Leprosy elimination campaigns in Orissa

Four Modified Leprosy Elimination Campaigns (MLECs) were conducted in Orissa by March 2003. Their impact on various leprosy indicators was analyzed. More than 70% of the people of the State were examined during these campaigns. The suspect rate decreased from 1.44% to 0.37% towards the fourth MLEC. About 15% of the suspects were clinically confirmed to be having leprosy. The total number of new cases detected during the MLEC years was on the decrease. A marked fall in new case-detection rate was observed during inter-MLEC years. This has resulted in fluctuation in the prevalence rate during the MLEC years, but the overall PR/10,000 population decreased from 12.18 in 1996-97 to 7.3 in March 2003. More than 40% of the total new cases and about 45% of total new child cases for the corresponding year were detected during the MLECs, and the proportion of total new case-detection was as high as 60.8% during the first MLEC. The proportion of female cases detected during succeeding MLECs improved and an almost equal number of female cases were detected during MLECs III and IV. Considering the present leprosy situation in Orissa and the effectiveness of MLECs in case-detection, it was recommended that such campaigns should be undertaken in select high prevalent blocks of the State at regular intervals, along with the strengthening of the integration of NLEP activities into primary health care activities.     

Atypical teratoid/rhabdoid tumors of the central nervous system: clinical,radiographic and pathologic features

INTRODUCTION: Atypical teratoid/rhabdoid tumors (ATT/RT) of the central nervous system (CNS) are uncommon malignancies of childhood with an aggressive course and a uniformly fatal outcome. METHODS: The medical records, radiographic images and pathologic files at the Rainbow Babies and Childrens Hospital over the previous 6 years were retrospectively reviewed. RESULTS: Eight children underwent surgery for CNS ATT/RT at our institution since 1996. There were 6 boys and 2 girls. Median age at presentation was 21 months. Four tumors had multifocal disease at the time of diagnosis. Six patients received multiagent chemotherapy including 3 patients with autologous bone marrow transplantation, and 6 patients received radiation therapy. Median survival was 9 months from the time of diagnosis. CONCLUSIONS: In spite of aggressive therapy, the prognosis for ATT/RT remains dismal. The search for effective treatment strategies will require a better understanding of the biology and molecular genetics of this tumor.     

Intracranial complications of frontal sinusitis in children: Pott's puffy tumor revisited

The objective of the present study is to describe the diagnosis and treatment of intracranial complications of frontal sinusitis (Pott's puffy tumor) in a series of pediatric patients at our institution. A rare entity, Pott's puffy tumor has been reported in only 21 pediatric cases in the literature of the antibiotic era. The hospital records and radiographic files at Rainbow Babies and Childrens Hospital, Cleveland, Ohio, USA, over the previous 16 years were retrospectively reviewed in a search for patients with the diagnosis of Pott's puffy tumor, defined as scalp swelling and associated intracranial infection. There were 6 male patients and 1 female patient. Ages ranged from 11 to 18 years (median 14.5 years). Intracranial infections consisted of epidural abscess in 5 patients, subdural empyema in 4 and brain abscess in 1. Intraoperative cultures grew anaerobic organisms in 1 patient, microaerophilic streptococcus in 5 patients, Klebsiella species in 1 patient and Streptococcus pneumoniae in another. All patients presented with frontal scalp swelling, and other common symptoms included headache, fever, nasal drainage and frontal sinus tenderness. Five patients were treated with antibiotics prior to their presentation. Four patients presented with neurologic decompensation characterized by varying degrees of hemiparesis, obtundation, pupillary dilatation or aphasia. All patients underwent craniotomy and evacuation of the intracranial infection. Even severely impaired patients demonstrated full neurologic recovery. Despite the widespread use of antibiotics, neurosurgical complications of sinusitis continue to occur. A high degree of suspicion, along with prompt neurosurgical intervention and the use of appropriate antibiotics, can result in favorable outcomes in even the sickest patients.     

