Hepatobiliary disease in cystic fibrosis.
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Biomedical subjects
Publications and source records attributed to C Colombo.
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This report describes a patient with a DSM-III-R diagnosis of obsessive compulsive disorder and a nuclear magnetic resonance picture of a normal pressure hydrocephalus. After neurosurgery, the patient showed marked improvement in his compulsions which previously had shown little response to pharmacological treatment.
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The human monocytic leukemia cell line THP-1 is depleted of the long-chain n-6, AA, when compared to human monocytes. This reflects the low availability of this FA in the growth medium generally used for cultured cells. The effects of AA, as well as EPA, supplementation of THP-1 cells on the incorporation of these FA in cell PL, especially in PC and PE, was investigated. In addition the incorporation of labeled AA in PL from THP-1 cells was compared to that in human monocytes. Measurements were done through HPLC separation of PL, detected by UV absorption and radioactivity, FA analysis by GC and characterization of PC subclasses by FAB-MS. Marked differences were observed in the incorporation of the two FA in cell PL, particularly two PC subclasses, and in the accumulation in individual PL after supplementation of THP-1 cells. Accumulation of AA and EPA in THP-1 cells appeared to be mutually independent. The incorporation of AA was also quite different in THP-1 from that in monocytes. Thus, characterization of the FA content in lipids of cultured cells is an essential requirement for optimal utilization of these cells.
19 schizophrenic patients and 15 normal controls, matched for sex and age, were evaluated by magnetic resonance imaging for corpus callosal size and had neuropsychological functioning assessed using an auditory comprehension test. Although the MRI data did not reveal any significant differences between groups, the degree of laterality to the left versus right ear response was significantly correlated with the size of the posterior part of the corpus callosum in male schizophrenics.
A previous magnetic resonance imaging (MRI) study from our group reported increased size of the right caudate nucleus in obsessive-compulsive patients compared with control subjects. To test the hypothesis of a structural abnormality underlying such volume alteration, MRI signal intensity (SI), as an index of T1 relaxation values, was measured in the caudate nucleus of the same sampling data. Results showed higher SI values in the left caudate nucleus compared with the right in the patient group, whereas no asymmetry was found in the control group.
Several psychopathological and morphological studies support the hypothesis of temporal-limbic involvement in the pathophysiology of schizophrenia. In the present study, magnetic resonance imaging was used to evaluate the areas of the temporal lobes and related structures in 18 schizophrenic patients and 18 normal control subjects who were homogeneous for sex and age. The Wechsler Memory Scale was used to assess the memory functions of all subjects. Although the MRI data did not reveal any significant differences between the two groups, the Wechsler Memory Scale indices of memory functions showed significant differences between the schizophrenic patients and the control subjects.
An animal model of leukotriene B4- (LTB4) induced neutropenia has been developed to evaluate LTB4 receptor antagonists in vivo. LTB4, a potent chemotactic inflammatory mediator, when administered intravenously, induces a profound, rapid, and transient redistribution of blood neutrophils from the circulating pool to the marginated pool. This phenomenon is applied in the neutropenia model whereby circulating blood neutrophil counts prior to and after intravenous infusion of LTB4 are compared. Kinetics of LTB4-induced neutrophil responses are determined through the use of a Technicon H*1 automated blood cell analyzer. LTB4 receptor antagonists are identified by inhibition of LTB4-induced neutropenia. Standard antiinflammatory compounds including BW-755C, Abbott A-64077 (zileuton), dexamethasone-21-acetate, indomethacin, and naproxen did not affect LTB4-induced neutropenia. A potent LTB4 receptor antagonist, designated "RPR," inhibited LTB4-induced neutropenia following oral administration in a dose-dependent fashion.
OBJECTIVE: This study used eye movement tests to examine whether frontal lobe dysfunction is present in delusional disorder. METHOD: Smooth pursuit and voluntary saccadic eye movements of 15 delusional patients, 40 schizophrenic patients, and 40 normal subjects were recorded and analyzed statistically. RESULTS: The schizophrenic patients differed significantly from the normal subjects in some smooth pursuit eye movement characteristics, whereas both the schizophrenic and the delusional patients showed more saccades than the normal subjects during the smooth pursuit test. The delusional patients and normal subjects differed significantly in some voluntary saccadic eye movement characteristics. CONCLUSIONS: The data support the idea of a biological dysfunction in eye tracking in delusional disorder.
