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Neonatal screening for hearing disorders in infants at risk: incidence, risk factors, and follow-up.

OBJECTIVE: To determine the incidence and risk factors for hearing disorders in a selected group of neonates and the feasibility of selective hearing screening. SETTINGS: Multicenter prospective trial at five centers in Germany. METHODS: Enrollment criteria: in addition to previously defined risk factors by the Joint Committee on Infant Hearing (family history of hearing loss, in utero infections, craniofacial anomalies, birth weight <1500 g, critical hyperbilirubinemia, ototoxic medications, bacterial meningitis, postnatal asphyxia, mechanical ventilation >5 days, stigmata, or syndromes associated with hearing loss), the impact of maternal drug abuse, birth weight <10th percentile, persistent pulmonary hypertension, and intracranial hemorrhage more than or equal to grade III or periventricular leukomalacia on infant hearing were evaluated. The screening procedure was performed by automated auditory brainstem response (A-ABR; ALGO 1-plus; Natus Med Inc, San Carlos, CA). STATISTICS: univariate analyses of risk factors versus A-ABR results and a multivariate regression analysis were used; additionally, the total test time was recorded. RESULTS: Seven hundred seventy recordings from 777 infants enrolled consecutively constitute the basis of this analysis. Mean gestational age was 33.8 +/- 4.3 weeks, birth weight 2141 +/- 968 g; 431 infants being male and 339 female; 41 (5.3%) infants exhibited pathologic A-ABR results (16 bilateral and 25 unilateral). Meningitis or sepsis, craniofacial malformations, and familial hearing loss were independent significant risk factors. Median total test time was 25 minutes. Follow-up examinations in 31 infants revealed persistent hearing loss in 18 infants (13 infants sensorineural, 5 from mixed disorders), 7 requiring amplification. CONCLUSION: Hearing screening in high-risk neonates revealed a total of 5% of infants with pathologic A-ABR (bilateral 2%). Significant risk factors were familial hearing loss, bacterial infections, and craniofacial abnormalities. Other perinatal complications did not significantly influence screening results indicating improved perinatal handling in a neonatal population at risk for hearing disorders.

Analysis of Variance↗

Treatment of tumour-induced hypercalcaemia with the bisphosphonate pamidronate: dose-response relationship and influence of tumour type.

BACKGROUND: Patients with humoral hypercalcaemia of malignancy appear to respond less well to biphosphonate therapy than hypercalcaemic patients with osteolytic metastases. On the other hand, pamidronate is currently the most potent of the commercially available biphosphonates and it is recommended that its dose be increased as a function of pretreatment calcium levels. PATIENTS AND METHODS: We reviewed our experience with pamidronate in 160 patients with tumour-induced hypercalcemia (TIH) persisting after rehydration, particularly the influence of the dose administered, the tumour type and the presence of bone metastatic involvement on the calcaemic and calciuric response to pamidronate therapy. RESULTS: Serum Ca was normalized in 92% of the cases (87% when Ca was corrected for protein levels). After therapy, 59% of the patients developed asymptomatic hypocalcaemia (30% for Corr. Ca levels). A multiparameter regression analysis revealed that the response to pamidronate was significantly (P < 0.01) influenced by initial Ca levels up to days 5-7 and, thereafter, only by the dose received. To confirm the dose effect, we divided the patients into three groups according to the median dose received, namely 0.5 mg/kg (n = 35), 1.0 mg/kg (n = 52), and 1.5 mg/kg (n = 73). The differences among the three groups became significant (P < 0.05) from days 5-7 until the end of the evaluation (days 22-26). Similarly, the success rate, considering Corr. Ca levels, was 80% for the 0.5 and 1.0 mg/kg groups combined, compared to 94% for the 1.5 mg/kg group (P < 0.05). The duration of normocalcaemia was similarly more prolonged in the high-dose group. There was a dose-response relationship only in patients with Ca levels above 3.0 mmol/L and in patients with an elevated index of tubular calcium reabsorption. By contrast, the decrease in Ca levels and in fasting urinary calcium excretion, a sensitive index of bone resorption, were not significantly influenced by the primary tumour site or by the presence of bone metastatic involvement. CONCLUSIONS: Our data demonstrate a dose-response relationship for pamidronate in TIH over an efficient hypocalcaemic dose range, at least in patients with an elevated tubular calcium reabsorption, which helps to resolve conflicting data in the literature. We suggest that a dose of around 1.5 mg of pamidronate/kg is optimal for the treatment of TIH, except in patients with mild hypercalcaemia, for whom a dose of 1 mg/kg appears to be sufficient. At these dose levels, the efficacy of pamidronate is not significantly influenced by the tumour type or the degree of metastatic bone involvement.

