Metalloproteinase inhibitors, nonantimicrobial chemically modified tetracyclines, and ilomastat block Bacillus anthracis lethal factor activity in viable cells

Lethal toxin, produced by the bacterium Bacillus anthracis, is a major contributor to morbidity and mortality in animals and humans who have contracted anthrax. One component of this toxin, lethal factor (LF), proteolytically inactivates members of the mitogen-activated protein kinase kinase (MAPKK or MEK) family. In this study we show that CMT-300, CMT-308, and Ilomastat, agents initially characterized as matrix metalloproteinase inhibitors which are in early stages of development as pharmaceuticals, effectively inhibit the zinc metalloproteinase activity of LF. All three inhibitors, CMT-300, CMT-308, and Ilomastat, inhibit LF-mediated cleavage of a synthetic peptide substrate based on the N-terminal domain of MEKs. Inhibition of LF-mediated MEK proteolysis by all three agents was also achieved using lysates of the human monocytoid line MonoMac 6 as sources of MAPKKs and visualization of the extent of cleavage after separation by sodium dodecyl sulfate-polyacrylamide gel electrophoresis followed by detection by Western blotting. Finally, we have demonstrated inhibition of intracellular MEKs in viable human monocytes and MonoMac 6 cells by these agents after incubation of the cells with a reconstituted preparation of recombinant lethal toxin. All three agents are effective inhibitors when incubated with LF prior to exposure to cells, while the CMTs, but not Ilomastat, are also effective when added after LF has already entered the viable cell targets. These results offer promise for strategies to combat effects of the lethal toxin of B. anthracis.     

The management of wringer injuries

Summary Between the years 1985–1988, 32 patients with wringer injury of the upper extremity were admitted to our institution. A uniform treatment program was carried out on all patients; this included aseptic wound care, immobilization and elevation of the involved extremity and early coverage of skin defects. The important aspects in the management of wringer injuries are reviewed, and the importance of early coverage of skin defects is emphasized. Furthermore, it was concluded that the surface area of deep ecchymosis measured 48 h after injury was useful as a simple and objective criterion to estimate the extent of final skin necrosis.Presented at 5th Congress of the Asian Pacific Section of the International Confederation for Plastic and Reconstructive Surgery, Istanbul, September 7–10, 1989, Turkey     

A case of spatial neglect dysgraphia in Wilson's Disease.

We report here on a single neuropsychological case study of a young girl, KH, who presented with Wilson's Disease (WD) associated with a peripheral spatial neglect dysgraphia without major problems in the standard clinical tests of spatial neglect. Few studies have demonstrated a visuospatial deficit in WD and to date there has been no report of neglect syndrome arising from WD. However, recent studies have demonstrated that neglect is frequently associated with brain damage including the primary site of WD, the basal ganglia. KHs writing abilities were evaluated just after her admission to the rehabilitation department and 6 months later. The baseline evaluation demonstrated that KH had neglect dysgraphia with verbal stimuli (e.g., words or sentences) although her deficit was less evident in drawing multiple geometric shapes. Six months after the initial evaluation, KH showed evidence of neglect dysgraphia only when writing was associated with a secondary memory task. KHs writing performance is discussed with reference to previous cases of spatial neglect dysgraphia and in the context of spatial neglect. We suggest that the asymmetry between verbal writing and nonverbal drawing disturbances was caused by different attentional loads.     

Magnetic resonance imaging findings in infantile spasms: etiologic and pathophysiologic aspects

An etiologic evaluation of 86 patients with infantile spasms is presented and the place of cranial magnetic resonance imaging (MRI) findings within this spectrum is discussed. A total of 103 cranial MRIs, performed between 4 and 72 months of age, were analyzed and classified according to the etiologic and pathophysiologic aspects. Ninety-one percent of cases were diagnosed as symptomatic infantile spasms, and hypoxic-ischemic encephalopathy was the primary cause (30%). The most common involvement was thinning of the corpus callosum in 43 patients (50%), followed by dilation of cerebral ventricles in 32 (36%), delayed myelination in 23 (26.7%), lesions of diencephalic deep gray matter in 17 (19.7%), and enlargement of the subarachnoid space in 12 (14%). Thin corpus callosum and diffuse atrophy were changes mainly associated with hypoxic-ischemic encephalopathy, whereas delayed myelination seemed to be independent from a specific etiology. The results showed that cranial MRI may provide considerable information regarding not only the etiology but also the pathophysiology of infantile spasms.     

MRI findings of hypoxic cortical laminar necrosis in a child with hemolytic anemia crisis

We present magnetic resonance imaging findings of a 5-year-old girl who had a rapidly installing hemolytic anemia crisis induced by trimethoprim-sulfomethoxazole, resulting in cerebral anoxia leading to permanent damage. Magnetic Resonance imaging revealed cortical laminar necrosis in arterial border zones in both cerebral hemispheres, ischemic changes in subcortical white matter of left cerebral hemisphere, and in the left putamen. Although cortical laminar necrosis is a classic entity in adulthood related to conditions of energy depletions, there are few reports available in children. A wide review of the literature is also presented.     

