Topical anaesthesia does not affect cutaneous vasomotor or sudomotor responses in human skin.

(1) The effects of local sensory blockade (topical anaesthesia) on eccrine sweat glands and cutaneous circulation are not well understood. This study aimed to determine whether topical lidocaine/prilocaine alters eccrine sweat gland and cutaneous blood vessel responses. (2) Sweating (capacitance hygrometry) was induced via forearm intradermal microdialysis of five acetylcholine (ACh) doses (1 × 10(-4) to 1 × 10(0) m, 10-fold increments) in control and treated forearm sites in six healthy subjects. Nitric oxide-mediated vasodilatory (sodium nitroprusside) and adrenergic vasoconstrictor (noradrenaline) agonists were iontophoresed in lidocaine/prilocaine-treated and control forearm skin in nine healthy subjects during blood flow assessment (laser Doppler flowmetry, expressed as% from baseline cutaneous vascular conductance; CVC; flux/mean arterial pressure). (3) Non-linear regression curve fitting identified no change in the ED50 of ACh-induced sweating after sensory blockade (-1.42 ± 0.23 logM) compared to control (-1.27 ± 0.23 logM; P > .05) or in Emax (0.43 ± 0.08 with, 0.53 ± 0.16 mg cm(-2) min(-1) without lidocaine/prilocaine; P > .05). Sensory blockade did not alter the vasodilator response to sodium nitroprusside (1280 ± 548% change from baseline CVC with, 1204 ± 247% without lidocaine/prilocaine) or vasoconstrictor response to noradrenaline (-14 ± 4% change from baseline CVC with, -22 ± 14% without lidocaine/prilocaine; P > 0.05). (4) Cutaneous sensory blockade does not appear to alter nitric oxide-mediated vasodilation, adrenergic vasoconstriction, or cholinergic eccrine sweating dose-response sensitivity or responsiveness to maximal dose. Thus, lidocaine/prilocaine treatment should not affect sweat gland function or have blood flow implications for subsequent research protocols or clinical procedures.

Age- and limb-related differences in the vasoconstrictor response to limb dependency are not mediated by a sympathetic mechanism in humans.

AIMS: We tested the hypotheses that vasoconstrictor responses to limb dependency are: (i) greater in the leg than the arm, (ii) impaired with age and (iii) not sympathetically mediated. METHODS: Vascular responses to limb dependency (i.e. lowering the limb from heart level to 30 cm below heart level) were determined in 17 young and 17 older adults. Indices of blood flow were obtained in the brachial and popliteal arteries (Doppler ultrasound) as well as in the cutaneous circulation (forearm and calf using laser-Doppler flowmetry). Vasoconstriction was quantified by calculating the indices of vascular resistance as height corrected mean arterial pressure/limb blood velocity or skin flux. A second group of subjects repeated the limb dependency trials after acute systemic sympathetic blockade. RESULTS: Limb dependency increased vascular resistance index in the brachial artery (∆59 ± 8%; P<0.05) and popliteal artery (∆99 ± 10%; P<0.05 for change in heart level and brachial vs. popliteal) of young and older adults (∆60 + 9% brachial and ∆61 ± 7% popliteal arteries; P<0.05 for change in heart level and response in popliteal young vs. older adults). In contrast, cutaneous vasoconstrictor responses to limb dependency were similar in the forearm (∆218 ± 29% and ∆200 ± 29% for young and older adults, respectively) and calf (∆257 ± 32% and ∆236 ± 29%; all P<0.05 from heart level) of young and older adults. Vasoconstrictor responses to limb dependency were not affected by sympathetic blockade in young or older adults. CONCLUSION: These findings indicate that age-, limb-, and tissue-related differences may exist in the vasoconstrictor response to limb dependency in healthy humans, which are not sympathetically mediated.

Colloid volume loading does not mitigate decreases in central blood volume during simulated haemorrhage while heat stressed.

