Relative resistance to HIV-1 infection of CD4 lymphocytes from persons who remain uninfected despite multiple high-risk sexual exposure.

Some individuals remain uninfected with human immunodeficiency virus type-1 (HIV-1) despite multiple high-risk sexual exposures. We studied a cohort of 25 subjects with histories of multiple high-risk sexual exposures to HIV-1 and found that their CD8+ lymphocytes had greater anti-HIV-1 activity than did CD8+ lymphocytes from nonexposed controls. Further studies indicated that their purified CD4+ lymphocytes were less susceptible to infection with multiple primary isolates of HIV-1 than were CD4+ lymphocytes from the nonexposed controls. This relative resistance to HIV-1 infection did not extend to T-cell line-adapted strains, was restricted by the envelope glycoprotein, was not explained by the cell surface density of CD4 molecules, but was associated with the activity of the C-C chemokines RANTES, MIP-1alpha, and MIP-1beta. This relative resistance of CD4+ lymphocytes may contribute to protection from HIV-1 in multiply exposed persons.

New acute and chronic black holes in patients with multiple sclerosis randomised to interferon beta-1b or glatiramer acetate.

BACKGROUND: Hypointense lesions on T1 weighted MRI, referred to as black holes (BH), are a marker of demyelination/axonal loss in multiple sclerosis (MS). There is some evidence that glatiramer acetate (GA) may decrease the conversion of new brain lesions to BH. METHODS: Monthly 3-Tesla brain MRI scans were used for up to 2 years to study the development and evolution of new BH in 75 patients with MS randomised to GA or Interferon beta-1b (IFNbeta1b) in the BECOME study. FINDINGS: Of 1224 newly enhancing lesions (NEL) appearing at baseline through 24 months in 61 patients, 767 (62.7%) showed an acute BH (ABH). The majority of ABH were transient and of similar duration by treatment group. Of 571 ABH in which MRI follow-up scans were available for >or=1 year, 103 (18.8%) were still visible >or=12 months after onset and were considered chronic BH (CBH). Only 12.1% of the 849 NEL with MRI follow-up >or=1 year converted to CBH, 9.8% with IFNbeta1b and 15.2% with GA (p = 0.02). The conversion from ABH to CBH was also lower with IFNbeta1b (15.2%) than with GA (21.4%), of borderline significance (p = 0.06). The majority of patients who developed NEL did not develop CBH; however, about a quarter had conversion rates from ABH to CBH greater than 20%. INTERPRETATION: Only a minority of new brain lesions in patients with MS treated with GA or IFNbeta1b convert to CBH.

Shortened telomere length in white blood cells of patients with IDDM.

IDDM is a polygenic and autoimmune disorder in which subsets of white blood cells (WBCs) are engaged in the destruction of beta-cells of the pancreas. The mechanisms that account for the abnormal behavior of these cells in IDDM are not fully understood. By measuring the mean length of telomeres of WBCs from patients with IDDM, we tested the concept that telomeres might play a role in IDDM. We examined the lengths of the terminal restriction fragments (TRFs) of DNA of WBCs from 234 white men comprising 54 patients with IDDM, 74 patients with NIDDM, and 106 control subjects. When adjusted for age, the TRF length from WBCs of patients with IDDM was significantly shorter than that of nondiabetic control subjects (mean +/- SE: 8.6 +/- 0.1 vs. 9.2 +/- 0.1, P = 0.002). No significant difference was observed between the TRF length from WBCs of patients with NIDDM versus nondiabetic subjects. Neither the duration nor the complications of IDDM (i.e., nephropathy and hypertension) had an effect on the TRF length of WBCs from patients with IDDM. The shortened TRF length of WBCs of patients with IDDM likely reflects a marked reduction in the TRF length of subsets of WBCs that play a role in the pathogenesis of IDDM.

Incipient and overt diabetic nephropathy in African Americans with NIDDM.

