Prevalence of pain and association with quality of life, depression and glycaemic control in patients with diabetes.

AIMS: To determine the prevalence of pain and its association with glycaemic control, mental health and physical functioning in patients with diabetes. METHODS: Cross-sectional data from a multi-site, prospective cohort study of 11 689 participants with diabetes. We analysed the associations of pain severity and interference with glycated haemoglobin (HbA(1c)) measurements and Medical Outcomes Study SF-Mental and Physical Component Summary-12 (MCS-12 and PCS-12) scores. RESULTS: Of participants, 57.8% reported moderate to extreme pain and, compared with those without pain, were somewhat older (60.8 vs. 59.9 years, P < 0.001), more obese (body mass index of 32.1 vs. 29.8 kg/m(2), P < 0.001), more likely to report being depressed or anxious (41.3 vs. 16.2%, P < 0.001) and more likely to report fair or poor health (48.5 vs. 23.1%, P < 0.001). Bivariate comparisons demonstrated that patients with extreme pain had higher HbA(1c) than those without pain (8.3 vs. 8.0%, P = 0.001). In multivariable analyses, pain was not associated with HbA(1c) (P = 0.304) but was strongly associated with worse MCS-12 (P < 0.001), PCS-12 (P < 0.001) and depression (P < 0.001). Depression was 1.3 (95% CI: 1.12, 1.96) times more likely in patients with moderate pain and 2.0 (95% CI: 1.56, 2.46) times more likely in patients with extreme pain. CONCLUSIONS: Moderate to extreme pain was present in 57.8% of diabetic patients. Pain was strongly associated with poorer mental health and physical functioning, but not worse glycaemic control. Recognizing the high prevalence of pain and its strong association with poorer health-related quality of life may be important to improve the comprehensive management of diabetes.

Emergence of resistance to fluconazole as a cause of failure during treatment of histoplasmosis in patients with acquired immunodeficiency disease syndrome.

In sequential clinical trials of treatment for histoplasmosis in patients with acquired immunodeficiency syndrome, therapy with fluconazole failed in a higher proportion of patients than did therapy with itraconazole. To determine the cause for failure with fluconazole, antifungal susceptibility testing that used modified National Committee on Clinical Laboratory Standards procedures was performed on all baseline and failure isolates. Failure occurred more frequently in patients with baseline isolates with fluconazole minimum inhibitory concentrations (MICs) > or =5 microg/mL versus lower MICs; 29% versus 3%, respectively. There was at least a 4-fold increase in fluconazole MIC in the isolates from 10 (59%) of 17 patients for whom paired pretreatment and failure or relapse isolates were available. Cross-resistance to itraconazole was not seen. In conclusion, fluconazole is less active than itraconazole for Histoplasma capsulatum and induces resistance during therapy, which accounted for treatment failure in some patients.

High fluoride intakes cause osteomalacia and diminished bone strength in rats with renal deficiency.

Renal insufficiency is known to increase plasma fluoride levels, which may increase the risk of fluorosis and osteomalacia. The purpose of this study was to determine the effects of fluoride on skeletal fragility and mineralization in renal-deficient animals. We evaluated the skeleton of rats with surgically induced renal deficiency (4/5 nephrectomy) that were chronically exposed to fluoridated water at concentrations of 0, 5, 15, and 50 ppm for a period of 6 months. The chosen fluoride doses caused plasma fluoride levels equivalent to those in humans consuming fluoridated water levels of 0, 1, 3, and 10 ppm, respectively. Animals with renal deficiency drank about 60% more water and excreted 85% more urine than control animals. Glomerular filtration rate (GFR) was decreased 68% and plasma BUN was increased fourfold in rats with renal deficiency. Plasma fluoride was strongly correlated with 1/GFR and was greatly increased by renal deficiency in all animals consuming fluoridated water. There was a strong positive, nonlinear relationship between plasma fluoride and bone fluoride levels, suggesting nonlinear binding characteristics of fluoride to bone. The amount of unmineralized osteoid in the vertebral bone was related to the plasma fluoride levels. Vertebral osteoid volume was increased over 20-fold in animals with renal deficiency that received 15 or 50 ppm fluoride, suggesting osteomalacia. Should osteomalacia be defined as a tenfold increase in osteoid volume, there appeared to be a threshold plasma fluoride level of about 20 micromol/L, above which osteomalacia was observed consistently. This plasma fluoride level was not achieved in control rats regardless of fluoride intake, nor was it achieved in renal-deficient rats receiving 0 or 5 ppm fluoride. A fluoride concentration of 50 ppm reduced femoral bone strength by 11% in control rats and by 31% in renal-deficient rats. Vertebral strength also was decreased significantly in renal-deficient rats given 50 ppm fluoride. In conclusion, fluoridated water in concentrations equivalent to 3 and 10 ppm in humans, caused osteomalacia and reduced bone strength in rats with surgically-induced renal deficiency.

