Pneumothorax in cystic fibrosis

BACKGROUND: Spontaneous pneumothorax is a complication that is commonly reported in patients with cystic fibrosis (CF). An understanding of the pathophysiology of this complication and its consequences is important for the management of patients with CF. OBJECTIVE: To identify risk factors associated with pneumothorax and to determine the prognosis of CF patients following an episode of pneumothorax. DESIGN: A retrospective observational cohort study of the National Cystic Fibrosis Patient Registry between the years 1990 and 1999. PATIENTS: The registry contained data on 28,858 patients with CF who had been followed up over those 10 years at CF centers across the United States. RESULTS: Pneumothorax occurred with an average annual incidence of 0.64% and in 3.4% of patients overall. There was no increased occurrence by sex, but CF was more prevalent in older patients (mean [+/- SD] age, 21.9 +/- 9.1 years) with more severe pulmonary impairment (nearly 75% of patients with FEV1 of < 40% predicted). The principal risks associated with an increased occurrence of pneumothorax included the presence of Pseudomonas aeruginosa (odds ratio [OR], 2.3), Burkholderia cepacia (OR, 1.8), or Aspergillus (OR, 1.3) in sputum cultures, FEV1 < 30% predicted (OR, 1.5), enteral feeding (OR, 1.7), Medicaid insurance (OR, 1.1), pancreatic insufficiency (OR, 1.4), allergic bronchopulmonary aspergillosis (OR, 1.5), and massive hemoptysis (OR, 1.4). There is an increased morbidity (eg, increased number of hospitalizations and number of days spent in the hospital) and an increased 2-year mortality rate following pneumothorax. CONCLUSION: Pneumothorax is a serious complication in CF patients, occurring more commonly in older patients with more advanced lung disease. Nearly 1 in 167 patients will experience this complication each year. There is an attributable mortality to the complication and considerable morbidity, resulting in increased health-care utilization and a measurable decline in lung function.     

Paroxysmal sympathetic storm

Introduction: Paroxysmal sympathetic storm (PSS) is a rare syndrome characterized by episodic hypertension, hyperhydrosis, hyperthermia, tachycardia, tachypnea, and extensor posturing. Case reports: This article describes two cases of PSS: one following traumatic brain injury and the other following cardiac arrest. Discussion: The first responded to labetalol, morphine, and codeine, whereas the second responded to labetalol. Conclusion: These observations underscore the importance of central opioid receptors and nonselective β-adrenergic antagonists in modulating catecholamine pathways     

A Prospective Evaluation of Positron Emission Tomography Scanning,Sentinel Lymph Node Biopsy,and Standard Axillary Dissection for Axillary Staging in Patients with Early Stage Breast Cancer

Background: Positron emission tomography (PET) is a noninvasive imaging modality that can detect malignant lymph nodes. This study determined the sensitivity, specificity, predictive values, and likelihood ratios of PET scanning compared with standard axillary lymph node dissection (ALND) and sentinel lymph node biopsy (SLNB) in staging the axilla in women with early stage breast cancer.Methods: Women with clinical stage I or II breast cancer had whole body PET scanning before ALND and SLNB, in a prospective, blinded protocol. ALND were evaluated by standard hematoxylin and eosin (H&E) staining techniques, while sentinel nodes were also examined for micrometastatic disease.Results: A total of 98 patients were recruited. PET compared with ALND demonstrated sensitivity of 0.40 (95% CI, 0.16, 0.68), specificity 0.97 (CI, 0.90, 0.99), positive likelihood ratio 14.4 (CI, 3.21, 64.5), positive predictive value 0.75 (CI, 0.35, 0.97), and false–negative rate of 0.60 (CI, 0.32, 0.84). Test properties were similar for PET compared with sentinel nodes positive by H&E staining. A few false–positive scans (0.028, CI, 0.003, 0.097) were seen. Multiple logistic regression analysis found that PET accuracy was better in patients with high grade and larger tumors. Increased size and number of positive nodes were also associated with a positive PET scan.Conclusions: The sensitivity of PET compared with ALND and SLNB was low, whereas PET scanning had high specificity and positive predictive values. The study suggests that PET scanning cannot replace histologic staging in early stage breast cancer. The low rate of false–positive findings suggests that PET can identify women who can forego SLNB and require full axillary dissection.     

