Adults only: the prevalence of tobacco promotions in bars and clubs in the Boston area.

OBJECTIVE: To document the nature and prevalence of tobacco promotions in bars and clubs in a major US city. DESIGN: We conducted systematic observations in a representative sample of 38 establishments in the Boston area, half of which had been advertised in a tobacco company ad. We also observed seven events in six additional clubs hosting Camel Casbah promotions. Telephone interviews were later completed with club managers. MAIN OUTCOME MEASURE: Use of branded give-away items, distribution of free cigarette samples, managers' reports of costs and benefits of hosting promotions. RESULTS: The majority of the 38 clubs were observed to use bar paraphernalia including matchbooks with tobacco brand logos, regardless of their history of appearing in tobacco sponsored ads. Free cigarette samples were not observed at any of the sampled clubs, but were a feature of every Casbah event. Managers of clubs in the advertised group were somewhat more likely to report having hosted promotions, but 44% of managers of non-advertised clubs indicated that tobacco promotions had occurred in their establishments in the past. Approximately one third of club managers viewed public links with a tobacco company as a negative feature of hosting promotions. CONCLUSIONS: Based on managers' reports, tobacco promotions occurred in more than 50% of the Boston area entertainment venues frequented by young adults. Cigarette companies should be required to inform the attorney general of plans to conduct promotions in adult-only venues to facilitate monitoring of compliance with the Master Settlement Agreement. The negative health and business consequences of hosting promotions should be communicated to bar owners.

Selective effect of tempol on renal medullary hemodynamics in spontaneously hypertensive rats.

The present study assessed the short- and long-term effect of tempol, a membrane-permeable mimetic of superoxide dismutase, on renal medullary hemodynamics in spontaneously hypertensive rats (SHR). Tempol was given in the drinking water (1 mM) for 4 days or 7 wk (4-11 wk of age), and medullary blood flow (MBF) was measured over a wide range of renal arterial pressure by means of laser-Doppler flowmetry in anesthetized rats. In addition, the response of the medullary circulation to angiotensin II (5-50 ng x kg(-1) x min(-1) iv) was determined in SHR treated for 4 days with tempol. Compared with control SHR, short- and long-term treatment with tempol decreased arterial pressure by approximately 20 mmHg and increased MBF by 35-50% without altering total renal blood flow (RBF) or autoregulation of RBF. Angiotensin II decreased RBF and MBF dose dependently (approximately 30% at the highest dose) in control SHR. In SHR treated with tempol, angiotensin II decreased RBF (approximately 30% at the highest dose) but did not alter MBF significantly. These data indicate that the antihypertensive effect of short- and long-term administration of tempol in SHR is associated with a selective increase in MBF. Tempol also reduced the sensitivity of MBF to angiotensin II. Taken together, these data support the idea that tempol enhances vasodilator mechanisms of the medullary circulation, possibly by interacting with the nitric oxide system. Increased MBF and reduced sensitivity of MBF to angiotensin II may contribute to the antihypertensive action of tempol in SHR.

Abnormal renal medullary response to angiotensin II in SHR is corrected by long-term enalapril treatment.

This study tested the hypotheses that renal medullary blood flow (MBF) in spontaneously hypertensive rats (SHR) has enhanced responsiveness to angiotensin (ANG) II and that long-term treatment with enalapril can correct this. MBF, measured by laser Doppler flowmetry in anesthetized rats, was not altered significantly by ANG II in Wistar-Kyoto (WKY) rats, but was reduced dose dependently (25% at 50 ng. kg(-1). min(-1)) in SHR. Infusion of N(G)-nitro-L-arginine methyl ester (L-NAME) into the renal medulla unmasked ANG II sensitivity in WKY rats while L-arginine given into the renal medulla abolished the responses to ANG II in SHR. In 18- to 19-wk-old SHR treated with enalapril (25 mg. kg(-1). day(-1) when 4 to 14 wk old), ANG II did not alter MBF significantly, but sensitivity to ANG II was unmasked after L-NAME was infused into the renal medulla. Endothelium-dependent vasodilation (assessed with aortic rings) was significantly greater in treated SHR when compared with that in control SHR. These results indicate that MBF in SHR is sensitive to low-dose ANG II and suggest that this effect may be due to an impaired counterregulatory effect of nitric oxide. Long-term treatment with enalapril improves endothelium-dependent vascular relaxation and decreases the sensitivity of MBF to ANG II. These effects may be causally related to the persistent antihypertensive action of enalapril in SHR.

