Results of the ACTH stimulation test in hirsute women

OBJECTIVE: To determine the incidence of late-onset congenital adrenal hyperplasia (LOCAH) due to 21-hydroxylase deficiency among hirsute women and to evaluate the results of the ACTH stimulation test with the clinical characteristics. STUDY DESIGN: Prospective, controlled study. One hundred women with hirsutism and 14 normally cycling women without hirsutism were included in this study at the Division of Reproductive Endocrinology, Department of Obstetrics and Gynecology, Cerrahpasa School of Medicine, Istanbul University. After basal serum progesterone (P) and 17 hydroxyprogesterone (17OHP) levels were determined, an ACTH stimulation test was performed on cycle day 3-5. The same parameters were checked 30 minutes later. We estimated the 21 hydroxylase activity by calculating the change in 17OHP (17OHP 30-0) and the summed rate of the change in P and 17OHP ([P30-0] + [17OHP30-01/30 minutes). The 95th percentile for these estimates in normal women were calculated, and values above three times the 95th percentile were considered to distinguish women with LOCAH due to 21-hydroxylase deficiency. RESULTS: The 95th percentile for 17OHP 30-0 and (P30-0) + (17OHP30-0)/30 minutes in normal women was 1.6 and 8.9 ng/dL/min, respectively. Regarding 17OHP 30-0 values, three women with hirsutism had levels above three times the 95th percentile of these estimates, and 28 women had estimates of more than the 95th percentile but less than threefold. Seventeen of 28 women had oligomenorrhea, and all had severe hirsutism. The women with severe hirsutism and oligomenorrhea had significantly higher ACTH-stimulated serum 17OHP levels and values for 17OHP 30-0 and (P30-0 + (17OHP30-0)/30 min) than did normally cycling women. CONCLUSION: The incidence of LOCAH due to 21-hydroxylase deficiency and mild 21-hydroxylase deficiency is 3% and 28%, respectively, in women with hirsutism. Clinical characteristics are not helpful in determining 21-hydroxylase deficiency. However, the incidence of 21-hydroxylase deficiency is more common among women with severe hirsutism and oligomenorrhea. The change in serum 17OHP 30-0 seems to be greater than the summed rate of change in serum 17OHP and P in the detection of 21-hydroxylase enzyme deficiency.     

The value of serum Bcl-2 levels in advanced lung cancer patients

Overexpression of the Bcl-2 protein was associated with a favorable prognostic factor for survival in lung cancer patients, especially nonsmall cell lung carcinoma. The present study was conducted to investigate the value of serum Bcl-2 levels in advanced lung cancer patients. Fifty patients with advanced lung carcinoma pathologically verified and 18 healthy controls were investigated. Serum samples were obtained on the first admission before the chemotherapeutic treatment were given. Serum Bcl-2 levels were determined by using anti-Bcl-2 monoclonal coating antibody. The baseline serum Bcl-2 levels were significantly higher in patients with lung cancer than in the control group (p<0.001). Serum Bcl-2 levels were elevated in 48 (96%) advanced lung cancer patients. None of the prognostic parameters analyzed, such as age of patient, gender, histology, stage of disease, erythrocyte sedimentation rate, serum albumin, hemoglobin, CEA, NSE, LDH, performance of patient, weight loss, and response to chemotherapy, was significantly correlated with Bcl-2 serum concentrations. The serum Bcl-2 concentrations were not changed with cisplatin-based cytotoxic chemotherapy regardless of response (p=0.76). No prognostic value of serum Bcl-2 was determined. In conclusion, the results of the present study, which is the first study to determine serum Bcl-2 levels in lung cancer, suggest that decreased apoptosis occurred due to the effect of serum Bcl-2 elevation in lung cancer patients. Serum Bcl-2 level was of diagnostic but not prognostic value in lung cancer patients. However, more studies are needed to define the role of Bcl-2 in the diagnosis and prognosis of lung cancer.     

The effect of preventive use of alanyl-glutamine on diaphragm muscle function in cecal ligation and puncture-induced sepsis model