An intervention on discharge polypharmacy.

OBJECTIVE: To determine if providing a way to cancel pre-admission prescriptions would reduce the number of active drug prescriptions (RXs) at discharge. DESIGN: A randomized non-blinded clinical trial. SETTING: Inpatient acute medical service of a university affiliated Veterans Administration medical center. PARTICIPANTS: Twelve medicine ward teams were randomized to control and intervention groups. Patients controlled had been discharged from these teams during 12 weeks and were receiving outpatient medications from this facility at hospital admission; control = 180, intervention = 168. INTERVENTION: At discharge, intervention teams used a computer-generated drug list to cancel or renew previous outpatient RXs or to prescribe new medications. Control teams could not cancel outpatient drugs and wrote all medications on individual prescriptions. MEASUREMENTS: The difference between admission and discharge RXs. RESULTS: There were no significant differences in patients' age, sex, race, Charlson Index (CI), or LOS between patient groups at discharge. The intervention group had fewer RXs on admission (5.4 vs 6.2, P < .05) and at discharge was not significantly different (2.9 vs 2.9, P = .87) from the control group. CONCLUSIONS: Providing a method for canceling pre-admission medications did not reduce the number of RXs at discharge. Further research is needed to evaluate the appropriateness of the large increase in RXs from admission to discharge for patients in acute hospital settings.

Subsequent sexually transmitted infection in urban adolescents and young adults.

OBJECTIVE: To compare the rates of subsequent infection with Chlamydia trachomatis, Neisseria gonorrhoeae, or Trichomonas vaginalis in a group of high-risk adolescents and young adults. METHODS: At the time of treatment, 444 unmarried teenagers and young adults aged 13 to 25 years were enrolled from an urban sexually transmitted disease clinic and 3 community-based primary care clinics. Subjects were infected with C trachomatis, N gonorrhoeae, or T vaginalis, were diagnosed as having nongonococcal urethritis (in men), or were uninfected sexual contacts with one of these infections. Subjects returned at 1, 3, 5, and 7 months. RESULTS: The rate of subsequent infection was substantial. Forty percent of men and 53% of women who were uninfected contacts at enrollment were estimated to be infected within 7 months; 60% of men and 73% of women infected at enrollment were estimated to be reinfected. Among women, subjects who were infected at enrollment had a shorter time to subsequent infection (median, 140 days) compared with uninfected contacts (median, 209 days) (P =.04). Among men, findings were similar, but the difference in median time to subsequent infection was not significant (P =.08). Baseline characteristics that predicted shorter time to reinfection were female sex and infection at enrollment. When sexual behaviors in the 2 months preceding each subsequent data collection visit were included in the model, only being female and reporting at least one new interval sexual partner were significant predictors of subsequent sexually transmitted infections. CONCLUSIONS: These data support recent research that has found high rates of subsequent infection among high-risk adolescents and young adults. Contacts of a sexually transmitted infection appear to be at equally high risk for subsequent infection as those with a personal history of infection. Our data suggest that more frequent than annual screening for N gonorrhoeae, C trachomatis, and T vaginalis would be appropriate in at-risk adolescent and young adult populations, including individuals who are uninfected sexual contacts to a sexually transmitted infection.