Induction of labor in toxemia with misoprostol

BACKGROUND: To compare the efficacy and complications of intravaginal misoprostol application with oxytocin infusion for induction of labor in toxemia of pregnancy with a modified Bishop score of < or =4. METHODS: A hundred preeclamptic women with a modified Bishop score of < or =4 were randomized into two groups of 50 patients one group receiving 50 microg intravaginal misoprostol 4 times at 4 hour intervals, the second group receiving oxytocin infusion for induction of labor starting from 1 mIU/per minute, increasing it every 30 minutes with 2 mIU/per minute increments up to maximum of 30 mIU/per minute. Modified Bishop scores 12 hours after induction, the time from induction to delivery, the route of delivery, fetal outcome and maternal complications were recorded. Statistical analyses were performed using Mann Whitney-U, Chi-Square and hypothesis tests about differences for two proportions (t test) to determine differences between the two groups. p< or =0.05 was considered significant. RESULTS: Misoprostol was significantly superior for induction of labor in toxemia of pregnancy with modified Bishop score of < or =4. After 12 hours median modified Bishop scores of misoprostol administered group and oxytocin administered group were 7 and 4 respectively. Misoprostol administered group 1 was significantly better than oxytocin administered group 2 (p=0.027). The rate of patients who were in labor after 12 hours were 94% and 80% in group 1 and 2 respectively and the difference showed significant difference (p<0.05). The median time from induction to delivery was 14 hours and 16 hours in the misoprostol and oxytocin administered group respectively with significant difference between the groups (p=0.003). The rate of vaginal delivery was significantly higher in the misoprostol administered group 1 (82%) when compared with the oxytocin administered group 2 (66%) (p<0.05). The 1 and 5 minutes median Apgar scores were 5-7 and 6-7.5 in group 1 and 2, respectively with no significant differences between the groups (p=0.96, p=0.64). The rate of admission to neonatal intensive care unit was similar in both groups. The complication rates were similar in all groups and no significant detrimental effects were noted. CONCLUSIONS: Intravaginal misoprostol is an efficacious, cheap and safe method of induction of labor in toxemia of pregnancy with modified Bishop score of < or =4.     

Gadolinium-enhanced MR cisternography to evaluate dural leaks in intracranial hypotension syndrome

Background and PURPOSE: We evaluated the use of MR cisternography after intrathecal administration of gadopentetate dimeglumine to detect the presence and localization of CSF leaks in 19 patients diagnosed with spontaneous intracranial hypotension syndrome according to the criteria of International Headache Society.MATERIALS AND METHODS: Lumbar puncture with an injection of 0.5 mL of gadopentetate dimeglumine into the subarachnoid space in the lumbar area was performed. MR images of the cervical, thoracic, and lumbar regions in axial, coronal, and sagittal planes with fat-saturated T1-weighted images were acquired.RESULTS: We observed objective CSF leakage in 17 (89%) of 19 patients. In 14 of these 17 patients, the site of dural tear was demonstrated accurately. In 3 of these 17 patients, the contrast leakage was diffuse, and site of the leak could not be located accurately. No leakage was observed in 2 patients. No complications were detected in any of the patients during the first 24 hours after the procedure or during the 6- to 12-month follow-up.CONCLUSION: The current results demonstrate the relative safety, accuracy, and feasibility of intrathecal gadolinium-enhanced MR cisternography to evaluate dural leaks.

The spontaneous intracranial hypotension (SIH) syndrome was originally described by the German neurologist Schaltenbrand^1,2 in 1938 as hypoliquorrhea. The Headache Classification Subcommittee of the International Headache Society has proposed diagnostic criteria for SIH.³ Evidence of CSF leakage was accepted as one of the main criteria for SIH diagnosis according to International Classification of Headache Disorders.³ Although many patients with SIH recover without intervention, many do not.^4,5 Some of these patients do not respond to multiple epidural blood patches and may require more targeted epidural injections, infusions, or surgical repair.^4–6 In these patients, confirmation of CSF leak, localization of the actual site or sites of CSF leak, and characteristics of the dural leaks become important. Despite advances in imaging and the availability of several different and potentially useful diagnostic modalities, accurate demonstration of the site of the CSF leakage remains a challenge for radiologists and clinicians. The purpose of our study was to evaluate and report our initial experience in analyzing CSF leaks in SIH using MR imaging combined with intrathecal administration of a gadolinium-based contrast agent, that is, gadolinium-enhanced MR cisternography.     

Serum prolidase level in ankylosing spondylitis: low serum levels as a new potential gold standard biomarker for disease activity

Ankylosing spondylitis (AS) is a chronic inflammatory disorder that mainly affects the sacroiliac joints and axial skeleton. The aim of this study was to assess serum prolidase level (SPL) and its association with disease activity in patients with AS. This prospective study included 75 AS patients. Thirty age- and gender-matched healthy controls were enrolled. AS patients were considered as active if BASDAI score was ≥4 or inactive if BASDAI score was <4. There were 34 AS patients in the active group and 41 AS patients in the inactive group. Anti-TNF-monoclonal antibody treatment was started in patients in the active group. These active patients were reassessed 6 months later. BASDAI, ASDAS, visual analogue scale, short-form-general health survey questionnaire, C-reactive protein, erythrocyte sedimentation rate and SPL were measured in all AS patients before and after treatment. The SPL was significantly lower in inactive AS patients than in control group, and also, SPL was significantly lower in active AS patients than in inactive patients. All activity parameters were successful in separating active and inactive AS patients. However, the only parameter that could distinguish active patients from inactive patients was prolidase. The optimum cutoff point of SPL to identify patients with active AS was 23.13 ng/mL with sensitivity, specificity, positive predictive value and negative predictive value of 100 %. Serum prolidase level was successful in measuring disease activity and had as high sensitivity and specificity as BASDAI and was superior to other activity parameters.