Renal response to volume expansion: learning the experimental approach in the context of integrative physiology.

We describe a laboratory experience for upper-level science students that provides a hands-on approach to understanding the basics of experimental physiology. A pre-lab, interactive tutorial develops the rationale for this experiment by reviewing the renal and cardiovascular mechanisms involved in the response to extracellular fluid volume expansion. After a hypothesis is stated, an experiment is designed to determine the relative importance of dilution of plasma proteins to the overall renal excretory response following volume expansion with intravenous saline. In the lab, students collect data from two groups of anesthetized rats. The protocol involves continuous monitoring of arterial pressure and periodic collection of urine and blood samples after volume expansion with either isotonic NaCl or isotonic NaCl plus 5% albumin. A post-lab tutorial is used to analyze, interpret, and discuss the data. Students next prepare an oral presentation, practice it, and finally present their results and answer questions before peers and instructors. This overall experience involves all of the components of doing a "real" experiment, starting with a question that is not answered in general textbooks of physiology and finishing with an oral presentation of the results. Along the way, students gain a better understanding of a complex homeostatic response and learn the care and value of using animals in research and teaching.

Smoke knows no boundaries: legal strategies for environmental tobacco smoke incursions into the home within multi-unit residential dwellings.

OBJECTIVE: To describe legal theories that non-smoking residents of multiple occupancy buildings may employ when affected by environmental tobacco smoke (ETS) from neighbouring units. DESIGN: Legal research was conducted in several US states. Research was performed among statutes and regulations. State health regulations were examined as well as common law claims of nuisance, warranties of habitability, and the right of quiet enjoyment. RESULTS: Through the use of state regulations, such as a sanitary code, several states provide general language for protecting the health of residents in multi-unit buildings. State law also supports more traditional claims of nuisance, warranties of habitability, and the right of quiet enjoyment. CONCLUSIONS: The use of state regulations has the potential to provide an effective, existing vehicle for resolution of ETS incursion problems. The general health protection language of the regulations, in conjunction with the latest evidence of the harmful effects of ETS, gives state agencies authority to regulate environmental tobacco smoke incursions among apartments in multi-unit dwellings. Where state regulations are not available, other common law legal remedies may be available.

Differing effects of enalapril and losartan on renal medullary blood flow and renal interstitial hydrostatic pressure in spontaneously hypertensive rats.

OBJECTIVE: To determine the effect of short-term angiotensin converting enzyme inhibition (enalapril) or angiotensin II AT1 receptor blockade (losartan) on medullary hemodynamics in the spontaneously hypertensive rat (SHR). DESIGN: Laser-Doppler flowmetry allowed for the characterization of medullary blood flow (MBF) over a wide range of renal arterial pressure (RAP), and was used for comparison among treatment groups. Renal interstitial hydrostatic pressure (RIHP) was also determined over a wide range of RAP. METHOD: Enalapril or losartan was given to male 12-13-week-old SHR for 3 days (25 mg/kg per day in drinking water). Rats were anesthetized with Inactin, renal function was measured at resting levels of RAP and then RAP was varied over a range of 50-150 mmHg in 25 mmHg steps. MBF and RIHP were determined at each pressure. RESULTS: Resting mean arterial pressure (MAP) (mmHg +/- SE) for enalapril- and for losartan-treated SHR [114 +/- 3 (n = 18) and 124 +/- 3 (n = 20), respectively] were both significantly lower than for untreated SHR [159 +/- 5 (n = 20)]. Renal function at resting levels of MAP was not significantly different among groups. Enalapril and losartan both increased MBF by 30% at levels of RAP of 125 mmHg and over. Enalapril did not alter the relation between RAP and RIHP, but losartan shifted the RAP versus RIHP curve by approximately 40 mmHg to lower levels of RAP. Acute administration of the B2 kinin receptor antagonist HOE 140 [20 microg/kg intravenous (i.v.) bolus, then 10 microg/kg per h i.v.] did not significantly alter MAP in any group. HOE 140 did not significantly alter MBF or RIHP in the untreated or losartan-treated SHR. MBF in enalapril-treated rats receiving HOE 140 was not significantly different from that of the enalapril-only group; however, the relation between RAP and RIHP was shifted to lower levels of RAP by approximately 45 mmHg. CONCLUSIONS: Both enalapril and losartan increase MBF in SHR, suggesting that the medullary circulation of SHR is influenced by endogenous levels of angiotensin II. The failure of enalapril to increase RIHP in parallel with MBF appears to be due to an enhanced effect of kinins.