Adult↗

Macrophage serum markers in pneumococcal bacteremia: Prediction of survival by soluble CD163.

OBJECTIVE: Soluble CD163 (sCD163) is a new macrophage-specific serum marker. This study investigated sCD163 and other markers of macrophage activation (neopterin, ferritin, transcobalamin, and soluble urokinase plasminogen activator receptor [suPAR]) as prognostic factors in patients with pneumococcal bacteremia. DESIGN: Observational cohort study. SETTING: Five university hospitals in Denmark. PATIENTS: A total of 133 patients with Streptococcus pneumoniae bacteremia (positive blood culture) and 133 age- and gender-matched controls. INTERVENTIONS: Samples were collected for biochemical analyses at the time of first positive blood culture. MEASUREMENTS AND MAIN RESULTS: sCD163 was highly correlated with other macrophage markers and was significantly elevated (median [25-75 percentiles], 4.6 mg/L [2.8-8.9]) compared with healthy controls (2.7 mg/L [2.1-3.3], p < .0001). Increased levels were observed in patients who needed intensive care (hemodialysis, p = .0011; hypotension, p = .0014; mechanical ventilation, p = .0019). Significantly lower levels of sCD163, ferritin, transcobalamin, and suPAR (but not C-reactive protein) were measured in patients > or =75 yrs. In patients <75 yrs, all macrophage markers were increased in patients who died from their infection compared with survivors, whereas no change was observed in any of the markers in the very old age. At cutoff levels of 9.5 mg/L (sCD163) and 1650 nmol/L (C-reactive protein), the relative risk for fatal outcome in patients <75 yrs was 10.1 (95% confidence interval 3.4-31.0) and 7.0 (95% confidence interval 2.4-21.6) for sCD163 and C-reactive protein, respectively. In a multivariate logistic regression model for patients <75 yrs, ferritin, transcobalamin, neopterin, and suPAR contained no significant information on the probability of survival when sCD163 and CRP were known (p = .25). CONCLUSIONS: Macrophage marker response in pneumococcal bacteremia was compromised in old age. In patients <75 yrs old, sCD163 was superior to other markers, including C-reactive protein, in predicting fatal disease outcome.

Adult↗

Toluene exposure below 50 ppm and cognitive function: a follow-up study with four repeated measurements in rotogravure printing plants.

OBJECTIVE: There are findings of cross-sectional studies on slight cognitive effects due to toluene exposure below 50 ppm. The critical points of the earlier studies will be scrutinised by a follow-up study with four examinations in 5 years. METHODS: Employees from 14 magazine rotary printing plants were classified into groups of "high" (printing area) vs "low" (end-processing) and "short" vs "long" exposure. The sample size of 333 in examination 1 decreased to 216 in examination 4. A repeated-measurement design could be applied for 192 persons. Current exposure was measured by personal air sampling (n=2,521). Data for past exposure (lifetime weighted average exposure, LWAE) were based on job exposure matrices. High-exposure and low-exposure groups were characterised by 26 ppm vs 3 ppm (current exposure) and 45 ppm vs 9 ppm (LWAE). For long-exposure and short-exposure groups 21 vs 6 years were ascertained. Attention (symbol digit substitution, switching attention, simple reaction), memory (digit span forward and backwards, immediate and delayed reproduction of pictures), and psychomotor functions (steadiness, line tracing, aiming, tapping, peg board) were measured as dependent variables. RESULTS: Separate stepwise regressions for examinations 1 to 4, which included the co-variables age, level of education, carbohydrate-deficient transferrin as an alcohol marker, and trait anxiety as personality characteristic, did not exhibit remarkable exposure impacts on the performance variables. Repeated-measures analyses of covariance, which included all examination periods, also did not exhibit significant impacts of LWAE or current exposure on the functions measured. Age and education were the dominant factors for the variability of the data. Additionally, carbohydrate-deficient transferrin and trait anxiety showed sporadic impacts on the test results. CONCLUSION: Evidence for psychological performance effects due to long-term toluene exposure below 50 ppm could not be proved.

