Prevalence of HIV in Mayotte

Mayotte is a little French island, located in the Indian ocean, between Madagascar and Mozambic. Officially, the population goes up to 150,000 inhabitants, but in fact, it probably comes up to about 200,000 people, because of a very numerous illegal immigration, especially coming from Anjouan, the nearest Comorian island. Up to now there are no data about HIV in Mayotte. There is only one adult medical unit (except intensive care). All patients detected as seropositive for HIV are sent for treatment in this unit. The only case of systematically proposed HIV serology is pregnancy, and this since 1994. 70% to 80% of women accept it. There are annually 6000 deliveries in Mayotte. When a seropositivity is detected, screening is systematically proposed to other members of the family. Epidemiology does not seem to worsen, even if detection is increasing: 8675 tests done in 1998, 9142 in 1999, 12,085 in 2000. All cases of seropositivity attended to at present time in our unit have been registered and studied, apart from patients who died before this study, and those who did not consult for more than two years. There were 8 HIV positive people who died since 1990 in Mayotte, most of them in 1991, 1992. There was no death in the last years, nor sanitary evacuation, except one. 50 people are registered: 20 males, 30 females. Average age is 34. 39 Comorian people, 10 metropolitans, and one from another origin. Contamination was heterosexual in 43 cases, intravenous drug user in 1 case, homosexual in 2 cases, professional in 1 case, unknown in 3 cases. There are 4 double contamination Ag Hbs/HIV, and 2 HCV/HIV. 39 subjects are at A stage, 5 B, 6 C. The beginning of the epidemic in Mayotte took place probably around 1990, among militaries and prostitutes. Now, transmission keeps going on, in most cases, heterosexual, as it occurs in the nearby Africa. Polygamy, official or officious, has a leading role. Females who were detected during pregnancy have obtained zidovudine, or have been able to pursue previous therapy. Medical care and therapy are free in Mayotte, but sometimes there are delays in supplying medicines or in returning results. Epidemic has not increased up to now; even though screening has. There are very few pediatric cases: only 4 cases were notified in Mayotte until now: one who died very soon, one who has gone to live in Reunion island, and two who are still in Mayotte: one is 12 years old, and another one 5 years old.     

Adrenocortical, beta-endorphin and behavioral responses to graded stressors in differentially reared rats

Isolation rearing has long been suspected to alter hormonal and behavioral responses to stress. Two experiments were conducted to test the hypothesis that isolates are more timid or fearful than socially reared rats when exposed to novel test environments. In both, isolate response to 3 graded stressors was compared to that of socially-reared rats. In the first experiment, animals were handled, shocked or not treated prior to testing to produce three levels of conditioned fear. They were then tested on four paradigms previously shown sensitive to conditioned fear: open field activity, emergence latency, auditory startle, and latency to accept food from the experimenter. In the second experiment, rats were given a 0-, 5- or 20-min forced swim, then sacrificed for analysis of plasma corticosterone and pituitary and hypothalamic beta-endorphin. It was found that isolates showed little evidence of enhanced behavioral timidity, although rearing effects were seen on all 4 behavioral measures. Plasma corticosterone levels increased in a graded fashion over the course of the forced swim, but there was no effect of rearing conditions. While there were no effects of rearing or stress on hypothalamic beta-endorphin, pituitary beta-endorphin content was lower in females than in males, and isolate males had lower pituitary endorphin than social males. In summary, these experiments provide no evidence that isolation rearing produces a primary, global increase in fearfulness, but identify several behavioral and hormonal differences associated with differential housing in rats.     

Spontaneous keloids in siblings

The authors report two rare cases of 'non-syndromic spontaneous keloids' occuring in siblings. This represents another unexplored area in the field of 'keloid challenge', warranting further research and development.     

Effect of titanium surface topography on macrophage activation and secretion of proinflammatory cytokines and chemokines

