Telomere length identifies two different prognostic subgroups among VH-unmutated B-cell chronic lymphocytic leukemia patients.

Some evidences suggest that telomere restriction fragment length (TRF-L) is an effective indicator of histopathogenesis in B-cell tumors. As histopathogenesis is relevant for B-cell chronic lymphocytic leukemia (B-CLL) prognosis, TRF-L was assessed by Southern blot in 201 patients and compared to variable immunoglobulin heave chain gene mutational status (VH-MS) and to other known prognostic features. Overall survival (OS), time to first treatment (TTFT) and progression-free survival (PFS) were evaluated. Our results indicate the following: (1) TRF-L is heterogeneous among B-CLL patients (median 6014 bp, range 1465-16 762); (2) TRF-L correlates to VH-MS (r(2)=0.1994, P<0.0001) with VH-mutated patients showing long and VH-unmutated short telomeres; however, 41% of VH-unmutated and 5% of VH-mutated patients did not show this correlation and were thus defined as 'discordant'; (3) TRF-L effectively predicts outcome in terms of TTFT, PFS and OS; (4) VH-unmutated discordant patients have a better clinical outcome than VH-unmutated concordant patients (OS P<0.01, PFS P<0.05) and similar to that of VH-mutated patients (OS, PFS P=NS). Compared to VH-unmutated concordant patients, VH-unmutated discordant patients showed no peculiarity in their immunoglobulin rearrangement nor in their flow cytometry or fluorescence in situ hybridization profile. In conclusion, TRF-L can be helpful to refine prognostication of B-CLL patients, particularly those with a VH-unmutated immunoglobulin sequence.     

Intimal-medial thickness of the common carotid arteries and lower limbs atherosclerosis in the elderly

BACKGROUND: In the present study, the authors consider the possible association between intimal-media thickness of the common carotid arteries and lower limb atherosclerosis, in a group of elderly patients; the authors also consider the presence of cardiovascular risk factors. METHODS: B-mode ultrasound measurement of the intimal-media thickness of the common carotid arteries was performed on 80 subjects. Lower limbs atherosclerosis was defined as the presence of intermittens claudicatio and/or ankle-arm index < 0.9. Baseline clinic examination and blood tests were performed in all subjects to consider the presence of cardiovascular risk factors. Linear regression analysis was used to assess the linear relationship between intimal-media thickness of the common carotid arteries and lower limb atherosclerosis. RESULTS: Linear regression analysis showed a statistical association between increased values of intimal-media thickness of the common carotid arteries and lower limb atherosclerosis. Sixty-four (80%) subjects presented one or more associated cardiovascular risk factors. CONCLUSIONS: The results of the the present study confirm that intimal-media thickness of the common carotid arteries is a marker for the identification of generalized atherosclerosis and may be useful for the identification of subjects, even at early stages, at risk of cardiovascular diseases.     

Cancer incidence among first generation Scottish, Irish, West Indian and South Asian migrants living in England and Wales

Objectives. To examine the incidence of cancers among persons born in Scotland, Northern Ireland, the Irish Republic, Caribbean Commonwealth and Indian subcontinent and living in England and Wales. Methods. Longitudinal Study of 1% of population of England and Wales followed from 1971 to 1989. Standardised incidence ratios (SIRs) were derived for commonly occurring cancers and all cancers using the age-sex-specific rates for all females and all males in the Longitudinal Study. Results. The incidence of all malignant neoplasms among West Indians (females SIR = 67, male SIR = 70) and Indians (female SIR = 32, male SIR = 52) was low. Among South Asians, this pattern was consistent for Hindus, Sikhs and Moslems. Scottish females showed raised incidence of lung cancer (SIR = 149) and those from the Irish Republic of oral cavity and pharynx (SIR = 321), oesophageal (SIR = 219) and liver (SIR = 373) cancers. Among Northern Irish females, incidence of lung cancer (SIR = 193) was raised. West Indian and South Asian females showed low incidence of breast cancer (SIR = 55 and 45, respectively). High incidence of laryngeal (SIR = 229) and renal (SIR = 203) cancers was observed for Scottish males and of oral cancer (SIR = 259) for males from the Irish Republic. At ages 15-64, raised incidence of prostate cancer (SIR = 129) and of leukaemia (SIR = 252) was also observed for men from the Irish Republic. Northern Irish males showed raised incidence of stomach cancer (SIR = 200). Conclusion. This study describes patterns of cancer incidence among migrant groups, most of which reflect environmental influences. This has challenging implications for sensitive targeting of primary interventions. It is important not to be complacent about lower risks of main cancers among West Indians and South Asians. In all Longitudinal Study members, breast cancer was the most common malignancy among females and lung cancer among males. This was also true for all migrant groups with the exception of Northern Irish women for whom lung cancer was the most common.     

