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Biomedical subjects

M Colombo

Publications and source records attributed to M Colombo.

At least 127 records · Page 7Linked to original sources
PubMed1996

Obesity and the sympathetic nervous system.

Several epidemiological studies have shown that obesity represents an independent risk factor for development of cardiovascular diseases, including hypertension, myocardial ischaemia, and cardiac arrhythmias. Although the metabolic and the haemodynamic alterations occurring in the obese state have been well defined for several years, our knowledge on the sympathetic alterations occurring in this condition is more scarce and controversial. This paper reviews the evidence that human obesity is characterized by abnormalities in sympathetic cardiovascular control, in the light of the results of recent studies performed by employing a sensitive technique to assess sympathetic activity in humans, i.e. microneurography. Evidence is provided that sympathetic overactivity is a common hallmark of the obese state, even when blood pressure levels are within the normal range. It will also discuss the potential mechanisms responsible for this sympathetic activation, suggesting that overweight-related metabolic alterations, such as the insulin resistance state, and abnormalities in sympathetic cardiovascular control exerted by arterial baroreceptors may play a pathogenetic role. Finally, the effects of body weight reduction on the sympathetic overactivity which characterizes the obese state will also be examined.

Energy Intake↗
PubMed1996

[Cognitive functions of school children with normal IQ and histories of severe and early malnutrition].

This is a cross section study designed to evaluate the long lasting consequences of early and severe undernutrition on the development of basic cognitive functions. Attention, memory and problem-solving capacity were assessed in a group of 16 school children, who were severely undernourished during the first two years of age. They were compared with a group of 16 children with a normal growth. All subjects, age 8 to 10, had a normal intellectual coefficient and they belonged to the me same socioeconomical level. Memory was measured with a modified version of subtest of digits from WISC; attention was evaluated with a modified version of the Continuous Performance Task and problem-solving was measured with the Anstey Domino Test. A personal computer was used to assess the cognitive functions. The children who were undernourished during infancy presented lower scores in memory (number of the digits) and in problems solving (number of correct answers). They also had a worse performance than the control group in the same response time, when attention was evaluated. These results suggest that early severe undernutrition had deletereous effects on basic cognitive functions.

Attention↗
PubMed1995

Effects of a novel 5-HT1A receptor agonist, E4424, on gastric adherent mucus levels following restraint stress in rats.

Several novel arylpiperazine serotonin 1A receptor agonists, developed as anxiolytics, have antisecretory and gastroprotective effects in rats. E4424 (2-¿4-[4-(4-chloropyrazol-1-yl)butyl]-1-piperazinyl ¿pyrimidine; Lesopitron dihydrochloride), has potent anti-gastric secretory and antiulcer effects. Preliminary data indicated an enhancing effect of E4424 on gastric mucus that may underlie its gastroprotective actions. We therefore tested the effects of acute and chronic administration of E4424 and of a reference 5-HT1A receptor agonist, 8-OHDPAT [8-hydroxy-2-(di-n-propylamino)tetralin], on gastric mucus levels in rats subjected to cold-restraint stress, a procedure associated with depletion of gastric mucus and the development of mucosal injury. Acute oral administration of E4424 increased adherent mucus levels by 12%, 11%, and 13%, relative to controls. Chronic E4424 significantly increased gastric mucus relative to controls (69% increase). Acute oral treatment with 8-OHDPAT did not affect gastric mucus level. Acute intraperitoneal 8-OHDPAT slightly increased mucus levels. Chronic twice per day 8-OHDPAT did not affect mucus levels; however, chronic once per day treatment with 8-OHDPAT significantly elevated gastric mucus levels at the highest doses used. For E4424, there is a strong correlation between reduction of gastric mucosal injury and increase in gastric mucus level, suggesting that the action of E4424 on glandular mucus levels is an important mechanism underlying its gastroprotective effects.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1995

A randomized trial of open versus closed vaginal vault in the prevention of postoperative morbidity after abdominal hysterectomy.

