Evidence that gene expression of ovarian follicular tight junction proteins is regulated in vivo and in vitro in cattle.

Tight junctions (TJ) are common paracellular sealing structures that control the transport of water, ions, and macromolecules across cell layers. Because the role of TJ in bovine follicular development is unknown, we investigated the developmental and hormonal regulation of the transmembrane TJ protein, occludin (OCLN), and the cytoplasmic TJ proteins, TJ protein 1 (TJP1) and cingulin (CGN) in bovine granulosa cells (GC) and theca cells (TC). For this purpose, bovine GC and TC were isolated from large (>8 mm) and/or small (1 to 5 mm) follicles and either extracted for real-time PCR (qPCR) or cultured in vitro. The abundances of both and mRNA were greater ( < 0.05) in TC than GC, whereas the mRNA abundance was greater ( < 0.05) in GC than TC. The abundance of mRNA in both GC and TC was greater ( < 0.05) in small follicles compared with large follicles, whereas the GC of large follicles had less ( < 0.05) mRNA abundance than the GC of small follicles. The abundance of mRNA in GC or TC did not differ ( > 0.10) among follicle sizes. In vitro treatment with various growth factors known to affect ovarian folliculogenesis indicated that , , and were hormonally regulated. Fibroblast growth factor 9 (FGF9) decreased ( < 0.05) the and mRNA abundances. Tumor necrosis factor α (TNFα) and vascular endothelial growth factor A (VEGFA) increased ( < 0.05) the mRNA abundance but decreased ( < 0.05) the mRNA abundance. Dexamethasone (DEX) increased ( < 0.05) and mRNA abundances. Epidermal growth factor (EGF) decreased ( < 0.05) and dihydrotestosterone (DHT) increased ( < 0.05) the abundances of , , and mRNA. We propose that the downregulation of OCLN and other TJ proteins during follicular development could reduce barrier function, thereby participating in increasing follicle size by allowing for an increase in the volume of follicular fluid as well as by allowing additional serum factors into the follicular fluid that potentially may directly impact GC functions. The results of the current study indicate the following in cattle: 1) gene expression of TJ proteins (i.e., , , and ) differs between GC and TC and changes with follicle size, and 2) autocrine, paracrine, and endocrine regulators, such as FGF9, EGF, DHT, TNFα, and glucocorticoids, modulate , , and mRNA abundance in TC in vitro.

Posaconazole in lung transplant recipients: use, tolerability, and efficacy.

BACKGROUND: Fungal infection is a common cause of mortality and morbidity in lung transplant recipients (LuTR). Treatment failure to first-line antifungals because of resistance or intolerance is an increasing problem. Posaconazole (PCZ), a triazole antifungal, is an attractive treatment option. METHODS: We performed a single-center retrospective study to describe the use, tolerability, efficacy, and drug interaction effect (with tacrolimus) of PCZ oral suspension in LuTR. RESULTS: Seventy-eight patients were treated with PCZ oral suspension for prophylaxis (n = 15), pre-emptive treatment (n = 31), and treatment of possible (n = 7) and probable (n = 25) invasive fungal infection. A range of fungal isolates was encountered. Resolution was observed in 52.4% (probable, possible, and pre-emptive treatment groups). Aggregate all-cause 1-year mortality was 12.8%. PCZ was well tolerated with 11.5% of patients experiencing adverse effects. Despite dose adjustment strategies, 11.7% of patients experienced supratherapeutic tacrolimus levels, which in 5 cases was associated with a rise (mean 21.6 µmol/L) in serum creatinine. CONCLUSIONS: PCZ is well tolerated and appears effective in the management of fungal infection after lung transplantation. Patients receiving concurrent tacrolimus require careful therapeutic drug monitoring.

Disclosing genetic risk for coronary heart disease: effects on perceived personal control and genetic counseling satisfaction.

We investigated whether disclosure of coronary heart disease (CHD) genetic risk influences perceived personal control (PPC) and genetic counseling satisfaction (GCS). Participants (n = 207, age: 45-65 years) were randomized to receive estimated 10-year risk of CHD based on a conventional risk score (CRS) with or without a genetic risk score (GRS). Risk estimates were disclosed by a genetic counselor who also reviewed how GRS altered risk in those randomized to CRS+GRS. Each participant subsequently met with a physician and then completed surveys to assess PPC and GCS. Participants who received CRS+GRS had higher PPC than those who received CRS alone although the absolute difference was small (25.2 ± 2.7 vs 24.1 ± 3.8, p = 0.04). A greater proportion of CRS+GRS participants had higher GCS scores (17.3 ± 5.3 vs 15.9 ± 6.3, p = 0.06). In the CRS+GRS group, PPC and GCS scores were not correlated with GRS. Within both groups, PPC and GCS scores were similar in patients with or without family history (p = NS). In conclusion, patients who received their genetic risk of CHD had higher PPC and tended to have higher GCS. Our findings suggest that disclosure of genetic risk of CHD together with conventional risk estimates is appreciated by patients. Whether this results in improved outcomes needs additional investigation.

