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Biomedical subjects

C Colombo

Publications and source records attributed to C Colombo.

At least 55 records · Page 3Linked to original sources

Ongoing lithium treatment prevents relapse after total sleep deprivation.

Forty bipolar depressed inpatients underwent three consecutive cycles of total sleep deprivation (TSD). At the beginning of the study, 20 patients were free of psychotropic drugs and 20 had been receiving lithium medication for at least 6 months. Mood was rated on the Hamilton Rating Scale for Depression before and after TSD; perceived mood changes during treatment were evaluated with self-administered visual analog scales. Patients undergoing long-term lithium treatment showed a significantly better response to TSD as rated on both scales: 13 of 20 patients (vs. 2 of 20 patients without lithium) showed a sustained response during a follow-up period of 3 months. This preliminary evidence of a positive interaction of TSD and long-term lithium treatment could be explained by a synergistic effect of both treatments on brain serotonergic function, possibly via a desensitization of 5-hydroxytryptamine-1A inhibitory autoreceptors.

Bipolar Disorder↗

Influence of a functional polymorphism within the promoter of the serotonin transporter gene on the effects of total sleep deprivation in bipolar depression.

OBJECTIVE: A functional polymorphism in the transcriptional control region upstream of the coding sequence of the 5-hydroxytryptamine transporter (5-HTT) has been reported. This polymorphism has been shown to influence the antidepressant response to fluvoxamine and paroxetine. The authors tested the hypothesis that the allelic variation of the 5-HTT-linked polymorphic region (5-HTTLPR) could influence the response of depressed patients to total sleep deprivation. METHOD: Sixty-eight drug-free inpatients with bipolar depression underwent a night of total sleep deprivation. 5-HTTLPR was genotyped in these patients. Changes in perceived mood were rated on a visual analogue scale and analyzed by using repeated measures analysis of covariance. RESULTS: Patients who were homozygotic for the long variant of 5-HTTLPR showed a significantly better mood amelioration after total sleep deprivation than those who were heterozygotic and homozygotic for the short variant. CONCLUSIONS: The influence of 5-HTTLPR on response to total sleep deprivation is similar to its observed influence on response to serotonergic drug treatments. This finding supports the hypothesis of a major role for serotonin in the mechanism of action of total sleep deprivation in depression.

Adult↗

[Association of Lynch syndrome and non-Hodgkin's malignant lymphoma. A case report].

A patient is described, with Lynch syndrome, typified by hereditary appearance in young age of synchronous and metachronous proximal colorectal cancer, without polyposis, and often associated with extracolonic cancer, particularly ovarian and endometrial carcinomas. The study of our patient's pedigree showed the occurrence of eleven colonic cancers. Our patient had ovarian carcinoma, tumor of the rectum and non-Hodgkin's lymphoma.

Adenocarcinoma, Mucinous↗

The unipolar-bipolar dichotomy and the response to sleep deprivation.

Fifty-one inpatients affected by a major depressive episode were divided into four groups according to mood disorder diagnosis and previous clinical history (bipolar disorder type I; bipolar disorder type II; major depressive disorder with at least three previous depressive episodes; and single depressive episode patients) and administered three consecutive total sleep deprivation (TSD) cycles. Mood changes were rated with a reduced version of the Hamilton Depression Rating Scale and with self-administered visual analogue scales. TSD caused better clinical effects in bipolar and single-episode patients; in particular, unipolar patients lacked effects in perceived mood after the first TSD and showed worse Hamilton ratings in respect to the other groups after the three TSD treatments. Discriminant function analysis could correctly classify 80% of bipolar patients, post hoc, based on TSD response. Further researches on the clinical efficacy of TSD must take into account the heterogeneity of depression and of its biological substrate.

Adult↗

Oxidation of individual fatty acids yields different profiles of oxidation markers.