Short- and long-term enalapril affect renal medullary hemodynamics in the spontaneously hypertensive rat.

Long-term angiotensin-converting enzyme (ACE) inhibition in the spontaneously hypertensive rat (SHR) resets pressure natriuresis and shifts the relationship between renal arterial pressure (RAP) and renal interstitial hydrostatic pressure (RIHP) to lower levels of arterial pressure. These effects persist after withdrawal of treatment. The purpose of this study was to determine the effect of short- and long-term ACE inhibition on medullary blood flow (MBF). Enalapril (25 mg. kg-1. day-1 in drinking water) was given to male SHR from 4 to 14 wk of age. Four weeks after stopping treatment, we measured MBF over a wide range of RAP using laser-Doppler flowmetry in anesthetized rats. Additional rats, either untreated or previously treated for 10 wk, received 3-day enalapril treatment just before the experiment. MAP (mmHg +/- SE) was 178 +/- 6 (n = 8), 134 +/- 6 (n = 8), 138 +/- 5 (n = 9), and 111 +/- 6 mmHg (n = 9) for the untreated, 3 day, 10 wk, and 10 wk + 3 day groups, respectively. Total renal blood flow for the groups receiving 3-day treatment was significantly higher when compared with that in rats with an intact renin-angiotensin system. Three-day treatment had no effect on the relationship between RAP and RIHP, whereas that in rats receiving 10-wk treatment was shifted to lower levels of RAP by approximately 30 mmHg. Both 10-wk and 3-day treatment independently increased the slope of the RAP versus MBF relationship at values of RAP > 100 mmHg. The slopes in perfusion units/mmHg were 0.12 +/- 0.01 (n = 8), 0.26 +/- 0.01 (n = 8), 0.27 +/- 0.01 (n = 9), and 0.30 +/- 0.02 (n = 9) for the untreated, 3 day, 10 wk, and 10 wk + 3 day groups, respectively. These results indicate that the effect of short-term and the persistent effect of long-term enalapril alter renal medullary hemodynamics in a way that may contribute to the resetting of the pressure-natriuresis relationship in treated rats.

Complementary antihypertensive action of rilmenidine on the pressure-natriuresis relationship and sodium preference in spontaneously hypertensive rats.

Previously, changes in position and slope of the pressure-natriuresis relationship have been used to characterize antihypertensive drugs in basic research. Rilmenidine may chronically reduce arterial pressure via central nervous system and renal imidazoline receptors. The present experiments were used to examine the shift in the pressure-natriuresis relationship during rilmenidine administration. We examined the effects of twice daily doses (1 and 3 mg/kg) for 6 days on the pressure-natriuresis relationship determined for control and treated spontaneously hypertensive rats (SHR) drinking tap water or 1% NaCl. The pressure-natriuresis relationship was shifted to the left for the 3 mg/kg dose and the slope was no different from the control. These experiments also indicated that rilmenidine might have an effect on sodium preference which was confirmed in a third series of experiments by permitting control and treated (3 mg/kg) SHR access to both tap water and 1% NaCl. This lack of change in slope indicates that, during rilmenidine treatment, the arterial pressure is relatively insensitive to sodium intake. The shift to the left indicates a restoration of the pressure-natriuresis relationship after chronic treatment with rilmenidine and a resetting of the long-term blood pressure control. Rilmenidine also reduces salt appetite in the SHR.

