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Biomedical subjects

M Colombo

Publications and source records attributed to M Colombo.

At least 19 recordsLinked to original sources

Treatment of primary sclerosing cholangitis with low-dose ursodeoxycholic acid: results of a retrospective Italian multicentre survey.

BACKGROUND: Data concerning the usefulness and type of drugs employed to treat patients with primary sclerosing cholangitis are controversial. Ursodeoxycholic acid has been shown to be a useful agent, however the drug dosage and its effect on the clinical course are still under debate. AIM: To evaluate the efficacy of low-dose ursodeoxycholic acid in the treatment of primary sclerosing cholangitis. METHODS: We retrospectively analysed data from 86 patients with primary sclerosing cholangitis from eight centres in Italy between 1987 and 1997: 69 were treated with ursodeoxycholic acid (8-13 mg/kg/day), while 17 received symptomatic treatment and served as controls. The effect of therapy was evaluated by standard liver function tests and symptom analysis. RESULTS: Ursodeoxycholic acid treatment was associated with significant improvement in serum alkaline phosphatase (735+/-833 vs. 519+/-448 U/l, p<0.001), gamma-glutamyl transpeptidase (401+/-352 vs. 234+/-235 U/l, p<0.001), aspartate aminotransferase (87+/-70 vs. 56+/-42 U/l, p=0.001), alanine aminotransferase (146+/-139 vs. 76+/-73 U/l, p<0.001), and total bilirubin (1.88+/-2.44 vs. 1.76+/-4.12 U/l, p=0.01); there was also amelioration of fatigue (p=0.007), jaundice (p=0.002), and body weight loss (p=0.002). CONCLUSIONS: Ursodeoxycholic acid, at a dose of 8-13 mg/kg/day was beneficial for the general condition and liver biochemistry of patients with primary sclerosing cholangitis; high-dose ursodeoxycholic acid treatment requires further evaluation.

Adult↗

Antihyperglycemic and blood pressure-reducing effects of stevioside in the diabetic Goto-Kakizaki rat.

Stevioside, a glycoside present in the leaves of the plant, Stevia rebaudiana Bertoni (SrB), has acute insulinotropic effects in vitro. Its potential antihyperglycemic and blood pressure-lowering effects were examined in a long-term study in the type 2 diabetic Goto-Kakizaki (GK) rat. Rats were fed 0.025 g x kg(-1) x d(-1) of stevioside (purity > 99.6%) for 6 weeks. An intra-arterial catheter was inserted into the rats after 5 weeks, and conscious rats were subjected to arterial glucose tolerance test (2.0 g x kg(-1)) during week 6. Stevioside had an antihyperglycemic effect (incremental area under the glucose response curve [IAUC]): 985 +/- 20 (stevioside) versus 1,575 +/- 21 (control) mmol/L x 180 minutes, (P <.05), it enhanced the first-phase insulin response (IAUC: 343 +/- 33 [stevioside] v 136 +/- 24 [control] microU/mL insulin x 30 minutes, P <.05) and concomitantly suppressed the glucagon levels (total AUC: 2,026 +/- 234 [stevioside] v 3,535 +/- 282 [control] pg/mL x 180 minutes, P <.05). In addition, stevioside caused a pronounced suppression of both the systolic (135 +/- 2 v 153 +/- 5 mm Hg; P <.001) and the diastolic blood pressure (74 +/- 1 v 83 +/- 1 mm Hg; P <.001). Bolus injections of stevioside (0.025 g x kg(-1)) did not induce hypoglycemia. Stevioside augmented the insulin content in the beta-cell line, INS-1. Stevioside may increase the insulin secretion, in part, by induction of genes involved in glycolysis. It may also improve the nutrient-sensing mechanisms, increase cytosolic long-chain fatty acyl-coenzyme A (CoA), and downregulate phosphodiesterase 1 (PDE1) estimated by the microarray gene chip technology. In conclusion, stevioside enjoys a dual positive effect by acting as an antihyperglycemic and a blood pressure-lowering substance; effects that may have therapeutic potential in the treatment of type 2 diabetes and the metabolic syndrome.