Prevalence and risk factors for allergic rhinitis in two resource-limited settings in Peru with disparate degrees of urbanization.

BACKGROUND: Allergic rhinitis is a disease with a high global disease burden, but risk factors that contribute to this condition are not well understood. OBJECTIVE: To assess the prevalence and risk factors of allergic rhinitis in two Peruvian populations with disparate degrees of urbanization. METHODS: We conducted a population-based, cross-sectional study on 1441 children aged 13-15 years at enrollment (mean age 14.9 years, 51% boys) to investigate the prevalence of allergic disease. We used a standardized, Spanish validated questionnaire to determine the prevalence of allergic rhinitis and asked about sociodemographics and family history of allergies. Children also underwent spirometry, exhaled nitric oxide, allergy skin testing to 10 common household allergens and provided a blood sample for measurement of 25OH vitamin D and total serum IgE. RESULTS: Overall prevalence of allergic rhinitis was 18% (95% CI 16% to 20%). When stratified by site, the prevalence of allergic rhinitis was 23% Lima vs. 13% in Tumbes (P < 0.001); however, this difference was no longer significant after controlling for subject-specific factors (P = 0.95). There was a strong association with other allergic diseases: 53% of children with asthma had allergic rhinitis vs. 15% in those without asthma (P < 0.001) and 42% of children with eczema vs. 17% of those without eczema (P < 0.001). Important risk factors for allergic rhinitis were parental rhinitis (adjusted OR = 3.0, 95% CI 1.9-4.7 for 1 parent and adjusted OR = 4.4, 95% CI 1.5-13.7 for 2 parents); allergic sensitization to common household aeroallergens (1.6, 1.1-2.3); being overweight (1.5, 1.0-2.3); exhaled nitric oxide ≥ 20 ppb (1.9, 1.3-2.7); and total serum IgE ≥ 95th percentile (2.4, 1.2-4.8). Population attributable risk of important factors for allergic rhinitis were 25% for high exhaled nitric oxide, 22% for allergic sensitization to common household aeroallergens, 22% for paternal rhinitis, 10% for being overweight and 7% for an elevated total serum IgE. CONCLUSION AND CLINICAL RELEVANCE: Allergic rhinitis was prevalent in both settings, and important risk factors include elevated exhaled nitric oxide, allergic sensitization to common household aeroallergens, parental rhinitis, being overweight and high total serum IgE. When considering subject-specific factors, the difference in prevalence between the urban and rural settings became non-important.

25-hydroxy vitamin D levels are associated with childhood asthma in a population-based study in Peru.

BACKGROUND: Vitamin D deficiency may be associated with an increased risk of asthma. OBJECTIVE: We studied the association between 25-hydroxy (25-OH) vitamin D deficiency and asthma prevalence in two Peruvian populations close to the equator but with disparate degrees of urbanization. METHODS: We conducted a population-based study in 1441 children in two communities in Peru, of which 1134 (79%) provided a blood sample for 25-OH vitamin D analysis. RESULTS: In these 1134 children, mean age was 14.8 years; 52% were boys; asthma and atopy prevalence was 12% in Lima vs. 3% in Tumbes (P < 0.001) and 59% in Lima vs. 41% in Tumbes (P < 0.001), respectively; and, mean 25-OH vitamin D level was 20.8 ng/mL in Lima vs. 30.1 ng/mL in Tumbes (P < 0.001). Prevalence of 25-OH vitamin D deficiency (< 20 ng/mL) was 47% in Lima vs. 7% in Tumbes (P < 0.001). In multi-variable logistic regression, we found that lower 25-OH vitamin D levels were associated with an increased odds of asthma (OR = 1.7 per each 10 ng/mL decrease in 25-OH vitamin D levels, 95% CI 1.2-2.6; P < 0.01). In stratified analyses, the association between lower 25-OH vitamin D levels and asthma was limited to children with atopy (OR = 2.2, 95% CI 1.3-3.6) and not in those without atopy (OR = 0.9, 95% CI 0.5-2.0). We did not find associations between 25-OH vitamin D levels and other clinical biomarkers for asthma, including exhaled nitric oxide, total serum IgE and pulmonary function. CONCLUSION AND CLINICAL RELEVANCE: Both asthma and 25-OH vitamin D deficiency were common among children living in Lima (latitude = 12.0 °S) but not among those in Tumbes (3.6 °S). The relationship between 25-OH vitamin D deficiency and asthma was similar in both sites and was limited among children with atopy. Future supplementation trials may need to consider stratification by atopy at the time of design.