OBJECTIVE--To determine the prevalence of incipient and overt nephropathy in African-American subjects with non-insulin-dependent diabetes mellitus (NIDDM) attending a hospital clinic. Contributory factors, such as blood pressure (BP), duration and age at onset of diabetes, hyperglycemia, hyperlipidemia, and body mass index (BMI) also were evaluated. RESEARCH DESIGN AND METHODS--We recruited 116 African-American subjects with NIDDM for this cross-sectional, descriptive, and analytical study. BP, BMI, 24-h urine albumin excretion, creatinine clearance, serum creatinine, lipids, and GHb levels were measured. Albumin excretion rate (AER) was calculated, and subjects were divided into three groups: no nephropathy (AER < 20 micrograms/min), incipient nephropathy (AER 20-200 micrograms/min), and overt nephropathy (AER > 200 micrograms/min). Frequency of hypertension and nephropathy was analyzed by chi 2 testing, group means were compared using analysis of variance, and linear correlations were performed between AER and other variables. Multiple regression analysis was used to examine the association of these variables while controlling for the effects of other variables. RESULTS--Increased AER was present in 50% of our subjects; 31% had incipient and 19% had overt nephropathy. Hypertension was present in 72.4%; nephropathy, particularly overt nephropathy, was significantly more prevalent in the hypertensive group. Mean BP and diastolic blood pressure (dBP) were higher in the groups with incipient and overt nephropathy, and systolic blood pressure (sBP) was increased in overt nephropathy. Men with either form of nephropathy had higher sBP, dBP, and mean BP, whereas only women with overt nephropathy had increased sBP and mean BP. Subjects with incipient or overt nephropathy had a longer duration of diabetes, and those with overt nephropathy had a younger age at onset of diabetes. By multiple regression analysis, AER correlated with younger age at diabetes onset, but not with diabetes duration. No correlation with age, lipid levels, or GHb was noted. BMI correlated with AER. CONCLUSIONS--Incipient and overt nephropathy were observed frequently in these African-American subjects with NIDDM. Albuminuria correlated with BP, younger age at diabetes onset, and BMI. Association of albuminuria and increased cardiovascular mortality may place 50% of inner-city African-American patients with NIDDM at risk for developing cardiovascular complications.

Family support for heterosexual partners in HIV-serodiscordant couples.

OBJECTIVE: To ascertain the extent of family member support to heterosexual HIV-serodiscordant couples, and to identify associated sociodemographic and clinical characteristics. DESIGN: Discordant couples enrolled in a cohort study of heterosexual HIV transmission were interviewed with structured questionnaires to obtain sociodemographic data, family member awareness of HIV and perceived support from family members. Clinical characteristics were established by medical history, physical examination and laboratory tests. RESULTS: Awareness and support of family members were associated with sex of family member and HIV seropositivity, sex, education, and race of the partner. HIV-seropositive partners were more likely to have a sister aware than were HIV-negative partners (P = 0.01). More educated HIV-positive partners had fewer aware family members than less educated HIV-positive individuals (P = 0.02). Mothers of HIV-positive women were more often aware than mothers of all other partners (P = 0.04). Black HIV-negative partners had fewer aware family members than whites or Hispanics (P = 0.02). CONCLUSION: This research shows both encouraging and disturbing patterns of family awareness of HIV and support to serodiscordant partners.

Psychological distress, drug and alcohol use as correlates of condom use in HIV-serodiscordant heterosexual couples.

OBJECTIVE: To investigate the relationship between psychological distress, alcohol, drug and condom use in HIV-serodiscordant heterosexual couples. METHODS: Structured interviews were conducted to collect demographic information, detailed data on psychological distress, drug and alcohol use and sexual behavior. RESULTS: Analyses were based on 106 pairs of sexually active discordant couples. Significant differences among heterosexual condom users and non-users varied according to gender and HIV serostatus. Affect domains of interpersonal sensitivity and hostility were significant, as were the variables of regular drug or alcohol use and combining sex with drugs or alcohol. Employment was strongly associated with condom use in HIV-negative women whose regular sexual partners were HIV-positive men. CONCLUSION: The risk of vaginal sex without condoms in HIV-serodiscordant heterosexual couples may be reduced by specific psychological counseling and attention to drug and alcohol use as risk factors. Further research on the effect of employment of HIV-negative women is required.