Heat stress results in profound reductions in the capacity to withstand a simulated haemorrhagic challenge; however, this capacity is normalized if the individual is volume loaded prior to the challenge. The present study tested the hypothesis that volume loading during passive heat stress attenuates the reduction in regional blood volumes during a simulated haemorrhagic challenge imposed via lower-body negative pressure (LBNP). Seven subjects underwent 30 mmHg LBNP while normothermic, during passive heat stress (increased internal temperature ∼1◦C), and while continuing to be heated after intravenous colloid volume loading (11 ml kg⁻¹). Relative changes in torso and regional blood volumes were determined by gamma camera imaging with technetium-99m labelled erythrocytes. Heat stress reduced blood volume in all regions (ranging from 7 to 16%), while subsequent volume loading returned those values to normothermic levels. While normothermic,LBNP reduced blood volume in all regions (torso: 22 ± 8%; heart: 18 ± 6%; spleen: 15 ± 8%). During LBNP while heat stressed, the reductions in blood volume in each region were markedly greater when compared to LBNP while normothermic (torso: 73 ± 2%; heart: 72 ± 3%; spleen: 72 ± 5%, all P<0.001 relative to normothermia). Volume loading during heat stress did not alter the extent of the reduction in these blood volumes to LBNP relative to heat stress alone (torso: 73 ± 1%; heart: 72 ± 2%; spleen: 74 ± 3%, all P>0.05 relative to heat stress alone). These data suggest that blood volume loading during passive heat stress (via 11 ml kg⁻¹ of a colloid solution) normalizes regional blood volumes in the torso, but does not mitigate the reduction in central blood volume during a simulated haemorrhagic challenge combined with heat stress.

Insufficient cutaneous vasoconstriction leading up to and during syncopal symptoms in the heat stressed human.

As much as 50% of cardiac output can be distributed to the skin in the hyperthermic human, and therefore the control of cutaneous vascular conductance (CVC) becomes critical for the maintenance of blood pressure. Little is known regarding the magnitude of cutaneous vasoconstriction in profoundly hypotensive individuals while heat stressed. This project investigated the hypothesis that leading up to and during syncopal symptoms associated with combined heat and orthostatic stress, reductions in CVC are inadequate to prevent syncope. Using a retrospective study design, we evaluated data from subjects who experienced syncopal symptoms during lower body negative pressure (N = 41) and head-up tilt (N = 5). Subjects were instrumented for measures of internal temperature, forearm skin blood flow, arterial pressure, and heart rate. CVC was calculated as skin blood flow/mean arterial pressure × 100. Data were obtained while subjects were normothermic, immediately before an orthostatic challenge while heat stressed, and at 5-s averages for the 2 min preceding the cessation of the orthostatic challenge due to syncopal symptoms. Whole body heat stress increased internal temperature (1.25 ± 0.3°C; P < 0.001) and CVC (29 ± 20 to 160 ± 58 CVC units; P < 0.001) without altering mean arterial pressure (83 ± 7 to 82 ± 6 mmHg). Mean arterial pressure was reduced to 57 ± 9 mmHg (P < 0.001) immediately before the termination of the orthostatic challenge. At test termination, CVC decreased to 138 ± 61 CVC units (P < 0.001) relative to before the orthostatic challenge but remained approximately fourfold greater than when subjects were normothermic. This negligible reduction in CVC during pronounced hypotension likely contributes to reduced orthostatic tolerance in heat-stressed humans. Given that lower body negative pressure and head-up tilt are models of acute hemorrhage, these findings have important implications with respect to mechanisms of compromised blood pressure control in the hemorrhagic individual who is also hyperthermic (e.g., military personnel, firefighters, etc.).

Effect of volume loading on the Frank-Starling relation during reductions in central blood volume in heat-stressed humans.