CT perfusion for detection of delayed cerebral ischemia in aneurysmal subarachnoid hemorrhage: a systematic review and meta-analysis.

BACKGROUND AND PURPOSE: Delayed cerebral ischemia is a significant cause of morbidity and mortality after aneurysmal SAH, leading to poor outcomes. The purpose of this study was to evaluate the usefulness of CTP in determining delayed cerebral ischemia in patients with aneurysmal SAH. MATERIALS AND METHODS: We conducted a systematic review evaluating studies that assessed CTP in patients with aneurysmal SAH for determining delayed cerebral ischemia. Studies using any of the following definitions of delayed cerebral ischemia were included in the systematic review: 1) new onset of clinical deterioration, 2) cerebral infarction identified on follow-up CT or MR imaging, and 3) functional disability. A random-effects meta-analysis was performed assessing the strength of association between a positive CTP result and delayed cerebral ischemia. RESULTS: The systematic review identified 218 studies that met our screening criteria, of which 6 cohort studies met the inclusion criteria. These studies encompassed a total of 345 patients, with 155 (45%) of 345 patients classified as having delayed cerebral ischemia and 190 (55%) of 345 patients as not having delayed cerebral ischemia. Admission disease severity was comparable across all groups. Four cohort studies reported CTP test characteristics amenable to the meta-analysis. The weighted averages and ranges of the pooled sensitivity and specificity of CTP in the determination of delayed cerebral ischemia were 0.84 (0.7-0.95) and 0.77 (0.66-0.82), respectively. The pooled odds ratio of 23.14 (95% CI, 5.87-91.19) indicates that patients with aneurysmal SAH with positive CTP test results were approximately 23 times more likely to experience delayed cerebral ischemia compared with patients with negative CTP test results. CONCLUSIONS: Perfusion deficits on CTP are a significant finding in determining delayed cerebral ischemia in aneurysmal SAH. This may be helpful in identifying patients with delayed cerebral ischemia before development of infarction and neurologic deficits.

Lip commissure to eyelid transposition for repair of feline eyelid agenesis.

Repair of eyelid agenesis in nine eyes of five cats using a lip commissure to eyelid transposition is described. The procedure is a modification of the technique described by Pavletic for reconstruction of the canine inferior eyelid and provides skin, mucosa, a mucocutaneous junction, and muscle to reconstruct the superior and inferior eyelid and lateral canthus. The technique was successful in all eyes and resulted in improvement in corneal protection, cosmesis and in several cats a return of the palpebral reflex.

Deriving the indications for laparoscopic appendectomy from a comparison of the outcomes of laparoscopic and open appendectomy.

BACKGROUND: Indications for laparoscopic appendectomy (LA) remain controversial and poorly defined. We sought to identify indications for LA through a comparison of LA and open appendectomies (OA). METHODS: We reviewed demographics, coexisting medical conditions, radiology and pathology data, hospital course, and complications from charts on all LA patients and a comparison group of OA done from 1991 to 1998. RESULTS: The following were significantly associated with LA: female sex, higher mean body mass index (BMI), coexisting medical problems, private insurance, and daytime surgery. The OA group was significantly more likely to have: a radiology report suggesting the diagnosis of acute appendicitis, perforation of the appendix, intensive care unit admission, and complications in their hospital course. Forty-one percent of the LA patients did not have appendicitis, compared with 20% of the OA patients. CONCLUSIONS: Daytime surgery, women, private insurance, coexisting medical problems, prior abdominal surgery, higher BMI, and less severe disease appear to be used by surgeons as indicators for LA. The threshold for surgical exploration appears to be lower for LA.

Multiple primary bronchogenic carcinomas: treatment and follow-up.

