Homozygosity mapping of achromatopsia to chromosome 2 using DNA pooling

Achromatopsia is an autosomal recessive disease of the retina, characterized clinically by an inability to distinguish colors, impaired visual acuity, nystagmus and photophobia. A genome-wide search for linkage was performed using an inbred Jewish kindred from Iran. To facilitate the genome-wide search, we utilized a DNA pooling strategy which takes advantage of the likelihood that the disease in this inbred kindred is inherited by all affected individuals from a common founder. Equal molar amounts of DNA from all affected individuals were pooled and used as the PCR template for short tandem repeat polymorphic markers (STRPs). Pooled DNA from unaffected members of the kindred was used as a control. A reduction in the number of alleles in the affected versus control pool was observed at several loci. Upon genotyping of individual family members, significant linkage was established between the disease phenotype and markers localized on chromosome 2. The highest LOD score observed was 5.4 (theta = 0). When four additional small unrelated families were genotyped, the combined peak LOD score was 8.2. Analysis of recombinant chromosomes revealed that the disease gene lies within a 30 cM interval which spans the centromere. Additional fine-mapping studies identified a region of homozygosity in all affected individuals, narrowing the region to 14 cM. A candidate gene for achromatopsia was excluded from this disease interval by radiation hybrid mapping. Linkage of achromatopsia to chromosome 2 is an essential first step in the identification of the disease-causing gene.      

The chemotherapy of lymphoblastic lymphoma

Thirty-two patients treated on consecutive Southwest Oncology Group (SWOG) protocols for malignant lymphoma were subsequently diagnosed as having lymphoblastic lymphoma. Combination chemistry, usually adriamycin-based, produced complete responses (CR) in 17 patients (53%). Median survival was 15 mo. Patients achieving a CR survival significantly longer than patients with partial or no response (p < 0.01). Ten of 24 patients not receiving central nervous system (CNS) prophylaxis developed leptomeningeal lymphoma while none of the seven patients who received prophylactic intrathecal cytosine arabinoside or methotrexate developed CNS lymphoma (p = 0.04). Implications of these results for planning future treatment programs of lymphoblastic lymphoma are discussed.     

Effect of previous hormone replacement therapy on endometrial polyps during menopause

The aim of this study was to evaluate the effect of hormone replacement therapy (HRT) on the expression of Ki-67, bcl-2 and c-erb.B2 in endometrial polyps during menopause. Sixteen patients using HRT and 24 untreated controls with endometrial polyps were enrolled in this study. Polypectomy was carried out by hysteroscopy. The presence of c-erb.B2, bcl-2 and Ki-67 expression was determined by immunohistochemistry. HRT was found to decrease Ki-67 and bcl-2 expression in endometrial polyps without affecting the c-erb.B2 staining reaction. HRT may cause endometrial polyp involution by decreasing proliferation and stimulating apoptosis.     

US-guided percutaneous biopsy: use of a screw biopsy stylet to aid needle detection

Insertion of a screw biopsy stylet into a thin-walled biopsy needle greatly enhances detection of the needle during ultrasound-guided percutaneous biopsy. This technique is helpful when precise needle-tip localization is needed for biopsies of small lesions.     

Glial cell line-derived neurotrophic factor-dependent recruitment of Ret into lipid rafts enhances signaling by partitioning Ret from proteasome-dependent degradation

The receptor tyrosine kinase (RTK) Ret is activated by the formation of a complex consisting of ligands such as glial cell line-derived neurotrophic factor (GDNF) and glycerophosphatidylinositol-anchored coreceptors termed GFRalphas. During activation, Ret translocates into lipid rafts, which is critical for functional responses to GDNF. We found that Ret was rapidly ubiquitinated and degraded in sympathetic neurons when activated with GDNF, but, unlike other RTKs that are trafficked to lysosomes for degradation, Ret was degraded predominantly by the proteasome. After GDNF stimulation, the majority of ubiquitinated Ret was located outside of lipid rafts and Ret was lost predominantly from nonraft membrane domains. Consistent with the predominance of Ret degradation outside of rafts, disruption of lipid rafts in neurons did not alter either the GDNF-dependent ubiquitination or degradation of Ret. GDNF-mediated survival of sympathetic neurons was inhibited by lipid raft depletion, and this inhibitory effect of raft disruption on GDNF-mediated survival was reversed if Ret degradation was blocked via proteasome inhibition. Therefore, lipid rafts sequester Ret away from the degradation machinery located in nonraft membrane domains, such as Cbl family E3 ligases, thereby sustaining Ret signaling.     