Adult↗

IP-10 predicts viral response and therapeutic outcome in difficult-to-treat patients with HCV genotype 1 infection.

Plasma from 173 patients with HCV genotype 1 infection was analyzed for IP-10 levels prior to treatment with pegylated interferon-alpha-2a and ribavirin. Significantly lower IP-10 levels were observed in patients achieving a rapid viral response (RVR) (P < .0001), even in those with body mass index (BMI) > or = 25 kg/m2 (P = .004) and with baseline viral load > or = 2 million IU/mL (P = .001). Similarly, significantly lower IP-10 levels were observed in patients obtaining a sustained viral response (SVR) (P = .0002), including those having higher BMI (P < .05), higher viral load (P = .0005), and both higher BMI and viral load (P < .03). In multivariate logistic regression analyses, a low IP-10 value was independently predictive of both RVR and SVR. A baseline cutoff IP-10 value of 600 pg/mL yielded a negative predictive value (NPV) of 79% (19/24) for all genotype 1-infected patients, which was comparable with that observed using a reduction in HCV-RNA by at least 2 logs after 12 weeks of therapy (NPV 86%; 19/22); by combining the two, 30 of 38 patients (NPV 79%) potentially could have been spared unnecessary therapy. In patients having both higher BMI and viral load, cut-off levels of 150 and 600 pg/mL yielded a positive predictive value (PPV) of 71% and NPV of 100%, respectively. In conclusion, pretreatment IP-10 levels predict RVR and SVR in patients infected with HCV genotype 1, even in those with higher BMI and viral load. A substantial proportion of the latter patients may achieve SVR in spite of unfavorable baseline characteristics if their pretreatment IP-10 level is low. Thus, pretreatment IP-10 analysis may prove helpful in decision-making regarding pharmaceutical intervention.

Adult↗

Predictive factors of response to first-line chemotherapy in 1426 women with metastatic breast cancer.

Since response to chemotherapy is a major determinant of survival in metastatic breast cancer, the purpose of our study was to analyse the predictive factors of response. 1426 patients enrolled into eight consecutive randomised trials of anthracycline-based first-line chemotherapy in metastatic breast cancer, between 1977 and 1992, were analysed. A forward stepwise logistic regression analysis was used. The objective response rate (ORR) to chemotherapy in the total population was 63.6% (95% confidence interval (CI): 61.5-67.7). The complete response rate was 17.5%. Multivariate analysis defined adjuvant chemotherapy, lactate dehydrogenase (LDH), Karnofsky index (KI), and pleural and lung metastases to be the five main variables correlated with ORR. A predictive score was calculated using the coefficient of these five variables, The score was established as follows: -1.32+0.54 (if prior adjuvant chemotherapy) +0.80 (low KI) +0.75 (raised LDH) +0.49 (lung metastases) +0.51 (pleural metastases). A low score (less than -0.78) was associated with an ORR greater than 70.0%, representing 41.2% of our population. An intermediate score (between -0.78 and 0) was associated with an ORR of 50 to 70%, representing 37.5% of our population and a positive score was associated with an ORR of less than 50%, representing 21.3% of our population. This score can be used to predict objective response rates to first-line anthracycline-based chemotherapy. This method now needs to be evaluated prospectively in phase II trials. Identification of various risk groups may also be useful for interpretation and design of clinical trials.

Adult↗

The differing prognostic utility of exercise radionuclide ventriculography in coronary artery disease patients with and without prior myocardial infarction.

