Meta-analysis of the association of beta2-adrenergic receptor polymorphisms with asthma phenotypes

BACKGROUND: Two common polymorphisms of the beta2-adrenergic receptor gene (Arg16Gly and Gln27Glu ) have been extensively studied for their possible association with asthma-related phenotypes, but the results of individual studies have been inconclusive. OBJECTIVE: We aimed to integrate quantitatively the available evidence on the association of the Arg16Gly and the Gln27Glu polymorphisms with asthma, nocturnal asthma, asthma severity, and bronchial hyperresponsiveness. METHODS: Meta-analysis of case-control and cohort studies using random effects models. RESULTS: A total of 28 studies were included in the meta-analysis. The summary estimates suggested that neither the Gly16 nor the Glu27 allele contributes to asthma susceptibility overall (odds ratio [OR], 1.01; 95% CI, 0.90-1.13; and OR, 0.95; 95% CI, 0.83-1.09, respectively) or to bronchial hyperresponsiveness (OR, 0.90; 95% CI, 0.77-1.05; and OR, 1.07; 95% CI, 0.94-1.22, respectively). There was a strong association of Gly16 with nocturnal asthma (OR, 2.20; 95% CI, 1.56-3.11) and a less strong association with severe or moderate rather than milder asthma (OR, 1.42; 95% CI, 1.04-1.94). No such effects were seen for the Glu27 allele (OR, 1.02; 95% CI, 0.74-1.40; and OR, 0.82; 95% CI, 0.59-1.14, respectively). Moreover, there was evidence that Gly16 homozygotes had a much higher risk for nocturnal asthma (OR, 5.15; 95% CI, 2.44-10.84) and asthma severity (OR, 2.84; 95% CI, 1.62-4.96) than the Arg16 homozygotes. CONCLUSION: The Gly16 allele of the beta2-adrenergic receptor gene predisposes to nocturnal asthma, and this may also explain the association with asthma severity. Neither polymorphism modulates the risk for bronchial hyperresponsiveness or mild asthma.     

Epinephrine,vasopressin, and nitroglycerin improve neurologic outcome in porcine asphyxial cardiac arrest

Aim

The aim of the present study was to assess whether the combination of epinephrine, vasopressin, and nitroglycerin would improve initial resuscitation success, 24-hour survival, and neurologic outcome compared with epinephrine alone in a swine model of asphyxial cardiac arrest (CA).

Materials and Methods

This prospective randomized experimental study was conducted at a laboratory research department. Twenty male Landrace/Large-White pigs 12 to 15 weeks of age were investigated. Asphyxial CA was induced by occlusion of the endotracheal tube. Pigs remained untreated for 4 minutes before attempting resuscitation by unclamping the endotracheal tube, mechanical ventilation, chest compressions, and epinephrine (group E) or a combination of epinephrine with vasopressin and nitroglycerin (group EVN) administered intravenously. In case of restoration of spontaneous circulation, the animals were supported for 30 minutes and then observed for 24 hours.

Results

Coronary perfusion pressure and mean arterial pressure were significantly increased during cardiopulmonary resuscitation in group EVN. In both groups, restoration of spontaneous circulation and survival rates were comparable (P value, nonsignificant). At 24 hours after CA, neurologic deficit score was significantly better in animals treated with the combination pharmacotherapy (P < .001). Brain histologic damage score was also higher in group EVN compared with group E (P < .001). Total histologic damage score and neurologic deficit score showed a statistical significant correlation (P < .001).

Conclusion

In this porcine model of asphyxial CA, the addition of nitroglycerin to vasopressin and epinephrine maintained elevated coronary perfusion pressure during asphyxia CA and resulted in significantly better neurologic and histopathologic outcome in comparison with epinephrine alone.     

Multiple Nevoid Hypertrichosis as An Isolated Developmental Defect

Abstract:   A 3-year-old girl presented with longer hair on the left side of her scalp, coarse hair of abnormal length on her extremities, and a tuft of hair in the lumbosacral region, with all hair distributed on normally pigmented skin. Neither similar or relevant family history nor associated extracutaneous abnormalities was detected after a thorough examination. Clinical diagnosis of patchy nevoid hypetrichosis was confirmed by histology. Nevoid hypertrichosis is a rare hair growth disorder that usually presents at or soon after birth. It is characterized by patches of hypertrichosis distributed in a segmental pattern. It may be accompanied by mental, ocular, or myoskeletal abnormalities. Cases of nevoid hypertrichosis with multiple patches presenting as a solitary developmental defect have been rarely described in the literature.     

