Association of elevated levels of vascular endothelial growth factor in obstructive sleep apnea syndrome with patient age rather than with obstructive sleep apnea syndrome severity

BACKGROUND: Although certain studies report high levels of vascular endothelial growth factor (VEGF) in obstructive sleep apnea syndrome (OSAS), the effect of systemic hypoxia on circulating VEGF remains controversial. OBJECTIVES: To study the association of serum VEGF and OSAS in a large group of patients. METHODS: One hundred patients with OSAS (mean age 58.1+/-12.4 years, mean body mass index 30.6+/-5.4 kg/m2) were tested for serum VEGF levels, and the findings were correlated with the severity of OSAS, as determined by the apnea-hypopnea index (AHI) on the basis of polysomnography and background data. RESULTS: The mean AHI was 40.0+/-21.2 (range 10-106). Mean minimal oxygen saturation was 80.6+/-11.7% (range 43-98%) and mean time of oxygen saturation under 90% was 50.0+/-75.0 min (range 0-300 min). The mean VEGF level was 445.2+/-289.8 pg/ml in the study group (vs. 280 pg/ml reported in normal controls). The mean platelet count was 233.8+/-64.4 10(3)/ml and the mean VEGF/platelet ratio was 1.95+/-1.40 pg/10(6). There was no association of VEGF or VEGF/platelets with the severity of OSAS. However, both factors showed a significant correlation with patient age (r=0.224, p=0.01 and r=0.425, p=0.01, respectively). Age was the only parameter to significantly predict VEGF and VEGF/platelets on multivariate analysis (R2=0.713, p=0.001 and R2=0.844, p=0.001, respectively). CONCLUSION: The elevation of serum VEGF in OSAS is not associated with the severity of the disease, but it is associated with patient age. VEGF might be involved in the long-term adaptive mechanism in OSAS, and its age-dependent increase might partly explain the reduced mortality in elderly OSAS patients.     

Right upper lobe 'window' in right main bronchus stenting.

Stent insertion for bronchial stenosis has become common practice in lung transplantation and advanced lung malignancy, and for external compression of the airways for other reasons. Right main bronchus stenting may require blocking the right upper lobe by the stent, placing the patient at risk of recurrent pneumonia and atelectasis. In this study, three patients after insertion of a metal stent to the right main bronchus are described. In all cases, the right upper lobe was covered by the stent, and a laser (Nd:YAG) procedure was used to open a 'window' in the stent toward the right upper lobe with a follow-up of 1 year. We conclude that stent insertion to the right main bronchus may be followed by a laser therapy to open a 'window' toward the right upper lobe.     

The Response to Bronchodilators in Adults is not Predictive of Bronchial-hyperreactivity

Background. In some subjects with suspected asthma who have normal spirometry, administration of bronchodilators (BD) improves expiratory flow rates. The predictive value of this phenomenon in adults is not known. Objectives. To evaluate the predictive value of the response to BD for bronchial hyper-responsiveness (BHR) using the metacholine challenge test (MCT). Patients and methods. The study population included 62 non-smoking adult patients (41.9% women) 29.5 ± 15.5 years of age (range 18–64 years) with suspected asthma with normal spirometry that underwent MCT within 1 week. The response to BD (200 μ g inhaled salbutamol) was compared between subjects with positive and negative MCT using cutoff levels of provocative concentrations of metacholine causing a 20% decrease in forced expiratory volume in 1 second (FEV₁) (PC₂₀) of 4 and 8 mg/mL. Results. Mean (± SD) baseline FEV₁ was 87.8 ± 12% of predicted. After BD administration the mean FEV₁ increased by 4.3 ± 3.9%. The prevalence of BHR was 17.7% and 25.8% for PC₂₀ for PC₂₀ of 4 mg/mL and 8 mg/mL, respectively. The post-BD FEV₁ increment for subjects with positive and negative MCT tests was 3.9% ± 3.3% versus 4.4% ± 4.1%, respectively; p = 0.89, using cutoff of 4 mg/mL. The corresponding figures for cutoff of 8 mg/ml were 4.3% ± 3.1% vs. 4.3% ± 4.2%, respectively; p = 0.8465. There was no correlation between post-BD FEV₁ increment and PC₂₀ values in patients with positive MCT test for the above-mentioned cutoff levels (correlation coefficient r = 0.1645, p = 0.6289; and r = 0.2417, p = 0.4051, respectively). Conclusions. In adults with suspected asthma who have normal spirometry, the response to BD cannot be used to predict BHR.     

Physical illness among all discharged psychiatric inpatients in a national case register

Previous studies have found that although psychiatric patients tend to have more physical illness than the rest of the population, it frequently goes unrecognized and untreated in psychiatric settings. This study investigated rates of reported physical illness among hospitalized psychiatric patients in preparation for national reform in mental health services. Data from the Israeli National Psychiatric Case Registry were analyzed on reported physical illness among all 38,714 psychiatric discharges during 1989–1991. Physical illness was reported for 10.62% of patients under age 25, 14.4% of patients 25 to 44, 34.27% of patients 45 to 65, and 61.26% of patients 65 and older. Rates differed among hospitals. Reported physical illness was considerably lower than expected as compared with other studies. Underdiagnosis is suggested as a possible explanation. Study results were used to add differential payment for physical comorbidity under the new National Health Insurance Law. Other corrective measures are discussed.     

Correlation of 99mTc-DTPA SPECT of the blood-brain barrier with neurologic outcome after acute stroke.

