Keratin 6a marks mammary bipotential progenitor cells that can give rise to a unique tumor model resembling human normal-like breast cancer.

Progenitor cells are considered an important cell of origin of human malignancies. However, there has not been any single gene that can define mammary bipotential progenitor cells, and as such it has not been possible to use genetic methods to introduce oncogenic alterations into these cells in vivo to study tumorigenesis from them. Keratin 6a is expressed in a subset of mammary luminal epithelial cells and body cells of terminal end buds. By generating transgenic mice using the Keratin 6a (K6a) gene promoter to express tumor virus A (tva), which encodes the receptor for avian leukosis virus subgroup A (ALV/A), we provide direct evidence that K6a(+) cells are bipotential progenitor cells, and the first demonstration of a non-basal location for some biopotential progenitor cells. These K6a(+) cells were readily induced to form mammary tumors by intraductal injection of RCAS (an ALV/A-derived vector) carrying the gene encoding the polyoma middle T antigen. Tumors in this K6a-tva line were papillary and resembled the normal breast-like subtype of human breast cancer. This is the first model of this subtype of human tumors and thus may be useful for preclinical testing of targeted therapy for patients with normal-like breast cancer. These observations also provide direct in vivo evidence for the hypothesis that the cell of origin affects mammary tumor phenotypes.

Vaginal algometer: development and application of a device to monitor vaginal wall pressure pain threshold.

We describe a device (which we have named a vaginal algometer) which can measure the pressure pain threshold (PPT) on the lateral walls of the vagina. The device was assessed in 63 healthy women and a normal range for this measurement was established. Each woman had her vaginal wall PPT measured and was asked about the acceptability of the procedure. We demonstrate that the vaginal algometer can provide a quantitative assessment of vaginal PPT and that the procedure is acceptable to most women.

A practical demonstration of improved technique factors in paediatric fluoroscopy.

Dose incurred with fluoroscopic procedures accounts for a significant proportion of medically induced diagnostic exposure. Children are particularly vulnerable and it is therefore important to minimize exposure where practicable. A recent theoretical study has highlighted the potential for X-ray equipment to produce significant dose savings during paediatric fluoroscopy without incurring loss of diagnostic image quality. This is achieved by hardening the beam with additional copper (Cu) filtration (approximately 0.2 mm Cu) and biasing exposure factors towards low tube potential, high tube current output. In practice, this method will have limited applicability because the high powered and programmable generator characteristics required are not commonly available in installations used for paediatric imaging. However, we describe a simple experiment in which our clinical equipment was modified to approximate desired low dose performance by altering the filtration and automatic exposure control characteristics of ordinary clinical equipment in the Sheffield Children's Hospital. This enabled us to obtain significant savings in dose. We performed a comparative study (normal dose vs low dose) using water phantoms to simulate patient attenuation in the age range 0-15 years. The Leeds N2 contrast sensitivity phantom was used to provide a measure of image quality. Dosimetric measurements recorded up to 40% reduction in dose rate with only marginal loss of image quality when 0.1-0.2 mm Cu filtration was used with the modified settings. This is a strong indication that significant dose reduction is achievable on routine clinical equipment without compromising image quality. Such simple and cost effective methods of dose reduction should be considered for wider implementation.

Assessment of response to treatment in vulvar vestibulitis syndrome by means of the vulvar algesiometer.

OBJECTIVE: A pilot study was undertaken to investigate the utility of the vulvar algesiometer in correlating symptom improvement with treatment response. STUDY DESIGN: Women with a diagnosis of vulvar vestibulitis syndrome attending a specialist vulvar clinic were assessed with the vulvar algesiometer before and after treatment. RESULTS: The conditions of 25 patients had improved to the point of discharge, and readings from before and after treatment were compared. There was a statistically significant difference in the vulvar algesiometer readings before and after treatment and this improvement was reflected in patient response. Nine patients had no response to treatment and also no significant improvement in vulvar algesiometer score. CONCLUSION: The vulvar algesiometer provides an easy noninvasive means of assessing vestibular tenderness in vulvar vestibulitis syndrome that is well tolerated by the patients and provides a degree of biofeedback for them.

Ultrastructural study of the epithelium of the normal human vulva.

An ultrastructural study of the pathology of vulvar vestibulitis syndrome (Friedrich, 1987) necessitated a detailed knowledge of the epithelial surface of the vulva. As this has previously been characterised only at the light microscopy level, a comprehensive electron microscopical study of the vulva was considered critical to the study of the pathological tissue. A comparison between vulvar, vaginal and keratinised perineal epithelia, confirmed the resemblance of vulvar epithelium to partially keratinised mucosal-like epithelia. No conclusive evidence of keratinisation was observed and the characteristic granular and spiny cell layers found in skin were absent. The prominent cell type was the glycogenated intermediate cell, which formed a structurally homogeneous layer of cells. Other cell types present were: superficial flattened cells, many having nuclei, traces of organelles and large glycogen deposits; suprabasal cells; and basal cells, some of which appeared mitotically active rich in organelles. All cell layers were characterised by the presence of numerous interdigitating cytoplasmic processes, small numbers of infrequent desmosomal junctions and pale staining cytokeratin filaments.

Entrance doses during lateral lumbar spine and antero-posterior abdomen examinations: generator waveform dependence.