The effect of prestorage irradiation on posttransfusion red cell survival

Transfusion-associated graft-versus-host disease (TA-GVHD) may occur whenever immunologically competent allogeneic lymphocytes are transfused to an immunocompromised recipient. Irradiation of blood components eliminates the risk of TA-GVHD but may damage the cellular elements in the transfused component, particularly if the cells are stored for prolonged periods in the irradiated state. To study the effect of irradiation on long-term storage of red cells, AS-1 red cells from eight normal subjects were prepared on two occasions. On one occasion, the units were stored as standard AS-1 red cells for 42 days at 4 degrees C; on the other, they were exposed to 3000 cGy radiation within 4 hours of collection and then were stored as AS-1 red cells for 42 days at 4 degrees C. The donations were at least 12 weeks apart. Irradiated units demonstrated significant elevations in poststorage plasma hemoglobin (Hb) (623 +/- 206 vs. 429 +/- 194 g/dL [6230 +/- 2060 vs. 4290 +/- 1940 g/L], p less than 0.02) and plasma potassium (78 +/- 4 vs. 43 +/- 9 mEq/L [78 +/- 4 vs. 43 +/- 9 mmol/L], p less than 0.01) and significant decreases in red cell ATP (1.9 +/- 0.2 vs. 2.1 +/- 0.3 microM/g Hb, p less than 0.04) and 24-hour posttransfusion red cell recovery (68.5 vs. 78.4%, p less than 0.02), as compared to nonirradiated units. It can be concluded that irradiation with 3000 cGy damages red cells and that long-term storage in the irradiated state may enhance this damage. Red cells should not be stored for 42 days after irradiation with 3000 cGy.     

Fractionation of Spatial Memory in GRM2/3 (mGlu2/mGlu3) Double Knockout Mice Reveals a Role for Group II Metabotropic Glutamate Receptors at the Interface Between Arousal and Cognition

Group II metabotropic glutamate receptors (mGluR2 and mGluR3, encoded by GRM2 and GRM3) are implicated in hippocampal function and cognition, and in the pathophysiology and treatment of schizophrenia and other psychiatric disorders. However, pharmacological and behavioral studies with group II mGluR agonists and antagonists have produced complex results. Here, we studied hippocampus-dependent memory in GRM2/3 double knockout (GRM2/3^−/−) mice in an iterative sequence of experiments. We found that they were impaired on appetitively motivated spatial reference and working memory tasks, and on a spatial novelty preference task that relies on animals'' exploratory drive, but were unimpaired on aversively motivated spatial memory paradigms. GRM2/3^−/− mice also performed normally on an appetitively motivated, non-spatial, visual discrimination task. These results likely reflect an interaction between GRM2/3 genotype and the arousal-inducing properties of the experimental paradigm. The deficit seen on appetitive and exploratory spatial memory tasks may be absent in aversive tasks because the latter induce higher levels of arousal, which rescue spatial learning. Consistent with an altered arousal–cognition relationship in GRM2/3^−/− mice, injection stress worsened appetitively motivated, spatial working memory in wild-types, but enhanced performance in GRM2/3^−/− mice. GRM2/3^−/− mice were also hypoactive in response to amphetamine. This fractionation of hippocampus-dependent memory depending on the appetitive-aversive context is to our knowledge unique, and suggests a role for group II mGluRs at the interface of arousal and cognition. These arousal-dependent effects may explain apparently conflicting data from previous studies, and have translational relevance for the involvement of these receptors in schizophrenia and other disorders.     

Moving toward the petroclival region: a model for quantitative and anatomical analysis of tumor shift

OBJECT: The authors quantitatively assessed the effects of balloon inflation as a model of tumor compression on the brainstem, cranial nerves, and clivus by measuring the working area, angle of attack, and brain shift associated with the retrosigmoid approach. METHODS: Six silicone-injected cadaveric heads were dissected bilaterally via the retrosigmoid approach. Quantitative data were generated, including key anatomical points on the skull base and brainstem. All parameters were measured before and after inflation of a balloon catheter (inflation volume 4.8 ml, diameter 20 mm) intended to mimic tumor compression. RESULTS: Balloon inflation significantly shifted (p < 0.001) the brainstem and cranial nerve foramina (mean [+/- standard deviation] displacement of upper brainstem, 10.2 +/- 3.7 mm; trigeminal nerve exit, 6.99 +/- 2.38 mm; facial nerve exit, 9.52 +/- 4.13 mm; and lower brainstem, 13.63 +/- 8.45 mm). The area of exposure at the petroclivus was significantly greater with balloon inflation than without (change, 316.26 +/- 166.75 mm2; p < 0.0001). Before and after balloon inflation, there was no significant difference in the angles of attack at the origin of the trigeminal nerve (p > 0.5). CONCLUSIONS: This study adds an experimental component to the emerging field of quantitative neurosurgical anatomy. Balloon inflation can be used to model the effects of a mass lesion. The tumor simulation created "natural" retraction and an opening toward the upper clivus. The findings may be helpful in selecting a surgical approach to increase the working space for resection of certain extraaxial tumors.     