BACKGROUND: Low muscle glutamine levels during sepsis are associated with reduced protein synthesis and elevated protein breakdown, in particular myofibrillar protein breakdown. Thus, in a cecal ligation and puncture (CLP)-induced sepsis model in the rat, we hypothesized that glutamine pretreatment would protect the diaphragm muscle function. METHODS: Eighty-four male Wistar rats weighing between 180 g and 200 g received standard amino acid solution 1.2 g kg(-1) per day intraperitoneally (IP) or standard amino acid solution 1.2 g kg(-1) per day plus alanyl-glutamine (GLN) 0.25 g kg(-1) per day (IP) during the first 6 days of the experiment. On the seventh day, CLP or sham procedures were applied. The sham and CLP groups were equally divided into 3 subgroups according to the termination of the experiment, which took place at either the 24th hour, 48th hour, or 72nd hour. After the compound muscle action potentials (CMAP) were recorded from the diaphragms of the rats at these selected times, they were decapitated under ketamine/xylazine anesthesia, and diaphragms were harvested for biochemical and histopathological examination. RESULTS: The mean area and amplitude of CMAP were significantly larger in sham+GLN groups when compared with CLP and CLP+GLN groups at all times (p < .05). Diaphragm Ca+2 -ATPase levels were found to be significantly decreased in CLP group at all times compared to sham groups (p < .05). Diaphragm reduced glutathione levels were significantly higher in sham+GLN groups when compared with CLP and CLP+GLN groups at all times (p < .05). In histopathologic assessment, moderate neutrophil infiltration, which was observed in CLP48, was significantly reduced with alanyl-glutamine supplementation in CLP+GLN48 group (p < .05). CONCLUSIONS: This study showed that glutamine pretreatment did not improve diaphragm muscle function, but prevented the biochemical and histopathological changes in diaphragmatic muscle in CLP-induced sepsis. However, further studies are needed to clarify whether a higher dose of glutamine supplementation might protect the diaphragmatic muscle functions.     

The comparison of the efficacy of scoring systems in organophosphate poisoning

The purpose of this study was to evaluate the impact of the Glasgow Coma Scale (GCS), Acute Physiology and Chronic Health Evaluation (APACHE) II and Simplified Acute Physiology Score (SAPS) II scoring systems for organophosphate poisoning (OPP) in an intensive care unit (ICU). The following data were collected on all consecutive patients who were admitted to the ICU between June 1999 and December 2004. Demographic data, GCS, APACHE II and SAPS II scoring systems were recorded. Predicted mortality was calculated using original regression formulas. Standardized mortality ratio (SMR) was computed with 95% confidence intervals (CI). The sensitivity and specificity for each scoring system were evaluated by calculating the Area Under the Receiver Operating Characteristic Curves. The actual mortality in OPP was 21.9%. Predicted mortality by all systems was not significantly different from actual mortality [SMR and 95% CI for GCS: 1.00 (0.65 1.35), APACHE II: 0.87 (0.54-1.03), SAPS II: 1.40 (0.98-1.82)]. The area under the ROC curve for APACHE II is largest, but there is no statistically significant difference when compared with SAPS II and GCS (GCS 0.900 +/- 0.059, APACHE II 0.929 +/- 0.045 and SAPS II 0.891 +/- 0.057). In our ICU group of patients, in predicting the mortality rates in OPP, the three scoring systems, which are GCS, APACHE II and SAPS II, had similar impacts; however, GCS system has superiority over the other systems in being easy to perform, and not requiring complex physiologic parameters and laboratory methods.     

Rate-dependent AV delay optimization in cardiac resynchronization therapy

BACKGROUND: During cardiac resynchronization therapy (CRT), cardiac performance is dependent on an optimized atrioventricular delay (AVD). However, the optimal AVD at different heart rates has not been defined yet during CRT. METHOD: The effects of an increase in heart rate by pacing or physical exercise on optimal AVD were studied in 36 patients with biventricular pacemakers/defibrillators. The velocity time integral (VTI) in the left ventricular outflow tract (LVOT) was measured with pulsed Doppler either at three different paced heart rates in the supine position or in seated position before and after physical exercise. RESULTS: The baseline AVD was optimized to 99 +/- 19 ms in the supine and 84 +/- 22 ms in the seated position. When the heart rate was increased by DDD pacing, there was a positive linear relationship between an increase in heart rate, in AVD and in VTI (LVOT-VTI + 0.047 cm/s per 10 beats per minute (bpm) heart rate increase per 20 ms increase in AVD, P = 0.007). A similar but more pronounced relationship was found after physical exercise in the seated position (LVOT-VTI + 0.146 cm/s per 10 bpm heart rate increase per 20 ms increase of AVD, P = 0.013). This effect was observed in patients with and without AV block and mitral regurgitation. CONCLUSIONS: In conclusion, the systolic performance of the dilated ventricle, which depends on an elevated preload, is critically affected by the appropriate timing of the AVD during exercise. In contrast to normal pacemaker patients, in CRT the relatively short baseline AVD should be prolonged at increased heart rates. Further studies with other means of measuring exercise cardiac performance are needed to confirm these unexpected findings.     

