MRI findings in Hirayama’s disease: flexion-induced cervical myelopathy or intrinsic motor neuron disease?

Hirayama’s disease is a benign juvenile form of focal amyotrophy affecting the upper limbs. Previous studies have suggested that the disorder is a neck flexion induced cervical myelopathy. We report clinical and magnetic resonance imaging findings in nine patients with Hirayama’s disease. Cervical imaging of seven patients revealed spinal cord changes consisting of focal atrophy and foci of signal alterations. On neck flexion a forward movement and mild reduction in the anteroposterior diameter of the lower cervical cord against the vertebral bodies was noted in affected individuals as well as in five normal controls. In contrast to earlier reports, none of our patients showed complete obliteration of the posterior subarachnoid space. Measurement of the anteroposterior spinal cord diameter in each vertebral segment (C4–C7) revealed no significant differences in the degree of spinal cord flattening between the two groups. Furthermore, two of our patients had significant degenerative changes in the cervical spine (disc herniation, retrospondylosis) contralateral to the clinically affected side. These degenerative changes resulted in a marked cord compression on neck flexion but were not associated with ipsilateral clinical abnormalities or spinal cord alterations. Our results argue against a flexion-induced cervical myelopathy and support the view that Hirayama’s disease is an intrinsic motor neuron disease. Received: 15 March 1999 Received in revised form: 25 May 1999 Accepted: 1 June 1999     

Striatal grafts in a rat model of Huntington's disease: time course comparison of MRI and histology

Survival and integration into the host brain of grafted tissue are crucial factors in neurotransplantation approaches. The present study explored the feasibility of using a clinical MR scanner to study striatal graft development in a rat model of Huntington's disease. Rat fetal lateral ganglionic eminences grown as free-floating roller-tube cultures were grafted into the quinolinic acid-lesioned striatum, and T1- and T2-weighted sequences were acquired at 2, 7, 21, and 99 days posttransplantation. MR images were then compared with images of corresponding histological sections. The lesion-induced striatal degeneration caused a progressive ventricle enlargement, which was significantly different from controls at 21 days posttransplantation. Seven days posttransplantation, T1-weighted images revealed a defined liquid-isointense signal surrounded by a hyperintense rim at the site of graft placement, which was found unaltered for the first 21 days posttransplantation, whereas a hypointense graft signal was detected at 99 days posttransplantation. At 2 days posttransplantation, T2-weighted images showed the graft region as a hyperintense area surrounded by a rim of low signal intensity but at later time-points graft location could not be further verified. Measures for graft size and ventricle size obtained from MR images highly correlated with measures obtained from histologically processed sections (R = 0.8, P < 0.001). In conclusion, the present study shows that fetal rat lateral ganglionic eminences grown as free-floating roller-tube cultures can be successfully grafted in a rat Huntington model and that a clinical MR scanner offers a useful noninvasive tool for studying striatal graft development.     

Preoperative infection prophylaxis with 1 % polyvidon-iodine solution based on the example of conjunctival staphylococci

Background: Most germs causing postoperative endophthalmitis derive from the conjunctival bacterial normal flora. Postoperative endophthalmitis is often induced by staphylococcal germs. The application of polyvidone-iodine solution to the conjunctiva is one possibility to reduce potential endophthalmitis-causing bacteria. The aim of this study was to evaluate the effectiveness of 1 % polyvidone-iodine solution concerning the reduction of colonization with staphylococci in the course of intraocular surgery. This is to evaluate the effectiveness of 1 % polyvidone-iodine solution concerning coagulase-negative and positive staphylococci.     

Influence of the concentration of metipranolol eye drops on the drug concentration in human aqueous humour

The concentration of the metabolite of the beta-blocker metipranolol was determined in the aqueous humour of 89 cataract patients. At 1, 2 or 5 h before surgery, they received one drop (30 l) of a 0.1 % or 0.3% solution of the drug. At 1, 2 or 5 h after the application of 0.1 % metipranolol eye drops, desacetylmetipranolol concentrations of 624.55, 235.29 and 88.02 ng/ ml, respectively, were measured. At the same intervals after the instillation of 0.3% metipranolol eye drops, the respective values of 1289.20, 1120.88 and 327.36 ng/ ml were found. The metabolite concentration in the eye drops and the values measured show no consistent correlation.Offprint requests to: H. Bleckmann     