Free radicals attack lipid molecules and initiate a chain of reactions that may trigger several diseases such as atherosclerosis and cancer. Several markers of oxidative stress have been proposed, including measurements of lipid peroxides and short-chain aldehydes levels and evaluation of conjugated diene formation. Although it is generally assumed that fatty acid oxidizability is directly proportional to their degree of unsaturation, little is known about the contribution of individual fatty acids to each of these markers. We investigated such contributions in a model of AAPH-mediated peroxidation of individual fatty acid micelles by assessing several indices of oxidative stress. The results suggest that the generation of oxidation products by individual fatty acids is not directly related to their degree of unsaturation and indicate that the differential contribution of individual fatty acids should be taken into account and more than one marker of lipid peroxidation should be included in in vivo studies of oxidative stress.

Amidines↗

The occurrence of percutaneous injuries to health care workers: a cross sectional survey in seven Swiss hospitals.

OBJECTIVES: In 1995, a cross sectional survey was conducted in 7 Swiss hospitals to estimate the incidence of percutaneous injuries among nurses, surgeons, anesthetists and domestic personnel, and to describe the circumstances of these injuries and the reporting process within the hospital. METHODS: An anonymous questionnaire was distributed and filled out on-site in the case of nursing staff and domestic personnel, and was sent by post to physicians (anesthetists and surgeons). Participants were asked to report in detail on percutaneous injuries of the last workday and the last working month (nurses and physicians), and of the last month and the last year for domestic personnel. The overall response rate was 72%, representing a total of 3116 health care workers. RESULTS: The annual incidence rates of percutaneous injury with material contaminated with blood or other biological fluids were calculated by type of worker for the two available units of time. For nurses, the incidence was 0.49 and 2.23, for surgeons 4.28 and 11.05, for anesthetists 2.11 and 3.14, and for domestic personnel 0.11 and 0.17 respectively. Most of the injuries occurred in a "normal" situation (no emergency, no stress, no fatigue) and were described as avoidable. Compliance with universal precautions was not optimal and declaration rates within the hospital rather low (nurses 39.7%, physicians 3.4%, domestic personnel 87.9%). CONCLUSION: Percutaneous injuries with blood-contaminated material are frequent in health care workers, and are not always adequately assessed because of under-reporting of accidents within the hospital. This may result in underestimation of current occupational exposure of health care workers to HIV and other blood-borne viruses.

Accidents, Occupational↗

S-adenosyl-L-methionine: role in phosphatidylcholine synthesis and in vitro effects on the ethanol-induced alterations of lipid metabolism.

Hepatic lipid metabolism is extremely modified by excessive ethanol consumption, but the cellular mechanisms of such alterations are still largely unexplored. S-Adenosyl-L-methionine (SAMe) is known as an important methylating agent and as a precursor of glutathione and it has been shown to prevent some of the toxic effects of ethanol in the liver. We therefore studied the effects of ethanol on cholesterol synthesis in a human hepatomal cell line (HepG2), the kinetics of SAMe, and its putative protective effects on the alterations of lipid metabolism induced by toxic concentrations of alcohol. Incubation of HepG2 cells with [3H]SAMe resulted in a progressive increase in the labelling of phosphatidylcholine and of its two intermediates during synthesis starting from phosphatidylethanolamine. This process is enzymatic, since it does not take place in heat-inactivated cells. Also, ethanol induced an increase in cholesterol and triglycerides syntheses and a decrease in phospholipid labelling. These alterations were not prevented by SAMe 10(-4) M, indicating that the protective effects of the drug are related to other mechanisms of action such as reduced formation of collagen, restoration of glutathione levels, and normalization of membrane functions.

Acetates↗

Perceived mood and skin body temperature rhythm in depression.

Eighteen inpatients affected by recurrent major depression were monitored in their clinical and biological features during the acute episode of illness. Diurnal mood variations rated with Visual Analogue Scale (VAS) and diurnal variations of skin body temperature were measured every 2 h consecutively for 2 days. Circadian rhythmicity of the two parameters was evaluated by cosinor analysis separately for each patient. The inspection of the individual cosine fitting shows that patients with a high circadian rhythmicity in perceived severity of symptomatology tend to show low circadian rhythmicity in skin body temperature, whereas patients with a low VAS oscillation tend to display a higher diurnal variation in skin body temperature. A chi-square test confirmed a statistical significance of the discordance between the two rhythms. We discuss our findings hypothesizing a different degree of entrainment of the disease process to the main circadian pacemaker.