Detecting pre-ovulatory luteinizing hormone surges in urine

The study objectives were to determine (i) if pre-ovulatory luteinizing hormone (LH) surges, undetected in urine by two immunoradiometric assays (IRMA), were detectable by an ultrasensitive immunofluorometric assay (IFMA) and (ii) the influence of creatinine adjustment on the detection and timing of the urinary LH surges. Daily urine specimens were contributed by healthy 25-36 year old volunteers during 14 ovulatory menstrual cycles for an epidemiological study conducted in 1983-1985. Specimens were selected as having been previously assayed by two IRMA without consistently detecting LH surges. These urine specimens were remeasured using an IFMA and adjusted for creatinine concentration. IFMA measurements revealed unambiguous LH surges in all cycles. Adjusting IRMA urinary LH values for creatinine concentrations revealed previously undetected LH surges in four of eight cycles. Creatinine adjustment also altered the timing of IRMA and IFMA LH surges by 1-5 days. These results demonstrate an IFMA that detects pre- ovulatory LH surges in unpreserved, frozen urine from cycles where such surges were previously undetectable. Further, creatinine adjustment can markedly affect detection and timing of the onset and peak of the urinary LH surge. While our analysis suggests that this adjustment improves the validity of the LH measure, this requires further investigation.      

Births of normal daughters after MicroSort sperm separation and intrauterine insemination, in-vitro fertilization, or intracytoplasmic sperm injection

The world's first deliveries of normal babies after use of flow cytometric separated human sperm cells (MicroSort) for preconception gender selection are reported. Offspring were of the desired female gender in 92.9% of the pregnancies. Most of these pregnancies and births were achieved after simple intrauterine insemination.      

Virulence alterations of Tacaribe virus infection in adult mice: Lethal model for encephalitis

Summary Selection of populations of Tacaribe virus strain 11573 lethal for mice was carried out by serial intracerebral passage of the virus in adult mice. Viral populations have been characterized by determination of virulence for suckling, weanling, and adult mice, and by histopathologic changes observed in brains of adult mice after intracerebral inoculation. Some of the virus preparations produced 80 to 90 per cent mortality after two or three intracerebral passages in adult mice and maintained this virulence for 1 to 3 passages, after which the virulence rapidly declined with subsequent passages. Clinical signs of infection in adult mice were manifested by a rough hair-coat, ventriflexed posture, diminished activity, increased excitability, flaccid hind-limb extension with progressive paralysis and death. Histologic examination revealed meningoencephalitis.With 2 FiguresIn conducting the research described in this report, the investigators adhered to the Guide for the Care and Use of Laboratory Animals, as promulgated by the Committee on the Revision of the Guide for Laboratory Animal Facilities and Care of the Institute of Laboratory Animal Resources, National Research Council. The facilities are fully accredited by the American Association for Accreditation of Laboratory Animal Care.The views of the authors do not purport to reflect the positions of the Department of the Army or the Department of Defense.     

Overview and update on molecular testing in non-small cell lung carcinoma utilizing endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) samples

Lung carcinoma remains one of the most frequent and aggressive human neoplasms. Fortunately, in the last decades, the increasing knowledge of the molecular mechanisms leading to cancer development has allowed the use of targeted therapies with improvement of prognosis in many patients. Clinical management has also changed after the introduction of endobronchialultrasonographic bronchoscopy that allows a conservative staging of lung tumors, avoiding the need of mediastinoscopy for lymph node staging. Lung pathologists and cytopathologists are facing the challenge of giving the more comprehensive prognostic and predictive information with ever smaller tissue or cytological samples. The aim of this review is to summarize the molecular testing for non-small cell lung carcinoma and how pathologists can contribute to the patient's outcome with a conscious management of biological samples.