During reductions in central blood volume while heat stressed, a greater decrease in stroke volume (SV) for a similar decrease in ventricular filling pressure, compared to normothermia, suggests that the heart is operating on a steeper portion of a Frank-Starling curve. If so, volume loading of heat-stressed individuals would shift the operating point to a flatter portion of the heat stress Frank-Starling curve thereby attenuating the reduction in SV during subsequent decreases in central blood volume. To investigate this hypothesis, right heart catheterization was performed in eight males from whom pulmonary capillary wedge pressure (PCWP), central venous pressure and SV (via thermodilution) were obtained while central blood volume was reduced via lower-body negative pressure (LBNP) during normothermia, whole-body heating (increase in blood temperature 1 degrees C), and during whole-body heating after intravascular volume expansion. Volume expansion was accomplished by administration of a combination of a synthetic colloid (HES 130/0.4, Voluven) and saline. Before LBNP, SV was not affected by heating (122 +/- 30 ml; mean +/- s.d.) compared to normothermia (110 +/- 20 ml; P = 0.06). However, subsequent volume loading increased SV to 143 +/- 29 ml (P = 0.003). LBNP provoked a larger decrease in SV relative to the decrease in PCWP during heating (8.6 +/- 1.9 ml mmHg(1)) compared to normothermia (4.5 +/- 3.0 ml mmHg(1), P = 0.02). After volume loading while heat stressed, the reduction in the SV to PCWP ratio during LBNP was comparable to that observed during normothermia (4.8 +/- 2.3 ml mmHg(1); P = 0.78). These data support the hypothesis that a Frank-Starling mechanism contributes to compromised blood pressure control during simulated haemorrhage in heat-stressed individuals, and extend those findings by showing that volume infusion corrects this deficit by shifting the operating point to a flatter portion of the heat stress Frank-Starling curve.

Effect of thermal stress on Frank-Starling relations in humans.

The Frank-Starling 'law of the heart' is implicated in certain types of orthostatic intolerance in humans. Environmental conditions have the capacity to modulate orthostatic tolerance, where heat stress decreases and cooling increases orthostatic tolerance. The objective of this project was to test the hypothesis that heat stress augments and cooling attenuates orthostatic-induced decreases in stroke volume (SV) via altering the operating position on a Frank-Starling curve. Pulmonary artery catheters were placed in 11 subjects for measures of pulmonary capillary wedge pressure (PCWP) and SV (thermodilution derived cardiac output/heart rate). Subjects experienced lower-body negative-pressure (LBNP) of 0, 15 and 30 mmHg during normothermia, skin-surface cooling (decrease in mean skin temperature of 4.3 +/- 0.4 degrees C (mean +/- s.e.m.) via perfusing 16 degrees C water through a tubed-lined suit), and whole-body heating (increase in blood temperature of 1.0 +/- 0.1 degrees C via perfusing 46 degrees C water through the suit). SV was 123 +/- 8, 121 +/- 10, 131 +/- 7 ml prior to LBNP, during normothermia, skin-surface cooling, and whole-body heating, respectfully (P = 0.20). LBNP of 30 mmHg induced greater decreases in SV during heating (-48.7 +/- 6.7 ml) compared to normothermia (-33.2 +/- 7.4 ml) and to cooling (-10.3 +/- 2.9 ml; all P < 0.05). Relating PCWP to SV indicated that cooling values were located on the flatter portion of a Frank-Starling curve because of attenuated decreases in SV per decrease in PCWP. In contrast, heating values were located on the steeper portion of a Frank-Starling curve because of augmented decreases in SV per decrease in PCWP. These data suggest that a Frank-Starling mechanism may contribute to improvements in orthostatic tolerance during cold stress and orthostatic intolerance during heat stress.

MLH1 deficiency enhances tumor cell sensitivity to ganciclovir.

Suicide gene therapy with herpes simplex virus thymidine kinase (HSV-TK) and ganciclovir (GCV) is notable for producing multi-log cytotoxicity in a unique pattern of delayed cytotoxicity in S-phase. As hydroxyurea, a ribonucleotide reductase inhibitor that activates mismatch repair, can increase sensitivity to GCV, we evaluated the role of MLH1, an essential mismatch repair protein, in GCV cytotoxicity. Using HCT116TK (HSV-TK-expressing) colon carcinoma cells that express or lack MLH1, cell-survival studies demonstrated greater GCV sensitivity in the MLH1-deficient cells, primarily at high concentrations. This could not be explained by differences in GCV metabolism, as the less sensitive MLH1-expresssing cells accumulated more GCV triphosphate and incorporated more of the analog into DNA. SiRNA suppression of MLH1 in U251 glioblastoma or SW480 colon carcinoma cells also enhanced sensitivity to high concentrations of GCV. Studies in a pa nel of yeast deletion mutants confirmed the results with MLH1, and further suggested a role for homologous recombination repair and several cell-cycle checkpoint proteins in GCV cytotoxicity. These data suggest that MLH1 can prevent cytotoxicity with GCV. Targeting mismatch repair-deficient tumors may increase efficacy of this suicide gene therapy approach to cancer treatment.