The macrophage has a major role in normal wound healing and the reparative process around implants. Murine macrophage-like cells RAW 264.7 were used to investigate the effect of titanium surfaces on macrophage activation and secretion of proinflammatory cytokines [interleukin (IL)-1 beta, IL-6, and tumor necrosis factor (TNF)-alpha] and chemokines (monocyte chemoattractant protein-1 and macrophage inflammatory protein-1 alpha). Four topographies were used: those produced by mechanically polishing, coarse sand blasting, acid etching, and sandblasting and acid etching (SLA). Macrophages were plated on the four titanium surfaces at a population density of 5 x 10(5) cells/mL/well. Tissue culture plastic and tissue culture plastic plus lipopolysaccharide (LPS) served as negative and positive control, respectively. In addition, all surfaces were tested for their effects on macrophages in the presence of LPS. Supernatants were collected for assays after 6, 24, and 48 h and the numbers of macrophages attached to the surfaces were quantified using the DAPI (4,6-di-amidino-2-phenylindole) assay. Cytokine and chemokine levels were measured with sandwich enzyme-linked immunosorbent assays. Statistical comparison between the surfaces and the controls was determined by using the two-way analysis of variance including interaction effect (two tailed and p < or = 0.05). Unstimulated macrophages increased their secretion of the proinflammatory cytokine (TNF-alpha) when attached to rough surfaces (acid etching and SLA, p < or = 0.05). In macrophages stimulated with LPS, the roughest surface SLA produced higher levels of IL-1 beta, IL-6, and TNF-alpha at 24 and 48 h than all other surfaces (p < or = 0.05). Surface topography also modulated the secretion of the chemokines monocyte chemoattractant protein-1 and macrophage inflammatory protein-1 alpha by macrophages. Unstimulated macrophages attached to the SLA surface down-regulated their production of chemokines (p < or = 0.05) whereas LPS-stimulated macrophages attached to the SLA surface up-regulated their production (p < or = 0.05). Moreover, the SLA surface was found to act synergistically with LPS as well as the combination of blasting and etching features of the SLA surface resulted in significant release of proinflammatory cytokines and chemokines by stimulated macrophages at 24 and 48 h (p < or = 0.05). This in vitro study has demonstrated that surface topography, in particular the SLA surface, modulated expression of proinflammatory cytokines and chemokines by macrophages in a time-dependent manner.     

Comparison of SPECT bone scintigraphy with MRI for diagnosis of meniscal tears

Background

Scintigraphy has been considered as competitive to MRI, but limited data are available on the accuracy of single photon emission tomography (SPECT) compared with MRI for the assessment of meniscal tears. Our objective was to assess the value of SPECT in comparison to MRI.

Methods

Between January 2003 and March 2004, sixteen patients were studied with both modalities and the accuracy rates of SPECT scan results, and MRI findings in the diagnosis of meniscal tears were compared. Arthroscopy was the gold standard.

Results

The respective sensitivity rate, specificity rate, and positive and negative predictive accuracies of MRI were 89%, 94%, 93%, and 79% and for SPECT those were 78%, 94%, 94%, and 88%. There was good agreement on the presence or absence of tears between two modalities (κ statistic = 0.699).

Conclusion

SPECT and MRI are both valuable imaging techniques. SPECT is a useful alternative when MRI is unavailable or unsuitable and it is beneficial when more possible accuracy is desired (such as when MRI results are either inconclusive or conflict with other clinical data).     

Conformational changes in Sindbis virions resulting from exposure to low pH and interactions with cells suggest that cell penetration may occur at the cell surface in the absence of membrane fusion

Alphaviruses have the ability to induce cell-cell fusion after exposure to acid pH. This observation has served as an article of proof that these membrane-containing viruses infect cells by fusion of the virus membrane with a host cell membrane upon exposure to acid pH after incorporation into a cell endosome. We have investigated the requirements for the induction of virus-mediated, low pH-induced cell-cell fusion and cell-virus fusion. We have correlated the pH requirements for this process to structural changes they produce in the virus by electron cryo-microscopy. We found that exposure to acid pH was required to establish conditions for membrane fusion but that membrane fusion did not occur until return to neutral pH. Electron cryo-microscopy revealed dramatic changes in the structure of the virion as it was moved to acid pH and then returned to neutral pH. None of these treatments resulted in the disassembly of the virus protein icosahedral shell that is a requisite for the process of virus membrane-cell membrane fusion. The appearance of a prominent protruding structure upon exposure to acid pH and its disappearance upon return to neutral pH suggested that the production of a "pore"-like structure at the fivefold axis may facilitate cell penetration as has been proposed for polio (J. Virol. 74 (2000) 1342) and human rhino virus (Mol. Cell 10 (2002) 317). This transient structural change also provided an explanation for how membrane fusion occurs after return to neutral pH. Examination of virus-cell complexes at neutral pH supported the contention that infection occurs at the cell surface at neutral pH by the production of a virus structure that breaches the plasma membrane bilayer. These data suggest an alternative route of infection for Sindbis virus that occurs by a process that does not involve membrane fusion and does not require disassembly of the virus protein shell.     

The determinants of bronchial hyperresponsiveness in patients with allergic rhinitis.