Influence of 5-Fluorouracil on Serum Lipids

The effect of the cytotoxic drug 5-fluorouracil (5-FU) on plasma lipid levels was studied in patients and animals. Seven patients with metastatic carcinoma of the colon and three with advanced breast cancer were treated with 5-FU monotherapy by i.v. push at a dose of 500 mg/m²/d for 3-5 consecutive days. The animal group comprised 9 rabbits treated with 5-FU by i.v. push at 12-18 mg/kg/d for 2 consecutive days. Measurements of serum lipid levels were performed before and 2 and 4 weeks after 5-FU administration. No obvious change of diet, body weight and bowel habits occurred during the study period. A significant reduction of total plasma cholesterol was observed in both patients and animals. The triglyceride levels were also reduced in the rabbits. Maximal cholesterol-lowering effect was observed in patients and rabbits with higher baseline cholesterol levels. The results suggest that 5-FU might interfere with lipid metabolism.     

Preoperative pulmonary evaluation (PPE) as a prognostic factor in patients undergoing upper abdominal surgery

BACKGROUND/AIMS: Upper abdominal operations are relatively high risk for postoperative pulmonary complications. The influences of general anesthesia and an operative procedure are well known to negatively impact pulmonary gas exchange. For this reason, the preoperative pulmonary evaluation (PPE) should emphasize risk factors for pulmonary complications. The prediction of these complications is still an under-investigated field. The aim of this study is to identify risk indicators for pulmonary complications after elective upper abdominal operations. METHODOLOGY: A standardized PPE was performed on 28 patients (mean age 53 years) who were admitted to the Intensive Care Unit (ICU) of the Hospital of Athens after scheduled extensive upper abdominal surgery. The PPE included physical examination, medical history, smoking history and general laboratory tests including chest X-ray, and arterial blood gases and spirometry. The type of surgical operation and duration of anesthesia were also evaluated. Postoperatively, data was collected on the occurrence of a symptomatic and clinically significant pulmonary complication. RESULTS: All 28 patients (57.2% female, 42.8% male) needed mechanical ventilator (MV) support after surgery because of respiratory failure and the mean time of MV was 4 +/- 2 days. During this period, 6 (21.4%) patients developed nosocomial pneumonia, 3 (10.7%) developed acute respiratory distress syndrome (ARDS), 2 (6.1%) had a small atelectasis and 4 (14.2%) developed bleeding disorders. Eventually, 2 (7.1%) of the patients with ARDS developed sepsis and died during hospitalization in ICU. All patients who developed complications had a medical history of mild COPD, chronic obstructive pulmonary disease (COPD), a smoking history, were operated on for underlying malignancies and also had abnormal preoperative laboratory results. CONCLUSIONS: Pulmonary complications have enormous implications for the patient and the health care system. The first step in reducing postoperative complications is to identify which patients are at increased risk. PPE is the better way to select clinical and laboratory factors that allow risk stratification for postoperative pulmonary complications after upper abdominal surgery.     

Long‐term outcomes of primary systemic light chain (AL) amyloidosis in patients treated upfront with bortezomib or lenalidomide and the importance of risk adapted strategies

Bortezomib and lenalidomide are increasingly used in patients with AL amyloidosis, but long term data on their use as primary therapy in AL amyloidosis are lacking while early mortality remains significant. Thus, we analyzed the long term outcomes of 85 consecutive unselected patients, which received primary therapy with bortezomib or lenalidomide and we prospectively evaluated a risk adapted strategy based on bortezomib/dexamethasone to reduce early mortality. Twenty‐six patients received full‐dose bortezomib/dexamethasone, 36 patients lenalidomide with oral cyclophosphamide and low‐dose dexamethasone and 23 patients received bortezomib/dexamethasone at a dose and schedule adjusted to the risk of early death. On intent to treat, 67% of patients achieved a hematologic response (24% hemCRs) and 34% an organ response; both were more frequent with bortezomib. An early death occurred in 20%: in 36% of those treated with full‐dose bortezomib/dexamethasone, in 22% of lenalidomide‐treated patients but only in 4.5% of patients treated with risk‐adapted bortezomib/dexamethasone. Activity of full vs. adjusted dose bortezomib/dexamethasone was similar; twice weekly vs. weekly administration of bortezomib also had similar activity. After a median follow up of 57 months, median survival is 47 months and is similar for patients treated with bortezomib vs. lenalidomide‐based regimens. However, risk adjusted‐bortezomib/dexamethasone was associated with improved 1‐year survival vs. full‐dose bortezomib/dexamethasone or lenalidomide‐based therapy (81% vs. 56% vs. 53%, respectively). In conclusion, risk‐adapted bortezomib/dexamethasone may reduce early mortality and preserve activity while long term follow up indicates that remissions obtained with lenalidomide or bortezomib may be durable, even without consolidation with alkylators.Am. J. Hematol. 90:E60–E65, 2015. © 2015 Wiley Periodicals, Inc.