Faculty Bibliography

OBJECTIVE: To determine the role of BRCA1 185delAG mutation in ovarian carcinogenesis. DESIGN: Genetic testing of a subset of cases from an ongoing study of ovarian cancer and of controls. SETTING: A community-based case-control incidence study. SUBJECTS: Seventy-nine patients with ovarian cancer, 62 hospitalized women without cancer (controls), and 120 healthy women participating in a fragile X screening program (also controls), examined for the presence of germline BRCA1 185delAG mutation. MAIN OUTCOME MEASURES: Polymerase chain reaction-amplified BRCA1 exon 2 fragments generated from patients' and controls' blood samples, analyzed by heteroduplex gel shift assay and direct sequence analyses. RESULTS: The 185delAG mutation was detected in 38.9% (7/18) of ovarian cancer patients with familial history, and 13.1% (8/61) of family history-negative ovarian cancer cases. Only 1 carrier was detected among the 120 healthy controls, and none in the hospital controls. A significant difference in mutation carrier rates between family history-negative cases and control groups of 120 and 62 subjects was identified (Fisher exact test, P=.001 and P=.003, respectively). The median age (+/-SE) at disease diagnosis was lower among both familial and family history-negative mutation carriers, as compared with mutation-negative, family history-negative cases--50 (+/-1.4) vs 60.5 (+/-3.5) years old, respectively (hazard ratio, 1.68; 95% confidence interval, 0.94-3.01). CONCLUSIONS: Our data are preliminary but suggest that BRCA1 185delAG germline mutation is frequent in Israeli ovarian cancer patients, irrespective of family history, and may confer an early-onset phenotype of ovarian cancer

We sought to define the role of fibrogenic peptides in subglottic stenosis (SGS). Biopsy specimens were obtained from patients with stenosis following endotracheal intubation (group 1, n = 5, mean age 5), patients without a history of any precedent trauma, ie. idiopathic stenosis (group 2, n = 3, mean age 40), and those without stenosis (group 3, n = 3, mean age 70). Formalin-fixed biopsy specimens were analyzed following immunohistochemical staining to determine if epidermal growth factor (EGF), platelet-derived growth factor-AA and -BB (PDGF-AA/BB), transforming growth factor-beta 1 and -beta 2 (TGF-beta 1, beta 2), or basic fibroblast growth factor (bFGF) was deposited in these tissues. Blinded analysis revealed TGF-beta 2 and PDGF-AA to be present in seven of eight biopsy specimens from SGS and absent in controls. Staining for PDGF-BB was observed in the mucosa and submucosa and occasionally within vessel walls. Staining of individual growth factors appeared to correlate closely with the presence of granulation tissue. Essentially no bFGF or TGF-beta 1 was observed. Differences were found between patients in groups 1 and 2; tissue from group 1 revealed deposition of EGF and PDGF-BB in submucosa, epithelium, and vasculature. In summary, our experimental findings implicate PDGF and TGF-beta 2, perhaps acting in concert, in mediating the pathologic fibrotic process observed in subglottic stenosis. Epidermal growth factor, in conjunction with TGF-beta and PDGF, may also have a role, but further investigation is needed to more precisely define it

OBJECTIVE: To determine the optimal treatment in pediatric patients with allergic fungal sinusitis (AFS). DESIGN: A retrospective review of 10 patients diagnosed as having AFS. SETTING: Academic tertiary medical center. PATIENTS: Pediatric patients who fulfilled 5 criteria necessary for diagnosis of AFS: (1) type 1 hypersensitivity; (2) nasal polyposis; (3) characteristic computed tomographic scan; (4) histological evidence of eosinophilic mucus without evidence of fungal invasion into sinus tissue; and (5) a positive fungal stain or culture of sinus contents. TREATMENT: All patients were treated with functional endoscopic sinus surgery with removal of fungal debris. Adjuvant therapy included nasal irrigations, postoperative endoscopic cleanings, and systemic corticosteroids in 9 of 10 patients. MEAN OUTCOME MEASURE: Clinical disease monitored endoscopically by means of an objective staging system. RESULTS: Five patients were without disease (stage 0), 1 had allergic mucin and mucosal edema (stage I), 1 had allergic mucin and polypoid edema (stage II), and 3 had polyps and/or fungal debris (stage III). CONCLUSIONS: The treatment and prognosis of pediatric AFS are similar to those of adult AFS. However, systemic corticosteroids should be weaned aggressively in children to minimize complications, particularly long-term growth retardation