Adult↗

Patterns of mood variation during antidepressant treatment.

Previous findings showed that, in a subgroup of patients administered heterogeneous antidepressant treatments, perceived mood levels during a major depressive episode fluctuate with day to day changes which follow cyclical patterns (termed "minicycles"). We investigated the predictability of infradian mood fluctuations during acute depressive episodes in patients standardly medicated with fluvoxamine. We applied time series analysis, by means of autocorrelation techniques, to time lagged serial recordings of perceived mood levels of 20 inpatients (13 Major Depression Recurrent, and 7 Bipolar Depressive Disorders). 5/20 patients exhibited predictable cyclical patterns in their perceived symptomathology, 8/20 exhibited an uneven, sawtooth pattern of progressive amelioration, and 7/20 showed an erratic pattern of unpredictable day-to-day variations. We confirmed the existence and the predictability of cyclical mood patterns in a subgroup of patients. The absence of a linear improvement in perceived mood did not worsen the final response to antidepressant therapy.

Antidepressive Agents, Second-Generation↗

Ethanol enhances cholesterol synthesis and secretion in human hepatomal cells.

Excessive consumption of alcohol leads to severe alterations of lipid metabolism, including hyperlipemia and hypercholesterolemia. Following these epidemiological observations, we investigated the effects of ethanol at the cellular level by employing a human hepatomal cell line (HepG2) and by evaluating the biosyntheses of lipid classes from different labeled precursors. Incubation of cells with 2% ethanol resulted in a decreased labeling of phospholipids and in an increase in cholesterol synthesis and secretion. Triglyceride synthesis was increased by ethanol but their secretion in the medium was reduced, suggesting that these alterations may be related to their accumulation in the liver. The alcohol-induced alterations of lipid metabolism are not due to its metabolite acetaldehyde and data suggest that alcohol enhances cholesterol synthesis by affecting the initial steps without increasing HMGCoA expression. The observed modifications of lipid metabolism in HepG2 may partially explain the enhanced incidence of cardiovascular disorders that has been associated with alcoholism.

Acetates↗

Liver and biliary problems in cystic fibrosis.

Liver disease associated with cystic fibrosis has been increasingly diagnosed during recent years probably due to the combined effect of systematic hepatic assessment and reduced death from extra-hepatic causes of CF patients. In a group of 173 CF patients regularly followed at our Center, cumulative incidence of liver disease was 17% over a mean period of 10 years. Although it generally runs a mild course, it is considered a major complication of CF which may limit survival and quality of life of affected patients. CF-associated liver disease should be considered as the first inherited liver disorder in which the primary defect affects cholangiocyte transport systems. Although data assessing the effects of defective CFTR on cholangiocyte pathobiology are not yet available, the impaired secretory function of the biliary epithelium is considered responsible for reduced biliary fluidity and alkalinity and for subsequent bile duct damage by cytotoxic compounds or infectious agents. No clear association with specific CFTR mutations has been observed. Treatment with ursodeoxycholic acid, aimed at improving biliary secretion in terms of bile viscosity and bile acid composition, is currently the most useful therapeutic approach in CF-associated liver disease. Beneficial effects on liver biochemistry, hepatic excretory function, liver histology, and essential fatty acid status have been reported, but no long-term data exist on its effectiveness on clinically relevant outcomes, such as death or need for transplantation. The effectiveness of bile acid therapy may be higher if started in patients with early stage liver disease, before symptoms have become clinically evident. Early diagnosis and identification of CF patients who are more liable to develop liver disease should be actively pursued.

Child↗

Low-dose clozapine in acute and continuation treatment of severe borderline personality disorder.