Animals↗

Proliferating cell nuclear antigen assessed by a computer-assisted image analysis system in patients with chronic viral hepatitis and cirrhosis.

BACKGROUND: Assessment of liver cell proliferation by immunodetection of proliferating cell nuclear antigen may predict regenerative potential and survival of liver and hepatocellular carcinoma risk in patients with chronic viral hepatitis. AIM: To evaluate proliferating cell nuclear antigen status and its clinical significance in a large cohort of patients with chronic viral hepatitis and different degree of liver damage by a computer assisted imaging analysis system. MATERIALS: Liver biopsies from 358 patients with chronic hepatitis (259 males, 49 years, 63% with hepatitis C infection, 27% with hepatitis B virus, 10% with multiple infections) were studied. METHODS: Proliferating cell nuclear antigen was localised by immunoperoxidase on microwave oven pre-treated formalin-fixed, paraffin embedded sections using PC10 monoclonal antibody. Proliferating cell nuclear antigen labelling index was calculated by an automated imaging system (Immagini e Computers, Milan, Italy). RESULTS: Mean proliferating cell nuclear antigen labelling index ranged from 0.1% for patients with minimal changes to 3.6% for those with cirrhosis and hepatocellular carcinoma. Overall, proliferating cell nuclear antigen labelling index was higher in males, in older patients, in multiple infections and in hepatitis C virus compared to hepatitis B virus related cases. By linear regression analysis, proliferating cell nuclear antigen labelling index correlated with older age, male gender; higher transaminase levels, hepatitis C virus, higher histological gradIng and staging: by multivariate analysis male gender, hepatitis C virus, higher grading and staging resulted as independent variables. Both hepatitis C virus or hepatitis B virus cirrhotics had similar liver cell proliferation rate but those with hepatitis B virus had higher prevalence of liver cell dysplasia with respect to those with hepatitis C virus. CONCLUSIONS: Proliferating cell nuclear antigen labelling index was a reliable assay for assessing liver cell proliferation rate in patients with chronic viral hepatitis and correlated with liver disease severity

Adult↗

Survival and naphthalene-degrading activity of Rhodococcus sp. strain 1BN in soil microcosms.

AIMS: The survival and activity of Rhodococcus sp. strain 1BN, inoculated into naphthalene-contaminated sandy-loam soil microcosms, were studied using classical and molecular methods. METHODS AND RESULTS: The naphthalene-degrading activity of 1BN in microcosms was examined through viable counts, CO2 production and naphthalene consumption, while its survival after inoculation was monitored by detecting the contemporary presence of alkane and naphthalene degradative genes and by analysing the 16S rDNA specific restriction profile. The inoculation of 1BN did not significantly enhance naphthalene degradation in the naphthalene-contaminated native soil, where 1BN maintained its catabolic activity also when in the presence of indigenous microflora. Instead the rate of naphthalene degradation by the inoculated 1BN was greater in sterile naphthalene-contaminated soil. The level of 1BN was only slightly higher after inoculation regardless of whether indigenous naphthalene-degrading bacteria were present or not and 1BN remained viable even when the substrate was depleted. CONCLUSIONS: This study documents the colonization and growth of 1BN in a non-sterile, naphthalene-added, sandy-loam soil having an active indigenous naphthalene-degrading population. SIGNIFICANCE AND IMPACT OF THE STUDY: An active and well-established naphthalene-degrading bacterial population in the native soil did not hamper the survival of the introduced 1BN that, through its activity, enhanced the mineralization rate of naphthalene.

Cytochrome P-450 CYP4A↗

Progressive hepatic fibrosis in healthy carriers of hepatitis C virus with a transaminase breakthrough.