UNLABELLED: Previous studies have documented the prognostic utility of left ventricular ejection fraction response to exercise primarily in populations without prior myocardial infarction. We undertook a study to assess the prognostic utility of exercise left ventricular ejection fraction and segmental wall motion response during exercise radionuclide ventriculography in coronary artery disease patients with and without prior myocardial infarction. METHODS: We examined the comparative prognostic utility of left ventricular ejection fraction and segmental wall motion response during upright bicycle exercise radionuclide ventriculography in 419 coronary artery disease patients with (n = 217) and without (n = 202) prior myocardial infarction using univariate and multivariate hierarchical regression analyses. RESULTS: During an average followup period of 61 months, 96 patients (23%) suffered cardiac events, including 55/217 (25%) of the patients with prior myocardial infarction and 41/200 (21%) of the patients without prior myocardial infarction (p = ns). Both cumulative Kaplan-Meier survival analyses and stepwise hierarchical Cox survival analyses demonstrated that peak left ventricular ejection fraction < 55% was a significant predictor of cardiac events in patients without prior myocardial infarction (p = 0.04), whereas an exercise wall motion worsening score > or = 2 was a significant predictor in patients with a prior myocardial infarction (p = 0.0001). CONCLUSIONS: The prognostic utility of exercise radionuclide ventriculography variables differ according to the presence or absence of prior myocardial infarction. Global function, assessed by peak left ventricular ejection fraction, adds the greatest prognostic information in patients without prior myocardial infarction, whereas regional function, assessed by exercise wall motion worsening, is the best predictor among patients with prior myocardial infarction.

Adult↗

Drug resistance factors in acute myeloid leukemia: a comparative analysis.

To compare the clinical relevance of drug resistance factors in de novo acute myeloid leukemia (AML), we determined their relationship to both response to induction chemotherapy and survival of the patients in univariate as well as multivariate analyses. The drug resistance factors immunocytochemically studied in 111 patients at the time of diagnosis included the lung resistance protein (LRP), P-glycoprotein (P-gp), multidrug resistance protein (MRP1) and bcl-2. In the univariate analyses, age (P = 0.005), karyotype (P = 0.03), LRP (P = 0.003), P-gp (P = 0.02) and bcl-2 (P = 0.03) predicted for response to induction chemotherapy, whereas MRP1 had no predictive value. Age (P = 0.05), karyotype (P = 0.05) and LRP (P = 0.03) retained their predictive value in the multivariate logistic regression analyses. With regard to overall survival, age (P = 0. 008), karyotype (P = 0.006), LRP (P = 0.001) and P-gp (P = 0.01) were of prognostic value in the univariate Cox regression analyses but only age (P = 0.01), karyotype (P = 0.02) and LRP (P = 0.01) retained their prognostic significance in the multivariate analyses. A risk score based on the number of independent prognostic factors allowed division of patients into four groups with different outcome. In these groups, the complete remission rates were 93%, 75%, 47% and 33%, respectively, and median overall survival was 2.4, 1.2, 0.6 and 0.2 years, respectively. Thus, several drug resistance factors did predict outcome in the univariate analyses but LRP was the only drug resistance factor with independent predictive and prognostic significance. The proposed risk score might be useful for risk-adapted treatment in the future. Leukemia (2000) 14, 68-76.

Acute Disease↗

Prognostic factors of mycological cure following treatment of onychomycosis with oral antifungal agents.

BACKGROUND: There is considerable literature on the efficacy and safety of various drugs used in treating onychomycosis; however, little information is available regarding prognostic factors which may be associated with non-response to conventional treatment. OBJECTIVES: To identify parameters influencing mycological cure at 72 weeks following treatment of toenail onychomycosis with oral antifungal agents. METHODS: Univariate and multivariate logistic regression analysis from a randomized double-blind controlled trial including 496 patients with toenail onychomycosis caused by dermatophytes. RESULTS: Baseline parameters including patient's age, gender, weight, number of toenails involved, percentage of nail involvement, duration of infection, history of previous treatment were not associated with mycological cure. In the multivariate prognostic factor analysis based on factors assessed at week 12, positive mycological culture at 12 weeks [odds ratio (OR): 0.583; 95% confidence interval (CI): 0.370-0.918] was negatively associated with mycological cure at 72 weeks. Similarly, in the multivariate prognostic factor analysis based on factors assessed at week 24, positive direct microscopy at 24 weeks (OR: 0.373; 95% CI: 0.211-0.659) and mycological culture at 24 weeks (OR: 0.293; 95% CI: 0.168-0.513) were negatively associated with mycological cure at 72 weeks. CONCLUSIONS: Mycological culture at 12 and 24 weeks and direct microscopic examination at 24 weeks can help in early identification of patients failing to respond to conventional oral antifungal treatment.

Adolescent↗

Intrapartum fever at term: serum and histologic markers of inflammation.

