Severe pyomyositis caused by Panton–Valentine leucocidin-positive methicillin-sensitive <Emphasis Type="Italic">Staphylococcus aureus</Emphasis> complicating a pilonidal cyst

Background To our best knowledge, Panton–Valentine leucocidin (PVL)-positive methicillin-sensitive Staphylococcus aureus (MSSA) has not been described yet as cause for severe pyomyositis. Case report We present a 23-year-old apparently healthy male patient without any typical predisposing findings who developed severe pyomyositis secondary to an operated pilonidal cyst. In the follow-up, the patient showed signs of immunocompromisation. The causative agent for purulent infection of multiple muscles was a MSSA strain harbouring PVL toxin. Results In the reported case, aggressive antibiotic and surgical treatment with additional application of immunoglobulins has lead to recovery from the disease without relapse. Conclusions PVL-positive S. aureus are associated with skin diseases, multiple abscesses and often complicated by severe sepsis and necrotising pneumonia. Under such circumstances, the mortality rate can reach up to 75%. In addition, the PVL toxin can cause immunocompromisation and might be therefore involved in the aetiology of pyomyositis. Aggressive antibiotic and surgical treatment with additional application of immunoglobulins is recommended for treatment.     

Comparison of the monoamine oxidase inhibiting properties of two reversible and selective monoamine oxidase-A inhibitors moclobemide and toloxatone, and assessment of their effect on psychometric performance in healthy subjects.

1. The effects of two reversible, predominantly monoamine oxidase-A (MAO-A) inhibitors, moclobemide (150 mg three times daily) and toloxatone (400-200-400 mg day-1) on monoamine metabolites and psychometric performance were compared in a double-blind placebo controlled crossover study in 12 healthy subjects. 2. After 7 days of moclobemide/toloxatone/placebo administration subjects were hospitalized for 24 h on day 8. Blood samples were drawn every 2 h for determination of plasma noradrenaline (NA), 3,4-dihydroxyphenylglycol (DHPG), homovanillic acid (HVA) and 5-hydroxyindolacetic acid (5-HIAA). Urine was collected for measurements of normetanephrine and 3-methoxytyramine excretion. Psychometric performance (short- and long-term memory, critical flicker fusion frequency, choice reaction time) and subjective feelings were assessed before each drug intake (in the morning, at noon, in the evening). 3. Compared with placebo, both reversible monoamine oxidase inhibitors decreased the plasma concentration of DHPG and HVA. The overall fall in DHPG (AUC from 0 to 24 h) was 44% during moclobemide and 12% during toloxatone (P less than 0.001) and the overall decrease in HVA was 38% and 20% (P less than 0.005) on moclobemide and toloxatone, respectively. 4. Before the next drug intake, MAO-A inhibition, as judged by the decrease of plasma DHPG concentration, was significantly different from placebo with moclobemide but not with toloxatone. 5. Moclobemide, but not toloxatone, exerted a moderate, but significant inhibition of the deamination of 5-hydroxytryptamine (5-HT) as judged by the fall in plasma 5-HIAA concentration. Neither drug influenced plasma NA concentration. 6. A significant rise in urinary excretion of normetanephrine was observed on moclobemide and to a lesser extent on toloxatone. The urinary excretion of 3-methoxytyramine was significantly raised by moclobemide but not by toloxatone. 7. Neither moclobemide nor toloxatone altered memory function, vigilance, subjective feelings or sleep characteristics of the subjects.     

PET examination of [11C]NNC 687 and [11C]NNC 756 as new radioligands for the D1-dopamine receptor

The benzazepines NNC 687 and NNC 756 have in animal studies been described as selective D₁-dopamine receptor antagonists. Both compounds have been labeled with¹¹C for examination by positron emission tomography (PET). In the present study central receptor binding was studied in monkeys and healthy men. After IV injection of both radioligands in Cynomolgus monkeys radioactivity accumulated markedly in the striatum, a region with a high density of D₁-dopamine receptors. This striatal uptake was displaced by high doses of the selective D₁-antagonist SCH 23390 (2 mg/kg) but not by the 5HT₂-antagonist ketanserin (1.5 mg/kg) or the selective D₂-antagonist raclopride (3 mg/kg). The cortical uptake after injection of [¹¹C]NNC 687 was not reduced in displacement experiments with ketanserin. The cortical uptake of [¹¹C]NNC 756 was reduced in displacement and protection experiments with ketanserin by 24–28% (1.5 mg/kg), whereas no reduction could be demonstrated on striatal uptake. In healthy males both compounds accumulated markedly in the striatum. For [¹¹C]NNC 687 the ratio of radioactivity in the putamen to cerebellum was about 1.5. For [¹¹C]NNC 756 the ratio was about 5. This ratio of 5 for [¹¹C]NNC 756 is the highest obtained so far for PET radioligands for the D₁-dopamine receptor.     

