Rotavirus and other Diarrheal Disease in a Birth Cohort from Southern Indian Community.

OBJECTIVE: To describe the incidence, severity and etiology of diarrheal disease in infants and young children residing in an urban slum community in Southern India. SETTING: Three contiguous urban slums in Vellore, Tamil Nadu. PARTICIPANTS: 452 children participating in a birth cohort study on diarrheal disease; 373 completed three years of follow-up. OUTCOME MEASURES: Diarrheal incidence (obtained by twice-weekly home visits) and severity (assessed by the Vesikari scoring system), and etiological agents associated with diarrhea (through examination of stool specimens by bacteriologic culture, rotavirus enzyme immunoassay, PCR for norovirus and microscopy for parasites). RESULTS: A total of 1856 diarrheal episodes were reported in 373 children. The overall incidence rate of diarrhea was 1.66 episodes per child year for three years, with 2.76 episodes per child year in infancy. The incidence peaked during the months of July and August. Severe diarrhea formed 8% of the total episodes. Rotavirus was the most common pathogen detected, being identified in 18% of episodes. Good hygiene status resulted in 33% protection against moderate-to-severe diarrhea. CONCLUSIONS: This study highlights the burden of diarrheal disease and the important etiological agents of childhood diarrhea in Southern India. Promotion of hygienic behavior through health education may help reduce diarrheal incidence in this and similar communities.

Proinflammatory cytokines secreted by monocytes of filarial patients.

The levels of interleukin 1, granulocyte macrophage colony stimulating factor (GM-CSF) and tumour necrosis factor (TNF)-alpha secreted by the monocytes of filarial patients, such as asymptomatic microfilaremics (MF), chronic pathology (CP), and normal individuals, residing in a Wuchereria bancrofti endemic area (EN) in response to whole Brugia malayi antigen (BmA) and Setaria digitata (Sd-cuticular) and a recombinant filarial antigen (pRJ51) were studied. Stimulation of peripheral blood adherent cells with whole parasite antigen showed marked increase in IL-1 levels in MF as compared to CP or EN. The recombinant antigen stimulation, however, resulted in similar levels of IL-1 in MF and CP. In contrast, stimulation of peripheral blood adherent cells with whole parasite antigen produced high levels of GM-CSF and TNF-alpha in CP as opposed to MF or EN. Recombinant antigen stimulation, however, produced high levels of GM-CSF in EN as compared to MF or CP, while no significant change in the release of TNF-alpha was observed in these patients. These results suggest that monocytes from filarial patients exhibit functional activity similar to that observed by the monocytes of endemic normals (control group).

Regulation of parasite antigen-driven immune responses by interleukin-10 (IL-10) and IL-12 in lymphatic filariasis.

We investigated the mechanisms by which interleukin-10 (IL-10) regulates antigen-specific hyporesponsiveness in asymptomatic microfilaremic (MF) individuals. Peripheral blood mononuclear cells from MF individuals (n = 11) were stimulated in vitro with Brugia malayi antigen (BMA) or mycobacterial purified protein derivative (PPD) in the presence of neutralizing anti-IL-10 or isotype control monoclonal antibodies. As expected, BMA stimulated little or no gamma interferon (IFN-gamma) secretion in MF individuals, whereas PPD stimulated IFN-gamma in all but one. Neutralization of endogenous BMA-driven IL-10 secretion led to augmentation of IFN-gamma in seven of nine MF individuals (1.5- to 10-fold) and did so in a BMA-specific manner (PPD-driven IFN-gamma was augmented in only two of eight MF individuals and only 1.5- to 2-fold), indicating that IL-10 downregulates type 1 responses in these individuals. Type 2 responses (IL-5 secretion) were unaffected by the IL-10 blockade. To assess whether IL-12 could reverse the type 1 downregulation observed, the effect of recombinant human IL-12 (rhIL-12) on BMA-driven IL-5 and IFN-gamma production was also evaluated. rhIL-12 augmented both BMA- and PPD-driven IFN-gamma production 5- to 10-fold in six of nine MF individuals. These data demonstrate that IL-10 downregulates BMA-driven type 1 responses and that IL-12 can overcome downregulation of Th1 responses associated with MF but does so in a non-antigen-specific manner.

Subacute encephalomyelitis presenting as stiff-person syndrome: clinical, polygraphic, and pathologic correlations.