OBJECTIVE: This study was undertaken to determine whether intrapartum fevers at term are associated with markers of acute inflammation in maternal, fetal, and placental compartments. STUDY DESIGN: Term cases with intrapartum fever (temperature >/=100.4 degrees F) were recruited with gestational age-matched controls. Maternal serum and umbilical vein blood were collected and assayed for interleukin-6 (IL-6) levels. Placentas were examined for histologic chorioamnionitis. Demographic and clinical data were collected and compared between cases and controls. RESULTS: Forty-seven case-control pairs were analyzed. Maternal IL-6 levels were higher in cases than in controls (median of 145 pg/mL vs 42 pg/mL, P <.0001). Umbilical vein IL-6 levels also were higher in cases than controls (median 9 pg/mL vs 3.5 pg/mL, P =.01), but more than half of levels in cases were below 11 pg/mL. Only 31.1% of febrile cases had moderate or severe histologic chorioamnionitis. Multivariable logistic regression identified maternal serum IL-6 levels, nulliparity, and number of vaginal examinations as the major predictors of intrapartum fever at term. CONCLUSION: The maternal inflammatory response as measured by maternal serum IL-6 levels is a strong marker for term intrapartum fever. The much weaker association of fetal and placental inflammatory responses suggest a smaller than expected contribution of intra-amniotic inflammation to term intrapartum fevers.

Adult↗

Biomarkers predictive for clinical efficacy of taxol-based chemotherapy in advanced breast cancer.

BACKGROUND: Several studies looked for tumor biomarkers predictive for paclitaxel sensitivity but till now no reliable biomarkers are available. The aim of this study was to verify the potential predictive value of beta-tubulin III and IV, vascular endothelial growth factor-receptor (VEGFR-1), HER2/neu and microvessel density (mVD), in a group of 70 patients with advanced breast cancer (ABC) treated with paclitaxel-based chemotherapy. PATIENTS AND METHODS: Immunohistochemical analysis (ICA) of HER2, VEGFR-1, mVd, beta-tubulin III and beta-tubulin IV expression were performed in a series of 72 advanced breast cancer. Furthermore apoptotic fraction with TUNEL analysis was evaluated. RESULTS: beta-tubulin III ICA expression was predictive of progression after chemotherapy. In fact only 2% of the patients with low beta-tubulin III expression progressed after paclitaxel chemotherapy vs 38% of those with high beta-tubulin III tumor expression (P=0.000; by chi(2)). This evidence was confirmed by a logistic regression analysis (OR 28.789; 95% CI 3.212-258,072; P=0.004). There was not a significant association between other biomarkers' characteristics and clinical response to chemotherapy. A Cox multivariate analysis, with overall survival as a dependent variable, showed that only HER2 expression was independently associated (OR 2.39; 95% CI 1.09-5.23; P=0.03) with overall survival. CONCLUSIONS: We suggest that class III beta-tubulin immunohistochemical expression analysis could be a potentially relevant tumor biomarker for paclitaxel resistance in advanced breast cancer patients.

Adult↗

Prevalence of genotypic and phenotypic HIV-1 drug-resistant strains among patients who have rebound in viral load while receiving antiretroviral therapy in the UNAIDS-Drug Access Initiative in Abidjan, Côte d'Ivoire.

OBJECTIVE: To determine the prevalence of genotypic and phenotypic antiretroviral (ARV) drug-resistant HIV-1 strains among patients with viral load rebound while receiving ARV therapy in Abidjan, Côte d'Ivoire. METHODS: Between August 1998 and April 2000, we selected all patients (n = 241) who had received ARV drug therapy for at least 6 months in the UNAIDS-Drug Access Initiative (DAI), in Abidjan. We analyzed for genotypic and phenotypic drug resistance among 97 (40%) of the 241 patients who had a rebound in plasma viral load, defined as an initial decrease of > 0.5 log10 copies/ml followed by a subsequent increase of > 0.25 log10 copies/ml. RESULTS: Of the viruses isolated from the 97 patients, 86 (88.7%) had usable sequences and 68 (79%) of the 86 patients had genotypic resistance to at least one reverse transcriptase inhibitor (RTI) or protease inhibitor (PI). Resistant mutations were found for zidovudine in 50 (78%) of 64 patients who had received the drug, 11 (68.7%) of 16 patients on lamivudine, for nevirapine in two (2%), for indinavir in one (1%), and for ritonavir in one (1%). Phenotypic resistance to at least one nucleoside RTI was seen in 45 (56%) of the 80 patients tested, to non-nucleoside RTIs in eight (10%), and to PIs in one (1.3%). Multivariate regression analysis showed factors associated with resistance to be initial treatment with dual therapy (P = 0.04) compared with highly active antiretroviral therapy, and maximal initial viral load response (P = 0.006). CONCLUSION: Our results demonstrate a high prevalence of ARV drug resistance associated with dual ARV therapy. These results indicate the limited role for dual ARV therapy.