OBJECTIVE: Our purpose was to evaluate the effects of two surgical techniques, closed vaginal vault with two layers of continous 3-0 polyglactin suture versus open vaginal vault with a locking 3-0 polyglactin suture, after abdominal hysterectomy. STUDY DESIGN: A prospective, randomized trial was performed. During the hospital stay and 4 to 8 weeks after the operation patients were observed for evidence of morbidity. RESULTS: Of the 273 evaluable subjects, 141 had the vaginal vault left open whereas 132 were closed. Ten (7.1%) and eight patients (6.1%) had infections at the operative site (pelvis or abdominal wound) (p = 0.92). A urinary tract infection was diagnosed in three (2.1%) and in four subjects (3.0%) (p = 0.46). A pelvic hematoma developed in two patients of each group (p = 0.66). Vault granulations were recorded in 11% and 12% of subjects (p = 0.97). CONCLUSIONS: This study failed to show some benefit in favor of either of the two surgical policies. A careful surgical technique and antibiotic prophylaxis seem to remain the most important factors in the prevention of postoperative morbidity.

Adult↗
PubMed1995

Chromocystoscopy in the urological monitoring of patients with cancer of the cervix.

OBJECTIVE: To determine whether chromocystoscopy could be used for the urological monitoring of cervical carcinoma. METHODS: The absolute ejaculation time (AET, the interval of time between the intravenous injection of dye and the ejaculation of dyed urine in the bladder from either of the ureters) and the relative ejaculation time (RET, the difference of time between the two ejaculations) were retrospectively studied in relation to intravenous urography (IVU) and radionuclide renography (RR) in 141 patients. RESULTS: A significant probability of normal IVU and RR was found when the AET was < or = 7 min or the RET < or = 4 min and when no interval occurred between the two ejaculations. Pathological IVU and RR were found when there was no ejaculation from one or both ureters after 12 min. CONCLUSIONS: Chromocystoscopy could be used for monitoring cervical cancer patients. An abnormal chromocystoscopy could indicate the need for further radiological examinations.

Cystoscopy↗
PubMed1995

Alpha interferon treatment of chronic hepatitis C.

Hepatitis C virus infection is a common disease with a high propensity to progress towards chronicity. Alpha interferon has been proposed to halt progression of the disease and prevent the development of more severe liver diseases such as cirrhosis and hepatocellular carcinoma. Unfortunately, less than 20% of treated patients show a long-lasting ALT normalization and HCV-RNA negativity. Factors which might be predictive of a long term response to interferon are debated. Univariate analysis of data collected in randomized clinical studies, has shown that IFN dose, age, duration of disease, cirrhosis and early response (primary) to IFN were all predictors of a sustained response to IFN, but with differences in different studies. When data were analyzed by a multivariate analysis, short duration of the disease and absence of cirrhosis were found to predict long-term response to interferon. Finally, many evidences indicate that response rates to therapy may be better in patients with low pretreatment levels of HCV-RNA measured either by polymerase chain reaction (PCR) or the branched-DNA assay (b-DNA).

Chronic Disease↗
PubMed1995

Long-term titrated recombinant interferon-alpha 2a in chronic hepatitis C: a randomized controlled trial.

The efficacy and tolerability of 12-month treatment with titrated doses of recombinant interferon-alpha 2a (IFN-alpha 2a) in chronic hepatitis C were studied in 67 consecutively recruited patients randomly assigned either to a starting dose of IFN-alpha 2a 6 MU, subsequently adjusted to the serum alanine aminotransferase (ALT) response (n = 35), or to no therapy (n = 32; controls). End-of-treatment ALT levels were normal and hepatitis C virus (HCV) RNA was negative by nested polymerase chain reaction (PCR) in 17 (49%) treated patients compared to none of the controls (P < 0.001). During the 12 months after stopping treatment the number of patients who remained in remission was eight (23%) and one respectively (4%) (P = 0.031). Follow-up liver biopsy showed reduced hepatic inflammation in 80% of treated patients and in 29% of controls (P < 0.001). The eight sustained responders and 27 non-responders or relapsers received similar mean total doses of IFN (565 MU vs 545 MU) and had a similar incidence of anti-IFN neutralizing antibodys (13% vs 19%). Absence of cirrhosis was the only independent pretreatment parameter that predicted a sustained response. In conclusion, a mean cumulative dose of IFN 549 MU, titrated over 12 months, was well tolerated, and resulted in the long-term clearance of HCV RNA and normal ALT levels in 23% of patients.