PIP: The authors investigated the relationship of psychological distress and drug and alcohol use to reported condom use in 106 sexually active HIV-serodiscordant heterosexual couples. Significant differences were found among heterosexual condom users and non-users which varied according to gender and HIV serostatus. Affect domains of interpersonal sensitivity and hostility were significant, as were the variables of regular drug or alcohol use and combining sex with drugs or alcohol. Further, employment was strongly associated with condom use HIV-negative women whose regular sex partners were HIV-positive men. The authors therefore conclude that the risk of vaginal sex without condoms in HIV-serodiscordant heterosexual couples may be reduced by specific psychological counseling and attention to drug and alcohol use as risk factors. Further research is, however, called for on the effect of employment on HIV-negative women.

Parameters of lymphocyte Na+-Ca2+ regulation and blood pressure: the gender effect.

Alterations in cellular Ca2+ and Na+ regulation play a role in the pathogenesis of essential hypertension. Using peripheral lymphocytes from 68 normal persons, we observed the following relationships for major cellular Ca2+ regulatory parameters. Among men and women, Na+-Ca2+ exchanger activity was positively correlated with the resting cytosolic free Ca2+ ([Ca2+]c) (r=0.43, P=0.0003), and the resting [Ca2+]c was positively correlated with cytosolic Na+ ([Na+]c) (r=0.50, P=0.0001). For men only, store-operated Ca2+ entry was positively correlated with Na+-Ca2+ exchanger activity (r=0.63, P=0.0001). In addition, systolic and diastolic blood pressures were positively correlated with [Na+]c in men (r=0.53, P=0.001, and r=0. 41, P=0.017, respectively) but not in women (r=0.30, P=0.088, and r=0.24, P=0.17, respectively). Some of the relationships between cellular and blood pressure parameters were confounded by serum triglycerides. These observations indicate a gender effect on cellular Ca2+-Na+ regulation and its relationship with blood pressure.

Characterization of reproductive hormonal dynamics in the perimenopause.

Medical therapy for women in the perimenopausal period is controversial, in part due to varying degrees of ovarian hormone secretion characteristic of this time of life. To extend our understanding of the reproductive endocrine milieu of perimenopausal women, we studied 6 cycling women, aged 47 yr and older, for 6 months with daily collections of first morning voided urine. Five additional older reproductive aged (43-47 yr old) women were studied with daily urine and serum sampling for a single menstrual cycle; their urinary hormone data were combined with the former group for menstrual cycle comparisons. Urine was assayed for LH, FSH, estrone conjugates, and pregnanediol glucuronide and normalized for creatinine (Cr). Eleven midreproductive aged (19-38 yr old) normally cycling women, 5 women with well defined premature ovarian failure, and 5 women aged 54 yr and older who were at least 1 yr postmenopausal were used for comparison. Perimenopausal women had shorter follicular phases (11 +/- 2 days vs. 14 +/- 1 days; P = 0.031) and, hence, shorter menstrual cycles than midreproductive aged controls. FSH excretion in perimenopausal women was greater than that in younger women (range of means, 4-32 vs 3-7 IU/g Cr; P = 0.0005). LH secretion was overall greater than that in younger normal subjects (range of means, 1.4-6.8 vs. 1.1-4.2 IU/g Cr; P < 0.026). Overall mean estrone conjugate excretion was greater in the perimenopausal women compared to that in the younger women [76.9 ng/mg Cr (range, 13.1-135) vs. 40.7 ng/mg Cr (range, 22.8-60.3); P = 0.023] and was similarly elevated in both follicular and luteal phases. Luteal phase pregnanediol excretion was diminished in the perimenopausal women compared to that in younger normal subjects (range for integrated pregnanediol, 1.0-8.4 vs. 1.6-12.7 microg/mg Cr/luteal phase; P = 0.015). Compared to postmenopausal women, perimenopausal women had more overall estrone excretion (2.5-6.2 ng/mg Cr in postmenopausal women; P = 0.02) and lower mean FSH (range of means for postmenopause, 24-85 IU/g Cr; P = 0.017) and LH (range for postmenopause, 4.3-14.8 IU/g Cr; P = 0.041). Compared to women with premature menopause, perimenopausal women again had lower FSH (range of means for premature menopause, 36-82 IU/g Cr; P = 0.0022), lower LH (range of means for premature menopause, 5.5-23.8 IU/g Cr; P = 0.0092), borderline higher mean estrone conjugates (range of means for premature menopause, 4-44 ng/mg Cr; P = 0.064), and far longer periods of ovarian activity (one to two cycles in prematurely menopausal women vs. three to six cycles in perimenopausal women). We conclude that altered ovarian function in the perimenopause can be observed as early as age 43 yr and include hyperestrogenism, hypergonadotropism, and decreased luteal phase progesterone excretion. These hormonal alterations may well be responsible for the increased gynecological morbidity that characterizes this period of life.