Effects of passive heating on central blood volume and ventricular dimensions in humans.

Mixed findings regarding the effects of whole-body heat stress on central blood volume have been reported. This study evaluated the hypothesis that heat stress reduces central blood volume and alters blood volume distribution. Ten healthy experimental and seven healthy time control (i.e. non-heat stressed) subjects participated in this protocol. Changes in regional blood volume during heat stress and time control were estimated using technetium-99m labelled autologous red blood cells and gamma camera imaging. Whole-body heating increased internal temperature (> 1.0 degrees C), cutaneous vascular conductance (approximately fivefold), and heart rate (52 +/- 2 to 93 +/- 4 beats min(-1)), while reducing central venous pressure (5.5 +/- 07 to 0.2 +/- 0.6 mmHg) accompanied by minor decreases in mean arterial pressure (all P < 0.05). The heat stress reduced the blood volume of the heart (18 +/- 2%), heart plus central vasculature (17 +/- 2%), thorax (14 +/- 2%), inferior vena cava (23 +/- 2%) and liver (23 +/- 2%) (all P

Effects of heat and cold stress on central vascular pressure relationships during orthostasis in humans.

Central venous pressure (CVP) provides information regarding right ventricular filling pressure, but is often assumed to reflect left ventricular filling pressure. It remains unknown whether this assumption is correct during thermal challenges when CVP is elevated during skin-surface cooling or reduced during whole-body heating. The primary objective of this study was to test the hypothesis that changes in CVP reflect those in left ventricular filling pressure, as expressed by pulmonary capillary wedge pressure (PCWP), during lower-body negative pressure (LBNP) while subjects are normothermic, during skin-surface cooling, and during whole-body heating. In 11 subjects, skin-surface cooling was imposed by perfusing 16 degrees C water through a water-perfused suit worn by each subject, while heat stress was imposed by perfusing 47 degrees C water through the suit sufficient to increase internal temperature 0.95 +/- 0.07 degrees C (mean +/- s.e.m.). While normothermic, CVP was 6.3 +/- 0.2 mmHg and PCWP was 9.5 +/- 0.3 mmHg. These pressures increased during skin-surface cooling (7.8 +/- 0.2 and 11.1 +/- 0.3 mmHg, respectively; P < 0.05) and decreased during whole-body heating (3.6 +/- 0.1 and 6.5 +/- 0.2 mmHg, respectively; P < 0.05). The decrease in CVP with LBNP was correlated with the reduction in PCWP during normothermia (r = 0.93), skin-surface cooling (r = 0.91), and whole-body heating (r = 0.81; all P < 0.001). When these three thermal conditions were combined, the overall r value between CVP and PCWP was 0.92. These data suggest that in the assessed thermal conditions, CVP appropriately tracks left ventricular filling pressure as indexed by PCWP. The correlation between these values provides confidence for the use of CVP in studies assessing ventricular preload during thermal and combined thermal and orthostatic perturbations.

Evidence of a myogenic response in vasomotor control of forearm and palm cutaneous microcirculations.