Adolescent↗
PubMed1995

Hepatitis B virus precore mutants in HBeAg carriers with chronic hepatitis treated with interferon.

Precore mutants of hepatitis B virus (HBV) were looked for in 18 hepatitis B e antigen (HBeAg) carriers who were treated with recombinant interferon-alpha (rIFN) and the results were compared with those obtained in 12 untreated carriers who underwent spontaneous HBeAb seroconversion. Molecular analysis of the HBV precore region was carried out by polymerase chain reaction (PCR) amplification and direct sequencing. Precore mutants with a stop codon at codon 28 were detectable at baseline in 19/30 carriers. However, wild-type strains predominated in the baseline sera of both treated (n = 16) and untreated (n = 10) patients. Sera from the remaining four patients contained predominantly or exclusively mutant virions. Following IFN treatment, there was a shift from the wild-type pattern to the mutant pattern in all patients, with the precore pattern prevailing in long-term responders (six out of nine) compared with the non-responders (none of nine). The wild-type pattern predominated among the non-responders (eight vs three), suggesting that the long-term response to IFN was associated with take-over of precore mutants. There were no relationships between any pretreatment precore molecular pattern and disease severity or outcome of treatment. Precore mutants also took over in 10 of the 12 untreated patients (83%), who underwent spontaneous HBeAb seroconversion. Thus, a shift from wild-type to precore mutant pattern occurs in most Italian patients undergoing IFN-induced or spontaneous HBeAb seroconversion.

Adolescent↗
PubMed1995

Sympathetic activation in obese normotensive subjects.

Human obesity is characterized by profound alterations in the hemodynamic and metabolic states. Whether these alterations involve sympathetic drive is controversial. In 10 young obese subjects (body mass index, 40.5 +/- 1.2 kg/m2, mean +/- SEM) with normal blood pressure and 8 age-matched lean normotensive control subjects, we measured beat-to-beat arterial blood pressure (Finapres technique), heart rate (electrocardiogram), postganglionic muscle sympathetic nerve activity (microneurography at the peroneal nerve), and venous plasma norepinephrine (high-performance liquid chromatography). The measurements were performed in baseline conditions and, with the exception of plasma norepinephrine, during baroreceptor stimulation and deactivation caused by increases and reductions of blood pressure via intravenous infusions of phenylephrine and nitroprusside. Baseline blood pressure and heart rate were similar in obese and control subjects. Plasma norepinephrine was also similar in the two groups. Muscle sympathetic nerve activity, however, was 38.6 +/- 5.1 bursts per minute in obese subjects and less than half that level in control subjects (18.7 +/- 1.3 bursts per minute), the difference being highly statistically significant (P < .02). Muscle sympathetic nerve activity and heart rate were reduced during phenylephrine infusion and increased during nitroprusside infusion, but the changes were about half as great in obese subjects as in control subjects. Thus, even in the absence of any blood pressure alteration, human obesity is characterized by a marked sympathetic activation, possibly because of an impairment of reflex sympathetic restraint. This may be involved in the high rate of hypertension and cardiovascular complications seen in obesity.

Adult↗
PubMed1995

Radial artery compliance in young, obese, normotensive subjects.

Obesity is characterized by a number of cardiovascular alterations, and whether these alterations involve arterial compliance is unknown. In 12 young, obese, normotensive subjects (age, 23.9 +/- 1.3 years; mean +/- SEM) and 12 age- and sex-matched lean control subjects we measured blood pressure, radial artery diameter, and radial artery compliance continuously over the systodiastolic pressure range with a Finapres device and recently developed echo-tracking device. Measurements were obtained at baseline and after prolonged ischemia, that is, when diameter and compliance are increased. Blood pressure values were normal in both groups (obese subjects: 109.2 +/- 4.9/68.2 +/- 2.7 mm Hg; lean control subjects: 108.2 +/- 4.1/60.7 +/- 3.8 mm Hg), but in addition to a marked increase in body mass index (38.5 +/- 0.8 versus 23.1 +/- 0.9 kg/m2, P < .01), obese subjects showed a slight and nonsignificant increase in heart rate (71.1 +/- 3.2 versus 66.7 +/- 3.3 beats per minute, P = NS), increases in left ventricular wall thickness and left ventricular mass index (121.5 +/- 4.8 versus 103.4 +/- 3.3 kg/m2, P < .01), no changes in plasma renin activity and plasma norepinephrine (compared with normal values), and a marked reduction in total body glucose uptake (glucose clamp technique). Obese subjects showed radial artery diameter and compliance values that were greater than those seen in control subjects throughout the systodiastolic pressure range. The differences were 13% (P < .05) and 96% (P < .01), respectively, and both diameter and compliance remained higher in obese than lean subjects after forearm ischemia. In obese and lean subjects baseline radial artery diameter values correlated highly with body weight, body surface area, and body mass index.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1995