Effect of tension-free vaginal tape procedure on urodynamic continence indices.

OBJECTIVE: To assess the difference in measured urethral function before and after tension-free vaginal tape procedure (TVT). METHODS: Women who underwent TVT for genuine stress incontinence with or without intrinsic sphincter deficiency completed this study. Multichannel urodynamic testing was performed preoperatively and 6 weeks postoperatively. Maximum urethral closure pressure and pressure transmission ratio were recorded. Valsalva leak point pressures were determined at 150 mL and at full bladder capacity. Resting and straining urethral angles were measured using the cotton swab technique. Subjects completed both the Incontinence Impact Questionnaire and Urodynamic Distress Inventory preoperatively and postoperatively. RESULTS: Thirty-five consecutive women were studied. Twenty-three (65.7%) had a preoperative diagnosis of intrinsic sphincter deficiency as defined by maximum urethral closure pressure less than 20 cm H(2)O and/or Valsalva leak point pressure less than 60 cm H(2)O. Subjective and objective success rates were 91% and 83%, respectively. Subjects showed an 86.8% (95% CI 71.9%, 100.0%) improvement in their Incontinence Impact Questionnaire score and a 72.9% (95% CI 62.6%, 83.1%) improvement in their Urodynamic Distress Inventory score. The mean change in maximum urethral closure pressure was -1.3 cm H(2)O (95% CI -5.9, 3.3), whereas the pressure transmission ratio increased 15.7% (95% CI 5.0%, 26.3%). The mean decrease in straining urethral angle was 16.3 degrees (95% CI -23.9 degrees, -8.7 degrees ). Cured subjects demonstrating hypermobility preoperatively continued to do so postoperatively. CONCLUSION: There was a significant increase in pressure transmission ratio, but not maximum urethral closure pressure, after TVT. These changes are similar to those reported after retropubic urethropexy and traditional sling procedures. The effectiveness of the TVT sling does not appear to depend on a clinically significant change in the straining urethral angle.

Lack of effect of long-term fluoride ingestion on blood chemistry and frequency of sister chromatid exchange in human lymphocytes.

Two studies were conducted to assess the potential for adverse physiologic and genotoxic effects of long-term fluoride ingestion in adults residing in three communities with varying water fluoride levels (0.2 ppm, 1.0 ppm, and 4.0 ppm). All were long-time (> or = 30 years) residents of their respective communities. Plasma and urine samples were collected for fluoride analyses. Additional plasma was collected to determine blood chemistry, and plasma lymphocytes were examined to determine the frequency of sister chromatid exchange. Significant differences in urine (P = 0.001) and plasma (P = 0.0001) fluoride levels were found in the three communities. Seven of the blood parameters were statistically different among the communities, although all were within the defined normal range of the pathology laboratory. Sister chromatid exchange frequency was statistically higher in the 4.0 ppm fluoride community as compared to the other communities. Because of the higher SCE frequency in the 4.0 ppm fluoride community, a second study was performed to determine if the increased frequency was potentially related to the fluoride level of the communal water supply. Of the 58 adults recruited; 30 had used city water and 28 had used well water (< or = 0.3 ppm fluoride) as their principal water source for 30 years. Data analyses showed that the sister chromatid exchange frequency did not differ between the groups, indicating that the increased sister chromatid exchange frequency was not related to the fluoride level of the communal water. The investigation provided evidence that the long-term ingestion of water containing 4.0 ppm fluoride did not have any clinically important physiologic or genotoxic effects in healthy adults.

Long-term exposure to fluoride in drinking water and sister chromatid exchange frequency in human blood lymphocytes.