Selecting the best and brightest: A comparison of residency match processes in the United States and Canada

BACKGROUND:

Selecting candidates for plastic surgery residency training remains a challenge. In the United States, academic measures (United States Medical Licensing Exam Step I scores, medical school class rank and publications) are used as primary criteria for candidate selection for residency. In contrast, Canadian medical education de-emphasizes academic measures by using a pass-fail grading system. As a result, choosing residents from many qualified applicants may pose a challenge for Canadian programs without objective measures of academic success.

METHODS:

A 25-question online survey was distributed to program directors of Canadian plastic surgery residency-training programs. Program directors commented on number of yearly residents and applicants; application sections (ranked in importance using a Likert scale); interview invitation and rank-order list determination; and their satisfaction with the selection process.

RESULTS:

Ten Canadian plastic surgery program directors responded (90.9% response rate). The most important application components determining invitation to interview were letters of reference from a plastic surgeon (mean importance of 5.0 on the Likert scale), clinical electives in plastic surgery (mean 4.6) and electives with their program (mean 4.5). Applicants invited for interview were assessed on the quality of their responses to questions, maturity and personality. The majority of program directors agreed that a clinical elective with their program was important for consideration on their rank-order list. Program directors were neutral on their satisfaction with the selection process.

CONCLUSION:

Canadian plastic surgery residency programs emphasize clinical electives with their program and letters of reference from colleagues when selecting applicants for interviews. In contrast to their American counterparts, Canadian program directors rely on clinical interactions with prospective residents in the absence of objective academic measures.     

Diminished concentrations of insulin-like growth factor I in cystic fibrosis

Cystic fibrosis is frequently accompanied by a catabolic condition with low body mass index caused by a number of disease complications. Insulin-like growth factor-I (IGF-I) is an anabolic hormone and an important marker of nutritional status, liver function, and linear growth. Available data on IGF-I in cystic fibrosis are sparse and conflicting. From 1990-3, 235 of our 240 patients (114 males, 121 females, median age 16.2 years, ranged 0.1-44.0 years) had IGF-I measured once by radioimmunoassay. IGF-I was significantly reduced compared with a healthy Scandinavian control population: mean (-2 SD to +2 SD) IGF-I SD score was -0.97 (-3.7 to 1.7) in males and -0.67 (-3.2 to 1.9) in females. Height SD score was -0.95 (-3.3 to 1.4) in males and -0.81 (-3.2 to 1.6) in females. In patients who were still in the growth period a significant correlation of IGF-I SD score to height SD score (r = 0.28, p < 0.001) was found. The low IGF-I concentrations may reflect the catabolic state of many patients with cystic fibrosis and play a part in their abnormal growth pattern.     

Parameters for the assessment of iron status

The assessment of iron status at individual and populational levels has been the target of many studies because some issues still need to be defined. A Medline, Lilacs and Dedalus literature review was carried out for the period of 1972 to 1998 and scientific publications in both English and Portuguese relating hematological and biochemical parameters were used in the assessment of iron status. The parameters reflect the three different stages of iron storage deficiency, which occur in a gradual and progressive way leading to the development of anaemia. In general, when used alone, these parameters are neither sensitive nor specific for detecting iron deficiency anaemia. Moreover, some advantages and limitations should be taken into consideration for the choice of the appropriate parameter. To improve both sensitivity and specificity, different parameters have been used in association and their specific contribution is determined according to the characteristics of the study population, methodological issues and the costs involved in the process.