"The lion, the witch and the wardrobe": impact on sibs of individuals with AAT deficiency

Alpha(1)-antitrypsin (AAT) deficiency is a genetic disorder that may cause serious pulmonary or liver impairment in children or adults. Although genetic sequencing of the AAT gene has only been available for 20 years, analysis of the amount and electrophoretic mobility of the AAT protein has allowed clinical phenotyping for more than 40 years. There have been no studies assessing the psychological impact of having a sib affected by AAT deficiency. Twenty-five participants drawn from the Alpha-1 Research Registry completed a questionnaire and semi-structured interview. Respondents were supportive of testing prior to adulthood for AAT status; 18 thought it was a good idea to test a child, three did not know, and four said children should not be tested, primarily citing insurance concerns. Of those 18 who stated it was a good idea, 14 would test at birth. Knowledge of genetics of AAT deficiency was limited; only 44% of respondents understood the inheritance pattern. We recommend: (1) parents and sibs need help in mourning the loss of children with AAT deficiency; young sibs are at risk for trauma and long-term developmental problems. (2) Teams evaluating donors for liver transplantation should be aggressive in ruling out AAT deficiency prior to invasive testing. (3) Testing should be offered to individuals with a family history of AAT deficiency to obtain the health benefits of lifestyle modification and limit the burden of disease discovery in symptomatic relatives. (4) Awareness of liver disease from AAT deficiency should be increased.     

Pharmacokinetics, ovulation suppression and return to ovulation following a lower dose subcutaneous formulation of Depo-Provera

Depo-Provera is a highly effective contraceptive, given intramuscularly (150 mg/mL) once every 3 months. It has been in use in the United States for over 10 years. A new lower-dose formulation of Depo-Provera (104 mg/0.65 mL), has been developed that allows subcutaneous injection, potentially increasing the convenience, ease of administration and tolerability of this contraceptive. This prospective, randomized, single-center, single-dose trial evaluates the pharmacokinetics of the lower-dose formulation of Depo-Provera and compares the lower-dose formulation to the original formulation with regard to efficacy and duration of ovulation suppression and the return to ovulation at 12 months. While delivering a 30% lower total dose than the intramuscular formulation, the lower-dose formulation of Depo-Provera suppressed ovulation for more than 13 weeks in all subjects and was not affected by body mass index or race. Median time for return to ovulation was 30 weeks, with a 97.4% cumulative rate of return to ovulation at 12 months.     

Ferrara intracorneal ring segments for keratoconus

PURPOSE: To assess the outcome of Ferrara intracorneal ring segments for keratoconus. SETTING: Private practice and university hospital, Porto Alegre, Brazil. METHODS: In this retrospective noncomparative interventional case series, 51 keratoconus eyes of 47 patients that had Ferrara intracorneal ring segment implantation were reviewed. Uncorrected visual acuity (UCVA), best spectacle-corrected visual acuity (BSCVA), central corneal curvature, corneal astigmatism, surface regularity index, surface asymmetry index, and complications were analyzed. RESULTS: At a mean follow-up of 13.0 months +/- 8.7 (SD), the BSCVA improved in 86.4% of eyes, was unchanged in 1.9%, and worsened in 11.7%. The UCVA improved in 86.4% of eyes, was unchanged in 7.8%, and worsened in 5.8%. The mean spherical equivalent (SE) was reduced from -6.08 +/- 5.01 diopters (D) to -4.55 +/- 5.71 D and the mean refractive astigmatism, from -3.82 +/- 2.13 D to -2.16 +/- 2.07 D. The mean central corneal curvature was reduced from 48.76 +/- 3.97 D to 43.17 +/- 4.79 D. Eyes with central keratoconus had statistically significantly better results than eyes with inferior keratoconus in topographic astigmatism, SE, and refraction cylinder. Penetrating keratoplasty was avoided in 38 eyes (74.5%) during the follow-up. Intracorneal ring segment decentration occurred in 2 eyes (3.9%), segment extrusion in 10 eyes (19.6%), bacterial keratitis in 1 eye (1.9%) with segment extrusion, and a disciform keratitis in 1 eye (1.9%). CONCLUSION: Implantation of Ferrara intracorneal ring segments in patients with keratoconus was a safe and reversible procedure that led to stable results and avoided or delayed PKP in many cases.     

Solution structure of amyloid beta-peptide (25-35) in different media

The design of molecules able to interact with the amyloid peptides either as inhibitors of fibril formation or as inhibitors of amyloid membrane pore formation represents one of the most relevant approaches in the development of anti-Alzheimer therapies. Abeta-(25-35), sequence GSNKGAIIGLM, is a highly toxic synthetic derivative of amyloid beta-peptides (Abeta-peptides), which forms fibrillary aggregates. Here, we report the NMR and CD investigation of Abeta-(25-35) in a membrane-mimicking environment and in isotropic mixtures of water and fluoro-alcohols to scan its conformational properties as a function of the medium. The analysis of the 3D structures in the mentioned conditions indicates a propensity of the peptide to behave as a typical transmembrane helix in the lipidic environment. In media characterized by different polarity, it loses the structural regularity at specific points of the sequence as a function of the environment. Furthermore, a comparison with the solution structure of full-length amyloid peptides suggests a role for the 25-27 kink region, which appears to be a general feature of all peptides under the solution conditions explored.