Elevation of an endogenous inhibitor of nitric oxide synthesis in experimental congestive heart failure.

OBJECTIVE: NG,NG-dimethylarginine (asymmetric dimethylarginine, ADMA) is an important endogenous substance with potent inhibitory actions on nitric oxide (NO) synthesis. The present study was designed to determine circulating ADMA levels and endothelium-dependent, NO mediated vasodilation in a rat model of congestive heart failure (CHF). METHODS: CHF was induced in rats by coronary artery ligation. Sham-operated rats served as normal controls. Plasma ADMA was determined by high performance liquid chromatography with fluorescence detection. Glomerular filtration rate (GFR) and renal blood flow (RBF) were measured by the clearance of inulin and p-aminohippuric acid, respectively. Endothelial function of the aorta was assessed in an organ bath. RESULTS: Plasma levels of ADMA in rats with CHF (0.94 +/- 0.05 mumol/l) were significantly increased compared with sham-operated controls (0.75 +/- 0.06 mumol/l, p < 0.05). Plasma levels of ADMA was negatively correlated with GFR (r = -0.65, p < 0.05). Decreased endothelium-dependent relaxation to acetylcholine in the aorta of CHF was completely restored by L-arginine (300 microM) (p < 0.01) while endothelium-independent relaxation to nitroprusside was not altered. ADMA potently inhibited endothelium-dependent relaxation in thoracic aorta of normal and CHF rats. The effect of ADMA was completely antagonized by L-arginine in both groups (p < 0.01). Moreover, L-arginine improved endothelium-dependent relaxation in CHF rats in the presence of ADMA. CONCLUSIONS: An endogenous NO synthesis inhibitor ADMA is increased in the circulation of rats with CHF. The increased plasma levels of ADMA may contribute to the decreased endothelium-dependent relaxation in CHF, which is restored by L-arginine, possibly by competitive antagonism of ADMA.

The persistent effect of long-term enalapril on pressure natriuresis in spontaneously hypertensive rats.

Long-term angiotensin-converting enzyme inhibitor treatment has been shown to have a persistent antihypertensive effect in spontaneously hypertensive rats (SHR) long after discontinuation of treatment. To test the hypothesis that this persistent effect involves a shift in the pressure-natriuresis relation, we performed experiments in male, anesthetized SHR at 18 wk of age with fixed neural and hormonal influences on the kidney. Renal function was assessed at various levels of arterial pressure using standard clearance techniques. Enalapril (25 mg.kg-1.day-1 in drinking water) was administered from 4 to 14 wk of age and again 3 days before renal function studies. The following four groups of SHR were studied: 1) 10-wk treatment, 2) 10-wk + 3-day treatment, 3) 3-day treatment, and 4) untreated. Groups 1 and 4 had an intact renin-angiotensin system; groups 2 and 3 had the renin-angiotensin system blocked. Mean arterial pressure (MAP, mmHg; means +/- SE) under Inactin anesthesia was 139 +/- 4 (n = 9), 109 +/- 3 (n = 8), 149 +/- 1 (n = 9), and 181 +/- 7 mmHg (n = 9) for each of the four groups, respectively. Glomerular filtration rate was similar in all groups at resting levels of MAP, whereas renal blood flow was elevated in all treatment groups when compared with that in untreated SHR. Pressure-natriuresis, pressure-diuresis, and pressure-fractional sodium excretion curves for the 10-wk treatment group and 3-day only treatment group were shifted leftward to significantly lower pressures by approximately 25 mmHg, compared with the untreated group. The curves for the treated +3-day group were shifted an additional 30 mmHg to the left. The relationship between renal artery pressure (RAP) and renal interstitial hydrostatic pressure was also shifted 25-30 mmHg but only in rats that received the long-term treatment with enalapril. Three-day enalapril had no significant effect on this relationship. These data indicate that the persistent effect of long-term enalapril treatment on arterial pressure in SHR is the result of a shift in the pressure-natriuresis relationship. The mechanism for this effect involves hemodynamic changes that act to improve transmission of RAP to the interstitium, resulting in enhanced sodium excretion for a given level of RAP.