BACKGROUND: Patients with allergic rhinitis and bronchial hyperresponsiveness (BHR) may be at higher risk of developing asthma. OBJECTIVE: To investigate whether reactivity to aeroallergens in skin prick testing (SPT) and serum eosinophil cationic protein levels can be used to predict BHR in allergic rhinitis patients. METHODS: Fifty-nine consecutive patients with allergic rhinitis underwent SPTs using grass, tree, weed, parietaria, Alternaria, Aspergillus, mites, and cat and dog dander extracts. Methacholine challenge tests were performed using spirometry. RESULTS: Methacholine-induced BHR was detected in 23 patients (39%). Of 59 patients, 14 had 1 positive SPT response, 35 had 2 to 4 positive responses, and 10 had more than 4 positive responses. There was a significant inverse correlation between methacholine provocation concentration that caused a decrease in forced expiratory volume in 1 second of 20% (PC20) and the number of positive SPT responses (r = -0.28; P = .03). The BHR-positive patients had a mean of 4 positive SPT responses, whereas BHR-negative patients had a mean of 2.6 (P = .04). Nine BHR-positive patients (39%) and only 1 BHR-negative patient (3%) had more than 4 positive SPT responses (P < .001). There was no correlation between serum eosinophil cationic protein levels and methacholine PC20 doses. There was a strong association between hyperresponsiveness to methacholine and both cat and dog dander sensitivity (P < .001 and P = .001, respectively). CONCLUSIONS: Allergic rhinitis patients with SPT responses to a higher number of allergens are more likely to have BHR. Whether the number of positive SPT responses correlates with the risk of developing asthma in allergic rhinitis patients remains to be determined.     

CD4 lymphocytes in the blood of HIV(+) individuals migrate rapidly to lymph nodes and bone marrow: support for homing theory of CD4 cell depletion

Recent studies have provided evidence that macrophages from Th1-prone mouse strains respond with an M1 profile, and macrophages from Th2-prone mouse strains respond with an M2 profile, characterized by the dominant production of NO or TGF-beta 1, respectively. We have shown that peritoneal macrophages from IL-12p40 gene knockout mice have a bias toward the M2 profile, spontaneously secreting large amounts of TGF-beta 1 and responding to rIFN-gamma with weak NO production. Moreover, IL-12p40KO macrophages are more permissive to Trypanosoma cruzi replication than their wild-type littermate cells. Prolonged incubation with rIL-12 fails to reverse the M2 polarization of IL-12p40KO macrophages. However, TGF-beta 1 is directly implicated in sustaining the M2 profile because its inhibition increases NO release from IL-12p40KO macrophages. IFN-gamma deficiency is apparently not the reason for TGF-beta 1 up-regulation, because rIFN-gamma KO macrophages produce normal amounts of this cytokine. These findings raise the possibility that IL-12 has a central role in driving macrophage polarization, regulating their intrinsic ability to respond against intracellular parasites.     

Levels of cytokine in bronchoalveolar lavage (BAL) fluid in patients with pulmonary fibrosis due to sulfur mustard gas inhalation.

This study was designed to analyze cytokine levels in bronchoalveolar lavage (BAL) fluid of patients with pulmonary fibrosis (PF) and was performed at a University hospital. Nineteen veterans had mustard gas-induced PF, and 19 normal veterans were used as a control group. Chest roentgenograms, pulmonary function tests (PFTs), the percentage diffusing capacity of carbon monoxide (D(LCO)), high-resolution CT scans of the chest, and analyses of BAL fluids for five cytokines interleukin-8 (IL-8), IL-1beta, IL-6, tumor necrosis factor-alpha (TNF-alpha), IL-12, and the growth factors transforming growth factor-beta (TGF-beta), insulin-like growth factor-1 (IGF-1), and epidermal growth factor (EGF) were performed in all cases. A transbronchial lung biopsy was done in all patients. There were significant differences in cytokine (IL-8, IL-1beta, IL-6, TNF-alpha, IL-12) levels of BAL fluid between patients with PF and healthy controls. TGF-beta, EGF, and IGF-1 levels were also significantly increased in patients with PF compared with controls. A significant negative correlation was observed between the percentage of D(LCO) and IL-8 levels in BAL fluid in patients with PF (r = -0.47, p = 0.04). A significant negative correlation was also seen between the percentage of D(LCO) and TGF-beta (r = 0.53, p = 0.02) in these patients. Except for the percentage and the absolute number of the BAL fluid neutrophils (r = 0.70, p = 0.001 and r = -0.62, p = 0.005, respectively), no correlation was found between D(LCO)% and the other BAL cells. Of all measured cytokines and growth factors, only IL-8 and TGF-beta showed a significant correlation with the degree of fibrosis (p = 0.004, p = 0.04). The increased levels of cytokines and growth factors in the BAL fluid suggest the possible causative mechanism in the lung in sulfur mustard gas-induced PF by recruitment of neutrophils and eosinophils into the lung.