HIV-Prävalenz bei ophthalmologischen Patienten in Kamerun

BACKGROUND: It is difficult to estimate the exact HIV infection rates in countries such as Cameroon because of diagnostic and statistical problems. The majority of people seek help from traditional healers outside the health system. PATIENTS AND METHODS: A screening for human immunodeficiency virus type 1 (HIV-1) and type 2 (HIV-2) was performed on 2452 patients of the western province of Cameroon. All data were evaluated regarding HIV seroprevalence and ophthalmological findings in HIV-seropositive patients. The test covered all patients who came for cataract surgery (group 1), all outpatients with suspicious ophthalmological findings (group 2), and all remarkable patients of the collaborating department of general medicine (group 3) between 20 September 2000 and 20 September 2001. RESULTS: Of the 2452 screened patients, 467 (19.0%) were HIV seropositive. A positive test result was obtained in 29 (5.5%) of the 525 patients in group 1, 154 (35.6%) of the 433 patients in group 2, and 284 (19.0%) of the 1494 patients in group 3. The main ocular manifestations of the 154 HIV-seropositive patients in group 2 were uveitis (17.6%), squamous cell carcinoma of the conjunctiva (14.9%), zoster ophthalmicus (14.9%), and corneal ulcers (11.0%). CONCLUSIONS: This study shows that the seroprevalence of the screened population of Cameroon lies between 5.5% (results of group 1) and 19.0% (results of group 3).     

Sex dimorphisms in the neuroprotective effects of estrogen in an animal model of Parkinson's disease

The incidence of certain neurological disorders, including Parkinson's disease, appears to be more prevalent in men. Studies involving estrogen treatment of ovariectomised rodents attribute this largely to the neuroprotective effects of estrogen. However, a neuroprotective role for physiological levels of circulating hormones in males and females is less clear. Using the 6-hydroxydopamine (6-OHDA) model of Parkinson's disease to lesion the nigrostriatal dopaminergic (NSDA) pathway, we have shown that in females, endogenously produced estrogen is neuroprotective, whereas in males, gonadal factors increase striatal 6-OHDA toxicity. Intriguingly, estrogen, but not dihydrotestosterone, a nonaromatizable androgen, reversed the effects of orchidectomy on lesion size, raising the novel the hypothesis that enhanced male susceptibility may be attributable to the effects of endogenous testosterone only after its aromatization to estrogen. Thus, estrogen appears to exert opposite effects in the NSDA in males and females, being neuroprotective in females, but not in males, where it may even exacerbate neurodegenerative responses, with important implications for the clinical potential of estrogen-related compounds as neuroprotective agents. Preliminary experiments support the hypothesis that sex differences in the adult NSDA may result from the organisational actions of gonadal steroids during the critical neonatal period for the masculinization of the brain. Further studies are needed to determine whether this early organisation of a sexually differentiated neural circuitry may contribute to the emergence of neurodegenerative conditions such as Parkinson's disease.     

Brca1 inactivation induces p27(Kip1)-dependent cell cycle arrest and delayed development in the mouse mammary gland

One common characteristic of breast cancers arising in carriers of the predisposition gene BRCA1 is a loss of expression of the CDK inhibitor p27(Kip1) (p27), suggesting that p27 interacts epistatically with BRCA1. To investigate this relationship, we examined expression of p27 in mice expressing a dominant negative allele of Brca1 (MMTV-trBr) in the mammary gland. While these mice rarely develop tumors, they showed a 50% increase in p27 protein and a delay in mammary gland development associated with reduced proliferation. In contrast, on a p27 heterozygote background, MMTV-trBrca1 mice showed an increase in S phase cells, and normal mammary development. p27 was the only protein in the cyclin-cyclin-dependent kinase network to show altered expression, suggesting that it may be a central mediator of cell cycle arrest in response to loss of function of BRCA1. Furthermore, in human mammary epithelial MCF7 cells expressing BRCA1-specific RNAi and in the BRCA1-deficient human tumor cell line HCC1937, p27 is elevated at the mRNA level compared to cells expressing wild-type BRCA1. We hypothesize that disruption of BRCA1 induces an increase in p27 that inhibits proliferation. Accordingly, reduction in p27 expression leads to enhancement of cellular proliferation in the absence of BRCA1.     

Phonological categorization of vowels: a mismatch negativity study

There is electrophysiological evidence that phonological categorization has occurred within 100-200 ms post stimulus onset for the syllables /tae/ and /dae/, which vary in voice onset time. Using a similar paradigm, this study investigated when phonological categorization occurred for the contrast between /I/ and /epsilon/, using synthesized speech tokens that differed in the frequency of the first formant. Here we show that phonological categorization of these tokens has not occurred 100-200 ms after stimulus onset. However, the presence of a late mismatch negativity (350 ms after stimulus onset) indicated that phonological categorization had taken place by this time.     