Zolpidem is a new imidazopyridine hypnotic with a pharmacological profile substantially different from benzodiazepines. In this observational multicenter study the possibility of shifting to zolpidem (10 mg at N1, 15 or 20 after N1) insomniac patients previously taking (for at least 15 days and not longer than 3 months) standard posology of triazolam (0.125-0.25 mg), lorazepam (1 mg) or lormetazepam (1 mg) was assessed. For ethical reasons the patients were mandatorily to be insomniacs despite their taking hypnotics or not tolerating them. Patients enrolled were 299 of whom 276 evaluable (139 males and 136 females; mean age 48.67 +/- 14.64, range 18-83). Study duration was 7 nights with visits at N0 (baseline), N1 (after 1st night), N3 (after 3rd night) and N7 (final evaluation); on each visit the Saint Mary Hospital Sleep Questionnaire and the benzodiazepine withdrawal symptom's rating scale were administered; moreover, after N7, investigators were asked a judgement of feasibility of such a shift. In 229 (83.5%) out of 274 patients such a shift to zolpidem was considered successfully (no occurrence of symptoms and/or signs of previously taken hypnotic withdrawal); in the remaining 45 patients, just 17 (6.2%) seemed to be real unsuccessful cases (reactions mild and transient, anyhow). In conclusion abrupt shift to zolpidem appeared to be largely feasible in the patients studied.
We have previously documented that ursodeoxycholic acid exerts a beneficial effect on liver function and bile acid metabolism in patients with cystic fibrosis. We hypothesized that the mechanism of action may be related in part to the choleretic properties of the administered bile acid. We therefore compared hepatobiliary scintigraphic images obtained before and 1 yr after initiation of ursodeoxycholic acid therapy to document an improvement in bile flow in 13 patients with cystic fibrosis and hepatobiliary involvement. Before therapy, hepatobiliary scintigraphy documented biliary stasis with retention of the isotope in intrahepatic and extrahepatic bile ducts in nine patients; during therapy, duct dilatation decreased substantially in eight patients, with decreased intrahepatic retention and more rapid biliary outflow of the tracer. The time of appearance of isotope in the intestine decreased (from a mean of 36.9 +/- 17.8 min to 18.8 +/- 9.0 min; p less than 0.01) in all patients in whom it had been abnormal, and the half-time of hepatic washout decreased from a mean of 35 +/- 20.7 min to 26 +/- 15.6 min (p less than 0.05). During ursodeoxycholic acid administration enrichment of bile was achieved, with the mean ursodeoxycholic acid percent composition increasing from 5.8% +/- 2.9% to 35.7% +/- 8.5%. Ursodeoxycholic acid became the predominant bile acid in serum. Liver function improved in all 10 of the patients with abnormal values at baseline. We conclude that hepatobiliary scintigraphy is of value in monitoring the therapeutic responses of cystic fibrosis patients with liver disease to ursodeoxycholic acid therapy.(ABSTRACT TRUNCATED AT 250 WORDS)
Previous studies from our groups have demonstrated improvements in biochemical markers of liver function when cystic fibrosis patients with associated liver disease were administered oral ursodeoxycholic acid. The magnitude of the response was somewhat less than that found when comparable doses (10 to 15 mg/kg body wt/day) of ursodeoxycholic acid are given to other liver disease patients; this may be explained by the bile acid malabsorption that is characteristic of the disease. For this reason a dose-response study was carried out in nine cystic fibrosis patients with liver disease to establish whether improved efficacy could be obtained with higher doses. Ursodeoxycholic acid in doses of 5, 10 and 15 mg/kg body wt/day was given orally for consecutive 2-mo periods in a replicated Latin-square design. After this, all patients received 20 mg/kg body wt/day. Liver function, individual serum bile acids and biliary bile acid composition were determined at entry and at the end of each treatment period. Our data demonstrate that the magnitude of the biochemical improvement in serum liver enzymes was significantly greater with higher doses of ursodeoxycholic acid; at 20 mg/kg body wt/day it was similar to that reported for patients with other liver diseases administered lower doses. Biliary ursodeoxycholic acid enrichment increased with increasing doses, attaining 42% +/- 6% of the total biliary bile acids with the highest dose. Fasting serum ursodeoxycholic acid concentrations increased during ursodeoxycholic acid administration but were variable and correlated poorly with the dose of ursodeoxycholic acid administered, whereas no correlation was found between serum ursodeoxycholic acid concentration and the proportion of ursodeoxycholic acid in bile.(ABSTRACT TRUNCATED AT 250 WORDS)
Magnetic resonance images were used to measure the volume of the head of the caudate nucleus in 20 patients with obsessive-compulsive disorder and 16 normal control subjects. The obsessive-compulsive patients showed a significant increase in the volume of the right side of the head of the caudate nucleus compared with that of control subjects. This finding was not correlated with demographic, psychopathological, or clinical characteristics.