Ca2+ in the dense tubules: a model of platelet Ca2+ load.

In this work, we explored the relationship between the freely exchangeable Ca2+ (FECa2+) in the dense tubules (DT) and the sarco(endo)plasmic reticulum (SER) Ca2+-ATPase (SERCA) in circulating human platelets and examined the relationship between blood pressure (BP) and these platelet parameters. Studying platelets from 32 healthy men, we showed that the maximal reaction velocity (Vmax) of the SERCA significantly correlated with FECa2+ in the DT and with the protein expressions of SERCA 2 and 3. BP positively correlated with both the Vmax of the SERCA (r=.462, P=.010) and the FECa2+ sequestered in the DT (r=.492, P=.005). The relationships between these platelet Ca2+ parameters and BP were in part confounded by increased levels of serum triglycerides and diminished HDL cholesterol with a higher BP. No correlation was observed between the resting cytosolic Ca2+ and BP. Collectively, these findings indicate that (1) an increase in the cellular Ca2+ load in platelets is expressed by a higher activity of the SERCA and an increase in the expressions of SERCA 2 and 3 proteins, coupled with an increase in the FECa2+ in the DT, and (2) a higher BP is associated with an increase in platelet Ca2+ load in human beings, expressed by a rise in the FECa2+ in the DT and the upregulation of SERCA activity.

Telomere length inversely correlates with pulse pressure and is highly familial.

There is evidence that telomeres, the ends of chromosomes, serve as clocks that pace cellular aging in vitro and in vivo. In industrialized nations, pulse pressure rises with age, and it might serve as a phenotype of biological aging of the vasculature. We therefore conducted a twin study to investigate the relation between telomere length in white blood cells and pulse pressure while simultaneously assessing the role of genetic factors in determining telomere length. We measured by Southern blot analysis the mean length of the terminal restriction fragments (TRF) in white blood cells of 49 twin pairs from the Danish Twin Register and assessed the relations of blood pressure parameters with TRF. TRF length showed an inverse relation with pulse pressure. Both TRF length and pulse pressure were highly familial. We conclude that telomere length, which is under genetic control, might play a role in mechanisms that regulate pulse pressure, including vascular aging.

Ovarian control of pituitary hormone secretion in early human pregnancy.

To determine the influence of ovarian relaxin on the secretion of pituitary GH and PRL in vivo, we evaluated circulating serum hormone levels in 17 pregnant patients with functional corpora lutea (group I) and compared them to levels in 10 patients with premature ovarian failure (POF; group II) who became pregnant with egg donation and did not have corpora lutea. Group II patients had exogenous hormonal support. Serum relaxin (RLX), GH, PRL, estradiol (E2), and progesterone levels were measured weekly by RIA from weeks 4-8 of pregnancy. Analysis of variance and covariance were used to determine hormonal relationships. Serum RLX was present in the natural pregnancy group, with a mean of 1.94 micrograms/L over the study period. Serum RLX was undetectable in the POF patients (less than 0.16 micrograms/L). No significant difference in PRL or progesterone levels between the two groups was noted. E2 levels showed an upward trend in both groups with time and were significantly higher in patients of the POF group than in group I women (P = 0.001). GH levels were significantly higher in the natural cycle patients (P = 0.02) despite lower E2 levels. These data provide additional support for the concept that RLX production in early pregnancy originates from the corpus luteum. They suggest that a luteal product, probably RLX, stimulates GH secretion in early pregnancy. This is a previously undescribed role for RLX in pituitary physiology during human pregnancy.

Luteal progesterone relates to histological endometrial maturation in fertile women.