In short-term studies, patients with chronic hepatitis C virus (HCV) infection, consistently normal serum aminotransferase (ALT) levels, and minimal or mild necro-inflammatory changes in the liver, did not progress to histologically severe hepatitis. There are no data on longer term outcome of liver disease in these patients. We describe two patients with HCV infection (genotype 2c) with a rise in serum ALT values greater than 10 times the upper normal value that occurred after an 8- and 15-year period of persistently normal or minimally elevated ALT levels. In both patients, the rise in ALT values lasted more than 16 weeks and was not associated with any symptom or risk factor for acute hepatitis. A liver biopsy performed 4 and 18 months after the ALT flare showed clear-cut progression from chronic hepatitis with mild activity to chronic hepatitis with severe activity and central to portal septal fibrosis (Ishak score: grading 14 and 6; staging: 4 and 5, respectively). Hence, extended surveillance of HCV carriers with consistently normal or minimally elevated ALT values is warranted as these patients are at risk of ALT flares and may develop progressive liver disease.

Adult↗

Participation of the hypothalamus-hypophysis axis in the sympathetic activation of human obesity.

Previous studies have shown that hypothalamic and hypophyseal factors are involved in the acute sympathoexcitation induced by a variety of laboratory stimuli. Whether a chronic condition of sympathetic activation, such as that characterizing human obesity, is also dependent on these factors has never been investigated. In 40 normotensive obese subjects ([mean+/-SEM] age, 39.1+/-0.8 years) we measured blood pressure (Finapres), heart rate (ECG), and postganglionic muscle sympathetic nerve activity (MSNA) (microneurography). In 20 subjects measurements were repeated, according to a double-blind randomized sequence, after a midnight oral dose of dexamethasone (1 mg) (n=10) or placebo (n=10), while in the remaining subjects they were performed again after 1 week of a daily evening oral administration of 1 mg of dexamethasone (n=10) or placebo (n=10). The same protocol was performed in 16 age-matched lean normotensives. In both groups acute dexamethasone administration markedly reduced plasma cortisol (radioimmunoassay), without affecting hemodynamic and neural variables. In contrast to the acute administration, in obese subjects prolonged dexamethasone administration, although not affecting blood pressure and heart rate, significantly reduced both plasma cortisol (from 16.0+/-1.3 to 0.7+/-0.1 microg/dL; P<0.01) and MSNA (from 59.5+/-2.8 to 39.6+/-2.9 bursts per 100 heartbeats; P<0.02; -33.1+/-4.1%). This was not the case in lean subjects, in which the dexamethasone-induced reduction in plasma cortisol was associated with a slight and nonsignificant MSNA decrease. In both lean and obese subjects, placebo administration caused no change in any variable. Thus, prolonged dexamethasone administration exerts in obese subjects marked sympathoinhibitory effects that are not detectable in lean individuals. This suggests that hypothalamic and hypophyseal factors substantially contribute to the sympathoexcitation of obesity.

Adult↗

The role of the avian hippocampus in orientation in space and time.

We examined the effects of hippocampus (Hp) and area parahippocampalis (APH) lesions in pigeons on their ability to perform a battery of tasks including autoshaping, time discrimination, spatial memory, and pattern discrimination. Pigeons with Hp-APH lesions were impaired in the acquisition of an autoshaped response, emitting fewer pecks to the stimulus than control animals. Hp-APH pigeons were also impaired in the acquisition of a radial-arm maze analogue task, and those birds that did learn the task seemed to do so by adopting a stereotypic response strategy. In contrast, Hp-APH lesions had no effect on the ability of the birds to discriminate on the basis of either temporal or visual information. Overall, these studies complement our earlier studies and suggest that the avian hippocampus is important for the processing and retention of spatial rather than non-spatial information.

Animals↗

Responses of ectostriatal neurons during delayed matching-to-sample behavior in pigeons (Columba livia).

We recorded from 71 neurons in the ectostriatum of awake behaving pigeons performing the delayed matching-to-sample task. The ectostriatum is considered to be equivalent to the primate extrastriate cortex. Many of the neurons (n=56, 78.9%) were visually responsive to either or both the red and green stimuli. In addition, a large number of neurons (n=51, 71.8%) exhibited delay activity, that is, a change in activity during the delay period when memory was required compared to the baseline intertrial interval period when memory was not required. We were more likely to encounter a delay neuron when the subjects performed well (>75% correct) compared to when the subjects performed poorly (<75% correct), suggesting that delay activity may carry some functional significance. Finally, the magnitude of the delay activity did not vary across the delay period but remained at a constant elevated or depressed level. Overall, our findings in pigeons are very similar to those reported for primates, and suggest that the pigeon may be an excellent model in which to study the neural mechanisms of visual information processing.