Mechanisms of atrial fibrillation: lessons from studies in patients

Recent clinical studies performed in human subjects have provided important clues that improved our understanding of the mechanisms of atrial fibrillation (AF) and facilitated development of new treatment strategies. When analyzed together, these studies confirm the complexity and multifactorial nature of AF. Because a variety of mechanisms such as focal drivers within the thoracic veins, rotors in the left atrium, multiple reentrant circuits, and autonomic innervation may play a role in the initiation and maintenance of AF alone or in combination, the best strategy to eliminate AF may be the accurate identification of one or more of the mechanisms critical to the genesis of AF and to target the specific mechanism(s).     

N-Acetylcysteine for Preventing Pump-Induced Oxidoinflammatory Response During Cardiopulmonary Bypass

Purpose To investigate the effect of N-acetylcysteine on preventing pump-induced oxidoinflammatory response during cardiopulmonary bypass (CPB).Methods Forty patients undergoing coronary artery bypass grafting (CABG) were randomly divided into a study group (n = 20), given 50mgkg^–1 N-acetylcysteine intravenously for 3 days, and a control group (n = 20) given saline. Serum samples were collected for measurement of myeloperoxidase (MPO), malondialdehyde (MDA), interleukin-6, ₁-acid glycoprotein (AAGP), and C-reactive protein (CRP) during surgery and postoperatively.Results The MPO and MDA values showed a similar pattern during and after CPB in the study group, with significantly less variance than in the control group. Interleukin-6 showed similar patterns in the two groups, but the data from 30min after the start of CPB and from 6h post-CPB were significantly different. The AAGP and CRP values were both elevated during CPB in the two groups without a significant difference, but 6 and 24h post-CPB, the values were significantly higher in the control group than in the study group.Conclusions N-Acetylcysteine decreased pump-induced oxidoinflammatory response during CPB, suggesting that it could be a novel therapy for assisting in the prevention of CBP-induced oxidoinflammatory damage.     

Incremental value of isolating the right inferior pulmonary vein during pulmonary vein isolation procedures in patients with paroxysmal atrial fibrillation

Electrical isolation of the left superior, left inferior, and right superior pulmonary veins (PVs) is often, but not always, effective in eliminating paroxysmal atrial fibrillation (PAF). The incremental clinical value of also isolating the right inferior PV has not been well defined. PV isolation by ostial applications of radiofrequency energy guided by PV potentials was performed in 176 consecutive patients (mean age 52 +/- 11 years) with PAF. The left superior, left inferior, and right superior PVs were targeted in 106 patients, and all four PVs were targeted 70 patients. Successful isolation was achieved in 96% of targeted PVs. The mean duration of follow-up was 15 +/- 7 months. At 1-year follow-up, 58% of patients in whom three PVs were isolated were free of recurrent PAF in the absence of antiarrhythmic drug therapy, compared to 73% of patients in whom all four PVs were isolated (P = 0.07). There is a trend towards a better outcome when all four PVs are isolated than when only the three major PVs are isolated. Whenever feasible, the right inferior PV should be isolated along with the other three PVs during the first ablation procedure in patients with PAF.     

Mechanism of immediate recurrences of atrial fibrillation after restoration of sinus rhythm

An immediate recurrence of AF may occur after restoration of sinus rhythm. Although pulmonary vein (PV) isolation has been shown to prevent immediate recurrence of AF, the specific trigger for immediate recurrence of AF has not been described. In 89 consecutive patients (mean age 53 +/- 11 years) who had sinus rhythm restored by spontaneous or transthoracic cardioversion in the course of a PV isolation procedure, electrograms recorded within a PV and in the adjacent left atrium were analyzed to determine the mechanism of initiation of immediate recurrence of AF. Immediate recurrence of AF was defined as a recurrence of AF within 90 seconds after restoration of sinus rhythm. There were 124 episodes of immediate recurrence of AF at a mean of 18 +/- 23 seconds after cardioversion. Recordings within the PV that triggered the immediate recurrence of AF were available in 23 (19%) of the 124 immediate recurrence of AF episodes. Among these 23 episodes of immediate recurrence of AF, all (100%) were triggered by a burst of PV tachycardia (P < 0.001). The coupling interval and prematurity index (coupling interval/preceding sinus cycle length) of the premature depolarizations that did and did not trigger immediate recurrence of AF were 246 +/- 67 ms and 0.30 +/- 0.11 vs 378 +/- 117 ms and 0.49 +/- 0.16, respectively (P < 0.01). Immediate recurrence of AF was abolished by PV isolation. The mechanism of immediate recurrence of AF is a burst of PV tachycardia, not a single premature depolarization. Immediate recurrence of AF identifies patients with AF in whom the PVs may play a major role in the initiation of AF.