Urine test strips: reliability of semi-quantitative findings under tropical conditions

Semi-quantitative urinalysis with urine reagent strips (URS) for erythrocyturia (EU), leucocyturia (LU) and proteinuria (PU) was performed in Congolese and Sudanese school children withSchistosoma haematobium and/orS.mansoni infection. Quantitative urinalysis was performed on the same specimen using microscopy and a Neubauer counting chamber for EU and LU and the Coomassie blue dye-binding assay for PU. Microscopically detectable EU of more than 10 cells/l was found in 63% of all samples and LU of more than 20 cells/l was found in 60% of all samples. With the Coomassie blue method, PU of more than 150 mg/l was detected in 51% of all samples. URS gave positive results of grade 1–3 for EU in 69% of all samples, for LU in 63% of all samples and for PU in 66% of all samples. The sensitivity and specificity of URS compared with standard reference methods were as follows: EU 95% and 75%, LU 81% and 81% and PU 90% and 56%. When the results of all three test were combined, URS differentiated abnormal from normal urine specimens with a sensitivity of 94% and a specificity of 70%. Median quantitative results showed a good correlation with semiquantitative URS readings for all parameters, but there was a wide range of URS scores.We concluded that URS sensitively detect urinary abnormalities and thus may be used as a general screening method under field conditions when more specific methods cannot be performed. In the hospital laboratory,urine microscopy with a counting chamber would be preferred to URS as a sole method for EU and LU detection; URS is useful for the detection of PU in the tropical hospital laboratory where an appropriate quantitative method with a better specificity may not be available.     

Short time delays change pattern induced flicker colors (PIFCs)

Subjects decided on whether the colors of the rings on a modified Benham's top were the same or different. The cause of color differences was a variable time delay. Δt, of the black and white stimulus pattern on the disc. Time delays of Δt = 50 μsec and less caused detectable changes in color and brightness.     

An in vitro model for videoimaging of human bladder smooth muscle cell contractions

Knowledge regarding human bladder smooth muscle cell (SMC) physiology is very limited. Only a few specific medical therapies for bladder disorders have therefore been established. The objective of this study was to develop a model for videomicroscopy of bladder SMC contractions. Cells were isolated from human cystoprostatectomy specimens and cultured in a modified EMEM medium. These cells were identified as SMCs by means of immunohistochemistry. For videomicroscopy, the culture flasks were coated with a viscous agent to allow cell contraction. Contractions were visualized by means of a cell culture microscope with a time-lapse videosystem. For cholinergic stimulation of the cells, acetylcholine, in concentrations ranging from 100 μM to 10 mM, was applied. The percentage of contracting cells within the observation field was evaluated for quantitative analysis. In control experiments without contractile stimulant 6% of the cells were observed to contract. Stimulation with acetylcholine induced a significant dose-dependent increase to 47% in contracting cells. These results demonstrated that videomicroscopy is an appropriate tool to investigate the contraction mechanisms of bladder SMCs. This model offers the possibility of studying drug effects on the human detrusor in vitro. Received: 16 September 1999 / Accepted: 1 May 2000     

Hyperglycemia and retinopathy of prematurity in very low birth weight infants.

OBJECTIVE: Retinopathy of prematurity (ROP) remains a leading cause of morbidity in the very low-birth-weight (VLBW) infant. This study investigates a possible association between serum/blood glucose and the development of ROP. METHODS: A retrospective case-control study of all infants born between 1992 and 1997 at the Johns Hopkins Hospital with birth weights less than 1000 g who developed Stage 3 or 4 ROP was conducted. Controls either had Stage 1 ROP or no eye disease and were matched 2:1 with ROP patients for gestational age, birth weight and year of birth. Odds ratios (ORs) of ROP were calculated for multiple exposures over the first month after birth, including oxygen concentration (FiO(2)), blood glucose levels, vitamin E, mean airway pressure and mean blood pressure. RESULTS: In a simple logistic regression analysis, we found an increased ROP risk for: (1) each 10 mg/dl increase of mean glucose (OR 1.96; 95% CI 1.13 to 3.42), (2) each 1% increase of mean FiO(2) (OR 1.06; 95% CI 1.004 to 1.13), (3) history of dopamine infusion (OR 5.4; 95% CI 1.16 to 25.2) and (4) intraventricular hemorrhage Grade 3 or 4 (OR 7.3; 95% CI 1.53 to 34.7). Using a multiple regression model, we found an increased ROP risk for each 10 mg/dl increase of mean glucose (OR 2.7; 95% CI 1.003 to 7.27). Each IU/kg/day of vitamin E supplementation reduced ROP risk (OR 0.37; 95% CI 0.16-0.86). CONCLUSION: In this study, we could demonstrate that glucose levels in the first month of life are associated with the development of ROP. Further studies have to determine if this association is causal or if hyperglycemia is just an expression of severity of illness.     

