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.      

Underlying cause of death in incident unprovoked seizures in the urban community of Northern Manhattan, New York City

We determined underlying cause-specific mortality for incident unprovoked seizures from Northern Manhattan, New York City. We calculated the case fatality, proportionate mortality, and the underlying cause-specific standardized mortality ratios (SMRs), with U.S. death rates as the standard. Thirty-two deaths were observed between 2003 and 2007 among 209 participants. Case fatality was significantly lower for idiopathic/cryptogenic seizures versus symptomatic seizures. About 31.3% of the deaths were attributed to malignant neoplasms, 25.0% to diseases of the heart, 15.6% to influenza and pneumonia, 3.1% to cerebrovascular diseases, and 25.0% to other causes. Significant SMRs were observed for all causes (SMR = 1.6), influenza and pneumonia (SMR = 7.1), and malignant neoplasms (SMR = 2.9). Younger cases (<65 years) had increased SMRs for all causes, malignant neoplasms, and other causes. Older cases (≥65 years) had increased SMRs for influenza and pneumonia. Underlying cause of death paralleled the underlying cause of seizure in patients with symptomatic etiologies.     

Investigation of the safety and accuracy of intraoperative gamma probe directed biopsy of bone scan detected rib abnormalities in prostatic adenocarcinoma

PURPOSE: We evaluated the technique of intraoperative gamma probe directed rib biopsy in patients with suspected metastatic prostate adenocarcinoma. This technique can be used to identify accurately the rib in question, reliably obtain sufficient tissue for diagnosis, be performed with minimal patient morbidity and potentially alter the course of therapy. MATERIALS AND METHODS: From 1996 to 2001, 8 patients with biopsy proved adenocarcinoma of the prostate and suspicious rib lesions on radionuclide bone scanning underwent open rib biopsy as part of the evaluation for metastatic disease. Mean prostate specific antigen in the patient population was 17.1 ng/ml (range 6.1 to 36.5) and clinical stage was T1c to T3c. A new technique of intraoperative gamma probe directed biopsy was used to localize and resect the rib in question. At 6 to 12 hours before the operation each patient received an intravenous injection of 28 mCi. (99m)technetium-oxidronate. The hand held, pencil sized gamma probe in a sterile sleeve was used to localize the area of greatest activity in the target bone and 3 cm. of bone were resected. RESULTS: Of the 8 patients who underwent the procedure 2 had metastatic prostate cancer on final rib pathological findings. Four of the remaining 5 patients had benign rib lesions (an old rib fracture) and 1 had metastatic lung cancer. The hot spot on bone scan was localized with 100% accuracy using our technique and a pathological diagnosis was made in all cases. Mean operative time was 61 minutes and estimated blood loss was less than 20 ml. in all cases. Seven of the 8 patients were discharged home the same day, while 1 required overnight hospitalization. There was 1 intraoperative complication of inadvertent entry into the pleural cavity, resulting in a small pneumothorax, which was treated with small chest catheter drainage and observation. CONCLUSIONS: Intraoperative gamma probe directed rib biopsy of suspected metastatic lesions in patients with prostate cancer can be safely and accurately performed with minimal patient morbidity. The information obtained using this technique can be used to tailor treatment decisions for this subset of patients with prostate cancer.     

Glenoid labrum: preliminary work with use of radial-sequence MR imaging

The authors describe a magnetic resonance imaging method for examination of the glenoid labrum of the shoulder joint that utilizes a radial fast-imaging sequence. Seven shoulders were examined: a total of five in three healthy asymptomatic volunteers, one in a symptomatic patient not suspected of having a lesion of the glenoid labrum, and one in a patient with recurrent shoulder dislocation and surgical proof of an extensive tear of the labrum. The preliminary results suggest that this technique may advantageously demonstrate pathologic changes in the glenoid labrum and may contribute to the evaluation of the unstable and painful shoulder.     

Multiple cerebral metastases: detectability with Gd-DTPA-enhanced MR imaging

Sixteen patients with suspected cerebral metastases were studied with magnetic resonance (MR) imaging before and after the intravenous administration of 0.1 mmol/kg of gadolinium diethylenetriaminepenta-acetic acid. The images were interpreted blindly by two neuroradiologists; all clinical, radiologic (computed tomographic and MR imaging), and pathologic data were reviewed to arrive at a final "best diagnosis," which was then compared with the prior blinded interpretations. Of seven patients found to have multiple metastases, six (86%) had at least one tumor nodule depicted by postinfusion MR imaging that was missed by one or both observers on review of preinfusion images alone. Lesions missed on preinfusion studies were usually small nodules hidden by or not detected next to regions of high-signal edema thought to be related to the adjacent tumor nodule. The authors believe that contrast enhancement improves detection of metastatic foci with MR imaging and that the findings indicate broader implications for the detection of multiple lesions from other causes.     

Complement Alternative Pathway Deficiency in Recipients Protects Kidney Allograft From Ischemia/Reperfusion Injury and Alloreactive T Cell Response

Despite the introduction of novel and more targeted immunosuppressive drugs, the long‐term survival of kidney transplants has not improved satisfactorily. Early antigen‐independent intragraft inflammation plays a critical role in the initiation of the alloimmune response and impacts long‐term graft function. Complement activation is a key player both in ischemia/reperfusion injury (IRI) as well as in adaptive antigraft immune response after kidney transplantation. Since the alternative pathway (AP) amplifies complement activation regardless of the initiation pathways and renal IR injured cells undergo uncontrolled complement activation, we speculated whether selective blockade of AP could be a strategy for prolonging kidney graft survival. Here we showed that Balb/c kidneys transplanted in factor b deficient C57 mice underwent reduced IRI and diminished T cell–mediated rejection. In in vitro studies, we found that fb deficiency in T cells and dendritic cells conferred intrinsic impaired alloreactive/allostimulatory functions, respectively, both in direct and indirect pathways of alloantigen presentation. By administering anti‐fB antibody to C57 wt recipients in the early post Balb/c kidney transplant phases, we documented that inhibition of AP during both ischemia/reperfusion and early adaptive immune response is necessary for prolonging graft survival. These findings may have implication for the use of AP inhibitors in clinical kidney transplantation.