We previously demonstrated that inhibitory synaptic transmission influences dendrite development in vivo. We now report an analogous finding in an organotypic culture of a glycinergic projection nucleus, the medial nucleus of the trapezoid body (MNTB), and its postsynaptic target, the lateral superior olive (LSO) of gerbils. Cultures were generated at 6-7 days postnatal and grown in serum containing medium with or without the glycine receptor antagonist, strychnine (SN), at 2 microM. LSO neurons were then labeled with biocytin, and the dendritic arbors were analyzed morphometrically. Compared to neurons form age-matched in vivo tissue, the neurons cultured in control media were somewhat atrophic, including decreases in dendritic branching and length. Incubation in strychnine led to a dramatic increase in dendritic branching and total dendritic length. Control neurons averaged 6.3 branches compared to 18 branches/neuron in SN-treated cultures. There was a similar increase in primary dendrites and total dendritic length. The physical elimination of MNTB cells did not mimic SN treatment, presumably because glycinergic LSO neurons generated intrinsic connections. In fact, the LSO soma area was significantly greater following MNTB removal, suggesting that these afferents provide a second signal to postsynaptic neurons. These results suggest that spontaneous glycinergic transmission regulates the growth of postsynaptic processes

OBJECTIVE: To determine whether reverse transcriptase (RT) in situ polymerase chain reaction (PCR) can facilitate the diagnosis of nontuberculous ('atypical') mycobacterial (NTM) cervical adenitis. DESIGN: Retrospective review of 12 patients with neck masses clinically diagnosed as NTM cervical adenitis. SETTING: University medical center caring for both ambulatory and hospitalized children. PATIENTS: Twelve pediatric patients (all younger than 9 years) with cervicofacial masses. INTERVENTION: Surgical excision of the presenting mass. MAIN OUTCOME MEASURES: Reverse transcriptase in situ PCR was used to detect mycobacterial RNA in excised tissue. All specimens were also cultured and stained for acid-fast bacilli. RESULTS: Reverse transcriptase in situ PCR was positive for NTM in 7 of 12 cases. CONCLUSIONS: Infection with NTM may be an extremely indolent process, and the success of RT in situ PCR depends on the presence of mycobacterial nucleic acids. Even in cases in which the findings of RT in situ PCR were positive, infected cells were few in number. Because of the sparsity of infection in the positive cases, NTM may be even more rare in the negative cases, ie, those in which mycobacterial nucleic acids do not exist and cannot be detected by any means, including RT in situ PCR. Although RT in situ PCR, cultures, stains for acid-fast bacilli, and tuberculin tests using purified protein derivative are all helpful in diagnosing NTM cervical adenitis, when nucleic acids are present RT in situ PCR is the simplest, most reliable, and quickest to perform and the results are easiest to interpret

Serum ferritin isolated from the horse was structurally compared with horse spleen ferritin and was found to differ markedly in molecular weight, iron content, carbohydrate, subunit size and amino acid sequence. The results are summarized and initial results obtained with candidate clones of pieces of two serum ferritin subunits are described.

A review of more than 50 allergic fungal sinusitis (AFS) patients indicates that most patients experience postoperative recurrences once weaned from oral steroids, leaving a glaring need for improved treatment. Topical antifungal therapy has not been described for AFS, but it could potentially lower fungal antigen loads via postoperative irrigations. No information exists to direct the choice of antifungal agent. The purpose of this study was to identify the appropriate drug to use for postoperative irrigations in AFS patients. Twenty-two fungal cultures grown from 15 AFS patients were studied for in vitro susceptibility to five common antifungal drugs: ketoconazole, amphotericin B, itraconazole, nystatin, and fluconazole. Results demonstrated that ketoconazole and amphotericin B were the most effective. Clinical trials are indicated to evaluate the efficacy of these drugs as a supplement to current AFS treatment