Gallbladder dyskinesia in chronic acalculous cholecystitis

To test the hypothesis that there is an early stage of cholesterol gallstone formation in man characterized by symptoms of chronic cholecystitis, poor gallbladder emptying, and biliary cholesterol crystals, we studied cholecystokinin-stimulated gallbladder emptying by DISIDA scintigraphy and examined bile for cholesterol crystals in symptomatic patients with normal oral cholecystography and gallbladder sonography. Of 36 patients studied, 16 had biliary cholesterol crystals; their mean 30-min gallbladder ejection fraction was 25.9±14.8%. Among the 20 patients without crystals, the mean ejection fraction was 60.3±23.3%. Fifteen patients, 11 with crystals and four without, had cholecystectomy because of persistent symptoms. All with crystals preoperatively and three without had chronic cholecystitis histologically. One patient without crystals had normal histology. We conclude that poor gallbladder contractility, well-established as an etiologic factor in animal models of cholesterol cholelithiasis, is now linked to acalculous cholecystitis, an early stage of human cholesterol cholelithiasis.     

Hematological Complications of Alcoholism

Numerous clinical observations support the notion that ethanol has multiple pathologic effects on hematopoietic tissue. The effects of alcohol on blood are diverse. The long-term ingestion of large quantities of ethanol has been shown to alter a substantial number of physiologic and biochemical variables. Abnormalities involving leukocytes, platelets, and erythrocytes may occur singly or in various combinations. Due to the frequent concomitant presence of alcohol-related hepatic disease, nutritional deficiencies, infection, and other chronic diseases, it is often difficult to distinguish the specific hematologic toxicities of alcohol ingestion from the hematologic toxicities of associated morbid conditions. Depressed hematopoietic cell formation (Table 2), increased destruction, and alterations in morphology and function of hematopoietic cells have been described.     

Quantitative assessment of the microstructure of rat behavior: I.f(d), The extension of the scaling hypothesis

Previous studies demonstrated that drug effects on the movement sequences of rats in unconditioned motor activity paradigms can be quantified by scaling measures that describe the average relationship between a variable of interest and an experimental parameter. However, rats engage in a wide variety of geometrically distinct movements that can be influenced differentially by drugs. In this investigation, the extended scaling approach is presented to capture quantitatively the relative contributions of geometrically distinct movement sequences to the overall path structure. The calculation of the spectrum of local spatial scaling exponents,f(d), is based on ensemble methods used in statistical physics. Results of thef(d) analysis confirm that the amount of motor activity is not correlated with the geometrical structure of movement sequences. Changes in the average spatial scaling exponent,d, correspond to shifting the entiref(d) function, and indicate overall changes in path structure. With the extended scaling approach, straight movement sequences are assessed independently from highly circumscribed movements. Thus, thef(d) function identifies drug effects on particular ranges of movement sequences as defined by the geometrical structure of movements. More generally, thef(d) function quantifies the relationship between microscopically recorded variables, in this paradigm consecutive (x, y) locations, and the macroscopic behavioral patterns that constitute the animal's response topography.Exemplary calculations of path segments with different geometrical characteristics can be obtained from the authors. Questions regarding the computational implementation of this method should be addressed to MPP preferably via email (martin@rat.ucsd.edu) or FAX (619-543-2493)     

Coexistence of Neoplasia and Cortical Dysplasia in Patients Presenting with Seizures

Summary: Tumors and cortical dysplasia are associated with epilepsy, but few studies have examined the coexistence of neoplasia and dysplasia in these patients. We studied 13 patients (age 4–29 years) with recurrent seizures of 1 month to 21-year' duration (median 72 months). Ten patients were aged <21 years. Imaging studies localized the lesion to the temporal lobe (10 patients), parietal lobe (2 patients), and frontal lobe (1 patient). Tumors included ganglioglioma (8 patients), dysembryoplastic neuroepithelial tumor (DNT) (3 patients), and low-grade as- trocytoma (2 patients). Cortical dysplasia, including atypical aggregates of neurons (6 patients), multifocal loss of the cortical laminar architecture (7 patients), and neurons in the molecular layer of the cortex (3 patients) were observed near but separate from the tumor. Coexistence of certain tumors with cortical dysplasia, most frequently observed in the pediatric population, suggests a hamar-tomatous/dysplastic nature of the neoplasms.     