Allosteric modulators of NR2B-containing NMDA receptors: molecular mechanisms and therapeutic potential

N-methyl-D-aspartate receptors (NMDARs) are ion channels gated by glutamate, the major excitatory neurotransmitter in the mammalian central nervous system (CNS). They are widespread in the CNS and are involved in numerous physiological and pathological processes including synaptic plasticity, chronic pain and psychosis. Aberrant NMDAR activity also plays an important role in the neuronal loss associated with ischaemic insults and major degenerative disorders including Parkinson''s and Alzheimer''s disease. Agents that target and alter NMDAR function may, thus, have therapeutic benefit. Interestingly, NMDARs are endowed with multiple extracellular regulatory sites that recognize ions or small molecule ligands, some of which are likely to regulate receptor function in vivo. These allosteric sites, which differ from agonist-binding and channel-permeation sites, provide means to modulate, either positively or negatively, NMDAR activity. The present review focuses on allosteric modulation of NMDARs containing the NR2B subunit. Indeed, the NR2B subunit confers a particularly rich pharmacology with distinct recognition sites for exogenous and endogenous allosteric ligands. Moreover, NR2B-containing receptors, compared with other NMDAR subtypes, appear to contribute preferentially to pathological processes linked to overexcitation of glutamatergic pathways. The actions of extracellular H⁺, Mg²⁺, Zn²⁺, of polyamines and neurosteroids, and of the synthetic compounds ifenprodil and derivatives (‘prodils’) are presented. Particular emphasis is put upon the structural determinants and molecular mechanisms that underlie the effects exerted by these agents. A better understanding of how NR2B-containing NMDARs (and NMDARs in general) operate and how they can be modulated should help define new strategies to counteract the deleterious effects of dysregulated NMDAR activity.     

Biomechanical comparison of occipitoatlantal screw fixation techniques

OBJECT: The stability provided by 3 occipitoatlantal fixation techniques (occiput [Oc]-C1 transarticular screws, occipital keel screws rigidly interconnected with C-1 lateral mass screws, and suboccipital/sublaminar wired contoured rod) were compared. METHODS: Seven human cadaveric specimens received transarticular screws and 7 received occipital keel-C1 lateral mass screws. All specimens later underwent contoured rod fixation. All conditions were studied with and without placement of a structural graft wired between the skull base and C-1 lamina. Specimens were loaded quasistatically using pure moments to induce flexion, extension, lateral bending, and axial rotation while recording segmental motion optoelectronically. Flexibility was measured immediately postoperatively and after 10,000 cycles of fatigue. RESULTS: Application of Oc-C1 transarticular screws, with a wired graft, reduced the mean range of motion (ROM) to 3% of normal. Occipital keel-C1 lateral mass screws (also with graft) offered less stability than transarticular screws during extension and lateral bending (p < 0.02), reducing ROM to 17% of normal. The wired contoured rod reduced motion to 31% of normal, providing significantly less stability than either screw fixation technique. Fatigue increased motion in constructs fitted with transarticular screws, keel screws/lateral mass screw constructs, and contoured wired rods, by means of 19, 5, and 26%, respectively. In all constructs, adding a structural graft significantly improved stability, but the extent depended on the loading direction. CONCLUSIONS: Assuming the presence of mild C1-2 instability, Oc-C1 transarticular screws and occipital keel-C1 lateral mass screws are approximately equivalent in performance for occipitoatlantal stabilization in promoting fusion. A posteriorly wired contoured rod is less likely to provide a good fusion environment because of less stabilizing potential and a greater likelihood of loosening with fatigue.