BACKGROUND: Psychotic-like symptoms in patients affected by borderline personality disorder (BPD) are usually treated with low-dose neuroleptics, which show controversial acute effects and lead to a worsening of affective-related symptoms and to severe neurologic side effects after prolonged administration. Clozapine lacks the neurologic side effects of traditional neuroleptics and has been shown to successfully treat psychotic-like symptoms in BPD patients at medium dose. We performed an open-label trial of low-dose clozapine in severe BPD patients. METHOD: Twelve BPD inpatients (DSM-IV criteria) with severe psychotic-like symptoms were studied. Exclusion criteria included comorbid Axis I and medical pathologies. All patients had followed a therapeutic program without improvement for at least 4 months before admission. The clozapine dose was titrated upward on an individual basis until the complete disappearance of psychotic-like symptoms was achieved. Clinician-rated scales were completed at the beginning of the study and after 4 and 16 weeks. RESULTS: All patients completed the 16-week study. Individual clozapine doses ranged from 25 to 100 mg/day. Psychotic-like symptoms decreased within the first 3 weeks of treatment, as confirmed by a statistically significant decrease in Brief Psychiatric Rating Scale scores. This amelioration was coupled with an overall improvement, including a reduction in impulsive behaviors and in affective-related symptoms (Hamilton Rating Scale for Depression) and an increase in global functioning (Global Assessment of Functioning). CONCLUSION: Low-dose clozapine for acute and continuation treatment led to improvement in overall symptomatology in a small sample of severe BPD patients.

Adult↗

Association between longevity and allelic forms of human leukocyte antigens (HLA): population study of aged Italian human subjects.

Several arguments support the idea of a link between longevity and heredity, both in humans and in experimental animals. We have therefore investigated the possibility of an association between the human leukocyte antigens (HLA) and longevity in two groups of Italian subjects: 108 healthy subjects over 85 years old, and 749 healthy blood donors (controls). Only four antigens showed a higher frequency in the elder group: HLA-A31(19), B7, Cw7 and DQ1. These findings suggest an involvement of HLA antigens in human longevity, but the real biological meaning of these results is still unclear.

Aged↗

Primary lactase deficiency and past malarial endemicity in Sardinia.

BACKGROUND: It has recently been suggested that primary lactase deficiency might have been selected for by malaria, as occurred for beta-thalassaemia and glucose 6-phosphate dehydrogenase deficiency. However, recently we have found that the prevalence of primary lactase deficiency in the area of Sassari (Northern Sardinia), where, in the past, there was intermediate malarial endemicity, is comparable to that observed in the adult population from other areas of Southern Italy where malaria was less endemic. AIMS: To address the problem further, we have determined the prevalence of primary lactase deficiency, glucose 6-phosphate dehydrogenase deficiency deficiency and beta-thalassaemia trait in the populations of three Sardinian villages which differ in altitude above sea-level, socioeconomic features, history of endemic malaria and prevalence of b-thalassaemia and glucose 6-phosphate dehydrogenase deficiency. SUBJECTS: We tested 138 adult males: 53 were from Fonni (a non-malarial mountain village, with a strong pastoral tradition), 38 from Lodé (a village with a similar pastoral tradition, but high malarial endemicity in the past) and 47 from Terralba (a lowland fishing village with an agricultural tradition and heavy malarial morbidity and mortality). METHODS: A blood sample was obtained in all subjects for determination of HbA2 and glucose 6-phosphate dehydrogenase activity. Lactase deficiency was assessed by measuring breath hydrogen production after oral administration of lactose (50 g), by gas-chromatography. RESULTS: The frequencies of glucose 6-phosphate dehydrogenase deficiency and of beta-thalassaemia trait in the non-malarial village of Fonni were strikingly low, compared to frequencies found in the two villages (Terralba and Lodé) with a very high past malarial morbidity. In contrast, there was no significant difference in the prevalence of lactase deficiency in the three groups of subjects from the three villages. CONCLUSIONS: These data obtained in Northern Sardinia do not support the hypothesis of a selection of primary lactase deficiency by malaria. For definitive conclusions, however, the malaria hypothesis should be tested in other parts of the world.

Adolescent↗

Sleep deprivation hastens the antidepressant action of fluoxetine.