To examine the relationship between endometrial histological maturation and reproductive hormones, we studied 11 fertile women, aged 18-37 yr. All participants had had at least 1 previous pregnancy and cycled regularly, every 25-35 days. Women collected daily, first morning voided urine for measurement of estradiol and progesterone metabolite excretion, estrone conjugates (E1c), and pregnanediol glucuronide (Pdg), respectively, throughout the cycle of study. Hormones were normalized for creatinine. Between 7-9 days after home detection of a LH surge (Sure Step), participants underwent an endometrial biopsy using a small bore (Pipelle) catheter. Tissue was prepared for histological and biochemical analyses. The histological analysis is reported herein. Endometrium was dated by 3 authors (N.S., D.H., and S.P.), all of whom were blinded to the participant's identity or timing of biopsy within her cycle. Final dating was agreed upon based upon the method of Noyes et al. E1c and Pdg were integrated throughout the cycle using the trapezoidal rule, and correlations were sought between deviation from expected histology (based upon urinary hormones and LH surge) and integrated hormone values. E1c varied over a 2-fold range in these normal women, from 1196-2040 ng/cycle. Pdg excretion was much more variable, ranging from 22-119 microg/cycle. No relationship could be found between histological lagging of endometrial maturation and lower excretion of E1c. A moderate correlation was observed (Spearman's r = 0.6; P < 0.05) between degree of histological maturation and integrated Pdg. Of two women with evidence of a disparity between gland and stromal development (glands lagging behind stroma by >2 days), one excreted 24 microg Pdg/cycle, the next to lowest value. We conclude that normal fertile women experience a wide range of hormone concentrations in the face of normal endometrial maturation. Progesterone appears to exert a dose-related effect on endometrial maturation, and the techniques we used, although relatively crude clinical measures, appeared to be sufficient to detect this relationship.

Blood pressure inversely correlates with thrombin-evoked calcium rise in platelets.

Earlier investigations showed a positive correlation between basal cytosolic free calcium in human platelets and blood pressure; however, recent studies have failed to show this relation. We undertook the present work to examine which platelet cytosolic calcium parameters (namely, cytosolic calcium in resting or stimulated states in calcium-containing and calcium-free media) present the least variability and best correlation with blood pressure. We studied 17 healthy white men on three different occasions separated by 1- and 4-week intervals. Their manual and ambulatory automated 24-hour blood pressure measurements were correlated with cytosolic calcium in resting and stimulated (thrombin-treated) fura 2-loaded platelets. The following cytosolic calcium parameters were measured in 1 mmol/L calcium and calcium-free media: basal cytosolic calcium, peak thrombin-evoked cytosolic calcium, and post-transient cytosolic calcium 5 minutes after thrombin treatment. The highest and lowest coefficients of variation were respectively shown by the basal cytosolic calcium (22.8%) and peak thrombin-evoked cytosolic calcium (10.1%) in calcium medium. Basal cytosolic calcium did not correlate with any of the blood pressure parameters. Of the cytosolic calcium parameters, peak thrombin-evoked cytosolic calcium in calcium medium demonstrated consistent (negative) correlations with blood pressure, with better correlations shown with diastolic than systolic blood pressure of both automated and manual blood pressure readings. Peak thrombin-evoked cytosolic calcium in calcium medium showed similar correlations with nighttime and daytime automated blood pressure measurements. There were no correlations between peak thrombin-evoked cytosolic calcium in calcium-free medium and blood pressure.(ABSTRACT TRUNCATED AT 250 WORDS)

Status of selected nutrients and progression of human immunodeficiency virus type 1 infection.

