It's all about sex: gender, lung development and lung disease.

Accumulating evidence suggests that gender affects the incidence, susceptibility and severity of several lung diseases. Gender also influences lung development and physiology. Data from both human and animal studies indicate that sex hormones might contribute to disease pathogenesis or serve as protective factors, depending on the disease involved. In this review, the influence of gender and sex hormones on lung development and pathology will be discussed, with specific emphasis on pulmonary fibrosis, asthma and cancer.     

Chest Wall Implants: Their Use for Pectus Excavatum,Pectoralis Muscle Tears,Poland's Syndrome,and Muscular Insufficiency

Solid customized and prefabricated silicone implants have been used by the author for 15 years in a wide range of chest wall deformities. Chest wall implants are often used in males seeking to augment a muscularly deficient or underdeveloped chest; however, their greatest use has come in a variety of deformities both congenital and acquired, such as pectus excavatum, Poland's Syndrome, and pectoralis muscle tears. The implants can be either customized using a moulage technique or are prefabricated, manufactured implants which can be modified on the operating table to repair the contour deformity. The immediate postoperative problem of seroma and subcutaneous implant ``show' has been minimized by careful planning, gentle technique, deep insertion, improved patient positioning on the operating room table, and the use of oral anti-inflammatory medications. The long-term results of these implants seem very satisfactory. The patients are usualy physically active, and the implants show no long-term sequelae such as seroma, infection, displacement, or rupture.     

Chlamydial etiology of acute lower respiratory tract infections in children in the Sudan

The role of Chlamydia pneumoniae in 110 Sudanese children with signs of acute lower respiratory tract infections (ALRI) was investigated. Four (3.6%) had evidence of C. pneumoniae infection, of whom 3 were culture-positive, while 1 had an antibody response suggesting a recent infection. IgG antibodies at a titer of ≥1:32 to C. pneumoniae, Chlamydia psittaci and Chlamydia trachomatis were detected in 27 (24.5%), 27 (24.5%) and 7 (6.4%) of the 110 ALRI cases, respectively. C. pneumoniae, C. trachomatis or C. psittaci were not detected in nasopharyngeal secretions from any of 110 patients when fluorescence-labeled specific monoclonal antibodies were used. In a seroepidemiological survey, 318 healthy Sudanese persons aged between 1 month and 67 years were studied for C. pneumoniae antibodies.     

Sweet's syndrome—therapy with cyclosporin

We report the case of a 39-year-old female patient suffering from Sweet's syndrome after an upper respiratory tract infection. Cyclosporin A at a dose of 10 mg/kg per day was given as initial treatment. Skin lesions and general malaise resolved within 9 days. The cyclosporin dose was decreased within 21 days, without recurrence of the eruption. Cyclosporin is a potent inhibitor of T lymphocytes, but affects granulocyte and monocyte functions as well. Success of treatment in our case shows that cyclosporin represents an alternative to steroid treatment in patients with Sweet's syndrome.     

Glucocorticoid receptor enhancement of pregnane X receptor-mediated CYP2B6 regulation in primary human hepatocytes.

Although the glucocorticoid receptor (GR) facilitates the xenobiotic-induced expression of CYP2B in rodents, its role in the regulation of human CYP2B6 is unclear. In this report, the role of human GR in the regulation of CYP2B6 was evaluated using primary human hepatocytes and transfection assays with Huh7 cells. CYP2B6 expression was not induced in primary hepatocytes treated with dexamethasone (DEX) concentrations (0.01-1 microM) known to activate GR. In contrast, treatment with 0.1 microM DEX enhanced CYP2B6 induction by different pregnane X receptor (PXR) activators, including rifampin, phenytoin, clotrimazole, and phenobarbital. In Huh7 cells, cotransfection of human (h)GR and hPXR with CYP2B6-phenobarbital-responsive enhancer module (PBREM) reporter constructs revealed that all hPXR ligands induce CYP2B6 reporter gene activity, and this ligand-dependent activation is greatly enhanced by activated hGR. CYP2B6 reporter gene expression was not induced in the presence of hPXR ligands when hGR alone was cotransfected with CYP2B6 reporter construct. In hGR and human constitutive androstane receptor (hCAR) cotransfection assays, activated hGR increased the constitutive activation of PBREM reporter constructs by hCAR in the absence of inducers. In the presence of activated hGR and known inducers of CYP2B6, only PB treatment caused a further 2-fold activation of hCAR compared with control. These studies show that hGR is involved synergistically in the xenobiotic-responsive regulation of human CYP2B6 by hPXR and hCAR. Moreover, the results suggest that the GR-enhanced expression of CYP2B6 is mediated through an indirect mechanism that does not require increased expression of nuclear receptor.     

Conservatively Treated Breast Cancer: Outcome by Histologic Subtype

Abstract: Between 1970 and 1990, 1,008 patients with early-stage breast cancer were treated by conservative surgery without axillary dissection followed by radiation therapy to the intact breast in the Department of Therapeutic Radiology at Yale-New Haven Hospital. The patient population, broken down by histologic subtype, was as follows: 761 patients presented with infiltrating ductal carcinoma, 70 patients with pure intraductal, 38 intraductal with focal invasion, 54 infiltrating lobular, 21 tubular, 17 medullary, 16 mucinous, and 29 with other various histologic subtypes. Patients were followed on a regular basis by the referring physicians and radiation oncologists. Diagnostic studies for distant metastases were performed as clinically indicated. Annual mammography was a routine component of the follow-up program. As of 3/96, with a median follow-up of 10.5 years, 83 patients developed an ipsilateral breast tumor recurrence, and 109 patients developed distant metastases resulting in an overall 10-year breast recurrence-free rate of 84%, and a 10-year distant metastasis-free rate of 78%. There were significant differences in clinical stage, pathological nodal involvement, and administration of systemic therapy between various histologic subtypes. As expected, those patients with histologies of low metastatic potential (such as intraductal, tubular, and mucinous) had significantly superior distant recurrence-free survival rates. With respect to breast relapse rates, there were no statistically significant differences in the 5- and 10-year breast recurrence-free rates between any of the histologic subtypes. Patients with intraductal carcinoma with or without focal invasion had similar breast relapse rates as those with other histologic subtypes. Patients with lobular carcinoma in situ as a histologic component also had a similar overall breast relapse-free recurrence rate. In conclusion, long-term follow-up of conservatively treated breast cancer patients demonstrates no significant differences in ipsilateral breast tumor recurrence rates between various histologic subtypes. There are no histologies which had a statistically significantly higher breast-relapse rate than infiltrating ductal carcinomas and therefore no primary histologic subtype represents a relative contraindication to breast conservation therapy.