Adult↗

Environmental factors in inflammatory bowel disease: a co-twin control study of a Swedish-Danish twin population.

BACKGROUND: Genetics and environmental factors are implicated in the etiology of inflammatory bowel disease (IBD). We studied environmental factors in a population-based Swedish-Danish twin cohort using the co-twin control method. SUBJECTS AND METHODS: A questionnaire was sent to 317 twin pairs regarding markers of exposures in the following areas: infections/colonization and diet as well as smoking, appendectomy, and oral contraceptives. Odds ratios (OR) were calculated by conditional logistic regression. When confounding appeared plausible, multivariate conditional logistic regression was added. The questions were also divided into topic groups, and adjustment was made for multiple testing within each of the groups. RESULTS: The response rate to the questionnaire was 83%. In consideration of the study design, only discordant pairs were included (Crohn's disease [CD], n = 102; ulcerative colitis [UC], n = 125). Recurrent gastrointestinal infections were associated with both UC (OR, 8.0; 95% confidence interval [CI], 1.0-64) and CD (OR, 5.5; 95% CI, 1.2-25). Hospitalization for gastrointestinal infections was associated with CD (OR, 12; 95% CI, 1.6-92). Smoking was inversely associated with UC (OR, 0.4; 95% CI, 0.2-0.9) and associated with CD (OR, 2.9; 95% CI, 1.2-7.1). CONCLUSIONS: The observed associations indicate that markers of possible infectious events may influence the risk of IBD. Some of these effects might be mediated by long-term changes in gut flora or alterations in reactivity to the flora. The influence of smoking in IBD was confirmed.

Adult↗

Family communication and mental health after breast cancer.

In the context of a traumatic event, such as a breast cancer diagnosis, talking with others about the event can facilitate emotional adjustment and meaning-finding. Among women with a history of breast cancer, open communication is likely to be of particular importance in the family setting, as the family is frequently a primary source of support. The goal of this cross-sectional survey study was to determine the association between open family communication about cancer and breast cancer survivors' mental health. Responses from 230 women at various stages post-treatment suggest that the majority of women are able to talk openly with their family about breast cancer. Multivariate regression analysis further indicates that open family communication is independently associated with better mental health outcomes. Given that many women live long after a breast cancer diagnosis, maintaining mental health functioning is an important long-term goal. Efforts to enhance productive communication between patients and their family members may help women cope with and overcome the challenges of breast cancer survivorship.

Adaptation, Psychological↗

Oxidized LDL and small LDL particle size are independently predictive of a selective defect in microcirculatory endothelial function in type 2 diabetes.

AIM: To explore the associations of LDL (low-density lipoprotein) particle size and oxidized LDL with endothelium-dependent function of the forearm microcirculation in diabetes. METHODS: Endothelium-dependent function was examined in 43 middle-aged men and women with type 2 diabetes and 10 age-matched controls. All received aspirin to inhibit endothelial cyclo-oxygenase. Forearm blood flow (FBF) was measured using venous occlusion plethysmography with separate administration of acetylcholine (ACh) and bradykinin (BK) into the brachial artery. Endothelium-independent function was assessed using sodium nitroprusside (SNP). N(G)-monomethyl-L-arginine (L-NMMA) was co-infused with ACh (ACh + L-NMMA) and BK (BK + L-NMMA) to assess non-NO-mediated contributions to endothelium-dependent function. RESULTS: Subjects with diabetes had impaired endothelium-dependent and endothelium-independent function compared with controls (p < 0.01 for ACh, BK and SNP). In multivariate regression analysis, LDL size (r = 0.41 and p = 0.007), oxidized LDL (r = -0.41 and p = 0.007) and duration of diabetes (r = -0.37 and p = 0.02) predicted FBF response to ACh independently of age, gender and systolic blood pressure. There were no associations between LDL size, oxidized LDL, duration of diabetes and FBF response to BK, SNP, ACh + L-NMMA or BK + L-NMMA. CONCLUSION: In type 2 diabetes, small dense LDL particles, duration of diabetes and oxidized LDL may independently contribute to endothelial dysfunction of the microcirculation. These disturbances may occur via a selective defect, because ACh and BK activate endothelial NO synthase via different G-protein signal transduction pathways.