Autoimmunity and thyroid function in patients with chronic active hepatitis treated with recombinant interferon alpha-2a.

The occurrence of thyroid abnormalities and the appearance of organ- and non-organ-specific autoantibodies during long-term recombinant interferon alpha-2a (IFN-alpha) therapy were studied in 86 and 51 consecutive outpatients with hepatitis C and B virus-related chronic active hepatitis (CAH-HCV and CAH-HBV), respectively. Most patients had longstanding community-acquired hepatitis. At baseline, 9.3% of CAH-HCV and 3.9% of CAH-HBV patients showed clinical and/or biochemical signs of thyroid dysfunction. The remaining patients were euthyroid, although anti-thyroid autoantibodies were found in 33/78 (42.3%) of CAH-HCV and in 5/49 (10.2%) of CAH-HBV patients. During IFN-alpha treatment, increased anti-thyroid autoantibody levels were seen in 40% of CAH-HCV initially negative patients, while they became detectable in no more than 10% of CAH-HBV patients. Interferon-alpha-induced hypo- or hyperthyroidism was recorded in 12 of 35 CAH-HCV patients treated for 12 months (34.3%). Only one CAH-HBV patient developed hyperthyroidism. High titers of anti-nuclear autoantibodies (ANA) were recorded at enrollment in 5/36 (13.8%) of CAH-HCV and in 3/16 (18.7%) of CAH-HBV patients. Only one CAH-HCV patient displayed anti-parietal cell antibodies (PCA). After IFN-alpha treatment, ANA were found in 10/28 (35.7%) and PCA in 2/28 (7.1%) of CAH-HCV patients, while an additional CAH-HBV patient developed PCA, but not ANA. However, no signs of systemic autoimmune disease were recorded.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Vibrio cholerae in the horn of Africa: epidemiology, plasmids, tetracycline resistance gene amplification, and comparison between O1 and non-O1 strains.

The prevalence of Vibrio cholerae O1 and non-O1 has been investigated in numerous Somali regions of the Horn of Africa from 1983 to 1990. From January 1983 to January 1985 and between December 1986 and December 1990, no strains of V. cholerae O1 and 226 strains (5.3%) of V. cholerae non-O1 were isolated from 4,295 diarrhea cases. During a cholera epidemic in 1985 and 1986, the overall case-fatality rate was 13% and the attack rate was 3-3.5 per 1,000 population. Matched case-control studies identified a waterborne route of transmission. A drug-susceptible Ogawa strain from Ethiopia caused the introduction of the disease into northern Somalia. There were two major resistant derivatives of the original strain, and the one resistant to ampicillin, kanamycin, streptomycin, sulfonamide, and tetracycline (TC) predominated in the spreading disease. In 1986, susceptible Ogawa strains quickly displaced this resistant strain. The two incompatibility group C plasmids responsible for the resistance patterns had complex and scattered differences in their structures. Physical analysis of the plasmid DNA region coding for TC resistance demonstrated its genetic amplification in highly resistant variants of Ogawa strains.

Adolescent↗
PubMed1995

Behavioral and biochemical evidence of opioidergic involvement in cocaine sensitization.