BACKGROUND: Immune function is highly dependent on nutritional status because the large mass and high rate of cellular turnover of the immune system make it a major user of nutrients. Furthermore, nutrient requirements may be increased during acute and chronic infections, including HIV-1 infection. OBJECTIVE: The current study was designed to assess relations among HIV-1 progression and 11 nutritional and demographic variables. DESIGN: The participants were 106 HIV-infected outpatients and 29 uninfected control subjects (n = 89 men and 46 women; age range: 35-57 y). The HIV-infected subjects represented a broad range of disease progression. RESULTS: We found lower concentrations of plasma and erythrocyte magnesium and of erythrocyte reduced glutathione beginning early in the course of HIV-1 infection. Significantly decreased hematocrit and increased serum copper concentration developed only late in the course of the disease. Statistically significant univariate associations were found between the CD4(+) T lymphocyte count and hematocrit, plasma magnesium concentration, and plasma zinc concentration. The lowest erythrocyte magnesium concentrations occurred in HIV-infected subjects who consumed alcoholic beverages. Independent variables that were significant joint predictors of CD4(+) cell count in multiple regression analyses were hematocrit and plasma free choline and zinc concentrations. These 3 factors together explained 43% of the variability in CD4(+) cell counts. CONCLUSION: The results provide evidence that compromised nutritional and antioxidant status begin early in the course of HIV-1 infection and may contribute to disease progression.

Study of genetics, epidemiology, and vitamin usage in familial spina bifida in the United States in the 1990s.

We analyzed family structure, genetic patterns, epidemiology, and vitamin usage in a series of families with multiple cases of spina bifida (familial SB). Among 6,491 individuals ascertained in 72 families with familial SB, we identified 180 patients--85 males and 95 females. The number of collateral cases on the maternal side (49 of 3,588), analyzed by category of kinship, were significantly higher than those on the paternal side (16 of 2,903) (p = 0.0002). Genomic imprinting or a partial mitochondrial contribution are possible mechanisms for this maternal effect. The proportion of US-born SB families reporting some Irish ancestry (49%, 34 of 70) or some German ancestry (50%, 35 of 70) were significantly higher than those for the US population at large. In contrast, the proportion of families reporting some African-American ancestry (1%, 1 of 70) was significantly lower. The elevated proportions of families with Irish and German ancestry, the high frequency of SB in Northern Ireland and in certain regions of Germany, the reduced proportion of families with African-American ancestry, and the lower prevalence of SB in African-Americans all suggest a genetic contribution to the etiology of the disorder. In our study, the proportion of mothers who used supplemental vitamins during the periconceptional period (29%, 47 of 163) was not significantly different from that in the US population at large.

Telomere attrition of the human abdominal aorta: relationships with age and atherosclerosis.

Little is known about the turnover rate (i.e. the rate of replication and death) of cells in the intima and media of human arteries as a function of age and atherosclerosis. One indicator of the replicative history of cells is telomere length. In this work we explored the rate of telomere attrition as a function of age and atherosclerosis in cells of the human abdominal aorta. Telomere length, measured by the terminal restriction fragment using Southern analysis, was determined in the intima and media of the distal (infrarenal) versus proximal (suprarenal) segments of the abdominal aorta. Telomere length was then correlated with age and atherosclerotic grade. The rate of age-dependent telomere attrition was higher in both the intima and media of the distal versus proximal abdominal aorta. In addition, telomere length was negatively correlated with atherosclerotic grade. However, after adjustment for age, this relationship was not statistically significant. The high rate of age-dependent telomere attrition in the distal abdominal aorta probably reflects enhanced cellular turnover rate due to local factors such as an increase in shear wall stress in this vascular segment.

Age dependent aneuploidy and telomere length of the human vascular endothelium.

RATIONALE: Aneuploidy and telomere length are two major parameters that have been associated with cellular senescence in vitro. In order to explore the role of aneuploidy and telomere length in aging of the human vasculature, we studied these two parameters in direct preparations of endothelial cells of the human abdominal aorta. METHODS: Using fluorescent in situ hybridization on 'touch prep' slides, we evaluated aneuploidy of two autosomes (chromosomes 6 and 16) and sex chromosomes in non cultured endothelial cells of the abdominal aorta as a function of the donor's age. RESULTS: We found that the frequency of aneuploidy of vascular endothelial cells significantly increased with age. This was expressed by age-dependent tetrasomy (r(s)=0.56, P=0.006 for chromosome 6; and r(s)=0.54, P=0.008 for chromosome 16), and age dependent loss of the Y chromosome (r(s)=0.85, P=0.0003). In addition, we found that telomere length was inversely correlated with age (r=-0.38, P=0.008). DATA INTERPRETATION: These findings suggest that indicators of cellular senescence, earlier observed in vitro, are also expressed in the human vascular endothelium in vivo. Aneuploidy and telomere attrition might thus play a role in the aging of the human vasculature.

