A multiplatform real-time polymerase chain reaction detection assay for Vibrio cholerae

We report a multiplatform real-time polymerase chain reaction methodology based on genes encoding for the regulatory toxR activator and enterotoxin A protein to determine enterotoxigenic Vibrio cholerae types from other vibrios. This assay, which was successfully validated on a collection of 87 bacterial strains, including 63 representatives of V. cholerae and 8 noncholera vibrios provides a rapid tool for detection and identification of cholera.     

No Sib Pair Concordance for Breast or Ovarian Cancer in <Emphasis Type="Italic">BRCA1</Emphasis> Mutation Carriers

Modifying factors might theoretically determine whether a BRCA1 mutation carrier contracts breast or ovarian cancer. If so, one would expect concordance for breast or ovarian cancer in affected sibships. We identified 64 pairs with cancers where one or both sisters were demonstrated to carry a BRCA1 mutation, and 116 additional constructed pairs in sibships with three or more affected sisters. We analysed concordance for breast and for ovarian cancer both in the complete series and in the 64 sister pairs alone. The results were that concordance for both breast and ovarian cancer in sisters was in keeping with random distribution or multiple and frequent modifying genetic factors. In conclusion, there may be no major modifying factor of expression of BRCA1 mutations. The practical implication of our findings is that previous disease manifestations in close relatives may have no bearing on the first cancer to be expected in a young female mutation carrier.     

Genetic epidemiology of BRCA mutations--family history detects less than 50% of the mutation carriers

Ten BRCA mutations were demonstrated to be frequent in the Norwegian population. We present maps verifying the uneven distribution of prevalences according to municipality. We tested incident breast cancer cases treated in Mid-Norway from 1999 onwards for these mutations. Uptake of testing was 97% and 2.5% were demonstrated to be mutation carriers. Ten (77%) were outside families previously known to carry a mutation. Ten (77%) did not meet clinical criteria to be selected for mutation testing. We tested incident ovarian cancer cases in South-West Norway from 2001 onwards. Uptake of testing was 80% and 23% were mutation carriers. Twenty-one (88%) were outside families previously known. Twelve (67%) did not meet clinical criteria to be selected for testing. All patients with mutation collaborated actively to give our offer of predictive genetic testing to their relatives. No complaint on the activity was received.     

Causes and time-course of vertigo in an ear, nose, and throat clinic

The purpose of this study is to review etiologies and identify the time-course of vertigo presenting in an ear, nose, and throat clinic, and serve as a reference guide for other clinics. The study includes retrospective chart review in a tertiary care, university hospital. The patient data with reported ICD-10 codes as causes of vertigo between April 2005 and December 2007 were extracted from the database. At each visit, the main diagnosis as to etiology, characteristics of the vertigo, its time-course, and patient demographic data were recorded. Of 547 cases, 17 diagnoses were made in 73.9%. Diagnostic categories included peripheral vertigo 72.9%, central vertigo 0.8%, psychogenic cause 0.2%, and unknown 26.1%. Common causes of vertigo were benign paroxysmal positional vertigo (BPPV) 52.5%, Meniere’s disease 14.6%, and sudden idiopathic hearing loss 2.9%. Less common diagnoses were benign paroxysmal vertigo of childhood 0.7%, labyrinthitis 0.7%, and vestibular schwannoma 0.3%. Rare conditions were delayed endolymphatic hydrops, Ramsey Hunt syndrome, otosyphilis, vestibular neuritis, temporal bone fracture, post-concussion syndrome, cerebellar infarction, epilepsy, cervical vertigo, Streptococcus suis meningitis, and psychogenic vertigo. Ninety-nine cases who reported remission of vertigo during the study period had median onset of the remission at 4 weeks. In the ear, nose, and throat clinic at Chiang Mai University, a tertiary university hospital, peripheral vestibular disorders were the main etiology of vertigo. The three most common causes were BPPV, Meniere’s disease, and sudden idiopathic hearing loss. Half of the cases who returned for follow up had remitted symptoms within 4 weeks.     

Surveillance for familial breast cancer: Differences in outcome according to BRCA mutation status

Women with a family history of breast cancer are commonly offered regular clinical or mammographic surveillance from age 30. Data on the efficacy of such programmes are limited. Clinical, pathological and outcome data were recorded on all breast and ovarian cancers diagnosed within familial breast cancer surveillance programmes at collaborating centers in Norway and the UK up to the end of 2005. These have been analyzed according to the mutation status of the affected women (BRCA1+ve, BRCA2+ve or mutation-negative). Breast cancer was diagnosed in 442 patients subsequently followed for a total of 2095 years. Eighty-nine (20%) had BRCA1 mutations, 35 (8%) BRCA2 mutations and in 318 (72%) no mutation could be detected ("mut neg"). Five-year survival in BRCA1 was 73% compared to 96% in BRCA2 and 92% in mut neg (p = 0.000). Among BRCA1 mutation-carriers, 5-year survival was 67% for cases diagnosed as carcinoma in situ, 84% for node-negative invasive cancers and 58% for those with nodal involvement (p > 0.05). For BRCA2 mutation-carriers the corresponding figures were 100, 100 and 90% (p > 0.05), while for mut neg women they were 100, 97 and 71% (p = 0.03). Regular surveillance in women at increased familial risk of breast cancer is associated with a good outcome if they carry BRCA2 mutations or no detectable mutation. Carriers of BRCA1 mutations fare significantly worse, even when their tumors are diagnosed at an apparently early stage. The differences in outcome associated with different genetic causes of disease were associated with demonstrated differences in tumor biology. The findings demonstrate the outcome for genetically different breast cancers detected within a programme for early diagnosis and treatment, which is relevant to genetic counseling when women at risk have to chose between the options for preventing death from inherited breast cancer.     

Immunohistochemistry identifies carriers of mismatch repair gene defects causing hereditary nonpolyposis colorectal cancer.

PURPOSE: Hereditary nonpolyposis colorectal cancer (HNPCC) may be caused by mutations in mismatch repair (MMR) genes. The aim of this study was to validate immunohistochemistry and family history as prescreening tools to predict germline mutations in MLH1, MSH2, and MSH6. PATIENTS AND METHODS: Pedigrees from 250 families were extended, cancer diagnoses were verified, and families were classified according to the Amsterdam and the Bethesda criteria. Tumor specimens were examined with immunohistochemistry for the presence of MLH1, MSH2, and MSH6 proteins. Mutation analyses were performed in blood samples from the same patients. RESULTS: Blood samples from affected index persons in 181 families and tumor specimens from 127 of the affected index persons were obtained. Thirty tumors lacked one or more gene products. Sensitivity of immunohistochemistry to detect mutation carriers was 100%, specificity was 82%, and positive predictive value was 85%. Sensitivities, specificities, and positive predictive values for the Amsterdam criteria were 82%, 8%, and 45%, respectively, and for the Bethesda criteria were 100%, 0%, and 48%, respectively. Distribution of mutations was MLH1 = 4, MSH2 = 11, and MSH6 = 4. CONCLUSION: Wide clinical criteria to select HNPCC kindreds, followed by immunohistochemistry of tumor material from one affected person in each family, had high sensitivity and specificity to predict MMR mutations.