A 60-year-old woman presented with stiff-person syndrome (SPS). Treatment with diazepam controlled her painful spasms initially. Two and one-half years after the onset of SPS, new spells of paroxysmal leg jerking and apnea developed. A spell was recorded with simultaneous video and polygraphic techniques that revealed simultaneous firing of motor unit potentials in several muscles (paraspinal, internal hamstring, and abdominal muscles). Apnea was associated with arterial oxygen desaturation. An increase in the dose of diazepam decreased the number and severity of these episodes. Seventeen months later, the patient began to taper the diazepam dose. Shortly thereafter, she had a cardiorespiratory arrest and subsequently died. Autopsy showed small chronic inflammatory foci in the pancreas (some associated with islets) and findings of diffuse encephalomyelitis characterized by perivascular cuffing in the spinal cord, brainstem, thalamus, hippocampus, and amygdala and a dense mononuclear infiltrate in the anterior horns of the lumbar and cervical cord, with relative preservation of axons and myelin. Cell typing showed this infiltrate was polyclonal and reactive. There have been rare cases of SPS associated with encephalomyelitis reported previously. Although the prolonged course in our patient suggested that SPS may have preceded encephalomyelitis, the more likely explanation is that the patient had an unusually long course of encephalomyelitis alone.

Multiple intracerebral metastases from an islet cell carcinoma of the pancreas: case report.

Computed tomography and magnetic resonance imaging of an 85-year-old woman with bitemporal headaches revealed cystic lesions in the basal ganglia and cerebellum. The patient remained neurologically asymptomatic until just before her death at age 89. Autopsy revealed tumors of the brain, lungs, liver, periaortic lymph nodes, adrenal gland, and the pancreas. Light microscopy demonstrated a malignant small cell tumor with scant cytoplasm. Electron microscopy revealed intracytoplasmic dense core vesicles, characteristic of neuroendocrine tumors, which prompted the diagnosis of islet cell carcinoma. All lesions were found to be microscopically similar. Previous reports of islet cell carcinoma metastatic to the brain could not be found. This case emphasizes the importance of electron microscopy in cases of small cell neoplasms in the brain.

Immunocompromise in gnotobiotic pigs induced by verotoxin-producing Escherichia coli (O111:NM).

A verotoxin-producing Escherichia coli serotype O111:NM strain (strain 10049; verotoxin 1 positive) persistently infected experimentally inoculated gnotobiotic pigs, causing attaching-effecting intestinal lesions and chronic diarrhea. Experiments were performed to determine whether persistent infection might be associated with immunocompromise of the host of this organism. Pigs inoculated with this strain had a significant reduction in peripheral blood lymphocytes and lower antibody titers to sheep erythrocytes compared with control pigs. Compared with pigs given a verotoxin-negative pathogenic strain of the same serotype (O111:NM, strain 2430), pigs inoculated with the verotoxin-positive strain had lower peripheral lymphocyte counts and proliferative responses to concanavalin A, phytohemagglutinin, and pokeweed mitogens. The results of this study suggest that strain 10049 has an immunocompromising effect on gnotobiotic pigs.

Evidence for a calmodulin inhibitory substance(s) isolated from human meningiomas.

Calmodulin (CaM), a calcium-binding protein, is present in human tumor tissues and in meningioma. Following a purification procedure using DEAE-cellulose and the polymeric resin 3520, the CaM content of tumor extracts was assayed using CaM-deficient phosphodiesterase (PDE). In the presence of low amounts of the extracts, a concentration dependent stimulation of PDE was observed. However, further addition of higher concentrations of the extract produced a marked inhibition of the CaM stimulation of PDE in 13 of 15 specimens. A wide range (2.44-51.31 units/1 mg tumor [wet weight]) of inhibitor concentration was noted. However, no detectable inhibitory activity of this magnitude was observed in normal human meningeal extracts. The final extracts showed no calcineurin-phosphatase activity in the presence of Ni++, a known activator of this phosphatase. SDS-polyacrylamide gel (10%) electrophoresis of the extracts revealed the typical calmodulin band at 17 kDa plus two additional bands with apparent molecular masses of 21 and 36 kDa respectively. These bands were not seen using normal meningeal extracts.

Unusual dislocation of the temporo-mandibular joints. A case report.

A case of an unusual bilateral mediolateral dislocation of the mandibular joints is reported. The condyle of the laterally displaced side was additionally fractured at the neck. No other fractures were present.

Fracture of the styloid process associated with mandibular fracture. A case report.

A case of styloid process fracture associated with bilateral mandibular fracture is reported. The possible fracture mechanism, clinical features, radiographic diagnosis and treatment are discussed.

Giant-celled glioblastoma of brain. A clinico-pathological and radiological study of ten cases (including immunohistochemistry and ultrastructure).