The genetic toxicity of fluoride has been investigated extensively by various test systems. However, results obtained have been inconsistent. Fluoride has been reported to be non-genotoxic, genotoxic, and synergistic or antagonistic with certain mutagens. To date, there are no published human studies on the genotoxicity of fluoride. The purpose of this investigation was to determine genotoxic risks of long-term exposure to various concentrations of fluoride in drinking water in humans with normal or inadequate nutrition. Six groups of subjects with either normal or inadequate nutritional intakes were selected from areas of approximately 0.2, 1.0, or 4.8 ppm (10.5, 52.6, or 252.6 mumol/L) fluoride in water. The subjects had been continuous residents in the area for at least 35 years. Samples of drinking water, plasma, and urine were analyzed for fluoride content. Blood lymphocytes were examined to determine the frequency of sister chromatid exchange (SCE). Blood chemistry and electrolytes were also analyzed. The results showed that average daily fluoride intake as well as urine and plasma fluoride levels increased with increase in the fluoride content of the drinking water. The blood chemistry and electrolyte values were within the normal range for all populations, but several parameters were significantly different. While the numerical differences were small, the subjects with low fluoride in the water (0.11 and 0.23 ppm or 5.8 and 12.1 mumol/L) had significantly higher SCE frequencies than those with higher fluoride exposures.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of aging on animal response to chronic fluoride exposure.

This study was conducted to test the hypothesis that physiological changes which occur during aging increase the biological impact of fluoride and reduce the threshold of safe fluoride exposure. Four groups of rats were fed a low-fluoride diet (< 1.2 ppm) ad libitum and received 0, 5, 15, or 50 ppm fluoride in their drinking water. Animals were killed after three, six, 12, or 18 months of treatment. Blood and urine were monitored for biochemical markers of tissue function, and plasma, urine, feces, and representative tissues were analyzed for fluoride. In addition, bone marrow cells from animals killed after 18 months of treatment were examined for frequency of sister chromatid exchange (SCE), a marker of genetic damage. Study results indicated that, within treatment groups, fluoride intake, excretion, and retention did not change significantly between three and 18 months. Fluoride concentration in soft tissues did not change with treatment duration in the fluoride-treated animals. Mineralized tissue fluoride concentration and the total fluoride in the carcasses increased continually as the animals aged. In spite of significant, dose-related differences in tissue fluoride levels which occurred in all age groups in this study, there were no indications that increased fluoride in the tissues caused any adverse physiological or genotoxic effects. None of the monitored clinical "wellness" markers of tissue integrity and function was altered by fluoride in a clinically significant manner. Therefore, there was no evidence from this study that aging reduces the threshold of safe chronic fluoride exposure.

The effect of mitomycin C on Molteno implant surgery: a 1-year randomized, masked, prospective study.

PURPOSE: The authors assess whether adjunctive mitomycin C improves Molteno tube shunt surgery in terms of intraocular pressure (IOP), visual acuity, and complication rates. PATIENTS AND METHODS: Twenty-five eyes of twenty-five consecutive patients undergoing double-plate Molteno implant surgery were randomized to receive either mitomycin C (MMC) 0.4 mg/mL for 2 minutes or a control balanced salt solution in a masked, prospective study. Intraocular pressure, visual acuity, and complications were recorded 1 week and 1, 3, 6, and 12 months after surgery. A repeated measures analysis of variance (ANOVA) model was used to test the overall effect of the drug on IOP and percent change from preoperative IOP. RESULTS: Thirteen eyes received balanced salt solution and 12 eyes received MMC. There was no difference between the groups with respect to age, preoperative IOP, log mean angle of resolution (LogMar) visual acuity, or number of preoperative medications. Except for week 1, there were no differences between the groups at any of the clinic visits with respect to IOP and percent change from baseline IOP. Analysis of the visual acuity (LogMar) showed reduction in vision for both groups. Complications were similar in each group, as were number of postoperative hypotensive agents required. CONCLUSIONS: Adjunct MMC does not demonstrate a significant difference in outcomes compared with placebo in pressure-ridged Molteno implant surgery. Results of this study are limited by a small number of patients in each group and a fixed dose of MMC.