The ubiquitin ligase Rnf6 regulates local LIM kinase 1 levels in axonal growth cones

LIM kinase 1 (LIMK1) controls important cellular functions such as morphogenesis, cell motility, tumor cell metastasis, development of neuronal projections, and growth cone actin dynamics. We have investigated the role of the RING finger protein Rnf6 during neuronal development and detected high Rnf6 protein levels in developing axonal projections of motor and DRG neurons during mouse embryogenesis as well as cultured hippocampal neurons. RNAi-mediated knock-down experiments in primary hippocampal neurons identified Rnf6 as a regulator of axon outgrowth. Consistent with a role in axonal growth, we found that Rnf6 binds to, polyubiquitinates, and targets LIMK1 for proteasomal degradation in growth cones of primary hippocampal neurons. Rnf6 is functionally linked to LIMK1 during the development of axons, as the changes in axon outgrowth induced by up- or down-regulation of Rnf6 levels can be restored by modulation of LIMK1 expression. Thus, these results assign a specific role for Rnf6 in the control of cellular LIMK1 concentrations and indicate a new function for the ubiquitin/proteasome system in regulating local growth cone actin dynamics.     

Trends in HIV prevalence among public sexually transmitted disease clinic attendees in the Western region of the United States (1989-1999)

OBJECTIVES: Using data from anonymous unlinked testing of routinely collected sera, trends in HIV are compared among sexually transmitted disease patients in 4 Western urban centers. METHODS: Between 1989 and 1999, remnant sera obtained for routine syphilis testing from 256,819 patient visits to Denver, Los Angeles, San Francisco, and Seattle clinics were tested for HIV antibodies in an unlinked survey. HIV antibody test results were linked to anonymous demographic and risk information abstracted from the medical record. RESULTS: Overall cumulative HIV seroprevalences among women and among men who had sex exclusively with women were < or = 2%, declined over time, and did not exceed 8% among those who injected drugs. In contrast, cumulative HIV seroprevalences among men who have sex with men ranged from 13% in Seattle to 30% in San Francisco and declined a mean of 2.1% (95% CI, 1.6, 2.6) to 2.8% (CI 2.6, 3.1) per year, after adjustment. CONCLUSIONS: HIV infection declined over time across counties. Relative levels of HIV differed little by demographic and behavioral risk group despite differences in the severity of each county's epidemic. Because of the unique contribution of unlinked serosurveillance studies in monitoring these trends, their reinstitution in high-risk settings should be considered.     

Activin controls skin morphogenesis and wound repair predominantly via stromal cells and in a concentration-dependent manner via keratinocytes

The transforming growth factor-beta family member activin is a potent regulator of skin morphogenesis and repair. Transgenic mice overexpressing activin in keratinocytes display epidermal hyper-thickening and dermal fibrosis in normal skin and enhanced granulation tissue formation after wounding. Mice overexpressing the secreted activin antagonist follistatin, however, have the opposite wound-healing phenotype. To determine whether activin affects skin morphogenesis and repair via activation of keratinocytes and/or stromal cells, we generated transgenic mice expressing a dominant-negative activin receptor IB mutant (dnActRIB) in keratinocytes. The architecture of adult skin was unaltered in these mice, but delays were observed in postnatal pelage hair follicle morphogenesis and in the first catagen-telogen transformation of hair follicles. Although dnActRIB-transgenic mice showed slightly delayed wound re-epithelialization after skin injury, the strong inhibition of granulation tissue formation seen in follistatin-transgenic mice was not observed. Therefore, although endogenous activin appeared to affect skin morphogenesis and repair predominantly via stromal cells, overexpressed activin strongly affected the epidermis. The epidermal phenotype of activin-overexpressing mice was partially rescued by breeding these animals with dnActRIB-transgenic mice. These results demonstrate that activin affects both stromal cells and keratinocytes in normal and wounded skin and that the effect on keratinocytes is dose-dependent in vivo.     

Anorectal continence following manual and mechanical anastomosis suture. Results of a controlled study of rectal surgery

In a controlled clinical trial-manual vs. stapler anastomosis in rectal surgery-it was found that both suture techniques per se made no difference in the function of anal continence. The anal pressures at rest and sphincter contraction remained unchanged. A linear reduction of functional reservoir of the "neorectum" could be shown, which depended on the level and healing of the anastomosis. An anastomosis level at 6 cm from anocutaneous line is important for functional reasons. Anastomoses above this level do not cause any consequences for anal continence. Anastomoses below this level result in a reduced functional reservoir for at least 6 months. Within this period a decrease in anal continence is possible, especially in cases of disturbed healing of the anastomosis.