[Effect of acupuncture on radial artery hemodynamics. Two controlled studies in pre-exposed and naive healthy subjects]. / Effets de l'acupuncture sur l'hémodynamique de l'artère radiale. Deux essais contrôlés chez des patients pré-exposés et chez des sujets sains naïfs.

Palpation of the radial pulses is one of the most important techniques in traditional Chinese medicine. Two double-blind randomised trials of the effects of real and sham acupuncture on radial artery hemodynamics were conducted in 19 patients regularly exposed to acupuncture (sensitised subjects), and in 8 healthy subjects devoid of previous exposure (naive subjects), respectively. Radial artery diameter and pulse waveform was measured with a high-resolution echotracking system and aplanation tonometry, respectively, before and during a 20-minute's acupuncture period. In sensitised patients, arterial diameter significantly increased during real acupuncture, compared to the sham group (+7.5 +/- 2.8% vs -2.9 +/- 2.7%, respectively; p < 0.01). By contrast, in naive subjects, arterial diameter did not change during real or sham acupuncture. In both populations, no significant difference was observed between real and sham acupuncture, concerning the time-course of blood pressure, radial artery distensibility and pressure waveform. Our results demonstrate that real acupuncture can determine an objective vasodilatation of the radial artery in patients regularly exposed to acupuncture, but not in naive subjects.

Influence of the M235T polymorphism of human angiotensinogen (AGT) on plasma AGT and renin concentrations after ethinylestradiol administration.

The T235 allele of the angiotensinogen (AGT) gene is associated with plasma AGT concentration and pregnancy-induced hypertension. The aim of this study was to compare changes in the circulating renin-angiotensin system after short-term (2 days) and repeated (7 days) administration of 50 microg ethinylestradiol (EE) in homozygous normotensive men (TT and MM). After repeated EE administration, renin stimulation was induced by a single oral dose of 40 mg furosemide, followed by 50 mg captopril, 12 h later. The short-term administration of EE did not induce a significant differential genotype-dependent increase in AGT concentration. In the 7-day study, TT subjects had higher peak plasma AGT concentrations than MM subjects. The more pronounced AGT increase in TT subjects resulted in similar plasma renin activity at a lower plasma active renin concentration, with a higher plasma renin activity/active renin ratio. The difference between genotypes in renin secretion resulted in readjustment of angiotensins production. In conclusion, the T235 allele of the AGT gene is associated with greater stimulation of AGT secretion in plasma after EE administration. In the short-term, complete readjustment of the circulating renin-angiotensin system occurs, through a decrease in renin release, which blunts the effects of the increase in AGT concentration.

High levels of drug-resistant human immunodeficiency virus variants in patients exhibiting increasing CD4+ T cell counts despite virologic failure of protease inhibitor-containing antiretroviral combination therapy.

The genotypic mutations associated with indinavir resistance were analyzed in 27 patients who exhibited sustained CD4+ T cell responses to highly active antiretroviral therapy (HAART), despite virologic failure of treatment. After 12 months of HAART, 1 or 2 primary resistance mutations had occurred in 18 (66%) of the patients, and secondary mutations had accumulated in 22 (88%) of the patients. The number and patterns of mutations in the patients who exhibited discrepant responses to HAART did not differ from those observed in patients who exhibited immunologic and virologic failure to therapy. Results indicate that many patients have prolonged immunologic benefits, despite the development of virologic failure and protease inhibitor mutations. The clinical course of this group of patients calls into question the relevance of genotypic resistance and plasma human immunodeficiency virus RNA level as surrogate markers in patients receiving HAART.

Human herpesvirus 8 infection in patients with POEMS syndrome-associated multicentric Castleman's disease.

The polyneuropathy, organomegaly, endocrinopathy, M protein, skin changes (POEMS) syndrome is a rare multisystemic disorder associated with osteosclerotic myeloma and multicentric Castleman's disease (MCD). Human herpesvirus type 8 (HHV-8) DNA sequences have been detected in lymph nodes of about 40% of human immunodeficiency virus (HIV)-negative patients with MCD, and in bone marrow stromal cells of patients with multiple myeloma. Considering these data, we investigated the presence of HHV-8 in 18 patients with POEMS syndrome (9 with MCD), by nested polymerase chain reaction (N-PCR) to detect DNA sequenses in various cells and tissues obtained by biopsy or at autopsy (13 patients, of whom 7 had MCD), and by an immunofluorescence assay to detect anti-HHV-8 IgG antibodies in blood (18 patients, of whom 9 had MCD). Detection of HHV-8 DNA was performed using three different N-PCR, targeting nonoverlapping regions in open reading frame (ORF) 25 and ORF26. Seven of 13 (54%) POEMS patients had HHV-8 DNA sequences in their tissues, as assessed by all three N-PCR, and 9 of 18 (50%) had circulating anti-HHV-8 antibodies. HHV-8 was mainly detected in the subset of POEMS patients with MCD (6 of 7 [85%] for DNA sequences; 7 of 9 [78%] for antibodies). The percentage of positive N-PCR was higher in lymph nodes than in bone marrow samples (P <.02). Sequencing of amplicons showed a homogeneous restricted variability in the ORF26 region, characteristic of the minority subgroup B defined by Zong, and responsible for isoleucine and glycine substitutions at amino acid positions 134 and 167. These findings strongly suggest an association of HHV-8 infection with POEMS syndrome-associated MCD.