Absence of detrimental effects of fluoride exposure in diabetic rats.

This study is part of a comprehensive programme to investigate fluoride toxicity and the hypothesis that fluoride ingested by "medically compromised' animals will result in altered physiological function. Its objectives were to monitor fluoride retention, tissue fluoride concentrations and genetic variables in diabetic and control rats chronically exposed to fluoride, and to determine whether or not adverse effects occurred. Male, Zucker fatty diabetic rats and Zucker age-matched lean controls were fed a low-fluoride diet ( < 1.2 parts/10(6) F-) ad libitum and received 0, 5, 15 or 50 parts/10(6) fluoride in their drinking water for 3 or 6 months. Fluoride metabolic balance was determined for 4 days before the end of each study phase. Plasma and urine were analysed for biochemical markers of tissue function, and plasma, urine, faeces and tissues were analysed for fluoride. Bone marrow cells from animals killed after 6 months of treatment were examined for frequency of sister chromatid exchange, a marker of genetic damage. The diabetic rats consumed, excreted and retained significantly greater amounts of fluoride than the controls (p < 0.05). There were dose-related increases in fluoride excretion, retention and tissue concentrations in both classes of animals, which were significantly greater in the diabetic rats. In spite of greater amounts of fluoride in the tissues of diabetic animals, there was no evidence, under these experimental conditions, that any of the fluoride exposures tested caused measurable adverse effects on the physiological, biochemical or genetic variables that were monitored.

Severe dental fluorosis in a Tanzanian population consuming water with negligible fluoride concentration.

OBJECTIVES: To identify risk factors for dental fluorosis that cannot be explained by drinking water fluoride concentration alone. METHODS: Two hundred eighty-four Tanzanian children ages 9 to 19 (mean 14.0+/-SD 1.69), who were lifetime residents at differing altitudes (Chanika, 100 m; Rundugai, 840 m; and Kibosho, 1,463 m; Sites 1, 2, and 3 respectively) were examined for dental fluorosis and caries. They were interviewed about their food habits, environmental characteristics and use of a fluoride-containing food tenderizer known locally as magadi. Meal, urine, water and magadi samples supplied by the participants were analyzed for fluoride content. Urine samples were also analyzed for creatinine concentration. Four magadi samples from Sites 1 and 3 were analyzed for complete element composition. RESULTS: Of the 13 water samples from Site 2, 10 contained > or =4 mg/L F, ranging from 1.26 to 12.36 mg/L with a mean+/-SD of 5.72+/-4.71 mg/L. Sites 1 and 3 had negligible water fluoride of 0.05+/-0.05 and 0.18+/-0.32 mg/L respectively. Mean TFI fluorosis scores (range 0-9) for Site 2 were high: 4.44+/-1.68. In Sites 1 and 3, which both had negligible water fluoride, fluorosis scores varied dramatically: Site 1 mean maximum TFI was 0.01+/-0.07 and Site 3 TFI was 4.39+/-1.52. Mean DMFS was 1.39+/-2.45, 0.15+/-0.73 and 0.19+/-0.61 at Sites 1, 2, and 3, respectively. There were no restorations present. Urinary fluoride values were 0.52+/-0.70, 4.34+/-7.62, and 1.43+/-1.80 mg/L F at Sites 1, 2, and 3, respectively. Mean urinary fluoride values at Site 3 were within the normal urinary fluoride reference value range in spite of pervasive severe pitting fluorosis. Meal and magadi analyses revealed widely varied fluoride concentrations. Concentrations ranged from 0.01 to 22.04 mg/L F for meals and from 189 to 83211 mg/L F for magadi. Complete element analysis revealed the presence of aluminum, iron, magnesium, manganese, strontium and titanium in four magadi samples. There were much higher concentrations of these elements in samples from Site 3, which was at the highest altitude and had severe enamel disturbances in spite of negligible water fluoride concentration. An analysis of covariance model supported the research hypothesis that the three communities differed significantly in mean fluorosis scores (P<0.0001). Controlling for urinary fluoride concentration and urinary fluoride:urinary creatinine ratio, location appeared to significantly affect fluorosis severity. Urinary fluoride:urinary creatinine ratio had a stronger correlation than urinary fluoride concentration with mean TFI fluorosis scores (r=0.43 vs r= 0.25). CONCLUSIONS: The severity of enamel disturbances at Site 3 (1463 m) was not consistent with the low fluoride concentration in drinking water, and was more severe than would be expected from the subjects' normal urinary fluoride values. Location, fluoride in magadi, other elements found in magadi, and malnutrition are variables which may be contributing to the severity of dental enamel disturbances occurring in Site 3. Altitude was a variable which differentiated the locations.