Human dolasetron pharmacokinetics: II Absorption and disposition following single-dose oral administration to normal male subjects

Dolasetron is a 5-hydroxytryptamine antagonist active at type III receptors; it is presently undergoing clinical evaluation for the reduction/prevention of cancer chemotherapyinduced nausea and vomiting. A previous study demonstrated that following intravenous administration to healthy male subjects, dolasetron disappeared extremely rapidly from plasma, and less than 1 per cent of the dose appeared in the urine. A major plasma metabolite, reduced dolasetron, peaked rapidly in the plasma. In this study, dolasetron was administered orally to healthy male subjects at doses ranging from 50 to 400 mg (mesylate monohydrate). Plasma concentrations of dolasetron were low and sporadic, and there was little excreted in urine; this prevented dolasetron pharmacokinetic analysis. Reduced metabolite concentrations peaked rapidly, with a median value of 1.00 h. The median terminal disposition half-life was 7.80 h. Median values for fraction of dose excreted in urine and renal clearance were 22.2 per cent and 2.56 ml min^?1 kg^?1. Whereas areas under the plasma concentration—time curves were proportional to dose, renal clearance increased with dose (p < 0.05). However, given dose proportionality to AUC, this is probably of little therapeutic consequence. Since reduced dolasetron has significant anti-emetic activity in the ferret model, it appears that this metabolite may play a significant role in pharmacodynamic activity.     

Adult-onset rod disease with abundant intranuclear rods

Summary The third case of adult-onset rod disease (nemaline myopathy) with abundant myofibrillar as well as intranuclear rods is described. The 61-year-old woman suffered from progressive weakness of proximal extremities and of the neck, mimicking polymyositis. Muscle biopsy revealed a striking myopathic pattern, with intranuclear rods occurring in 31% of the fibres. On light and electron microscopy and by immunohistochemical study, the rods differed from myofibrillar rods. The absence of -actinin in intranuclear rods suggests an enhanced readiness of actin filaments to bind to diverse proteins, instead of overproduction of -actinin as the pathogenetic basis of the rod formation.     

Seizure Elicitation Blocked by Pretreatment with Lidocaine

A patient is reported in whom pretreatment with intravenous lidocaine resulted in failure to elicit a seizure even at stimulus intensity markedly greater than that used successfully at prior and subsequent treatments. Together with one other report, this experience suggests that lidocaine may prevent a seizure by raising the seizure threshold. An alternative explanation is proposed for the classic findings of Ottosson that lidocaine-modified seizures are reduced in therapeutic efficacy.     

“Afterwork”: A clinical-phenomenological report

This paper explores a number of the dimensions of the process of afterwork: the psychological work that former patients engage in after treatment has terminated. Ten former patients, who had worked with 10 different therapists, were interviewed utilizing a semi-structured interview protocol, and their experiences form the basis for the findings and observations that are described. It was found that subjects remembered little by way of lessons or insights; rather, what remained with them were changes of perspective, the internalization of the process of the treatment, and the experience of their therapists' human qualities. In addition, it was found that most subjects had had some form of contact with their therapists post-termination. The implications of these findings are discussed.     

Arterial endothelial function in a porcine model of early stage atherosclerotic vascular disease

Cardiovascular disease (CVD) is the leading cause of morbidity and mortality in the United States and is projected to become the leading cause of mortality in the world. Atherosclerosis is the most important single factor contributing to this disease burden. In this study, we characterize relationships between endothelial dysfunction and vascular disease in an animal model of diet-induced, early-stage atherosclerotic vascular disease. We tested the hypothesis that hypercholesterolaemia induces vascular disease and impairs endothelium-dependent relaxation (EDR) in conduit arteries of adult male Yucatan pigs. Pigs were fed a normal fat (NF) or high fat cholesterol (HFC) diet for 20-24 weeks. Results indicate that, while the HFC diet did not alter EDR in femoral or brachial arteries, EDR was significantly decreased in both carotid and coronary arteries. Sudanophilic fatty streaks were significantly present in the abdominal aorta and common carotid artery. Histopathology revealed increased intima-media thickness (IMT) and foam cell accumulation in Stary Stage I-III lesions in the abdominal aorta, common carotid artery and femoral arteries. In the coronary arteries, the accumulation of foam cells in Stary Stage I and II lesions resulted in a trend for increased IMT. There was no evidence of vascular disease in the brachial arteries. These results indicate that early stages of CVD (Stary Stage I-III) precede decreases in EDR induced by HFC diet, because femoral arteries exhibited foam cell accumulation and an increased IMT but no change in endothelial function.