Previous investigations of autoregulatory mechanisms in the control of skin blood flow suffer from the possibility of interfering effects of the autonomic nervous system. To address this question, in 11 subjects cutaneous vascular responses were measured during acute changes in perfusion pressure (using Valsalva maneuver; VM) before and after ganglionic blockade via systemic trimethaphan infusion. Cutaneous vascular conductance at baseline (CVC(base)) and during the last 5 s of the VM (CVC(VM)) were measured from forearm (nonglabrous) and palm (glabrous) skin. During the VM without ganglionic blockade, compared with CVC(base), CVC(VM) decreased significantly at the palm [0.79 +/- 0.17 to 0.55 +/- 0.17 arbitrary units (AU)/mmHg; P = 0.002] but was unchanged at the forearm (0.13 +/- 0.02 to 0.16 +/- 0.02 AU/mmHg; P = 0.50). After ganglionic blockade, VM induced pronounced decreases in perfusion pressure, which resulted in significant increases in CVC(VM) at both forearm (0.19 +/- 0.03 to 0.31 +/- 0.07 AU/mmHg; P = 0.008) and palm (1.84 +/- 0.29 to 2.76 +/- 0.63 AU/mmHg; P = 0.003) sites. These results suggest that, devoid of autonomic control, both glabrous and nonglabrous skin are capable of exhibiting vasomotor autoregulation during pronounced reductions in perfusion pressure.

Prolonged head-down tilt exposure reduces maximal cutaneous vasodilator and sweating capacity in humans.

Cutaneous vasodilation and sweat rate are reduced during a thermal challenge after simulated and actual microgravity exposure. The effects of microgravity exposure on cutaneous vasodilator capacity and on sweat gland function are unknown. The purpose of this study was to test the hypothesis that simulated microgravity exposure, using the 6 degrees head-down tilt (HDT) bed rest model, reduces maximal forearm cutaneous vascular conductance (FVC) and sweat gland function and that exercise during HDT preserves these responses. To test these hypotheses, 20 subjects were exposed to 14 days of strict HDT bed rest. Twelve of those subjects exercised (supine cycle ergometry) at 75% of pre-bed rest heart rate maximum for 90 min/day throughout HDT bed rest. Before and after HDT bed rest, maximal FVC was measured, via plethysmography, by heating the entire forearm to 42 degrees C for 45 min. Sweat gland function was assessed by administering 1 x 10(-6) to 2 M acetylcholine (9 doses) via intradermal microdialysis while simultaneously monitoring sweat rate over the microdialysis membranes. In the nonexercise group, maximal FVC and maximal stimulated sweat rate were significantly reduced after HDT bed rest. In contrast, these responses were unchanged in the exercise group. These data suggest that 14 days of simulated microgravity exposure, using the HDT bed rest model, reduces cutaneous vasodilator and sweating capacity, whereas aerobic exercise training during HDT bed rest preserves these responses.

Absence of arterial baroreflex modulation of skin sympathetic activity and sweat rate during whole-body heating in humans.

1. Prior findings suggest that baroreflexes are capable of modulating skin blood flow, but the effects of baroreceptor loading/unloading on sweating are less clear. Therefore, this project tested the hypothesis that pharmacologically induced alterations in arterial blood pressure in heated humans would lead to baroreflex-mediated changes in both skin sympathetic nerve activity (SSNA) and sweat rate. 2. In seven subjects mean arterial blood pressure was lowered (approximately 8 mmHg) and then raised (approximately 13 mmHg) by bolus injections of sodium nitroprusside and phenylephrine, respectively. Moreover, in a separate protocol, arterial blood pressure was reduced via steady-state administration of sodium nitroprusside. In both normothermia and heat-stress conditions the following responses were monitored: sublingual and mean skin temperatures, heart rate, beat-by-beat blood pressure, skin blood flow (laser-Doppler flowmetry), local sweat rate and SSNA (microneurography from peroneal nerve). 3. Whole-body heating increased skin and sublingual temperatures, heart rate, cutaneous blood flow, sweat rate and SSNA, but did not change arterial blood pressure. Heart rate was significantly elevated (from 74 +/- 3 to 92 +/- 4 beats x min(-1); P < 0.001) during bolus sodium nitroprusside-induced reductions in blood pressure, and significantly reduced (from 92 +/- 4 to 68 +/- 4 beats x min(-1); P < 0.001) during bolus phenylephrine-induced elevations in blood pressure, thereby demonstrating normal baroreflex function in these subjects. 4. Neither SSNA nor sweat rate was altered by rapid (bolus infusion) or sustained (steady-state infusion) changes in blood pressure regardless of the thermal condition. 5. These data suggest that SSNA and sweat rate are not modulated by arterial baroreflexes in normothermic or moderately heated individuals.