We conducted a study on humans to determine whether quantitative evaluation of blood-brain barrier (BBB) breakdown using the (99m)Tc-diethylenetriaminepentaacetic acid ((99m)Tc-DTPA) SPECT technique at the peak time of stroke evolution can predict neurologic outcome. METHODS: Thirty consecutive patients with acute stroke of the middle cerebral artery occurring >24 h and <48 h before admission were included in the study. Each patient underwent a complete neurologic examination according to the Scandinavian stroke score at 72 h after the stroke (S1) and again at 30 d (S2). The difference between initial and late scores was calculated (Delta S) and used to evaluate the change in neurologic status. A CT scan was obtained on all patients to determine the volume of stroke. The integrity of the BBB was evaluated using (99m)Tc-DTPA brain SPECT. A quantitative index of BBB disruption was defined as the ratio of the mean counts/pixel in the infarcted region compared with the mean counts/pixel in the contralateral nonaffected hemisphere. SPECT perfusion imaging was also performed with (99m)Tc-hexamethylpropyleneamine oxime ((99m)Tc-HMPAO) at 24 h after the (99m)Tc-DTPA study. The relative perfusion in the infarct region was expressed as the percentage of contralateral perfusion. RESULTS: The mean (99m)Tc-DTPA disruption index was 6.8 +/- 6.9 (range, 1-26.2). Seven patients (23%) had no BBB disruption. Statistical analysis showed that the disruption index was negatively correlated with Delta S (r = -0.423, P < 0.02). A disruption index of <2.5 was associated with a significantly better neurologic outcome (mean Delta S, 17.5 +/- 9.5) compared with patients with an index of >2.5 (mean Delta S, -0.85 +/- 4.97, P < 0.0001) with a sensitivity of 95% and a specificity of 89%. S2 was significantly correlated with S1 (r = 0.738, P < 0.001) and with Delta S (r = 0.656, P < 0.001). Perfusion abnormalities on the (99m)Tc-HMPAO SPECT studies ranged between 12% and 90% (mean, 37.6% +/- 17.8%) compared with those on the contralateral nonaffected side. No correlation was found between (99m)Tc-HMPAO uptake and Delta S, infarct volume by CT, or disruption index. The CT volume measurements were negatively correlated with S2 (r = -0.560, P < 0.004) but not with Delta S. CONCLUSION: (99m)Tc-DTPA SPECT of the BBB combined with quantitative analysis in patients with acute stroke is significantly related to clinical outcome, with a distinct prognostic cutoff threshold of 2.5. The use of this radionuclide brain SPECT technique represents a unique application of conventional nondiffusible brain agents.     

Halothane Prevents Postischemic Production of Hydroxyl Radicals in the Canine Heart

Background: Recent studies indicate that during regional myocardial ischemia and subsequent reperfusion, volatile anesthetics may provide protection against free radical-related injury. The effect of halothane on free radical production during ischemia and reperfusion, in the canine heart, was investigated. The level of hydroxyl radical ([center dot] OH)-mediated conversion of salicylate to its dehydroxybenzoate derivatives (2,3-DHBA and 2,5-DHBA) was monitored.

Methods: Under general anesthesia, the heart was exposed through median sternotomy. Salicylate (100 mg/kg given intravenously) was administered 30 min before left anterior descending artery occlusion. Six dogs were studied using inhaled halothane (1.6%) 10 min before and during the 10-min ischemic period, followed by 50 min of reperfusion, and then they were compared with seven other dogs used as controls. Blood concentrations of salicylate, 2,3-DHBA and 2,5-DHBA, K+, lactate, oxygen content, and pH were monitored.

Results: An acute increase in the normalized concentrations of 2,3-DHBA and 2,5-DHBA was observed in the control animals during reperfusion. In contrast, halothane inhalation completely inhibited the production of both metabolites (P < 0.02), but 2,5-DHBA concentrations in the halothane-treated group were even less than the basal level (P <0.05).

The increase in lactate concentrations in the experimental animals was significantly less than that of controls (P < 0.05) and followed the same time-dependent pattern as the changes in K+ and pH. Halothane significantly decreased (P < 0.0001) the difference in oxygen content between coronary sinus and aortic root blood, suggesting decreased oxygen utilization during reperfusion.     

Genetic screening for autosomal recessive nonsyndromic mental retardation in an isolated population in Israel

Nonsyndromic mental retardation (NSMR) is the diagnosis of exclusion in mentally retarded individuals without additional abnormalities. We have recently identified a protein-truncating mutation, G408fsX437, in the gene CC2D1A on chromosome 19p13.12 in nine consanguineous Israeli Arab families with severe autosomal recessive NSMR, and have developed a comprehensive prevention program among the at-risk population in the village. The subjects tested were healthy women who were invited to undergo the genetic screening test as a part of their routine pregnancy monitoring. One hundred and seventeen subjects reported a family history positive for mental retardation. We tested 524 pregnant or preconceptional women and found 47 carriers (approximately 1/11), whose spouses were then recommended to undergo testing. We identified eight carrier couples, who were given genetic counseling and offered prenatal diagnosis. Of all the marriages, 28.6% were consanguineous; 16.5% of the total were between first cousins. The high prevalence of the mutation can be explained both by the founder effect owing to the generally high consanguinity rate among the inhabitants of the village, and also because two families with excessive numbers of mentally retarded offspring were unacceptable as marriage partners by the rest of the families. This is the first example of the establishment of a large-scale genetic screening program for autosomal recessive NSMR, which was made possible owing to the high frequency of the specific causative mutation in this isolated population.