Dental fluorosis in children residing in communities with different water fluoride levels: 33-month follow-up.

PURPOSE: The purpose of these examinations was to monitor changes, in the prevalence of dental fluorosis. METHODS: In February 1992 and December 1994, children who were residents of one of three communities with varying levels of fluoride in their communal water supply were examined for dental fluorosis. Since some children were available at both examination periods, it was also possible to determine changes in the incidence of dental fluorosis. RESULTS: The prevalence of fluorosis increased by approximately 14%, 20%, and 6% in the negligibly, optimally, and 4X optimally fluoridated communities, respectively. In the negligibly and optimally fluoridated communities, the incidence of dental fluorosis increased by 12% and 7%, respectively. In the 4X optimally fluoridated community, all the children examined had evidence of fluorosis at both examinations. CONCLUSION: Fluoride continues to be the primary therapeutic agent for the prevention of dental caries in adults and children. With the downward adjustment in the fluoride supplement schedule, continued monitoring of the prevalence of dental fluorosis in young children is needed to determine if any additional steps are even necessary to restrict fluoride intake during the years that enamel formation is occurring.

Methods for combining rates from several studies.

When several independent groups have conducted studies to estimate a procedure's success rate, it is often of interest to combine the results of these studies in the hopes of obtaining a better estimate for the true unknown success rate of the procedure. In this paper we present two hierarchical methods for estimating the overall rate of success. Both methods take into account the within-study and between-study variation and assume in the first stage that the number of successes within each study follows a binomial distribution given each study's own success rate. They differ, however, in their second stage assumptions. The first method assumes in the second stage that the rates of success from individual studies form a random sample having a constant expected value and variance. Generalized estimating equations (GEE) are then used to estimate the overall rate of success and its variance. The second method assumes in the second stage that the success rates from different studies follow a beta distribution. Both methods use the maximum likelihood approach to derive an estimate for the overall success rate and to construct the corresponding confidence intervals. We also present a two-stage bootstrap approach to estimating a confidence interval for the success rate when the number of studies is small. We then perform a simulation study to compare the two methods. Finally, we illustrate these two methods and obtain bootstrap confidence intervals in a medical example analysing the effectiveness of hyperdynamic therapy for cerebral vasospasm.

Comparison of an established antibody sandwich method with an inhibition method of Histoplasma capsulatum antigen detection.

