<Emphasis Type="Italic">BRCA1</Emphasis> and <Emphasis Type="Italic">BRCA2</Emphasis> mutations in a population-based study of male breast cancer

Background

The contribution of BRCA1 and BRCA2 to the incidence of male breast cancer (MBC) in the United Kingdom is not known, and the importance of these genes in the increased risk of female breast cancer associated with a family history of breast cancer in a male first-degree relative is unclear.

Methods

We have carried out a population-based study of 94 MBC cases collected in the UK. We screened genomic DNA for mutations in BRCA1 and BRCA2 and used family history data from these cases to calculate the risk of breast cancer to female relatives of MBC cases. We also estimated the contribution of BRCA1 and BRCA2 to this risk.

Results

Nineteen cases (20%) reported a first-degree relative with breast cancer, of whom seven also had an affected second-degree relative. The breast cancer risk in female first-degree relatives was 2.4 times (95% confidence interval [CI] = 1.4–4.0) the risk in the general population. No BRCA1 mutation carriers were identified and five cases were found to carry a mutation in BRCA2. Allowing for a mutation detection sensitivity frequency of 70%, the carrier frequency for BRCA2 mutations was 8% (95% CI = 3–19). All the mutation carriers had a family history of breast, ovarian, prostate or pancreatic cancer. However, BRCA2 accounted for only 15% of the excess familial risk of breast cancer in female first-degree relatives.

Conclusion

These data suggest that other genes that confer an increased risk for both female and male breast cancer have yet to be found.

     

Transabdominal sonography of the normal gastroesophageal junction in children.

PURPOSE: Because sonography identifies abnormalities of the gastroesophageal junction, it is essential to understand the normal sonographic anatomy. The aim of this study was to determine the normal sonographic appearance of the gastroesophageal junction and its variations and to provide measurements of the abdominal esophagus in asymptomatic, healthy children. METHODS: In this prospective study, 124 healthy children (75 boys and 49 girls), aged 2 days-12 years, underwent abdominal sonography. With the patient in a supine position, the transducer was placed under the xiphoid and the ultrasound beam was directed cephalad through the window of the left lobe of the liver. The length of the abdominal esophagus was measured from the point at which it penetrated the diaphragm to the gastroesophageal junction. The thickness was measured on the anterior wall at the midpoint of the abdominal esophagus. RESULTS: The gastroesophageal junction was identified by sonography in all of the children. The mean length of the abdominal portion of the esophagus ranged from 18 mm in the newborns to 34 mm in children older than 6 years. The wall thickness ranged from 2.4 mm to 5.7 mm. CONCLUSIONS: Our results indicate that visualization of the gastroesophageal junction and measurement of the abdominal esophagus are readily achievable with real-time sonography in healthy children.     

Antibody-mediated marrow failure after allogeneic bone marrow transplantation

Marrow graft failure observed in association with histocompatibility differences between donor and recipient is often attributed to rejection mediated by host-derived cytolytic T lymphocytes. The data presented in this report indicate that persistent host antibodies specific for donor antigen may also mediate graft failure, either by antibody-dependent cell-mediated cytotoxicity (ADCC), or complement- mediated cytotoxicity. In the case of HLA Class I disparity, where all donor cells express the target antigen, the presence of alpha-donor antibody was associated with complete graft failure and death. In the case of ABO blood group antigen disparity, the presence of alpha-donor antibody resulted in erythroid hypoplasia. The latter cases proved informative insofar as they established that host antibodies could persist for more than 18 months after chemoradiotherapy and impair marrow function.     

Effectiveness of infection control measures in controlling a nosocomial outbreak of multidrug-resistant tuberculosis among HIV patients in Italy.