Acetylcholine↗

Mortality of Swedish horses with complete life insurance between 1997 and 2000: variations with sex, age, breed and diagnosis.

The aim of this study was to evaluate the potential usefulness of the database maintained by the Swedish insurance company Agria for providing mortality statistics on Swedish horses. Mortality statistics (incidence rates and survival) were calculated, both crudely and stratified by sex, age, breed, breed group and diagnosis, for the horses with complete life insurance, which covers most health problems. The total mortality was 415 (95 per cent confidence interval [CI] 399 to 432) deaths per 10,000 horse-years at risk, and the diagnostic mortality, including only deaths with an assigned diagnosis, was 370 (95 per cent CI 355 to 386) deaths per 10,000 horse-years at risk. The diagnostic mortality of geldings was 459 (95 per cent CI 431 to 487), of mares 345 (95 per cent CI 322 to 365) and of stallions 214 (95 per cent CI 182 to 247) deaths per 10,000 horse-years at risk. The mortality rates increased with age and differed widely between breeds. Survival analysis showed that the median age at death of the horses enrolled before they were one year of age was 18.8 years. The most common cause of death or euthanasia was joint problems, which were responsible for 140 (95 per cent CI 130 to 149) deaths per 10,000 horse-years at risk. The results of multivariable models developed by using Poisson regression generally agreed well with the crude results.

Age Distribution↗

Prognostic significance of changes in short-term prostate volume and serum prostate-specific antigen after androgen withdrawal in men with metastatic prostate cancer.

OBJECTIVE: Endocrine therapy is the standard treatment for metastatic prostate cancer although progression to androgen independence is inevitable. To evaluate prognostic factors in metastatic prostate cancer, patients who had been treated with endocrine therapy were investigated especially for the change in prostate volume. METHODS: Fifty-nine patients with untreated metastatic prostate cancer who received endocrine therapy were included in the present study. Blood chemistry, histological grade, extent of bony metastasis, clinical response to hormone therapy including the short-term change in prostate volume and serum prostate-specific antigen (PSA), and prognosis of the patients were evaluated. RESULTS: With univariate analysis, hemoglobin concentration, serum alkaline phosphatase, lactate dehydrogenase (LDH), histological grade, extent of bony disease, the short-term change of prostate volume and response of PSA at 3 months were shown to be significant prognostic factors. Response of PSA, LDH and the change in prostate volume were significant for predicting prognosis with multivariate analyses. Five-year survival rate in patients whose prostate had regressed 20% or more at 1 month and whose PSA had been normalized at 3 months was 67%, whereas that in patients whose prostate had regressed less than 20% and whose PSA had not been normalized was 0%. CONCLUSIONS: The patients in whom PSA had not been normalized at 3 months and the prostate volume had regressed less than 20% at 1 month were in the high-risk group. New or more aggressive treatment should be considered.

Aged↗

Gender, weight concerns, and adolescent smoking.

This study examined the beliefs that adolescents' hold regarding smoking and weight. In particular, this study examined the relationship between smoking status and self-perceptions of body weight. In addition, it examined gender and age differences in adolescent male and female smokers' beliefs about smoking and weight control. Analyses were conducted on the telephone interview responses of 1,200 adolescent smokers and nonsmokers between the ages of 12 and 17. Chi-square analyses were utilized for univariate comparisons, and logistic regression for multivariate comparisons. Results revealed gender and age differences in perceptions of body weight. In addition, female smokers were more likely than male smokers to adhere to the belief that smoking controlled weight. While no relationship was observed between males' perceived weight and their smoking status, females who perceived themselves to be either overweight or underweight were more likely to smoke. Findings suggest a gender bias in processing social/environmental cues linking smoking and weight control.

Adolescent↗