22例皮质醇增多症的临床研究

目的：探讨皮质醇增多症的临床表现和内分泌检查等辅助检查的意义.方法：从年龄、性别、病程及实验室检查等方面,观察22例不同原因所致皮质醇增多症患者不同的临床表现和测定实验室检查指标.结果：22例中诊断库欣病（增生型）14例[63.6％,其中13例（92.9％）得到MRI检查证实],肾上腺腺瘤6例[27.3％,均得到MRI检查证实（100％）],另有肾上腺结节样增生1例（4.5％）,异位ACTH综合征1例（4.5％）.临床表现：按出现的频率前4位依次为,库欣病：高血压（100％）、满月脸（92.9％）、向心性肥胖（85.7％）、多血质（85.7％）,肾上腺腺瘤：高血压（100％）、满月脸（100％）、向心性肥胖（100％）、多血质（83.3％）.实验室检查：小剂量地塞米松不能抑制：库欣病与肾上腺腺瘤均为100％.结论：根据高血压、满月脸、向心性肥胖,小剂量地塞米松抑制试验和MRI检查可诊断绝大多数皮质醇增多症.     

Patient‐reported convenience of once‐daily versus three‐times‐daily dosing during long‐term studies of pramipexole in early and advanced Parkinson’s disease

Background and purpose: In chronic diseases including Parkinson’s disease (PD), complex pharmacotherapy dosing schedules are reported to reduce adherence, perhaps leading to less‐effective symptom control and, in PD, more erratic stimulation of dopamine receptors. However, blinded clinical‐trial designs preclude direct comparisons of adherence to various schedules. Methods: In two double‐blind (DB) studies of early PD and one of advanced PD, subjects received three‐times‐daily (t.i.d.) pramipexole or placebo. In open‐label (OL) extensions, subjects took extended‐release, once‐daily (q.d.) pramipexole. At 24 or 32 OL weeks, q.d. versus t.i.d. dosing preference was surveyed by questionnaire. Results: Of 590 DB‐trial completers with early PD, 511 entered the OL extension. Of 374 survey respondents, 94.4% preferred q.d. dosing (72.2% of them found it ‘very much more convenient’ and 27.8%‘more convenient’), 2.7% preferred t.i.d., and 2.9% chose ‘no difference’. Of 465 DB‐trial completers with advanced PD, 391 entered its OL extension. Of 334 survey respondents, 88.9% preferred q.d. dosing (59.9% of them found it ‘very much more convenient’ and 40.1%‘more convenient’), 5.7% preferred t.i.d., and 5.4% chose ‘no difference’. Results excluding DB‐placebo recipients were highly similar. Conclusions: In this first direct comparison of patient preference for q.d. versus t.i.d. dopamine‐agonist dosing, patients with early or advanced PD had a strong preference for q.d. rather than t.i.d. pramipexole. The high proportion of advanced‐PD patients declaring this preference indicates that it does not depend on whether a patient is taking concomitant PD medications dosed more frequently than q.d.     

Estimating the prevalence of drinking problems among physicians

Objective

Surveys assessing alcohol use among physicians have most commonly employed the Alcohol Use Disorders Identification Test (AUDIT) or the AUDIT-C, the most common short version of the AUDIT. As with other screeners, prevalence estimation is dependent on the accuracy of the test as well as choice of the cutoff value. The aim of the current study is to derive more precise prevalence estimates of alcohol problems in physicians by correcting for false-positive and false-negative results.

Method

In the context of a survey, the AUDIT was sent out via email or standard postal service to all 2484 physicians in Salzburg, Austria. A total of 456 physicians participated. A published correction formula was used to estimate the real prevalence of alcohol use problems.

Results

Applying a cutoff of 5 points for the AUDIT-C, 15.7% of female and 37.7% of male physicians screened positive. Use of a correction based on general population data and the sensitivity and specificity of the AUDIT-C resulted in much lower prevalence rates: 4.0% for female and 9.5% for male physicians. Using the full AUDIT, 19.6% of the female physicians and 48% of the male physicians were screened positive. Using the correction, the estimated prevalence rates for females and males were 6.3% and 15.5%, respectively.

Conclusions

Our findings demonstrate that uncorrected screening results may markedly overestimate the prevalence of physicians drinking problems.     

