to 39.6) to 25 mmol/L (95% CI, 21.8 to 28.2). With continued CVVHD, the mean plasma urea reached a plateau level of 17.6 mmol/L (95% CI, 15.8 to 19.4) at 72 hours. This degree of azotemia control was achieved with ease and essentially without complications during 8,360 hours of therapy despite the presence of multi-organ failure and the aggressive administration of protein nitrogen (0.25 to 0.35 g/kg/day). No abnormalities of serum electrolytes developed during treatment. Survival to intensive care discharge was 46.6% and to hospital discharge 41.6%, despite a mean Acute Physiology and Chronic Health Evaluation (APACHE) Il score at presentation of 27.7. Continuous veno-venous hemodiafiltration offers superior azotemia control and a safe approach to renal replacement therapy in critically ill patients. Its use is associated with a comparatively favorable outcome. CVVHD may be regarded as the treatment of choice in such patients.     

Is reducing variability of blood glucose the real but hidden target of intensive insulin therapy?

Since the first report that intensive insulin therapy reduced mortality in selected surgical critically ill patients, lowering of blood glucose levels has been recommended as a means of improving patient outcomes. In this initial Leuven trial, blood glucose control by protocol using insulin was applied to 98.7% of patients in the intensive group but to only 39.2% (P < 0.0001) of patients in the control group. If appropriately applied, such protocols should decrease both the mean blood glucose concentration and its variability (variation of blood glucose concentration). Thus, it is logically possible that the benefit of intensive insulin therapy in the first Leuven trial was due to a decrease in mean glucose levels, a decrease in their variability, or both. Several recent studies have confirmed significant associations between variability of blood glucose levels and patient outcomes. Decreasing the variability of blood glucose levels might be an important dimension of glucose management, a possible mechanism by which an intensive insulin protocol exerts its putative beneficial effects, and an important goal of glucose management in the intensive care unit. Clinicians need to be aware of this controversy when considering the application of intensive insulin therapy and interpreting future trials.     

The 17-year single-center experience with the use of azathioprine to maintain remission in ulcerative colitis

Despite the accumulation of positive data, the role of azathioprine (AZA) in the maintenance of remission of ulcerative colitis is still controversial. We looked at the follow-up of the ulcerative colitis patients who, after responding to either steroids or cyclosporin (CsA), received AZA at our referral center for over a decade. The 39 patients (29 m/10f) were treated between 1991 and 2007. Twenty-five of them had responded to CsA, the remaining 14 to corticosteroids. AZA was usually overlapped with either of the two agents at the initial dose of 2 mg/kg/day. The definitions of remission, relapse, and AZA toxicity followed commonly agreed criteria. The median duration of the AZA treatment was 14 months (<1–201). Fifty-two percent and 14%, respectively, of the CsA and the steroid responders needed surgery (overall rate = 38%). The figures were 32 and 15 at the first year. The majority of the patients had 1–2 relapses often in connection with withdrawal of AZA; only 3 of these relapsers needed hospitalization. AZA caused toxicity in 16/39 (41%) patients, requiring withdrawal in 23% of the cases; leukopenia (17%) and hepatitis/cholestasis (10%) ranked first and second for frequency. All of the patients in whom AZA was stopped (or reduced) relapsed. In conclusion, the 1-year colectomy rates compare favorably with the figures reported by the literature. By contrast, the toxicity rates were higher than expected. Failure to genotype or to use escalating AZA doses can only be hypothesized as causes.     

Paroxysmal itch caused by gain-of-function Nav1.7 mutation

Itch is a common experience. It can occur in the course of systemic diseases and can be a manifestation of allergies or a consequence of diseases affecting the somatosensory pathway. We describe a kindred characterized by paroxysmal itch caused by a variant in SCN9A gene encoding for the Na_v1.7 sodium channel. Patients underwent clinical and somatosensory profile assessment by quantitative sensory testing, nerve conduction study, autonomic cardiovascular reflex, and sympathetic skin response examination, skin biopsy with quantification of intraepidermal nerve fiber density, and SCN9A mutational analysis. The index patient, her mother, and a sister presented with a stereotypical clinical picture characterized by paroxysmal itch attacks involving the shoulders, upper back, and upper limbs, followed by transient burning pain, and triggered by environmental warmth, hot drinks, and spicy food. Somatosensory profile assessment demonstrated a remarkably identical pattern of increased cold and pain thresholds and paradoxical heat sensation. Autonomic tests were negative, whereas skin biopsy revealed decreased intraepidermal nerve fiber density in 2 of the 3 patients. All affected members harbored the 2215A>G I739V substitution in exon 13 of SCN9A gene. Pregabalin treatment reduced itch intensity and attack frequency in all patients. The co-segregation of the I739V variant in the affected members of the family provides evidence, for the first time, that paroxysmal itch can be related to a mutation in sodium channel gene.     

A method to estimate EMG crosstalk between two muscles based on the silent period following an H-reflex

The crosstalk phenomenon consists in recording the volume-conducted electromyographic activity of muscles other than that under study. This interference may impair the correct interpretation of the results in a variety of experiments. A new protocol is presented here for crosstalk assessment between two muscles based on changes in their electrical activity following a reflex discharge in one of the muscles in response to nerve stimulation. A reflex compound muscle action potential (H-reflex) was used to induce a silent period in the muscle that causes the crosstalk, called here the remote muscle. The rationale is that if the activity recorded in the target muscle is influenced by a distant source (the remote muscle) a silent period observed in the electromyogram (EMG) of the remote muscle would coincide with a decrease in the EMG activity of the target muscle. The new crosstalk index is evaluated based on the root mean square (RMS) values of the EMGs obtained in two distinct periods (background EMG and silent period) of both the remote and the target muscles.In the present work the application focused on the estimation of the degree of crosstalk from the soleus muscle to the tibialis anterior muscle during quiet stance. However, the technique may be extended to other pairs of muscles provided a silent period may be evoked in one of them.     

Prenatal diagnosis and neonatal monitoring of a fetus with glutaric aciduria type II due to electron transfer flavoprotein (beta-subunit) deficiency.

The prenatal diagnosis of a male fetus with glutaric aciduria type II and the time course of metabolite urinary excretion, starting immediately after birth, are described. Prenatal diagnosis was undertaken at the 17th wk of gestation by immunoblot analysis and pulse labeling experiments of amniocytes and, retrospectively, by stable isotope dilution analysis of six metabolites in amniotic fluid. The results were as follows: 1) The immunochemical analysis on cultured amniocytes showed that the fetus, as the previous index case in this family, was affected with a deficiency of the beta-subunit of electron transfer flavoprotein. 2) Glutarate concentration was significantly increased in the cell-free supernatant of the amniotic fluid. In the postnatal period, most of the organic acids and acylglycines characteristic of the disorder appeared in urine within a week, although an increased excretion of hexanoylglycine was the only biochemical abnormality detectable in the first urine sample collected at 9 h after birth. Growth and development of this infant were normal during the following 6 mo of life, when he was receiving oral supplementation with L-carnitine and riboflavin. It should be underscored that transient abnormalities in routine blood tests (glutamic oxaloacetic transaminase, lactate dehydrogenase, and creatine phosphokinase) were present soon after birth, despite his asymptomatic clinical course. Early detection and aggressive treatment could be effective in such a form of glutaric aciduria type II.