Giant-celled glioblastoma multiforme is characterized by bizarre multinucleated giant cells with abundant eosinophilic cytoplasm, paucity of vascular endothelial proliferation, and increased reticulin fibers. It is considered by Rubinstein to be a variant of glioblastoma multiforme and by Zülch to be of mesenchymal origin. We studied retrospectively ten cases of giant-celled glioblastoma to correlate clinical and pathological features including immunohistochemistry and ultrastructure, radiology and survival time. Seven men and three women ranging in age from 23-75 years had variable clinical presentations and well defined lesions on computed tomography (eight patients). Well-defined at surgery, the tumor was located in temporal (six patients), frontal (three patients), and parieto occipital (one patient) lobes. Besides characteristic histology, glial-fibrillary acidic protein was positive in all, along with intracytoplasmic fibrils on electron microscopy. Three patients died within 3 days of surgery. Of the surviving seven treated with radiation and/or chemotherapy, three had a survival time of more than 36 months and four less than 15 months. Our study identifies this tumor to be of astrocytic lineage, with temporal lobe predilection, and overall a longer survival rate than glioblastoma multiforme.

Muscle biopsy findings in primary fibromyalgia and other forms of nonarticular rheumatism.

Virtually all the reports on muscle biopsy in chronic muscle pain conditions, except those of primary fibromyalgia syndrome (PFS) published recently, have inadequate methodologic information, particularly on definition of cases, and lack controlled materials, so that no firm conclusions may be made. A limited number of controlled studies of muscle biopsy in PFS suggest that results are negative by usual light microscopic, histochemical, and electron microscope examinations. The findings of abnormal rubber band-like structures and interconnecting network of reticular or elastic fibers in muscle fibers of certain PFS patients in a single study need to be confirmed by other centers by careful controlled and blinded observations. The findings that high-energy phosphate levels in tender PFS muscles are significantly reduced appear valid and important, and need to be independently confirmed by well-designed controlled and blinded studies. Finally, biopsy reports of unspecified or unclarified muscle pain syndromes should not be assumed to be those related to PFS, and such invalid references must be avoided.

Electron microscopic studies of muscle biopsy in primary fibromyalgia syndrome: a controlled and blinded study.

Trapezius muscle biopsy was carried out in 21 patients with primary fibromyalgia syndrome (PFS) and 11 healthy controls, and assessed blindly by electron microscopy. Common findings in both the PFS and control groups were mild myofibrillar separation, papillary projections and subsarcolemmal accumulation of glycogen. However, the differences between the 2 groups were not statistically significant in any of the findings.

Primary fibromyalgia syndrome and myofascial pain syndrome: clinical features and muscle pathology.

Primary fibromyalgia syndrome (PFS) is a common form of nonarticular rheumatism with diffuse musculoskeletal aching and stiffness at multiple sites and tender points at characteristic locations. Nonmusculoskeletal "systemic" symptoms, eg, fatigue, poor sleep, irritable bowel symptoms, and chronic headaches, are also common. Although PFS is similar to myofascial pain syndrome (MPS) in that both conditions cause muscle pain and tenderness, important differences exist. Unlike PFS, muscle pain in MPS is usually local or regional, accompanied by trigger points. Unlike tender points, trigger points produce a referral pain pattern specific to each muscle. Moreover, "systemic" features of PFS are usually absent in MPS. Common and important pathologic changes in muscle in PFS are moth-eaten appearance of Type I fiber by histochemistry, and myofibrillar lysis with glycogen and mitochondria deposition by electron microscopy; inflammatory changes are absent by light microscopy. Recent investigations have shown that PFS is a characteristic clinical entity. Further controlled studies are, however, essential to establish the pathologic changes in tender muscles in PFS.

Demyelinating disease of corpus callosum presenting as glioma on magnetic resonance scan: a case documented with pathological findings.

Magnetic resonance imaging (MRI) has improved the diagnosis of several pathological entities of the brain. MRI especially has been credited with distinguishing demyelinating diseases of the central nervous system from other diseases. The presence of a mass effect in a demyelinating disorder, however, makes difficult the distinction between tumor and a demyelinating disease. We report a case of a demyelinating disorder simulating an infiltrating glioma of the corpus callosum on MRI scan, resulting in surgical intervention. To our knowledge, this is the first case to be reported with MRI and documented pathological findings.

Ganglioglioma: a correlative clinicopathological and radiological study of ten surgically treated cases with follow-up.

