Diagnosis and treatment of perilymph fistulas without hearing loss

In 1978, I reported on the diagnostic criteria and therapy based on the treatment of 34 cases of perilymph fistula. Of that group, 20 patients had no hearing loss associated with the fistula. Since that time, an additional 30 cases of fistula--15 without hearing loss--have been seen and treated operatively. The 30 significant variables of history and physical findings identified in the first study were statistically reviewed, along with a new finding that seems highly significant. Twenty-three of the 26 new cases so evaluated had a positive "eyes-closed turning test" (staggering when turning to the side of the lesion after walking with eyes closed). A further finding has been the presence of an abnormally placed round window membrane, in most cases involving the round window. The total operative population of fistulas, both those with and without hearing loss, is reviewed to identify the operative technique best suited for each window and the graft material most likely to succeed. Perichondrium is the choice tissue for graft material, except for very small fistulas at the annular ligament. The graft must be held firmly in place, with either a prosthesis or appropriate packing, carefully avoiding adhesions between the round window and the tympanic membrane.     

Inhibition of the human ether-a-go-go-related gene (HERG) potassium channel by cisapride: affinity for open and inactivated states.

1 Cisapride is a prokinetic agent which has been associated with QT prolongation, torsades de pointes and cardiac arrest. The cellular mechanism for these observations is high affinity blockade of IKr (encoded by HERG). 2 In a chronic transfection model using CHO-K1 cells, cisapride inhibited HERG tail currents after a step to +25 mV with similar potency at room and physiological temperatures (IC50 16. 4 nM at 20-22 degrees C and 23.6 nM at 37 degrees C). 3 Channel inhibition exhibited time-, voltage- and frequency-dependence. In an envelope of tails test, channel blockade increased from 27+/-8% after a 120 ms depolarizing step to 50+/-4% after a 1.0 s step. These findings suggested affinity for open and/or inactivated channel states. 4 Inactivation was significantly accelerated by cisapride in a concentration-dependent manner and there was a small (-7 mV) shift in the voltage dependence of steady state inactivation. 5 Channel blockade by cisapride was modulated by [K+]o, with a 26% reduction in the potency of channel blockade when [K+]o was increased from 1 to 10 mM. 6 In conclusion, HERG channel inhibition by cisapride exhibits features consistent with open and inactivated state binding and is sensitive to external potassium concentration. These features may have significant clinical implications with regard to the mechanism and treatment of cisapride-induced proarrhythmia.     

Investigation of three new mouse mammary tumor cell lines as models for transforming growth factor (TGF)-β and Neu pathway signaling studies: identification of a novel model for TGF-β-induced epithelial-to-mesenchymal transition

Introduction  

This report describes the isolation and characterization of three new murine mammary epithelial cell lines derived from mammary tumors from MMTV (mouse mammary tumor virus)/activated Neu + TβRII-AS (transforming growth factor [TGF]-β type II receptor antisense RNA) bigenic mice (BRI-JM01 and BRI-JM05 cell lines) and MMTV/activated Neu transgenic mice (BRI-JM04 cell line).     

Response to influenza virus vaccination in vertical HIV infection

OBJECTIVE: To assess the antibody response to influenza vaccine of children vertically infected with HIV. DESIGN: Prospective study in HIV infected children vaccinated during the winter of 1994-5. SETTING: Family HIV clinic at St Mary's Hospital, Paddington. SUBJECTS: 25 children, aged 1-11 years, vertically infected with HIV. MAIN OUTCOME MEASURES: Responses to influenza antigens (H1N1-A/Taiwan/1/86, H3N2-A/Shandong/9/93, B/Panama/45/ 90) were tested by haemagglutination inhibition. Antibody responses were assessed according to clinical symptoms and immune function, stratified according to the 1994 revised classification for HIV infection in children. RESULTS: 23 children (92%) had either very low or no detectable antibody before vaccination. New protective antibody responses were made by 10 children (40%): in seven to a single antigen, in two to two antigens, and in one to all three antigens. For each antigen there was an overall small increase in the mean geometric titre of antibody produced, but this only reached a protective level for antigen H1N1 and for children with minimal symptoms. Less symptomatic children were significantly more likely to produce a protective antibody response to influenza vaccination. No association was found between immune function, as measured by CD4 count, and vaccine response. CONCLUSIONS: Only vaccination of the least symptomatic HIV infected children against influenza is likely to be effective. This will not only protect them against influenza, but will also protect other more immunosuppressed and vulnerable members of their families.     

"Early-peak" carbon monoxide production in certain erythropoietic disorders

The "early-labeled" peak (ELP) of 14CO excretion following injection of glycine-2-14C was used to study erythropoiesis in a patient with sideroblastic anemia and in four subjects with myeloproliferative disorders. The ELP was greatly enlarged in all patients, as compared with a normal volunteer. The contour of the peaks from the hematologically abnormal subjects suggested the presence of increased erythroid heme degradation. In the patient with sideroblastic anemia, all hours of the early peak were significantly reduced after transfusion. This was interpreted to mean that even the earliest or "nonerythroid" phase of the peak is influenced by erythropoietic activity, at least under conditions of erythropoietic stress.     

Geriatric medicine curriculum consultations for family practice residency programs: american academy of family physicians residency assistance program/hartford geriatrics initiative

Increasing the quality and quantity of geriatric medicine training for family practice residents is a particular challenge for community-based programs. These programs have an average of only seven full-time equivalent physician faculty. This report summarizes results of the Residency Assistance Program/Hartford Geriatric Initiative (RAP/HGI) geriatric medicine curriculum consultations for family practice (FP) residency programs conducted from 1996 to 2001. This project was developed as part of the RAP in family practice. Ten experienced FP educators were selected and trained as special consultants. Between 1996 and 2001, 39 FP residency programs participated in the 1- to 4-day RAP/HGI consultations. The programs were diverse in size and location. The consultations reached 308 family practice residency faculty members involved in training 807 residents. Program evaluations of the consultants were uniformly in the very good to excellent range, with a mean rating of 4.6 (5-point scale, with 5 indicating excellent). At the end of the initial consultation visit, the residency program faculty and the consultant developed short-term goals for geriatrics program development. Eighty-five percent (33/39) of the programs submitted their curriculum goals in writing. The mean number of goals per program was 4.8 (range = 3-11). Of the 33 programs with written goals, follow-up was documented for 29 programs. Seventy-nine percent of the programs' self-defined educational goals were met during the 6 to 12 months of follow-up (range 50-100%). Ten of the programs implemented all of their educational goals. The RAP/HGI project demonstrated that achievable geriatric medicine curriculum improvements could occur as part of an onsite consultation process.