The Histoplasma antigen immunoassay utilizes an antibody sandwich method that provides a rapid and reliable means of diagnosing the more severe forms of histoplasmosis. Inhibition assays have been developed for antigen detection and offer at least one potential advantage, namely, reduced antibody requirements. We have developed an inhibition assay using the polyclonal antibody employed in our standard sandwich assay. Urine and serum specimens from patients with culture-proven histoplasmosis and controls were tested using both methods. The two methods had similar sensitivities for detection of antigen in urine (antibody sandwich = 92.5% versus inhibition = 87.5%, P = 0.500) and serum (82.5% versus 80.0%, P = 1. 000). With serum, the specificities of both methods were similar (antibody sandwich assay = 95.0% versus inhibition assay = 92.5%, P = 1.000), and with urine, the specificity of the antibody sandwich method was superior (97.5% versus 80.0%, P = 0.039). While the overall reproducibility of both methods was excellent (with urine, antibody sandwich assay intraclass correlation coefficient = 0.9975 and with serum = 0.9949; correlation coefficient of the inhibition assay with urine = 0.9736 and with serum = 0.9850), that of the inhibition method was only fair to poor for the controls: urine = -0. 0152, serum = 0.5595. Reproducibility was good for the controls using the sandwich method: urine = 0.7717, serum = 0.9470. Cross-reactivity was observed in specimens from patients infected with Blastomyces dermatitidis, Paracoccidioides brasiliensis, and Penicillium marneffei. In conclusion, the decreased specificity and inferior reproducibility with control specimens suggest that the inhibition assay has poorer precision toward the lower end of the detection range.

Cervical human papillomavirus deoxyribonucleic acid persists throughout pregnancy and decreases in the postpartum period.

OBJECTIVE: Our goal was to determine the persistence of human papillomavirus infection of the cervix in a prospectively evaluated cohort of pregnant women observed from the first trimester until after delivery. STUDY DESIGN: A group of 232 women were enrolled in the first trimester of pregnancy and had cervico-vaginal lavage specimens collected for detection of the deoxyribonucleic acid of human papillomavirus. They underwent sampling again in the third trimester (146 patients available) and at 4 to 12 weeks after delivery (83 patients available). Human papillomavirus deoxyribonucleic acid was detected by means of the Hybrid Capture assay. RESULTS: In the first trimester of pregnancy, 31% of the patients had positive test results for human papillomavirus deoxyribonucleic acid, whereas 35.6% had positive results in the third trimester (P = 1.0). A comparison of first-trimester test results with postpartum results (paired data available from 83 patients) showed a decline from 39.8% positivity to 26.5% (P =.04). Comparing third-trimester results with postpartum results (paired data available from 74 patients) showed a decline from 35.1% to 25. 7% positivity (P =.12). When specimens positive for human papillomavirus were divided between those containing "high cancer risk" types (9 virus types often associated with dysplasia or malignancy) and "low cancer risk" types (5 types usually found in benign lesions), similar trends were seen, although not all comparisons were statistically significant. CONCLUSION: The increased prevalence, during pregnancy, of detectable human papillomavirus deoxyribonucleic acid, which was previously reported (Fife et al, Am J Obstet Gynecol 1996;174:1487-93), persists at a similar level throughout pregnancy but declines in the postpartum period. This observation is most consistent with activation of the virus by the physiologic changes of pregnancy.

Post-treatment sexual and prevention behaviours of adolescents with sexually transmitted infections.

OBJECTIVE: To evaluate sexual behaviour (including abstinence), sex partner change, and condom use during the 3 month period following treatment for Neisseria gonorrhoeae, Chlamydia trachomatis, Trichomonas vaginalis, or non-gonococcal urethritis. METHODS: 251 14-21 year old participants (83% female; 83% African-American) diagnosed with gonorrhoea, chlamydia, trichomonas, or non-gonococcal urethritis or sexual contacts of infected partners. Participants were clients of a public sexually transmitted diseases clinic or primary care adolescent clinics. Data were collected by structured interview at treatment, 1 month post-treatment, and 3 months post-treatment. At each visit, participants were asked about coital frequency and condom use for each recent partner. At 1 month, participants were asked when coitus occurred following treatment. At each follow up visit, sex partners were compared to partners named at treatment and classified as "same partner(s)," "new partner(s)," or both "same and new partner(s)." RESULTS: Post-treatment abstinence was reported by 26% and 19% for the 1 month and 3 month visits, respectively. Abstinence was associated with greater likelihood of infection at enrolment although abstainers reported fewer lifetime STI and fewer lifetime sex partners. A substantial proportion of participants reported additional sexual contact with a previous partner. The average proportion of condom protected coital events increased from about 45% at enrolment to 64% at 1 month and 58% at 3 months (p<0.05). Higher levels were sustained for the 3 months following treatment. CONCLUSIONS: Many adolescents adopt, at least temporarily, risk reduction behaviours such as abstinence or increased condom use. Sexual re-exposure to potentially untreated previous partners may increase risk of subsequent reinfection.