Among ten bipolar depressed patients admitted to our psychiatric ward, five patients were treated with fluoxetine alone and five subjects were treated with fluoxetine in association with total sleep deprivation (TSD) in order to evaluate the effect of the interaction between the administration of the serotonergic antidepressant compound fluoxetine and repeated cycles of TSD. Patients treated with fluoxetine plus repeated TSD showed a faster amelioration of depressive symptomatology compared with the other group. We discuss our findings hypothesizing an enhancement in dopaminergic and possibly in serotonergic transmission due to repeated TSD adding to the increase in serotonergic transmission due to fluoxetine medication.

Adult↗

Response to clozapine in acute mania is more rapid than that of chlorpromazine.

The purpose of the present study was to compare the efficacy of clozapine with that of chlorpromazine in an open label manner (both given in association with lithium salts) in the treatment of acute mania. Thirty hospitalized manic patients were entered into the study. All patients met DSM-IV criteria for bipolar disorder, Manic Episode; 27 patients completed the study and three patients dropped for noncompliance. The duration of the study was 3 weeks. Patients were randomly assigned to two treatment groups; group 1 (n = 15) was treated with clozapine at a mean dose of 166 mg/day and group 2 (n = 12) was treated with chlorpromazine at a mean dose of 310 mg/day. Manic symptomatology was rated on Young Rating Scale for Mania (YRSM) each week; side effects were recorded on dosage records and treatment emergent symptoms; extrapyramidal acute side effects were rated on the Simpson-Angus Rating Scale performed at the beginning of the study and after 3 weeks of treatment. A two-way repeated measures analysis of variance on YRMS scores showed a significant time effect (p < 0.0001) and a significant time-group interaction (p < 0.0001). Post-hoc comparison between the two groups showed a significant difference after 2 weeks of treatment (p = 0.0001), with clozapine treated patients showing lower YRSM scores than chlorpromazine treated patients. YRSM scores at the end of the study were not significantly different. Patients treated with clozapine showed a more rapid trend toward amelioration. No clinically relevant side effect was observed during the study.

Acute Disease↗

Sequencing and functional analysis of styrene catabolism genes from Pseudomonas fluorescens ST.

The nucleotide sequence of the 4,377-bp chromosomal region of Pseudomonas fluorescens ST that codes for the oxidation of styrene to phenylacetic acid was determined. Four open reading frames, named styA, styB, styC, and styD, were identified in this region. Sequence analysis and biotransformation assays, performed with batch and continuous cultures, allowed us to identify the functions of the sequenced genes. styA and styB encode a styrene monooxygenase responsible for the transformation of styrene to epoxystyrene; styC codes for the second enzyme of the pathway, an epoxystyrene isomerase that converts epoxystyrene to phenylacetaldehyde; and the styD gene produces a phenylacetaldehyde dehydrogenase that oxidizes phenylacetaldehyde to phenylacetic acid. StyA, 415-amino-acids long, was found to be weakly homologous to p-hydroxybenzoate hydroxylase from both P. fluorescens and P. aeruginosa and to salicylate hydroxylase from P. putida, suggesting that it might be a flavin adenine dinucleotide-binding monooxygenase. StyB was found to be partially homologous to the carboxyterminal part of the 2,4-dichlorophenol-6-monooxygenase encoded by plasmid pJP4, while the styC product did not share significant homology with any known proteins. The fourth open reading frame, styD, could encode a protein of 502 amino acids and was strongly homologous to several eukaryotic and prokaryotic aldehyde dehydrogenases. The order of the genes corresponds to that of the catabolic steps. The previously suggested presence of the gene for epoxystyrene reductase, which directly converts epoxystyrene to 2-phenylethanol (A.M. Marconi, F. Beltrametti, G. Bestetti, F. Solinas, M. Ruzzi, E. Galli, and E. Zennaro, Appl. Environ. Microbiol. 61:121-127, 1996), has not been confirmed by sequencing and by biotransformation assays performed in continuous cultures. A copy of the insertion sequence ISI162, belonging to the IS21-like family of elements, was identified immediately downstream of the styrene catabolic genes.

Base Sequence↗