Identification of a circulating soluble form of CD80: levels in patients with hematological malignancies

The release of soluble forms of CD80 provides a potentially powerful mechanism for the modulation of anti-tumor responses. In this report we investigated whether a soluble form of CD80 (sCD80) circulates in vivo and whether levels are altered in patients with hematological malignancies. Circulating sCD80 was detected by ELISA in all normal donor (0.024-0.318 ng/ml) and patient (0.02-3.75 ng/ml) blood analyzed. The majority of acute myeloid leukemia (13/17) and multiple myeloma (11/12) patients had normal sCD80 levels. Significantly elevated levels were detected in chronic lymphocytic leukemia (CLL, P = 0.0001) and mantle cell lymphoma (MCL, P = 0.0002) patients. MCL patients had the highest levels with 8/9 having levels > 0.318 ng/ml. Increased sCD80 levels in CLL were significantly associated with poor prognosis markers such as low platelet (P = 0.01) and hemoglobin (P = 0.002) levels, elevated WBC counts (P = 0.03) and expression of CD38 (P = 0.048). The immunoreactivity of the sCD80 in both normal and patient plasma was inhibited by the presence of CTLA-4-Ig, suggesting sCD80 is functional. Comparison of sCD80 and soluble CD86 levels demonstrated that these molecules were independently elevated in 39% of patients. The finding that a proportion of CLL and the majority of MCL patients contain elevated levels of sCD80 and the demonstration that sCD80 can interact with CTLA-4-Ig suggests a potential role for sCD80 in modulating anti-tumor responses during the malignant process.     

Laser Doppler imaging of burn scars: a comparison of wavelength and scanning methods

Laser Doppler perfusion imaging (LDI) is a useful tool for the early clinical assessment of burn depth and prognostic evaluation of injuries that may require skin grafting. We have evaluated two commercially available laser Doppler imagers for the perfusion measurement of normal and burn scar tissue. METHODS: A single wavelength (635 nm), step-wise scanning LDI and a dual wavelength (633 and 780 nm), continuous scanning LDI were used. Twenty patients with hypertrophic burn scars (time since injury: 1 month-8 years) were recruited and the color and elevation of the scar was clinically assessed using a modified Vancouver Burn Scar Scale. Perfusion of each scar region was measured using both imagers. A symmetric contralateral region of unburned skin was also imaged to record baseline perfusion. RESULTS: Comparisons of wavelength and scanning technique were made using perfusion values obtained from 22 burn scars. Highly significant positive correlation was observed in all comparisons. In addition, output from both instruments was strongly and significantly correlated with the clinical grading of the scar. SIGNIFICANCE: Both LDI scanners perform similar perfusion measurements. The results also indicate that red and near-infrared (NIR) wavelength photons provide similar blood flow information. The faster, continuous scanning method provides a clinical advantage without a significant loss of blood flow information. However, a critical evaluation of both instruments suggests that caution must be exercised when using these optical diagnostic techniques and that some knowledge of light-tissue interaction is required for the proper analysis and interpretation of clinical data.     

New insights into diabetic polyneuropathy

Michael Polydefkis, MD; John W. Griffin, MD; Justin McArthur, MBBS, MPH

JAMA. 2003;290:1371-1376.

Patients with complaints of numbness, tingling, and dysesthesias in the toes and feet are frequently referred to neurologists. Often, the only objective evidence for peripheral nerve dysfunction in these patients is limited to small-caliber sensory nerve fibers. On examination these patients may have reduced distal pinprick sensation, and distal leg skin biopsies show loss of small-caliber nerve fibers. Studies focusing on small-caliber nerve fibers have led to a growing impression that neuropathy can be associated with early diabetes or impaired glucose tolerance (IGT). Often, neuropathy can be the presenting symptom of either diabetes or IGT. Furthermore, the oral glucose tolerance test appears to be a more sensitive measure of glucose dysmetabolism in these patients than levels of fasting blood glucose or glycated hemoglobin. Patients with IGT-associated neuropathy may represent an attractive target population for future regenerative studies given that their neuropathy is less severe and presumably more easily reversed than neuropathy occurring in patients with diabetes.

Historically, small-caliber fibers have not been extensively evaluated due to a lack of objective measures. Several measures to evaluate these fibers are emerging, including skin biopsy with visualization of epidermal nerve fibers. The accessibility of epidermal nerve fibers makes them an attractive target for nerve injury models, which have potential for development as novel outcome measures. Such approaches may address some of the challenges of past diabetic polyneuropathy trials.