Functional status, perception of adjustment, occupational outcome and social functioning were investigated in a group of spinal cord injury (SCI) patients (mean age 34, range 10-74 years) seen at a specialised spinal unit over the period January 1984-December 1988. Functional status was assessed using a standardised scale measuring patients' performance of specific tasks, and other measures of outcome were investigated by a structured interview. Almost two thirds (68%) of the patients were independent according to the standardised scale (33% quadriplegic and 84% paraplegic). Patients' autonomy appeared to be threatened by architectural barriers in and about the house: approximately one third (34%) of those classified as 'independent' on the standardised rehabilitation scale used needed some help in their everyday life. A negative occupational outcome emerged: compared to the pre-morbid situation, 43 patients (44%) were worse off; 48 (49%) did not experience substantial changes--though it must be noted that 68% of these (33/48) were virtually unemployed (ie student, home maker, retired, unemployed) before the injury; and for 6 (7%) some improvement took place. With a multivariate analysis age was the only statistically significant predictor of poor occupational outcome, with older patients being worse off irrespective of the extent of disease and functional autonomy. The paper discusses these results and stresses the need for integrating results based on the use of standardised rehabilitation scales with the analysis of potential barriers influencing a patient's ability to exploit his/her autonomy.
Liver disease associated with cystic fibrosis (CF) is considered a secondary effect of the basic defect of the disease, leading to obstruction of bile ductules by abnormal mucoid secretions; additional factors have been involved in the pathogenesis, such as abnormalities in bile acid metabolism, nutritional deficiencies, drug hepatotoxicity, stenosis of the common bile duct by the fibrotic pancreas. Clinical presentation of liver disease in CF is rare during the first few years of life, although neonatal cholestasis can be occasionally the first manifestation of the disease. Isolated massive steatosis has been reported in less than 5% of cases as a consequence of malnutrition. Focal biliary cirrhosis is the pathognomonic hepatic lesion and is present in 25-30% of CF patients, most of whom are asymptomatic. The focally distributed lesions can extend leading to multi-lobular biliary cirrhosis with occurrence of signs and symptoms of cirrhosis and portal hypertension. Early diagnosis of CF-associated liver disease is difficult since liver function tests may be normal even in cases of overt cirrhosis: no test has proved to be sufficiently sensitive and specific and even liver biopsy is of questionable relevance due to the focal distribution of hepatic lesions. Clinical examination is of major importance, since the presence of hepatomegaly seems to correlate well with the histologic finding of fibrosis. The rationale for the use of the choleretic non-toxic bile acid ursodeoxycholic acid in CF-associated liver disease is to reduce the viscosity of bile and to replace toxic bile acids which accumulate in the hepatocyte.(ABSTRACT TRUNCATED AT 250 WORDS)
Factor Analysis represents an important method of extracting salient features from EEG data condensing functional as well as spatial informations in a few factors and so reducing redundancy of multi-channels computerized EEG data. A 16-channel computerized frequency analysis of background brain electrical activity during 3 functional conditions (eyes closed, eyes open and hyperventilation) were performed in 2 groups, 50 healthy subjects and 14 epileptic patients with generalized seizures. The differences in each frequency band between the 2 groups have been assessed by means of factor scores. Factor scores differences between control and epileptic patients have been found in theta and alpha frequency bands. These interictal EEG abnormalities were more evident in epileptic patients. This preliminary study shows the confirmatory capability of Factor Analysis and its usefulness in managing and comparing computerized EEG data.
In 11 children (mean age 44.2 months) with symptoms suggesting upper intestinal dysfunction (nonulcer dyspepsia), in nine children (mean age 27.3 months) with gastroesophageal reflux (GER) disease, and in seven controls (mean age 20.4 months) we investigated fasting [for 3 hr or until two migrating motor complexes (MMC) were observed] and fed (90 min) antroduodenal motility by means of perfused catheter system; furthermore, we measured both gastric emptying of a radiolabeled milk formula and fasting duodenogastric reflux during manometry by assessing bile salt concentration in gastric aspirates. No structural abnormalities of gastrointestinal tract and organic disorders were detected in the patients. In a high proportion of both groups of patients we found manometric abnormalities of interdigestive and fed motor patterns that were not seen in the controls: absence of antral phase III of MMC; significant decrease of antral and/or duodenal motor activity during fasting and/or fed periods; abnormal propagation or configuration of MMC phase III that was significantly shorter than in controls; bursts of sustained fasting and/or fed phasic duodenal activity, frequently uncoordinated with adjacent gut segments. When compared to controls, the mean intragastric concentration of bile salts during all MMC phases and the mean 1-hr percent gastric activity of the radiolabeled milk were significantly higher in the two groups of patients. We conclude that in a high proportion of children with nonulcer dyspepsia and of children with GER disease, gastrointestinal manometry may reveal significant irregularities of antral and duodenal motility, which are associated with increased duodenogastric reflux and delayed gastric emptying.
Injection of 2.5 mg of lambda-carrageenan into the rat pleural cavity resulted in a time-dependent increase in pleural exudate substance P (SP) levels up to 24 hr. Synergistic increases in the exudate formation were observed when a sub-optimal quantity of carrageenan was injected with SP. Pre-treatment of rats with capsaicin at 50 and 100 mg/kg s.c. daily for one week prior to the induction of pleurisy blocked the increase in exudate volume and SP levels when compared to that normally detected after carrageenan injection. These results suggest that inhibition of SP production may improve inflammatory conditions.