Effect of rilmenidine on arterial pressure and urinary output in the spontaneously hypertensive rat.

Rilmenidine is an antihypertensive agent acting at the imidazoline receptor that may have both central effects in the ventral lateral medulla and direct effects on the kidney to alter Na+ excretion. The present experiments examined whether rilmenidine induces a leftward shift or change in the slope of the pressure-natriuresis curve in the spontaneously hypertensive rat (SHR). A single oral gavage dose indicated that 3 and 10 mg/kg rilmenidine significantly lowers arterial pressure at 4-12 h after administration by oral gavage. The effect of rilmenidine on pressure-natriuresis was studied using twice daily doses of 1 and 3 mg/kg for control and treated SHR drinking tap water or 1% NaCl for 3 days. Na+ excretion was measured over 24 h, and mean arterial pressure was measured 6-8 h after the morning dose of rilmenidine. The results indicate that 1 mg/kg had no effect, while the pressure-natriuresis relationship for the rats receiving the 3 mg/kg dose was shifted to the left and was not significantly different from the vertical slope of the untreated SHR. This experiment also suggested that rilmenidine may attenuate the salt preference of the rats. This was confirmed in an additional series of experiments in which the rats had access to both tap water and 1% NaCl. Thus, rilmenidine shifts the pressure-natriuresis relationship to the left and reduces salt preference in SHR.

Long-term inhibition of the renin-angiotensin system in genetic hypertension: analysis of the impact on blood pressure and cardiovascular structural changes.

OBJECTIVE: To compare, using data from published studies, the efficacy of chronic inhibition of the renin-angiotensin system in inducing persistent downregulation of hemodynamic and cardiovascular structural changes in an adult rat with established genetic hypertension with the widely accepted known downregulation in young genetically hypertensive rats. STUDY SELECTION: We report on 36 studies that satisfied our inclusion criteria (angiotensin converting enzyme inhibitor or angiotensin II receptor antagonist treatment that lowered arterial pressure levels for at least 3 weeks). Of the 24 studies concerning developing hypertensive rats, a significant number (n = 17) also examined the persistence of any hemodynamic or cardiovascular effects after withdrawal of treatment. Conversely, of 15 studies using adult rats only seven and three reported on post-treatment hemodynamic and cardiovascular structural indices respectively. RESULTS: During treatment the hemodynamic and cardiovascular structural changes produced were qualitatively and quantitatively similar in the young and adult treated rats. Critical assessment of the persistence of these effects after withdrawal of treatment again found qualitatively similar responses. However, the strength of this finding is limited by the paucity of studies concerning adult rats in which equivalent treatment durations and equipressor doses of treatments were compared between these two age groups. CONCLUSIONS: Blockade of the renin-angiotensin system appears to have an efficacy in reversing established hypertension and hypertrophy similar to that with which it prevents the development of hypertension and hypertrophy. This partial 'cure' of hypertension after withdrawal of treatment is clearly evident when treatment is initiated during the development of hypertension and appears to be similar even when treatment is initiated in established hypertension.

Human stanniocalcin inhibits renal phosphate excretion in the rat.