SETTING: Between October 1992 and February 1994, 33 cases of multidrug-resistant tuberculosis (MDR-TB) were diagnosed among patients infected by the human immunodeficiency virus (HIV) and hospitalised in an HIV ward in Milan, Italy. This outbreak was part of a much larger outbreak, begun in another hospital and probably transferred through a patient. OBJECTIVE: To evaluate risk factors for transmission and the effectiveness of infection control measures. DESIGN: 1) Active follow-up of exposed patients, 2) cohort study among HIV-infected patients exposed to MDR-TB cases before and after the implementation of control measures, 3) screening of close contacts of MDR-TB cases, and 4) molecular typing by restriction fragment length polymorphism (RFLP) analysis. RESULTS: The risk of MDR-TB was higher in patients with lower CD4+ lymphocyte percentages and longer duration of exposure. No difference in the daily risk was observed for in-patients vs day-hospital patients or by room distance from an infectious case. Of the 90 patients exposed before the implementation of infection control measures (i.e., October 1992-June 1993) 26 (28.9%) developed MDR-TB, whereas none of the 44 patients exclusively exposed after implementation developed MDR-TB, despite the continuing presence of infectious MDR-TB cases in the ward. CONCLUSION: Simple control measures were effective in significantly reducing nosocomial transmission among patients.     

Methotrexate/narrowband UVB phototherapy combination vs. narrowband UVB phototherapy in the treatment of chronic plaque‐type psoriasis – a randomized single‐blinded placebo‐controlled study

Background Psoriasis is a chronic, recurring inflammatory disease affecting the skin, joints and nails that has a significant negative impact on the quality of life. Efficacy of combination of methotrexate/narrowband ultraviolet B (NBUVB) phototherapy in the treatment of psoriasis has been rarely assessed. Objectives To compare the efficacy of methotrexate/NBUVB phototherapy combination vs. NBUVB phototherapy in the treatment of chronic plaque psoriasis. Methods Forty patients with chronic plaque‐type psoriasis (body surface area involvement >10%) were randomized to receive either methotrexate/NBUVB phototherapy (group A) or placebo/NBUVB phototherapy (group B). End point of treatment was 75% reduction in Psoriasis Area and Severity Index (PASI) Score or upto 6 months, whichever was earlier. Patients were then followed up for a period of 12 weeks for assessment of relapse. Results Of 40 patients, 37 completed the treatment period and 29 both the treatment period and follow‐up. PASI 75 was achieved in 19/20 patients in group A and 14/20 patients in group B (P < 0.04). The mean number of weeks(P = 0.001), the mean cumulative dose of NBUVB (P = 0.001) and the mean number of phototherapy sessions (P = 0.0001) required to achieve PASI 75 were significantly less in group A compared with group B. There was no significant difference in the number of patients who relapsed during the follow‐up period (P = 0.68). Conclusion Combination of methotrexate and NBUVB phototherapy provides more rapid clinical improvement compared with NBUVB monotherapy in the treatment for chronic plaque‐type psoriasis.     

A prosthetic contact lens in the treatment of ocular manifestations of albinism

A patient with severe ocular albinism was fitted with a prosthetic soft contact lens which improved both photophobic symptoms and facial cosmesis.     

Normal deposition of brain iron in childhood and adolescence: MR imaging at 1.5 T

Magnetic resonance (MR) images of the brain in 285 patients between the ages of 2 and 25 years were retrospectively studied to determine the appearance of brain iron accumulation. The globus pallidus, red nucleus, substantia nigra, and dentate nucleus were evaluated with long TR/TE (repetition time/echo time) spin-echo sequences and staged. All four regions in most patients were initially hyperintense compared with white matter (stage I) before becoming isointense (stage II) and subsequently hypointense (stage III). The globus pallidus was the first to reach stage III, the red nucleus and substantia nigra were next, and the dentate nucleus was last. In general, decreased signal intensity (stage III) was not seen in these regions in patients less than 10 years old; in most patients it was seen by age 25 years. The dentate nucleus decreased in signal intensity more slowly and inconsistently; only one-third of patients had reached stage III by age 25 years. The temporal sequence of normal iron deposition as detected with MR imaging is helpful not only in the diagnosis of known iron-deposition diseases but also in the detection of iron-related pathologic changes.