High prevalence in Central Africa of blood donors who are potentially infectious for human herpesvirus 8.

BACKGROUND: In western countries, the transmission of human herpesvirus 8 (HHV-8) via blood transfusion has been recently postulated. In sub-Saharan African, the incidence of HHV-8-associated Kaposi's sarcoma and the seroprevalence for HHV-8 in autochthonous populations are high. STUDY DESIGN AND METHODS: The aim of this study was to estimate the prevalence of blood donations potentially infectious for HHV-8 in the general adult population of Central Africa. Forty-nine blood donors at the Centre de Transfusion Sanguine in Bangui, the capital of the Central African Republic, were selected. Forty-five inpatients of Broussais Hospital, Paris, France, who were known to be seronegative for HIV and hepatitis B and C viruses and who had not received heart or kidney transplants, were chosen as a European "control" group for comparison. HHV-8 DNA sequences were detected in peripheral blood mononuclear cells by nested polymerase chain reaction using primer sets located in the HHV-8 open reading frame 26. RESULTS: Eleven (22.5%; 95% CI: 12%-37%) of 49 blood donors were positive for HHV-8. Three (6%) were HIV-1 seropositive. Two (67%) of the 3 HIV-infected blood donors were also positive for HHV-8. All blood donors were apparently healthy; none was known to suffer from Kaposi's sarcoma. Only one (2.2%) control was carrying HHV-8 DNA on the peripheral blood mononuclear cells. The prevalence of HHV-8 was higher in blood donors from Bangui than in patients from Broussais Hospital. CONCLUSIONS: HHV-8 infection is highly prevalent in an apparently healthy adult population from Central Africa, which raises concerns about HHV-8 transmission through transfusion in this setting.

In vivo semen-associated pH neutralization of cervicovaginal secretions.

Physiological cervicovaginal acidity can partly inactivate human immunodeficiency virus (HIV). Basic semen components should be able to partially neutralize in vivo cervicovaginal pH. The goals of the study were to evaluate the relationship between cervicovaginal pH and presence of semen components in sexually active African women and to assess whether vaginal douching with water performed just after sexual intercourse could significantly reduce semen components and restore physiological cervicovaginal pH. Cervicovaginal secretion (CVS) from 56 heterosexual African women (19 to 45 years old), living in Bangui, Central African Republic, were evaluated for pH, semen components (prostatic acid phosphatase [PAP] and prostatic specific antigen [PSA]), cellularity, and hemoglobin at inclusion and after vaginal douching with 100 ml of water by using a bock. Before douching, semen components were found in 46 of 56 CVS (82%). The mean vaginal pH was 5.2 (range, 3.6 to 7.7), and concentrations of both PAP and PSA correlated positively and strongly with cervicovaginal pH (P < 0.001). After douching, semen components were found in 35 of 56 CVS (62%) (P = 0.03). Cervicovaginal PAP and PSA levels were significantly decreased (respectively, P < 0.0001 and P < 0.01; PAP, -72%; PSA, -87%), as was the total cell count (-60%; P < 0.0001). Furthermore, in CVS previously positive for both PAP and PSA, the mean vaginal pH was significantly decreased (6.5 versus 5.3, P < 0.01); no genital bleeding was observed. Frequent persistence of semen in CVS from heterosexually active African women leads to a shift from acidity to neutrality that could favor male to female HIV transmission. Vaginal douching provides significant elimination of semen after sexual intercourse; it should be considered for study as a supplementary means for the prevention of heterosexual HIV transmission.

Cervicovaginal synthesis of IgG antibodies to the immunodominant 175-199 domain of the surface glycoprotein gp46 of human T-cell leukemia virus type I.

Paired sera, saliva and cervicovaginal secretions from 17 HTLV-I-infected women (19-75 yr) were tested for total IgA and IgG, for IgA and IgG to the immunodominant region gp46/175-Pro-199, for serum IgG to the neutralizing domains gp46/ 190-Pro-199 and gp46/190-Ser-199, or for tax-rex proviral HTLV-DNA. Serum antibodies to gp46/ 175-Pro-199 were detected more frequently in the IgG (13/17) than in the IgA (5/17) isotypes. The majority (8/12) of anti-gp46/175-Pro-199-positive sera reacted also to gp46/190-Pro-199 or to gp46/ 190-Ser-199, demonstrating their neutralizing properties. In saliva, antibodies to gp46/175-Pro-199 were not generally detected. In cervicovaginal secretions, IgG to gp46/175-Pro-199, but not IgA, were detected in 6/15 (40%) patients. The mean specific activity of IgG to gp46/175-Pro-199 showed a trend to be higher in cervicovaginal secretions (218 +/- 109) than in sera (14 +/- 4). Furthermore, in all patients with cervicovaginal IgG to gp46/175-Pro-199, the cervicogaginal/serum ratio (19 +/- 6) of anti-gp46 IgG specific activities were markedly above 1. HTLV-DNA was detected in 4/17 salivas, and in 3/15 cervicovaginal secretions, all from patients demonstrating cervicovaginal synthesis of IgG to gp46/175-Pro-199. In conclusion, IgG to gp46/175-Pro-199 in cervicovaginal secretions, when present, appear to be produced primarily locally because of local HTLV-I excretion. Since anti-gp46/175-Pro-199 antibodies usually support reactivities to neutralizing domains, their presence could be relevant for limiting HTLV-I transmission via cervicovaginal secretions.

