Anterior horn changes of motor neuron disease associated with demyelinating radiculopathy

Morphologic study of the spinal cord of a patient with generalized motor deficits revealed changes in the anterior horns characterized by the selective loss of large motor neurons, gliosis and the abnormal accumulation of 10 nm filaments which appeared as argyrophilic spheroids in the perikarya and axons of motor neurons. The ventral roots were predominantly affected and showed a variable loss of axons. The remaining axons displayed prominent onion-bulb formations, frequent axonal sprouting and occasionally evidence of active demyelination. The coexistence of a demyelinating motor radiculopathy and anterior horn changes simulating those of amyotrophic lateral sclerosis (ALS) may contribute to our understanding of the unresolved question of whether the neuronal perikaryon or its axon is the primary target in the pathogenesis of ALS. These observations also indicate that a rigid separation of pathogenetic mechanisms into neuronopathy, axonopathy and myelinopathy may not be always possible.     

Atypical skull base paragangliomas.

We present two cases of unusually large skull base paragangliomas. The first tumor was accompanied by marked bony destruction of the central skull base and multiple associated cysts. The second tumor arose along the petrous ridge, with a large intracranial component. The CT, MR imaging, angiographic, histologic, and electron microscopic findings of these unusual lesions are described.     

Hepatic microsomal cytochrome P450 system during experimental hookworm infection

Experimental infection of golden hamsters with the hookworm, Ancylostoma ceylanicum, caused a profound decline in the hepatic microsomal cytochrome P450 content. Concomitant decrease was also noticed in aminopyrine N-demethylase and benzo[a]pyrene hydroxylase activities. However, aniline hydroxylase activity was only marginally elevated during the infection. Microsomal markers, viz., cytochrome b5, NADH-cytochrome-c reductase, and glucose-6-phosphatase, were not significantly altered. Hepatic tissue exhibited an accumulation of lipids, especially phospholipids, triglycerides, and cholesterol, resulting in fatty necrosis around the central vein region. Isolated hepatic microsomes showed a decrease in phosphatidylcholine content. Impairment in hepatic mixed function oxidase (MFO) activities was further confirmed by prolongation in hexobarbital sleeping time and zoxazolamine-induced paralysis. The hepatic MFO system of A. ceylanicum-infected hamsters responded qualitatively and quantitatively in a manner similar to that of control hamsters, upon stimulation with selective chemical inducers like phenobarbitone and 3-methylcholanthrene. Kinetic and in vitro substrate binding studies revealed that for aminopyrine the substrate affinity and the maximum enzyme activity (Vmax) were decreased, while for aniline the binding affinity was decreased and the binding capacity was enhanced. Results indicate specific/selective impairment of the hepatic microsomal cytochrome P450 system during hookworm infection and may have many practical implications in toxicology and pharmacology.     

Lewy bodies in the presence of Alzheimer's disease.

Large numbers of Lewy bodies in the substantia nigra were found in a case of Alzheimer's disease. Parkinsonian symptoms were not recognized. The patient appears to be an example of an association recognized by Woodard but not yet understood. The case is discussed in the context of reported relationships between Parkinson's disease or "Lewy body disease" and dementia, on the one hand, and reports linking various forms of psychoses with an unusually high incidence of Lewy bodies, on the other.     

Bile Acid at Low pH Reduces Squamous Differentiation and Activates EGFR Signaling in Esophageal Squamous Cells in 3-D Culture

Background

Barrett's esophagus is a preneoplastic metaplasia in which the normal squamous epithelium of the esophagus changes to an intestinal, columnar phenotype due to long-term gastro-esophageal reflux. The major components of this reflux are bile and stomach acid. Previous in vitro studies on the effect of bile and acid on esophageal cells have predominantly relied on transformed esophageal squamous cells or cancer cells grown in monolayer culture.

Discussion

In this study, we expanded our previous work using an immortalized primary esophageal squamous cell line (EPC1). We demonstrate that EPC1 cells form a multi-layer, stratified epithelium when grown on polyester transwell filters in media supplemented with calcium. When exposed to short pulses of bile and pH 5, but not either condition alone, EPC1 cells demonstrate a reduction in stratification layers and reduced expression of squamous epithelium-specific genes. Bile at pH 5 also causes activation of epidermal growth factor receptor and down-stream pathways. Blocking epidermal growth factor receptor activation partially attenuates the effects of bile acid and pH 5. These results suggest that bile at low pH, but not bile or low pH alone, promotes loss of differentiation status of stratified squamous esophageal epithelium in vitro, possibly by initiating a mucosal repair response through epidermal growth factor activation.     