HLA antigens associated with susceptibility/resistance to HIV-1 infection.

We studied the distribution of HLA-A, B, C, DR and DQ antigens in a cohort of HIV-1+ individuals and their heterosexual HIV seropositive (concordant) or seronegative (discordant) partners of Black non-Hispanic, Hispanic or Caucasian non-Hispanic ethnicity. The prevalence of DQ7 and Cw7 was significantly higher in the HIV-1+ compared to seronegative Black and Hispanic individuals, respectively. The frequency of DQ4 was significantly elevated in the Black seronegatives, whereas B53 was increased in the Hispanic seronegatives in comparison to the seropositives. No significant differences were observed between the Caucasian HIV infected and non-infected individuals. Analysis of the primary concordant HIV+ and discordant HIV+ individuals showed a marked increase in the prevalence of B44 in the Hispanic discordant seropositives, whereas the Caucasian primary concordants had a marked increase in the prevalence of A26. The prevalence of DQ7 and Cw7 was significantly increased in the Black and Hispanic secondary concordant seropositives, respectively in comparison to the seronegatives. The proportion of couples with matching HLA antigens was similar among the HIV-1+ concordant and discordant groups. These results provide additional evidence that HLA polymorphism may confer a genetic risk or protection for HIV-1 infection in individuals of various ethnic backgrounds.

Respiratory function in multiple sclerosis. Utility of clinical assessment of respiratory muscle function.

PURPOSE: The aim of this study was to assess the utility of clinical assessment of respiratory muscle weakness in MS. PATIENTS AND METHODS: We studied 40 MS patients who performed pulmonary function tests using standard procedures and measures of respiratory muscle strength. Descriptive clinical indices included a history of detailed neurologic findings, including upper and lower extremity weakness, cerebellar signs, and evidence of cerebral lesions and other clinical signs including dependence in activities of daily living, shortness of breath, weak voice, dysarthria and dysphagia. We devised an index comprised of four clinical signs: the patient's report of difficulty in clearing pulmonary secretions and his report of a weakened cough, the examiner's observation of the patient's cough, and ability to count on a single exhalation. RESULTS: Mean values of TLC (95 percent +/- 14) VC (91 percent +/- 19), and RV (106 percent +/- 34) were normal. By contrast, MVV (68 percent +/- 20), PImax (74 percent +/- 27) and PEmax (51 percent +/- 22) were decreased. Stepwise multiple regression indicated that the best single predictor of expiratory muscle weakness was the index score; the combination of index score, upper extremity weakness, and maximal voluntary ventilation accounted for 60 percent of the variance in PEmax. CONCLUSION: We conclude that clinical assessment is a better predictor of respiratory muscle weakness than spirometry and that a systematic clinical assessment supplemented by respiratory muscle assessment and MVV can uncover subtle respiratory muscle weakness in patients with MS.

Clinical chorioamnionitis is not predicted by umbilical artery Doppler velocimetry in patients with premature rupture of membranes.

Chorioamnionitis substantially increases fetal and neonatal morbidity. Infants born to women with chorioamnionitis have a fourfold increase in neonatal morbidity. If this condition could be predicted before the clinical manifestation and thereby treated earlier, an improved perinatal outcome might reasonably be expected. Based on the in vitro model of bacteria-induced vasoconstriction and pulmonary hypertension noted in sheep and lambs after exposure to the spent medium of a bacterial culture, we theorized that infected amniotic fluid may produce vasospasm of umbilical and placental vessels, reduce fetal perfusion, and increase perinatal asphyxia, morbidity, and mortality. Umbilical vessel vasospasm may be detected by measuring the systolic-diastolic ratio (S/D) of the umbilical artery. Continuous Doppler flow studies of the umbilical artery S/D were performed prospectively on 51 patients with premature rupture of membranes who were not in labor. The most recent test, done within 1 day of delivery, was compared with pregnancy outcome. Ten subjects developed clinical chorioamnionitis, of whom none had an abnormal S/D. Six of 41 women without clinical chorioamnionitis had abnormal S/Ds. These data do not support the use of Doppler measurement of the S/D as a predictor of clinical chorioamnionitis.