Chronic administration of cocaine produces sensitization to its behavioral effects in humans and experimental animals. In the present study, rats treated with cocaine (10 mg/kg, i.p.) once daily for 10 days showed an enhancement in the acute drug stimulation of locomotor activity and stereotypy. Biochemical analysis in the nucleus accumbens of chronic cocaine-treated animals indicated that sensitization of D1 dopamine (DA) receptors had also developed. In fact, stimulation of adenylyl cyclase activity by DA was increased in nucleus accumbens membranes from sensitized rats. Our findings suggest that a novel postsynaptic mechanism, i.e., an increased DA-D1 receptor function, may play a role in the sensitization. A causal relationship between the two events is supported by the observation that neither motor behavioral sensitization nor DA-dependent adenylyl cyclase hyperactivity developed when the opiate antagonist naltrexone (2 mg/kg, s.c.) was given daily for 10 days before cocaine. When given alone, naltrexone was inactive in all respects, which rules out any unspecific action and suggests that its effects may be due to competition at receptors with endogenous opioids mobilized by cocaine. This was indirectly supported by the finding that desensitization of opioid inhibition of adenylyl cyclase developed in nucleus accumbens membranes of cocaine-sensitized rats. Chronic blockade of opioid receptors by naltrexone also counteracted the reinforcing properties of cocaine; conditioned place preference, clearly displayed by cocaine-treated animals, was antagonized in a dose-related manner. Overall, these results confirm that endogenous opioid peptides play an important role in cocaine addiction.

Adenylyl Cyclases↗
PubMed1995

Some novel 5-hydroxytryptamine1A (5-HT1A) receptor agonists reduce gastric acid and pepsin secretion, reduce experimental gastric mucosal injury and enhance gastric mucus in rats.

The present studies examined the actions of a series of novel arylpiperazine 5-hydroxytryptamine1A (5-HT1A) agonists, developed originally for anxiolytic efficacy, in several models of gastric secretion and experimental gastric mucosal injury. These models included conscious gastric acid secretion, pylorus ligation (gastric acid and pepsin secretion), stress-induced gastric mucosal injury, ethanol-induced gastric mucosal damage and gastric adherent mucus levels. 2-(4-[4-(4-Nitropyrazol-1- yl)butyl]-1-piperazinyl)pyrimidine (E4414) and 2-(4-[4-(4-chloropyrazol-1-yl)butyl]-1-piperazinyl)pyrimidine dihydrochloride (E4424) significantly inhibited gastric acid secretion in conscious as well as in pylorus-ligated rats. Both compounds also significantly reduced pepsin secretion in pylorus-ligated animals. E4414 and E4424 significantly reduced both stress-induced and ethanol-induced gastric mucosal injury, and both compounds significantly maintained gastric adherent mucus levels in rats subjected to stress. The antisecretory and gastroprotective actions of E4414 and E4424 were of significantly greater magnitude than those of the reference 5-HT1A agonists, buspirone and 8-hydroxy-2-(di-n- propylamino)tetralin. These results suggest that some novel 5-HT1A agonists exert gastroprotection not only through reduction of aggressive elements in the gut (acid and pepsin secretion) but also through enhancement of defensive gastrointestinal factors such as adherent mucus.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1994

Adjuvant effect of low-dose interleukin-2 on antibody response to influenza virus vaccination in healthy elderly subjects.

It is well known that immune efficiency is frequently deteriorated in elderly people. The age-diminished antibody response to T-cell dependent antigens, such as influenza virus antigens, may explain the low protection offered by influenza vaccination in the elderly population. To investigate the possibility of increasing the antibody response to influenza virus vaccinations, we have conducted a nursing home-based study on the efficacy of IL-2. Seventy-five institutionalized elderly subjects (82 +/- 8 years) were enrolled in the study in the course of winter season 1991-1992. Thirty-nine subjects were treated with three subcutaneous daily injections of interleukin-2 (IL-2, 1 x 10(6) I.U./day) before vaccination and their antibody response was compared to that of 36 aged people receiving the vaccine only. An increased antibody response against influenza virus was present in vaccine plus IL-2 treated subjects (P < 0.001) but not in subjects treated with vaccine only. The number of protected subjects 45 days after vaccination was increased only in the IL-2-treated group (P = 0.045). The low-dose of IL-2 administered and the short-term treatment allowed a good tolerance to the IL-2 injection. In conclusion, the low-dose IL-2 treatment represents an effective means of inducing antibody response to influenza virus antigens in elderly subjects without appreciable toxicity.

Adjuvants, Immunologic↗