Animals↗

Treatment of hepatocellular carcinoma.

Treatment options have largely been selected according to empirical criteria, such as the presence or absence of cirrhosis, number and size of tumors, and degree of hepatic deterioration and taking into account the local technological and economic resources. There are virtually no controlled studies comparing the efficacy of the available treatments, and the substantial heterogeneity of survival between control groups does not allow us to obtain therapeutic evaluation by comparing results of separate trials. The reassessment of treatment outcomes on the basis of intention-to-treat analysis yielded less encouraging figures. Hepatic resection is the primary option for the few patients with a hepatocellular carcinoma arising in a normal liver with well-preserved hepatic function and for patients with a single tumor, compensated cirrhosis and low portal hypertension who are not candidable to liver transplantation. The latter is the best treatment modality for patients with a solitary tumor <5 cm in diameter or patients with less than three tumors <3 cm, resulting in a 5-year survival of 75%. Locoregional ablative treatments are curative options for patients with a "resectable" tumor who cannot be offered transplantation or hepatic resection. The 5-year survival is approximately 50% but it copes with a high risk of tumor recurrence. Patients with advanced tumor disease cannot be offered curative treatments but only symptomatic treatments.

Carcinoma, Hepatocellular↗

Screening for cancer in viral hepatitis.

Early diagnosis of HCC is possible because certain risk factors for this tumor are known and because sensitive and relatively inexpensive diagnostic tools are available. Early diagnosis of HCC is also possible because of the long phase of asymptomatic tumor growth and the tumor's tendency to grow as a solitary mass in many patients. In two consensus development conferences held in Anchorage, Alaska and in Milan, Italy, chronic carriers of HBsAg, patients with cirrhosis, patients with rare metabolic liver diseases, and individuals with family histories of HCC were identified as patients at high risk for HCC and therefore as candidates for periodic screening. At the Anchorage conference, it was recommended that healthy carriers have at least yearly determinations of serum AFP and that carriers with additional risk factors (e.g., cirrhosis) be screened every 6 months by abdominal US scans and determination of serum AFP levels. No specific recommendations were released for HBsAg-negative patients with chronic liver disease. At the Milan conference, it was recommend that patients with cirrhosis or with certain congenital metabolic conditions known to be at risk for HCC should be screened by AFP determination and US scan twice a year. It was also recommended that HBsAg carriers older than 35 years or with family histories of HCC should be screened for HCC by determinations of serum AFP levels and aminotransferase levels once a year.

Costs and Cost Analysis↗

High rates of hepatocellular carcinoma in cirrhotic patients with high liver cell proliferative activity.

The prevalence, risk factors, and clinical significance of high liver cell proliferative activity were investigated in 208 well-compensated cirrhotic patients (150 men; 50 years; 135 with chronic hepatitis C) who had been under prospective surveillance for hepatocellular carcinoma (HCC) with annual abdominal ultrasound (US) and serum alpha-fetoprotein (AFP) determination. Immunostaining for proliferating cell nuclear antigen (PCNA) was employed to assess liver cell proliferative activity in formalin-fixed, paraffin-embedded liver specimens. The percentage of reactive nuclei was calculated by a computer-assisted image analysis system. The overall PCNA labeling index (LI) ranged from 0.1% to 12.5% (mean, 2.1%), being significantly higher in the 50 patients who developed HCC during 88 +/- 42 months of follow-up than in the 158 patients who remained cancer-free (3.6% +/- 2.4% vs. 1.6% +/- 1.5%; P <.0001). By receiver operating curve (ROC), a 2.0% cut-off value of PCNA-LI discriminated between patients at high and low risk for developing cancer. By multivariate analysis, high histologic grading scores and gender were associated to PCNA LI >2.0%. The yearly incidence of HCC was 5.2% for the 80 patients with PCNA-LI >2.0% compared with 1.1% for the 128 with low PCNA-LI (relative risk, 4.90; 95% CI, 2.63-9.55). By multivariate analysis, PCNA-LI >2.0% was the strongest independent predictor of cancer (hazard ratio, 5.49; 95% CI, 2.90-10.37). Overall, survival was significantly lower in patients with high liver cell proliferative activity rates than in those with low proliferative rates (10% vs. 75%; P <.0001). In conclusion, development of HCC in patients with compensated cirrhosis seems to be reliably predicted by liver cell proliferation status.