A second primary bronchogenic carcinoma subsequently developed 8 to 156 months later in 19 patients who underwent curative resection of primary bronchogenic carcinomas. The second primary tumor was treated by surgical resection in 9 patients, 3 patients' tumors were considered unresectable, and the remaining 7 patients, despite having potentially resectable tumors, did not undergo resection because of insufficient pulmonary reserve or unwillingness to undergo resection. Actuarial life-table analysis of survival for the 9 patients who underwent resection showed a median survival time of 110.3 months compared with 19 months for the group with unresected but resectable tumors and 10.5 months for the group with unresectable tumors. There was no operative mortality in the group with resected tumors. We conclude that in patients in whom a second primary carcinoma of the lung develops, surgical resection prolongs survival and can be performed with a low operative mortality.

Clinical significance and measurement of the length of the right main bronchus.

It is important for surgeons, pathologists, anesthetists and anatomists to know the length of the right main bronchus. It extends from the carina of the trachea to the origin of the right upper lobe bronchus, but an exact method for measuring it has never been described. Using bronchography, the authors measured the length of the right main bronchus in 24 patients. The posteroanterior projection taken at a standard distance (1.8 m) from the patient was used to minimize distortion due to the technique; if present, the distortion would not be more than 5% and would be an increase rather than a decrease in length. The mean length of the right main bronchus was found to be 1.09 cm (range from 0 to 2.9 cm). The clinical importance of this measurement is discussed. The authors conclude that many anatomy textbooks err in describing the length of the right main bronchus as 2.0 to 5.0 cm, but are correct in describing the left main bronchus as being about 5 cm long.

Further remembrances of that revered anatomist, Dr. J. C. Boileau Grant.

From access to a detailed curriculum vitae written by Dr. Grant when he was about 75 years old, the author has learned some little-known facts of his background and life. His ancestors came from France and had been ennobled. One predecessor was a mayor of Paris. Several of his family decided to emigrate to Great Britain with the Huguenot movement. Grant graduated from the University of Edinburgh in 1908 in the same class as his future brother-in-law, William Boyd. When World War I was declared, he immediately volunteered for the army. During service on the Western Front, he was mentioned in dispatches in 1916, won the Military Cross in 1917 and a bar to the Military Cross in 1918. At the outbreak of World War II, Grant, who had been a professor of anatomy first in Winnipeg and then in Toronto for many years, volunteered again for war service, but was rejected as being too valuable a teacher to be allowed to enlist.

Autologous blood for pleurodesis in recurrent and chronic spontaneous pneumothorax.

Open operation for recurrent pneumothorax may be necessary to resect or oversew a bulla. At the same time, to stimulate adhesions, the pleura may be abraded with gauze, chemicals used to cause inflammation or a partial pleurectomy performed. Operation is necessary to decorticate the lung if it has developed a thick peel, in the presence of gross bleeding (hemopneumothorax) or if a large bulla is present. Occasionally, a chronic pneumothorax is due to a persistent leak caused by an adhesion holding open a bulla. The adhesion may be cut at thoracoscopy, using diathermy, and the leak will close. Many chemical agents have been used to encourage adhesions: iodized talcum powder, silver nitrate, 50% glucose and water, Atabrine, nitrogen mustard and tetracycline. In this series, one to three instillations each of 50 ml of autologous blood were used after the lung was fully expanded, usually after the use of an apical chest tube. This procedure was successful in 21 (85%) of 25 patients with difficult, chronic or recurrent pneumothoraces. It is a practical and easy method of causing a chemical pleurodesis, without serious side effects.

Benign metastasizing leiomyoma.

The cases of 2 patients with benign metastasizing leiomyofibroma are reviewed. Although extremely rare both in our experience and in the literature, benign metastasizing leiomyofibroma is an important differential diagnosis in young women seen with multiple lung nodules. Our patients underwent staged thoracotomies for diagnosis and treatment, and have experienced no evidence of recurrence over a six-year period.

The management of chylothorax.

A series of 15 patients was treated for chylothorax over a 20-year period. The anatomy, physiology, and diseases of the thoracic duct are described, and a plan for the management of chylothorax is presented. If conservative therapy (e.g., aspiration or drainage with restriction of oral intake and intravenous replacement) is not successful after two to three weeks, surgical treatment is necessary and efficacious. The thoracic duct is explored by a full thoracotomy on the side of the effusion. It is readily seen if 6 to 8 oz of a mixture of milk and cream is given to the patient a few hours before operation. The milky fluid drips from the open duct, which is easily oversewn.