Comparison of the subacute toxicity and efficacy of 3-hydroxypyridin-4- one iron chelators in overloaded and nonoverloaded mice

Five orally effective iron chelators of the 3-hydroxypyridin-4-one series have been administered intraperitoneally to iron-overloaded and nonoverloaded male mice at a dose of 200 mg/kg/24 h for a total of 60 days to investigate the effect on iron loading and toxicity. There was a significant reduction in hepatic iron at the end of the study in the iron-overloaded mice with all compounds studied using chemical iron quantitation (P less than .001) and with Perls' stain (P less than .01). Liver iron removal with the hydroxypyridinones ranged from 37% with CP20 to 63% with CP51, compared with 46% removal for desferrioxamine (DFO). There was no significant reduction in splenic or cardiac iron with any chelator. There were no deaths in iron-overloaded animals receiving any of the hydroxypyridin-4-ones, but significantly more deaths in the nonoverloaded groups as a whole (P less than .03). No weight loss was observed with any chelator. Significant reductions in hemoglobin and white cell count were observed with CP20(L1). No histologic abnormalities of kidney, spleen, bone marrow, or stifle joints were observed. Intracytoplasmic inclusion bodies were observed in the centrilobular hepatocytes of animals administered each of the hydroxypyridin-4-ones, while the DFO-treated and control groups showed no such changes.     

Regional neurovascular coupling and cognitive performance in those with low blood pressure secondary to high-level spinal cord injury: improved by alpha-1 agonist midodrine hydrochloride

Individuals with high-level spinal cord injury (SCI) experience low blood pressure (BP) and cognitive impairments. Such dysfunction may be mediated in part by impaired neurovascular coupling (NVC) (i.e., cerebral blood flow responses to neurologic demand). Ten individuals with SCI >T6 spinal segment, and 10 age- and sex-matched controls were assessed for beat-by-beat BP, as well as middle and posterior cerebral artery blood flow velocity (MCAv, PCAv) in response to a NVC test. Tests were repeated in SCI after 10 mg midodrine (alpha₁-agonist). Verbal fluency was measured before and after midodrine in SCI, and in the control group as an index of cognitive function. At rest, mean BP was lower in SCI (70±10 versus 92±14 mm Hg; P<0.05); however, PCAv conductance was higher (0.56±0.13 versus 0.39±0.15 cm/second/mm Hg; P<0.05). Controls exhibited a 20% increase in PCAv during cognition; however, the response in SCI was completely absent (P<0.01). When BP was increased with midodrine, NVC was improved 70% in SCI, which was reflected by a 13% improved cognitive function (P<0.05). Improvements in BP were related to improved cognitive function in those with SCI (r²=0.52; P<0.05). Impaired NVC, secondary to low BP, may partially mediate reduced cognitive function in individuals with high-level SCI.     

Aprotinin in cardiac surgery patients: is the risk worth the benefit?

Background: Aprotinin is the only Food and Drug Administration-approved agent to reduce haemorrhage related to cardiac surgery and its safety and efficacy has been extensively studied. Our study sought to compare the efficacy, early and late mortality and major morbidity associated with aprotinin compared with e-aminocaproic acid (EACA) in cardiac surgery operations. Methods: Between January 2002 and December 2006, 2101 patients underwent coronary artery bypass grafting (CABG), valve surgery or CABG and valve surgery in our institution with the use of aprotinin (1898 patients) or EACA (203 patients). Logistic regression and propensity score analysis were used to adjust for imbalances in the patients’ preoperative characteristics. The propensity score-adjusted sample included 570 patients who received aprotinin and 114 who received EACA (1–5 matching). Results: Operative mortality was higher in the aprotinin group in univariate (aprotinin 4.3% vs EACA 1%, p = 0.023) but not propensity score-adjusted multivariate analysis (4% vs 0.9%, p = 0.16). In propensity score-adjusted analysis, aprotinin was also associated with a lower rate of blood transfusion (38.8% vs 50%, p = 0.04), a lower rate of haemorrhage-related re-exploration (3.7% vs 7.9%, p = 0.04) and a higher risk of in-hospital cardiac arrest (3.7% vs 0%, p = 0.03) and a marginally but not statistically significantly higher risk of acute renal failure (6.8% vs 2.6%, p = 0.09). In Cox proportional hazards regression analysis, the risk of late death was higher in the aprotinin compared to EACA group (hazard ratio = 4.33, 95% confidence interval (CI) = 1.60–11.67, p = 0.004). Conclusion: Aprotinin decreases the rate of postoperative blood transfusion and haemorrhage-related re-exploration, but increases the risk of in-hospital cardiac arrest and late mortality after cardiac surgery when compared to EACA. Cumulative evidence suggests that the risk associated with aprotinin may not be worth the haemostatic benefit.