Adult↗

Chlamydia pneumoniae and cytomegalovirus seropositivity, inflammatory markers, and the risk of myocardial infarction at a young age.

BACKGROUND: Pathogens causing chronic infections may promote atherosclerosis. The aim of our study was to evaluate the association of Chlamydia pneumoniae (Cp) and cytomegalovirus (CMV) infection and of inflammatory activation with premature myocardial infarction (MI). METHODS: Specific anti-Cp and anti-CMV immunoglobulin G (IgG), fibrinogen, white blood cells (WBC), and C-reactive protein (CRP) were measured in 120 post-MI patients </=50 years old and in 120 age-matched controls. RESULTS: Seropositivity to Cp and elevated concentrations of anti-Cp and anti-CMV IgGs were more frequent (P =.01) in patients than in control subjects, and fibrinogen, CRP, and WBC levels (P =.02) were more elevated. After adjustment for coronary risk factors and socioeconomic status, the odds ratios (95% confidence intervals) for premature MI were 2.4 (1.3-4.6) for Cp infection and 2.9 (1.5-5.8) for CMV. The risk of Cp infection was greater in smokers (3.7, 1.8-7.6). When both infections were present (35% of patients vs 8% of controls, P =.001), CRP was higher (P =.01) and the risk increased by 12 times (12.5, 4-38.9) compared with that in subjects without any infection and by 5 times (4.9, 2.2-10.9) if only one was present. CONCLUSIONS: After adjustment for confounders, seropositivity to both Cp and CMV infections is associated with the diagnosis of premature MI. The combination of both infections is associated with an enhanced inflammatory response and a markedly increased risk of premature MI.

Adult↗

Ulcerated hemangiomas: clinical characteristics and response to therapy.

BACKGROUND: Hemangiomas represent the most common benign tumor of infancy, with ulceration its most frequent complication. OBJECTIVE: Our purpose was to review our experience with this challenging problem by evaluating the clinical features, management, and therapeutic responses of ulcerated hemangiomas. METHODS: A retrospective analysis of ulcerated hemangiomas at the University of California, San Francisco outpatient pediatric dermatology clinics and Oakland Children's Hospital from 1987 to 1997 was performed. RESULTS: The medical records of 60 patients were examined. Forty-nine female and 11 male patients were seen with a female/male ratio of 4.5:1. The majority of ulcerated hemangiomas were of the plaque type (n = 50; 83%) and relatively large; 47 (78%) were larger than 6 cm(2). The perineum was the single most frequently involved site, affected in 20 cases (33%). Topical antibiotics, barrier creams, and bio-occlusive dressings were used in most cases. Systemic antibiotics were used in 26 cases (43%) for overt or presumed infection. Systemic corticosteroids were used in 21 children (37%), 5 of whom did not show a response. Intralesional triamcinolone was used in 7 cases (12%), with 4 showing definite improvement. The flashlamp pulsed-dye laser was the modality used in 22 children (37%), 11 (50%) of whom showed definite improvement, 4 (18%) who showed no significant response, and 1 (5%) who showed definite worsening. Interferon alfa-2a was required in 5 patients (8%), all of whom showed improvement without appreciable neurologic side effects. Immediate surgical excision was required in only 2 cases (3%). Pain control with oral acetaminophen, acetaminophen with codeine, and topical 2.5% lidocaine ointment was effective in managing the pain of lip and perineal hemangiomas, with no side effects noted. CONCLUSION: No one uniformly effective treatment modality was found, and frequently several were used concurrently. The decision to use specific therapies was dependent on the age of the patient, as well as the location, size, and stage of growth or involution of the hemangioma. Our approach to management included 4 major areas: local wound care, management of infection, specific therapeutic modalities (systemic and intralesional corticosteroids, flashlamp pulsed-dye laser, and interferon alfa-2a), and pain management.