Repair of DNA strand breaks by the overlapping functions of lesion-specific and non-lesion-specific DNA 3' phosphatases.

In Saccharomyces cerevisiae, the apurinic/apyrimidinic (AP) endonucleases Apn1 and Apn2 act as alternative pathways for the removal of various 3'-terminal blocking lesions from DNA strand breaks and in the repair of abasic sites, which both result from oxidative DNA damage. Here we demonstrate that Tpp1, a homologue of the 3' phosphatase domain of polynucleotide kinase, is a third member of this group of redundant 3' processing enzymes. Unlike Apn1 and Apn2, Tpp1 is specific for the removal of 3' phosphates at strand breaks and does not possess more general 3' phosphodiesterase, exonuclease, or AP endonuclease activities. Deletion of TPP1 in an apn1 apn2 mutant background dramatically increased the sensitivity of the double mutant to DNA damage caused by H2O2 and bleomycin but not to damage caused by methyl methanesulfonate. The triple mutant was also deficient in the repair of 3' phosphate lesions left by Tdp1-mediated cleavage of camptothecin-stabilized Top1-DNA covalent complexes. Finally, the tpp1 apn1 apn2 triple mutation displayed synthetic lethality in combination with rad52, possibly implicating postreplication repair in the removal of unrepaired 3'-terminal lesions resulting from endogenous damage. Taken together, these results demonstrate a clear role for the lesion-specific enzyme, Tpp1, in the repair of a subset of DNA strand breaks.

A case-control study of beliefs and behaviors associated with sexually transmitted disease occurrence in Estonia.

BACKGROUND: Epidemiologic data document rapidly increasing sexually transmitted disease (STD) rates throughout Eastern Europe. GOAL: This case-control study was designed to delineate factors contributing to the STD epidemic in Estonia. STUDY DESIGN: For this study, 189 study participants and 112 control subjects completed a behavioral questionnaire and underwent testing for Neisseria gonorrhoeae, Chlamydia trachomatis, and Treponema pallidum. RESULTS: The prevalence of STDs among the control subjects was 32%. Although the participants believed that condoms prevent STDs, only 17% reported consistent use. Methods believed to prevent transmission included washing the genitals (65%), urinating (26%), douching (35%), and using oral contraceptives (19%). An interaction between sex and travel outside Estonia (odds ratio, 0.1; 95% CI, 0-0.7) reflects the fact that males with STDs were more likely to report travel (46% of participants and 45.5% of control subjects with STD) than were those without STD (16.1% of controls without STD). CONCLUSIONS: STD rates are related to high-risk sexual behavior among males traveling outside of Estonia. Intervention is needed to promote understanding of disease transmission dynamics in this area, and to decrease sexual risk behavior, particularly in the context of travel.

Baroreflex modulation of muscle sympathetic nerve activity during posthandgrip muscle ischemia in humans.

To identify whether muscle metaboreceptor stimulation alters baroreflex control of muscle sympathetic nerve activity (MSNA), MSNA, beat-by-beat arterial blood pressure (Finapres), and electrocardiogram were recorded in 11 healthy subjects in the supine position. Subjects performed 2 min of isometric handgrip exercise at 40% of maximal voluntary contraction followed by 2.5 min of posthandgrip muscle ischemia. During muscle ischemia, blood pressure was lowered and then raised by intravenous bolus infusions of sodium nitroprusside and phenylephrine HCl, respectively. The slope of the relationship between MSNA and diastolic blood pressure was more negative (P < 0.001) during posthandgrip muscle ischemia (-201.9 +/- 20.4 units. beat(-1). mmHg(-1)) when compared with control conditions (-142.7 +/- 17.3 units. beat(-1). mmHg(-1)). No significant change in the slope of the relationship between heart rate and systolic blood pressure was observed. However, both curves shifted during postexercise ischemia to accommodate the elevation in blood pressure and MSNA that occurs with this condition. These data suggest that the sensitivity of baroreflex modulation of MSNA is elevated by muscle metaboreceptor stimulation, whereas the sensitivity of baroreflex of modulate heart rate is unchanged during posthandgrip muscle ischemia.