Gangliogliomas are rare benign tumors of the central nervous system containing neoplastic ganglion and low grade glial cells. In studying 10 surgically treated cases, we evaluated the clinical, pathological, radiological, and immunocytochemical features, with follow-up. Ranging from 18 to 58 years in age, 7 patients were women, and 3 were men. The most common presenting symptom was seizure. Computed tomographic scan showed a low density enhancing mass in 8 and calcification in 5. Six had minimally abnormal vascularity on angiography. Seven patients had total and 3 had subtotal resections of the tumor. The temporal lobe was the location of the tumor in 6 cases. All of the cases met the histological criteria of Russell and Rubinstein for ganglioglioma. Four patients received postoperative radiotherapy because of subtotal resection or aggressive histological makeup. On follow-up, from 2.5 to 7 years, 8 patients are alive and tumor-free, and 7 are also seizure-free. Two died after operation: one immediately and the other of a glioblastoma that developed 5 years later. Our study confirms that ganglioglioma is a distinct histological entity, anatomically localized, with characteristic clinical and radiological findings and long term survival. Aggressive histological makeup is not a definite indication of malignant potential. The definitive role of follow-up radiotherapy for this tumor needs further study. Malignant evolution is rare, but warrants follow-up.

Pathologic changes in muscle in primary fibromyalgia syndrome.

Primary fibromyalgia syndrome, also inappropriately called "fibrositis," is a clinically recognizable nonarticular rheumatic condition with diffuse and chronic musculoskeletal aching and stiffness, accompanied by exaggerated tenderness at characteristic sites on physical examination. Results of muscle biopsy from 12 well-defined cases of primary fibromyalgia syndrome without any history of trauma have been published recently. Light microscopic examination revealed no evidence of inflammation. Histochemical analysis demonstrated type II fiber atrophy in seven patients and the "moth-eaten" appearance of type I fibers in five patients. Electron microscopic findings were most impressive, and included myofibrillar lysis with deposition of glycogen and abnormal mitochondria, as well as subsarcolemmal accumulation of glycogen and mitochondria in all 12 patients and papillary projections of sarcolemmal membrane in 11 patients. Mechanisms of these significant muscle changes in primary fibromyalgia syndrome are uncertain but may include subclinical injury of muscle spasm.

Radiological and pathological findings in three cases of childhood pineocytomas.

The radiological and pathological findings in three children with pineocytomas are described. The patients presented with symptoms and signs of increased intracranial pressure. CT scans demonstrated obstructive hydrocephalus, but failed to visualize pineal masses that were subsequently seen on MR scans. A suboccipital, supracerebellar approach was used to obtain tissue for histological diagnosis and, in one case, achieve a total removal. Light microscopy demonstrated typical pineocytomatous rosettes without evidence of gangliocytic or astrocytic differentiation. Electron microscopy revealed numerous dense core vesicles with synaptic ribbons, suggesting neurosecretory capability. These three cases demonstrate the diagnostic advantage of MR imaging for tumors in the pineal region as well as the relatively well-differentiated histopathological characteristics of pineocytomas.

Muscle pathology in primary fibromyalgia syndrome: a light microscopic, histochemical and ultrastructural study.

Upper medial trapezius muscle biopsy was obtained from 12 primary fibromyalgia syndrome (PFS) patients (age 17 to 40 years) and studied with histochemistry, light and electron microscopy (EM). No evidence of inflammation was found in any case. Significant histochemical abnormalities were Type II fiber atrophy in 7 and moth-eaten appearance of Type I fibers in 5. EM revealed segmental muscle fiber necrosis with lipid and glycogen deposition as well as subsarcolemmal mitochondrial accumulation in all cases. Papillary projections of sarcolemmal membrane were seen in 11 patients. These observations in 12 PFS cases without obvious muscle trauma indicate definite but nonspecific muscle changes which we suspect are secondary to chronic muscle spasm and ischemia of unknown etiology.

Cerebral amyloid angiopathy causing intracranial hemorrhage.

Ten cases of sporadic cerebral amyloid angiopathy (CAA) were seen as intracranial hemorrhage. CAA was seen as a stroke or catastrophic intracranial hemorrhage in all cases. CAA complicated by intracranial hemorrhage carried a high mortality; 9 of 10 patients died in spite of aggressive medical or surgical treatment. Senile dementia of Alzheimer's type was an associated finding in only 1 patient. Computed tomographic scanning in 4 patients initially was not diagnostic for hemorrhage. Lambda chains and amyloid P protein were demonstrated in the areas of amyloid angiopathy immunocytochemically. The pathogenesis of hemorrhage in CAA could be either increased fragility of amyloid-laden blood vessels or rupture of microaneurysms. Surgical treatment of intracranial hemorrhage in CAA should therefore be undertaken with caution.

Solitary, primary malignant astrocytoma of the spinal leptomeninges.

Malignant astrocytoma of leptomeningeal origin is a rare central nervous system neoplasm. A study of surgical and autopsy material from a primary leptomeningeal malignant astrocytoma of the spinal cord is presented. The initial presentation was focal; an extramedullary, intradural mass caused thoracic cord compression, although at autopsy the neoplasm involved the entire leptomeninges. The histological, ultrastructural and immunocytochemical findings of a tumor in this location and its histogenesis are discussed.