Adrenal Cortex Hormones↗

Comparison of luteal phase profile in gonadotrophin stimulated cycles with or without a gonadotrophin-releasing hormone antagonist.

BACKGROUND: The aim of our study was to explore luteal phase hormone profiles in gonadotrophin-stimulated cycles with or without gonadotrophin-releasing hormone (GnRH) antagonist therapy during intrauterine insemination (IUI). Forty-one infertile couples were recruited in this randomized clinical study. METHODS: The 19 patients included in group A were treated for 21 cycles with recombinant FSH 150 IU/day starting from day 3 of the cycle and with the GnRH antagonist cetrorelix at the dose of 0.25 mg/day starting from the day in which a follicle with a mean diameter of > or =14 mm was seen at ultrasound scan. Cetrorelix was administered until human chorionic gonadotrophin (HCG) administration. The 22 patients included in group B were administered recombinant FSH alone at the same dosage for 27 cycles. RESULTS: The two treatment groups showed a similar increase in progesterone concentration during the luteal phase. In the mid-luteal phase (day 6 after HCG), oestradiol concentrations in group B were significantly higher compared with group A (P < 0.05) but the oestradiol:progesterone ratio was similar in the two groups. Serum LH was completely suppressed during the follicular phase only in group A, concomitantly with GnRH antagonist administration. A total of six pregnancies, all ongoing, were achieved (14.3% per patient and 12.2% per cycle), equally distributed in group A and in group B. CONCLUSION: GnRH antagonists can be safely administered in gonadotrophin-stimulated IUI cycles without luteal phase supplementation because no deleterious effects of GnRH antagonist administration were noted on luteal progesterone concentration or on the duration of the luteal phase.

Adult↗

Representation of serial order in humans: a comparison to the findings with monkeys (Cebus apella).

In a number of studies, serially organized behavior in humans has been examined using a procedure developed for use with pigeons and monkeys. There have been few direct comparisons, however, between the data collected with humans and that collected with nonhumans, and none with respect to the interesting latency effects noted with nonhumans. The purpose of this experiment was to make this comparison. Human subjects were trained to respond to five simultaneously presented stimuli (A, B, C, D, and E) in a specific order (A-->B-->C-->D-->E) and were then tested with all 10 pairwise combinations of the five stimuli, followed by all 10 triplet combinations of the five stimuli. Mirroring the findings with monkeys (Cebus apella), humans showed a first-item effect, a missing-item effect, and a symbolic-distance effect. These results suggest that during the course of learning the five-item serial-order task humans form an internal representation of the series and access that representation to guide their behavior.

Adolescent↗

[Cystic dysplasia of the testis: report of a case and review of the literature].

Cystic dysplasia of the testis (CDT) is a rare, benign and congenital lesion causing scrotal mass in pediatric population that can mimic testicular cancer. This lesion consists of cystic dilation of the rete testis and it is frequently associated with renal or genitourinary tract anomalies as renal agenesis and multicystic dysplasia of the kidney. This frequent presentation suggests that testicular cystic dysplasia is associated with a defect of the metamesonephric system in particular with a defect in the connection between the efferent ducts derived from the mesonephros and the rete testis tubules derived from the gonadoblastoma. The role of ultrasound is of primary importance for clinical diagnosis and follow-up of untreated forms. The sonographic appearance of CDT consists of multiple cysts in the mediastinum testis. The cysts range in size from microscopic to several millimetres and may involve the whole testicular parenchyma or have a focal aspect. If the cysts are tiny, the ultrasound must be able to distinguish between CDT and testicular microlithiasis, a potential premalignant condition. Today it is possible thanks to high frequency 7.5 to 10 mHz probes. In the past orchiectomy has been considered as the treatment of the choice for CDT. Today, non operative management of CDT represents an effective alternative option in these patients and the primary benefit of this approach is the preservation of endocrine function and spermiogenic activity. However, the natural history of untreated CDT and its effect on normal testicular tissue are still unknown, therefore long-term follow-up is recommended.

Child, Preschool↗