Prognostic impact of ANX7-GTPase in metastatic and HER2-negative breast cancer patients.

PURPOSE: ANX7-GTPase located on chromosome 10q21 is significantly altered and associated with hormone-refractory metastatic prostate cancers. Therefore, we investigated whether levels of ANX7 correlate with breast cancer progression and survival EXPERIMENTAL DESIGN: A diagnostic tumor tissue microarray containing 525 human breast tissue specimens at different stages of the disease was assayed for ANX7 using immunocytochemical methods with ANX7 monoclonal antibody. A separate prognostic tumor tissue microarray containing 553 human breast tissue specimens annotated with clinicopathological parameters was assayed for ANX7, HER2, estrogen receptor, progesterone receptor, and p53 protein. RESULTS: We report here for the first time that the expression of ANX7-GTPase is significantly enhanced and associated with the presence of metastatic disease (P < 0.0001) in the 525 human breast tissue specimens analyzed. Furthermore, using a separate 553 case retrospective prognostic tumor tissue microarray, we found that increased ANX7 expression is also significantly associated with poor overall patient survival (P < 0.014). This is particularly true when restricted to patients in whom the BRE clinical grade is 2 (P < 0.001) or for whom there is a lack of HER2 expression (P < 0.002). Finally, Cox regression analysis shows that as the expression of ANX7 rises, the probability of survival decreases by more than 10-fold for those patients with HER2-negative tumors. These latter patients represented 66% of the population affected with breast cancer in this study. CONCLUSIONS: High levels of ANX7 in tumor correlate strongly with poor survival of HER2-negative patients and the most aggressive forms of breast cancer. This is the first study to demonstrate that ANX7 antibody has the potential for development into an in vivo diagnostic and therapeutic tool. This simple and reliable immunohistochemical assay may therefore become an important biomarker for metastatic breast cancer diagnosis and management of HER2-negative breast tumor patients.     

Immunomagnetic enrichment, genomic characterization, and prognostic impact of circulating melanoma cells.

PURPOSE: The finding of melanoma cells in the peripheral blood, thus far mainly inferred from the PCR-based demonstration of tyrosinase mRNA, has been associated with metastatic melanoma. Neither the malignant nature nor the prognostic significance of circulating cells could be established. To address this question, we analyzed immunomagnetically isolated circulating melanoma cells for chromosomal aberrations and performed a clinical follow-up study of the enrolled patients. EXPERIMENTAL DESIGN: In a prospective study, blood samples were taken from 164 melanoma patients and 50 donors without malignant disease. Circulating melanoma cells were enriched by immunomagnetic cell sorting using a murine monoclonal antibody against the melanoma-associated chondroitin sulfate proteoglycan. To prove the malignant origin of the positive cells and to define their chromosomal aberrations, we analyzed the genomes of 15 individually isolated cells from seven patients by single-cell comparative genomic hybridization (SCOMP). RESULTS: Absolute and relative frequencies of circulating melanoma cells were associated with stage and with the presence or absence of detectable tumor. The detection of two or more cells correlated significantly with a reduced survival of patients with metastatic melanoma. All of the cells that were analyzed by SCOMP displayed multiple chromosomal changes and carried aberrations typical for melanoma. CONCLUSIONS: Immunomagnetic enrichment enables isolation and genomic characterization of circulating melanoma cells. The prognostic impact on survival of metastatic patients apparently reflects the aggressiveness of an ongoing tumor spread. Direct genomic analysis of the enriched and isolated cells will help to clarify the molecular-genetic basis of the establishment of generalized melanoma.