Randomized controlled trial of effectiveness of lafutidine versus pantoprazole in uninvestigated dyspepsia

Objectives:

Lafutidine is a new H₂-blocker in India claimed to be more potent and effective than existing H₂-blockers. Proton pump inhibitors (PPIs), by virtue of their mechanism of action, have greater efficacy than H₂-blockers in gastric acid suppression. However, clinical trials comparing H₂-blockers directly with PPIs are limited. We carried out a head-to-head comparison of the effectiveness of lafutidine versus the PPI pantoprazole in uninvestigated dyspepsia [CTRI/2013/12/004261].

Materials and Methods:

A prospective, open label, randomized, controlled trial was conducted in a tertiary care hospital. Ambulatory adult patients with dyspepsia, not yet subjected to endoscopy, were recruited if they had at least moderately severe symptoms, defined as a score of ≥ 4 on a 7-point Global Overall Symptom (GOS) Scale. Those with alarm features or significant comorbidity were excluded. Subjects received either once daily lafutidine 10 mg or pantoprazole 40 mg, orally, for 8 weeks. Reflux, dysmotility and pain scores were assessed by Modified Frequency Scale for the Symptoms of Gastroesophageal Reflux Disease (mFSSGERD), and quality of life (QoL) by SF-8 scale. The latter had physical and mental components summarized by physical component summary score (PCS) and a mental component summary score (MCS).

Results:

Of 122 patients enrolled, data of 57 on lafutidine and 60 on pantoprazole were analyzed. At 4 weeks, proportion of subjects responding (GOS score ≤ 2) in the two arms (lafutidine 45.61% vs. pantoprazole 48.33%, P = 0.854) or showing symptom resolution (GOS score ≤ 1) (lafutidine 12.28% vs. pantoprazole 5.00%; P = 0.197) were comparable. Similarly at 8 weeks, both responder (lafutidine 52.63% vs. pantoprazole 56.67%; P = 0.712) and symptom resolution proportions (lafutidine 33.33% vs. pantoprazole 30%; P = 0.843) were comparable. Total score on mFSSGERD scale, as well as all its three component scores, and PCS and MCS scores on QoL SF-8 scale showed improvement but no statistically significant difference between the two arms. Tolerability of both drugs was excellent.

Conclusions:

Lafutidine is well-tolerated and there is no clinically worthwhile difference between the two drugs in the empirical treatment of uninvestigated dyspepsia.KEY WORDS: Dyspepsia, lafutidine, pantoprazole, randomized controlled trial     

Dystopic neurohypophysis

A dystopic neurohypophysis was noted incidentally at autopsy in a 51 -year-old man with no endocrine abnormality. The dystopic gland was situated in the upper region of the tuber cinereum and macroscopically simulated a neoplasm. The pituitary fossa contained only anterior hypophyseal elements. Review of the literature disclosed 19 such cases discovered at autopsy; 11 occurred in normal individuals with no endocrine abnormality. Radiological study revealed 145 additional cases. Except for the 6 occurrences described in normal individuals, the rest occurred in patients with anterior pituitary dysfunction. No instance of isolated diabetes insipidus has been reported due to dystopia of the neurohypophysis. Dystopia of the neurohypophysis in normal individuals should be distinguished from those occurring in patients with anterior pituitary abnormalities. The former represent a true dystopia and are not associated with perinatal injury, in contrast to the latter, which are acquired dystopias secondary to regeneration of the neurohypophysis and are associated with perinatal injury. Although anterior and posterior pituitary glands are formed by appositional growth, their development and functional status are entirely independent. Finally, the most significant clinical feature of dystopic neurohypophysis is the absence of any related symptoms and this condition should always be considered in the clinical differential diagnosis of hypothalamic lesions. In such patients, a surgical procedure may be avoided because other hypothalamic lesions, such as hamartomas and astrocytomas, are more frequently symptomatic.     

Perturbation of hyaluronan interactions inhibits malignant properties of glioma cells

Malignant progression of gliomas is characterized by acquisition of inappropriate growth and invasive properties. In vitro, these malignant properties are reflected in, and measured by, the ability to grow in an anchorage-independent manner and to invade artificial extracellular matrices. The results of numerous studies have suggested that the extracellular and pericellular matrix polysaccharide, hyaluronan, plays an important role in these attributes of malignant cancer cells. However, with respect to glioma cells, most studies have addressed the effect of exogenously added hyaluronan rather than the function of endogenous tumor cell-associated hyaluronan. In this study we manipulate hyaluronan-glioma cell interactions by two methods. The first is administration of small hyaluronan oligosaccharides that compete for endogenous hyaluronan polymer interactions, resulting in attenuation of hyaluronan-induced signaling. The second is overexpression of soluble hyaluronan-binding proteins that act as a competitive sink for interaction with endogenous hyaluronan, again leading to attenuated signaling. We find that both treatments inhibit anchorage-independent growth, as measured by colony formation in soft agar, and invasiveness, as measured by penetration of reconstituted basement membrane matrices. Based on our findings, we conclude that endogenous hyaluronan interactions are essential for these two fundamental malignant properties of glioma cells.