Brief report: condom use consistency associated with beliefs regarding HIV disease transmission among women receiving HIV antiretroviral therapy.

OBJECTIVE: To ascertain whether condom use consistency is associated with beliefs regarding a decreased likelihood of HIV transmission as a function of taking antiretroviral therapy. DESIGN: Cross-sectional analysis of HIV-positive women from Brooklyn (NY) enrolled in the Women's Interagency HIV Study (WIHS) who were taking any form of antiretroviral therapy at the time of data collection. METHODS: Between February and October, 1999, 145 HIV-positive eligible women participated in a structured, face-to-face interview. Interviews assessed attitudes and behaviors related to antiretroviral therapy and sexual risk behavior in the 6 months since a previous study visit. RESULTS: Over three fourths of the study sample (77%) disagreed with a statement that being on antiretroviral therapy decreases the chances of transmitting HIV to others. After controlling for number of sexual partners and HIV serostatus of partners, women reporting no association between HIV therapy and disease infectiousness were over three times more likely to report consistent condom use (odds ratio [OR], 3.1; 95% confidence interval [CI], 1.2-8.3; p <.05). CONCLUSIONS: Antiretroviral therapy may be associated with increased risk behavior when it is believed that regimens may decrease the risk of disease transmission. Education regarding potential deleterious consequences of inconsistent condom use should be part of ongoing HIV care.

Digital mammography: observer performance study of the effects of pixel size on the characterization of malignant and benign microcalcifications.

RATIONALE AND OBJECTIVES: The authors performed this study to evaluate the effects of pixel size on the characterization of mammographic microcalcifications by radiologists. MATERIALS AND METHODS: Two-view mammograms of 112 microcalcification clusters were digitized with a laser scanner at a pixel size of 35 microm. Images with pixel sizes of 70, 105, and 140 microm were derived from the 35-microm-pixel size images by averaging neighboring pixels. The malignancy or benignity of the microcalcifications had been determined with findings at biopsy or 2-year follow-up. Region-of-interest images containing the microcalcifications were printed with a laser imager. Seven radiologists participated in a receiver operating characteristic (ROC) study to estimate the likelihood of malignancy. The classification accuracy was quantified with the area under the ROC curve (Az). The statistical significance of the differences in the Az values for different pixel sizes was estimated with the Dorfman-Berbaum-Metz method and the Student paired t test. The variance components were analyzed with a bootstrap method. RESULTS: The higher-resolution images did not result in better classification; the average Az with a pixel size of 35 microm was lower than that with pixel sizes of 70 and 105 microm. The differences in Az between different pixel sizes did not achieve statistical significance. CONCLUSION: Pixel sizes in the range studied do not have a strong effect on radiologists' accuracy in the characterization of microcalcifications. The low specificity of the image features of microcalcifications and the large interobserver and intraobserver variabilities may have prevented small advantages in image resolution from being observed.

Barriers to universal prenatal HIV testing in 4 US locations in 1997.

OBJECTIVES: We determined rates of prenatal HIV testing and investigated barriers to testing. METHODS: We surveyed 1362 representative parturient women from 7 hospitals in 4 locations of the United States. RESULTS: Overall, 89.9% of women reported being offered HIV testing and 69.6% reported being tested. Proportions of women not offered testing differed by location (range = 5.2%-16.3%), as did proportions not tested (range = 12.2%-54.4%). Among women who perceived that their clinicians had not recommended testing, 41.7% were tested, compared with 92.8% of women who perceived a strong recommendation (P < .05). Private insurance for prenatal care was also associated with not being tested. Women gave multiple reasons for not being tested, most commonly not being at risk, having been tested recently, and the test's not being offered or recommended, cited by 55.3%, 39.1% and 11.1% of women, respectively. CONCLUSIONS: Although most parturient women were offered a prenatal HIV test and got tested, testing proportions did not reach national goals and differed significantly by location and payment status. Concern about testing consequences was not a major barrier. Perception of clinicians' recommendations strongly influenced testing. Changing provider practices will be essential to implementing universal prenatal HIV testing.