Sublingual hyoscyamine sulfate in combination with ketorolac tromethamine for ureteral colic: a randomized, double-blind, controlled trial.

STUDY OBJECTIVE: We evaluate the safety and efficacy of a single dose of hyoscyamine sulfate in combination with ketorolac tromethamine for the reduction of pain in emergency department patients with ureteral colic. METHODS: We conducted a prospective, randomized, double-blind study at 2 EDs with residency programs in emergency medicine. Patients were at least 18 years old and presented to the ED with an initial history and physical examination consistent with ureteral colic. Patients received a single intravenous dose of 30 mg of ketorolac tromethamine given over a 1-minute period with either a single sublingual dose of 0.125 mg of hyoscyamine sulfate or a placebo. If inadequate analgesia was noted after 30 minutes, a standard dose of meperidine could be administered for rescue. All other treatments including intravenous fluids and antiemetics were standardized. The main study outcome was change in visual analog scale pain score from baseline to 30 minutes. RESULTS: Seventy-two patients were evaluated for inclusion. Thirteen patients who had self-administered pain medications within 4 hours of presentation were excluded before randomization. Sixteen patients who did not have a renal calculus confirmed by either intravenous urogram or helical computed tomography were also excluded from efficacy analysis. There did not appear to be any clinically important differences in the baseline characteristics between the 2 groups. The repeated-measures analysis of the remaining 43 patients showed no clinically important difference in pain score using the visual analog scale at any time point. There were no clinically important differences between the 2 study groups for amount of rescue meperidine administered or end-of-study global satisfaction scores. CONCLUSION: Hyoscyamine sulfate did not provide any additional pain relief from ureteral colic when administered with ketorolac tromethamine. There was no clinically important difference in change of pain scores at 30 minutes in patients with ureteral colic receiving supplemental hyoscyamine sulfate.

Comparison of the echinocandin caspofungin with amphotericin B for treatment of histoplasmosis following pulmonary challenge in a murine model.

Twenty clinical isolates of Histoplasma capsulatum were tested for their in vitro susceptibilities to caspofungin in comparison to those to amphotericin B by following National Committee for Clinical Laboratory Standards guidelines for yeasts. The mean MICs were 16.6 microgram/ml (range, 8 to 32 microgram/ml) for caspofungin and 0.56 microgram/ml (range, 0.5 to 1.0 microgram/ml) for amphotericin B. Survival experiments used a 10(5) dose in a pulmonary challenge model with B6C3F(1) mice. All mice that received amphotericin B at 2 mg/kg of body weight every other day (q.o.d.), 30% of mice that received caspofungin at 8 mg/kg/day, and 20% of mice that received caspofungin at 4 mg/kg/day survived to day 15, while mice that received caspofungin at 2 mg/kg/day and all control mice that received the vehicle died by day 14. Amphotericin B at 2 mg/kg q.o.d. markedly reduced the fungal burden in the lungs and spleens, as measured by Histoplasma antigen detection techniques and quantitative cultures, for each comparison. Caspofungin at 10 mg/kg twice a day (b.i.d.) did not reduce the fungal burden, as measured by antigen detection techniques, but slightly reduced the levels of fungi in both the lungs and spleens, as determined by quantitative cultures. Caspofungin at 5 mg/kg b.i.d. did not affect fungal burden. Overall, caspofungin had only a slight effect on survival or fungal burden.