Stanniocalcin (STC) is a glycoprotein hormone first identified in bony fishes where it counteracts hypercalcemia by inhibiting gill calcium uptake and stimulating renal inorganic phosphate (Pi) reabsorption. Human STC (hSTC) has recently been cloned and sequenced and is highly homologous to the fish hormone at the amino acid level. The objective of this study was to examine the possible effects of hSTC on electrolyte homeostasis and renal function in the rat. Recombinant hSTC was expressed in bacteria and purified by metal-ion affinity chromatography and reverse-phase high performance liquid chromatography. Anesthetized animals were given bolus infusions of 1, 5, or 10 nmol hSTC per kilogram of body weight. Control animals received solvent alone. The most effective dosage was 5 nmol/kg, which caused significant reductions in both absolute and fractional phosphate excretion in comparison with control rats. The hSTC had no effect on the renal excretion of other ions, the glomerular filtration rate, renal blood flow, blood pressure, or plasma electrolytes (Na+, K+, Ca2+, Pi, Mg/+). The maximum effect of hSTC on phosphate excretion was observed 60-80 minutes postinjection. Lesser effects were obtained with higher and lower dosages of hormone. When renal cortical brush-border membrane vesicles were isolated from control and hormone-treated animals 80 minutes postinjection, the rate of Na+/Pi cotransport was found to be 40% higher in vesicles from hormone-treated animals (p < 0.01; 5 nmol hSTC/kg). Together, the renal clearance and membrane vesicle data indicate that hSTC participates in the renal regulation of Pi homeostasis in mammals.

Effect of endogenous L-arginine on the measurement of nitric oxide synthase activity in the rat kidney.

The endogenous level of L-arginine in renal cortex, outer medulla, and inner medulla and its effect on the measurement of nitric oxide synthase (NOS) activity in these regions was determined. L-Arginine was measured with an amino acid analyzer and total NOS activity was measured as the rate of formation of radiolabeled L-citrulline from L-[14C]arginine. Total NOS activity was that activity inhibited by NG-nitromonomethyl-L-arginine (300 microM). The endogenous L-arginine concentration was 452 +/- 45 (mean +/- SEM), 313 +/- 25, and 95 +/- 8 pmol/mg wet weight in the cortex, outer medulla, and inner medulla, respectively (n = 12). Total NOS activity was 61 +/- 19, 709 +/- 94, and 1347 +/- 76 pmol.h-1.mg protein-1 in the cortex, outer medulla, and inner medulla, respectively, when endogenous L-arginine was not considered in the calculation. Correcting for endogenous L-arginine gave values of 185 +/- 61, 1714 +/- 239, and 1707 +/- 104 pmol.h-1.mg protein-1, respectively. Dowex extraction to remove endogenous L-arginine from samples also increased NOS activity in cortex and medulla. The data indicate that there is a differential distribution of endogenous L-arginine in the kidney and that these levels must be taken into account when measuring NOS activity. NOS activity is also distributed differentially, with activity in the medulla being nearly 10-fold higher than in the cortex.

Evaluation of Chiron HIV-1/HIV-2 recombinant immunoblot assay.

In a study to determine the reliability, sensitivity, and specificity of the Chiron RIBA HIV-1/HIV-2 Strip Immunoblot Assay (RIBA HIV-1/2 SIA) for confirmation of human immunodeficiency virus type 1 (HIV-1) and HIV-2 antibodies, 1,263 serum samples from various populations in the United States, Caribbean, Africa, India, and Thailand were evaluated by RIBA HIV-1/2 SIA, and the results were compared with those obtained by an HIV-1 Western blot (immunoblot) assay. All sera were tested by HIV enzyme immunoassay, RIBA HIV-1/2 SIA, and Western blotting. Samples with discrepant results were further tested by an HIV-1 and/or HIV-2 immunofluorescent-antibody assay and HIV-1 p24 antigen assay. The RIBA HIV-1/2 SIA detected all 17 HIV-1 and HIV-2 dually reactive serum samples, all 215 HIV-2-positive serum samples, and 480 of 481 HIV-1-positive serum samples for a sensitivity of 99.8%. Of 548 negative samples, 523 were RIBA HIV-1/2 SIA negative, for a specificity of 95.4%, with 22 (4%) samples interpreted as indeterminate and 3 (0.6%) interpreted as falsely positive. Western blotting detected 391 of 548 negative samples (specificity, 71.4%), with 152 (27.7%) samples interpreted as indeterminate and 5 (0.9%) interpreted as falsely positive. In conclusion, the RIBA HIV-1/2 SIA had a sensitivity comparable to that of Western blotting and could discriminate HIV-1 from HIV-2 in one blot, providing a cost advantage. Because of its high degree of specificity, the RIBA HIV-1/2 SIA further reduced the number of indeterminate results found by Western blotting, providing a more accurate means of assessing seronegative individuals.