Blunted renal vascular response to angiotensin II is associated with a common variant of the angiotensinogen gene and obesity.

OBJECTIVE: Recently, we reported evidence for genetic linkage between human essential hypertension and the angiotensinogen gene (AGT) and an association with a common molecular variant of this gene (methionine 235 --> threonine or T235). Other studies had led us to hypothesize that blunted renal plasma flow responses to infused angiotensin II (Ang II) when in high salt balance may reflect increased intrarenal formation of Ang II, a condition that might promote hypertension. Here we examine the relationship between AGT genotype and renal vascular response to infused Ang II. METHODS: Hypertensive (n = 34, all off medication) and normotensive (n = 57) members of families with a history of hypertension (age 18-60 years) as well as 29 normotensive volunteers without a family history of hypertension were studied after controlled diets with 200 mequiv./day sodium. Ang II was infused at a mildly pressor dose (3 ng/kg/min) and renal plasma flow was determined by steady-state plasma para-aminohippurate concentration. RESULTS: After correction for covariates in multivariate analyses, participants homozygous for the T235 variant had significantly diminished renal plasma flow responses to the Ang II infusion (P = 0.005). Changes in renal arterial resistance were also blunted in the T235 homozygotes. Similar results were found when analysis was restricted to normotensive participants or subdivided based on family history of hypertension. No confounding factors associated with AGT genotype that could explain these differences were found. Furthermore, obesity, which also suppressed renovascular response to Ang II, was found to interact significantly (P = 0.017) with genotype such that, among T235 homozygotes, obesity had a greater blunting effect on renal vascular response. CONCLUSIONS: Expected renovascular response to infused Ang II was blunted in persons with the AGT TT genotype. This is the first report of an association between a specific gene variant and altered renal physiology in humans with particular relevance to essential hypertension.

Human T-lymphotropic virus type I excretion and specific antibody response in paired saliva and cervicovaginal secretions.

Paired sera, salivas, and cervicovaginal secretions from 17 HTLV-I-infected women (10-75 years) were evaluated for total IgA, IgG, IgM, for IgA and IgG to whole HTLV-I lysate, for albumin, and for tax-rex proviral HTLV-DNA. IgG to HTLV-I were constantly detected, with much higher titers in serum (mean titer: 97,800) than in saliva (53) or in cervicovaginal secretions (216). IgA to HTLV-I were detected in only 12 (70%) sera, 6 (35%) salivas, and 8 (53%) cervicovaginal secretions, with higher titers in serum (75) than in saliva (8). Using the relative coefficient of excretion by reference to albumin, as well as the comparison of specific activities, the HTLV-I-specific IgG appeared primarily originating from serum, whereas IgA to HTLV-I were primarily locally produced. Salivary synthesis of IgG to HTLV-I occurred in both patients with a sicca syndrome attesting salivary glands impairment. Local excretions of total IgA, IgG, and IgM evaluated in body fluids were normal. HTLV DNA was detected in 4 (24%) salivas and in 3 (20%) cervicovaginal secretions, always in patients demonstrating local synthesis of HTLV-I-specific IgA or IgG. HTLV-I excretion elicits a weak local immune response to HTLV-I in saliva as well as in cervicovaginal secretions, which could be relevant for HTLV-I transmission via body fluids.

[Renovascular arterial hypertension. Evaluation of ultrasonographic measurement of kidney length]. / Hypertension artérielle rénovasculaire. Evaluation de la mesure échographique de la longueur des reins.

In order to evaluate the ultrasonographic measurement of kidney length, 32 hypertensive patients with renal arterial stenosis treated by intraluminal angioplasty were examined by several ultrasonographies performed by the same observer before and after dilatation. The lack of variation in the contralateral kidney length ascertained the intra-observer reproducibility of the method. We found that ischaemic kidneys were smaller and that this diminution in size depended on the renal arterial lesion (kidneys below atheromatous lesions were of smaller size than those below fibrodysplastic lesions). The increase in size of kidneys treated by angioplasty was most probably due to an increase in perfusion pressure and was to be compared with the results of a separate evaluation of renal function. However, this method has no individual applications in view of the important kidney length distribution at cross-checkings.