In North Trent, UK, an entrance dose survey of lateral lumbar spine and antero-posterior (AP) abdomen examinations has been carried out in 17 radiology departments. The survey comprised 294 lateral lumbar spine and 322 AP abdomen entrance dose measurements. The mean entrance doses were found to be approximately half of the relevant national reference entrance dose levels of 30 mGy and 10 mGy, respectively. The effect of generator waveform on entrance dose was studied by separating the generators into two types: "pulsating potential" (PP) generators and "constant potential" (CP) generators for each examination. PP generators comprised 23% of the total number of examinations. The mean entrance dose and radiographic exposure factors from CP generators were found to be significantly lower than those from PP generators. The use of CP type generators, together with low attenuation components can significantly reduce patient entrance doses for these examinations.

A randomised, double-blind, parallel group study to compare subcutaneous interferon alpha-2a plus podophyllin with placebo plus podophyllin in the treatment of primary condylomata acuminata.

OBJECTIVES: The primary objective was to determine if six weeks treatment with subcutaneous interferon alpha-2a (IFN) and podophyllin 25% W/V administered twice per week, preceded by IFN alpha-2a three times weekly for one week showed a greater complete response rate in patients with primary condylomata acuminata when assessed at week 10 than treatment with podophyllin and placebo injections in the same schedule. The secondary objective was to compare recurrence rates in complete responders at six months in the two treatment groups. DESIGN: Randomised, double-blind parallel group study. SETTING: Multicentre study in six genitourinary clinics within the U.K. PATIENTS: One hundred and twenty-four patients with primary anogenital warts. MAIN OUTCOME MEASURES: Complete response rate at week 10, and recurrence rate at week 26 in complete responders. RESULTS: At week 10 analysis of the efficacy population showed complete response in 36% (15/42 patients) of IFN-treated group and 26% (11/43 patients) in the placebo group (no significant difference). Analysis of the safety population at week 26 showed persistence of the complete response in 57% (8/14 patients) of the IFN-treated group and 80% (12/15 patients) of the placebo group (no significant difference). Adverse effects were more common in IFN-treated patients, involved particularly application site reaction and malaise but were generally mild. CONCLUSIONS: At the dose and with the regime described treatment with IFN alpha-2a in combination with podophyllin is no more effective in the treatment of primary anogenital warts than podophyllin alone and is associated with more adverse events.

Immunological responses in late syphilis.

Thirty-one serum samples from 18 patients with clinically established late syphilis and 1319 from patients at other stages of the disease were fractionated by density gradient ultracentrifugation and examined for antilipoidal and antitreponemal antibodies of the IgM and IgG classes. Sera from the patients with late syphilis always showed persistent concentrations of antilipoidal IgM and IgG and of antitreponemal IgG but never yielded detectable concentrations of antitreponemal IgM. When treated, these patients' antibody titres did not decline. Patients with secondary or latent syphilis also showed this serological picture after treatment but only transiently; their antibody titres continued to decline in a way which clearly distinguished them from the cases of late syphilis. It is suggested that patients whose sera persist in showing the stable pattern described may develop late symptomatic syphilis.

Cefuroxime compared with penicillin for the treatment of gonorrhea.

One hundred seventy-eight men and women with acute gonorrhea were treated by intramuscular administration of cefuroxime. Use of 1 g of cefuroxime plus 1 g of probenecid gave a cure rate of 95.5%, which compared well with that of a standard treatment of 5 x 10(6) units of intramuscularly administered benzyl penicillin plus 1 g of probenecid. The latter gave a cure rate of 97.2% in a concurrent series of 178 patients. A subsequent comparison of 163 patients who received 750 mg of cefuroxime plus 1 g of probenecid with 145 patients who received 1.5 g of cefuroxime alone showed cure rates of 95.1% and 97.2%, respectively. Only two cases of possible hypersensitivity to cefuroxime were found. It is concluded that cefuroxime is a valuable drug for single-session treatment of acute gonorrhea in both men and women.

Prolonged use of the Greenland method of treatment of gonorrhoea.

Of 1081 patients with gonorrhoea treated with probenecid 1 g orally and benzyl penicillin 5 megaunits intramuscularly, 96.7% were cured and no complications were encountered. This treatment regimen was associated with a pronounced reduction in the proportion of gonococcal strains showing diminished sensitivity to penicillin, from 51% to between 4% and 14% over a period of four years. When this treatment method was abandoned, however, the percentage of less sensitive strains rose to 33% over the following 18 months.

Cultivation of Treponema pallidum in subcutaneous chambers implanted in golden hamsters.

Treponema pallidum was successfully grown in subcutaneous chambers in golden hamsters. Abnormally long forms of T. pallidum were found in these chambers. The cause of this abnormality may possibly be due to their being coated with antibody which could inhibit cell division or render the organism avirulent or both. T. pallidum was successfully passaged between hamsters but with a possible diminution in virulence.

A survey of the effectiveness of a telephone-answering service.

A survey was carried out over a two-year period in Exeter to find out what source of information led patients to attend the local clinic for venereal diseases and to evaluate the effectiveness of a tape-recorded telephone message advertising clinic times. Based on the response from patients it seems difficult to justify the cost of installing a telephone-answering service.