Pressure natriuresis following acute and chronic inhibition of nitric oxide synthase in rats.

Nitric oxide has been suggested to be an essential mediator of pressure natriuresis. To investigate this hypothesis, the effect of acute or chronic inhibition of nitric oxide synthase on pressure natriuresis and renal interstitial hydrostatic pressure was studied in anesthetized Sprague-Dawley rats with fixed neural and hormonal influences on the kidney. Both acute infusion (10 micrograms.kg-1.min-1 iv) and chronic administration (50 mg.kg-1.day-1 for 7 days in drinking water) of NG-nitro-L-arginine methyl ester (L-NAME) resulted in significantly increased mean arterial pressure, a 30% decrease in renal blood flow, and no change in glomerular filtration rate when compared with values in control rats. Pressure-diuresis, pressure-natriuresis, and pressure-fractional sodium excretion curves in L-NAME-treated rats were shifted to a higher pressure (by approximately 25 mmHg) when compared with those in control rats. The relationship between renal artery pressure and renal interstitial hydrostatic pressure was shifted similarly in L-NAME-treated rats. Acute administration of L-arginine completely reversed the renal effects of chronic L-NAME. These data indicate that, at the doses used in this study, both acute and chronic inhibition of nitric oxide synthase decreased the ability of the kidney to excrete sodium at least in part by a hemodynamic mechanism leading to an increased filtration fraction and a decreased renal interstitial pressure. The parallel shift of the pressure-natriuresis curve to a higher pressure suggests that nitric oxide is an important modulator but not an essential mediator of the pressure natriuresis.

Human immunodeficiency virus-specific IgA in infants born to human immunodeficiency virus-seropositive women.

OBJECTIVE: To determine the sensitivity and specificity of human immunodeficiency virus (HIV)-specific IgA for vertically transmitted HIV infection, particularly during the first month of life. DESIGN/SETTING/PATIENTS: Prospective cohort study of 140 infants born to HIV-seropositive women in a large urban teaching hospital and of 248 older infants and children referred for diagnosis and treatment of HIV infection. MAIN OUTCOME MEASURES: The HIV-specific IgA immunoblot results were compared with the infection status of patients as determined by Centers for Disease Control and Prevention (Atlanta, Ga) criteria or by sequential early diagnostic assays for HIV. Sensitivity, specificity, and predictive values were calculated for each age range. RESULTS: Among infants studied from birth, the rate of vertical transmission of HIV was 21.6% (25/116). The sensitivity of HIV-specific IgA for the first month of life was 8.0% (2/25), and the specificity was 90.1% (82/91). Sensitivity increased progressively during the first year of life, and the negative predictive value was 94.6% by 6 to 8 months of age. The positive predictive value of this assay was 18.2% for neonates but was 96% to 100% after the first month of life. CONCLUSIONS: False-positive test results for HIV-specific IgA occurred with diminishing frequency during the first 4 weeks of life, and the frequency of detectable HIV-specific IgA was similar among the HIV-infected and uninfected groups at this age. Beyond 1 month of age, detection of HIV-specific IgA is highly specific and is a useful serum-based assay for early diagnosis of HIV infection. These results suggest that maternal-fetal transfusion is common and support the hypothesis that the majority of maternal-fetal transmission of HIV occurs around the time of parturition.