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Biomedical subjects

M Malaguarnera

Publications and source records attributed to M Malaguarnera.

At least 73 records · Page 4Linked to original sources

Danazol induced cholestasis: pathogenetic hypothesis.

Numerous mechanisms have been proposed to account for deficient bilirubin excretion and the pathogenesis of estrogen and steroid (danazol) induced intrahepatic cholestasis. Our hypothesis is based on the fact that danazol is administered in the treatment of pulmonary emphysema because it stimulates synthesis of alpha-1 antitrypsin and that other estrogen glucuro-conjugated metabolites are P-glycoprotein substrates. We believe that genetic alterations of alpha-1 antitrypsin and P-glycoprotein, either alone or in association with known pathogenetic mechanisms, may explain the onset of danazol induced cholestasis and justify the difference in its varying duration and intensity.

Cholestasis, Intrahepatic↗

[Immunologic diseases and hepatitis C virus].

Active chronic hepatitis may be associated with various immunologic diseases. In the Mediterranean area and to a lesser extent elsewhere, hepatitis C virus, has often been detected in patients affected by mixed cryoglobulinemia, membranoproliferative glomerulonephritis, polyarteritis nodosa autoimmune type 2b hepatitis, Hashimoto's disease, Sjögren's syndrome and lichen ruber planus. These findings should not be considered fortuitous due to the elevated prevalence of autoantibodies and immunologic abnormalities observed in hepatitis C patients compared with subjects presenting other liver diseases. The pathogenetic evaluation of the association between these immunologic diseases and chronic hepatitis C has led us to suggest that diverse virus C and host induced factors may play a fundamental role in determining these immunologic diseases.

Disease Susceptibility↗

Mapped auditory evoked potentials before and after interferon treatment.

Neurotoxicity induced by interferon (IFN) is revealed by neurobehavioral changes, such as irritability, somnolence, lack of motivation, and delayed ideation. As these side effects persist throughout IFN-alpha treatment, we studied cerebral mapped auditory evoked potentials (MAEP) in 20 hepatitis C virus antibody (HCV Ab)-positive chronic active hepatitis patients before and after administration of leukocyte IFN-alpha (i.m. 3,000,000 IU). Some of the main components of MAEP, such as morphology, latency, and power spectra, were altered before IFN injection. These parameters changed 7 h after administration as revealed by increased quality and quantity of acoustic signal reaching the brain cortex and appearance of physiologic waves in patients with mild/intermediate liver disease. These effects revealed 48 h after IFN administration.

Adult↗

Hysterical neurosis of the conversion type: therapeutic activity of neuroleptics with different hyperprolactinemic potency.

To show a possible correlation between drug-induced hyperprolactinemia and improvement of hysterical neurosis of the conversion type, we followed 18 patients monitoring clinical somatic and psychic symptoms as well as serum prolactin levels. Six patients were treated with haloperidol and 12 with sulpiride; after 2 months sulpiride was administered at half the daily dose to 6 patients previously treated with the same drug. Clinical evaluation showed that sulpiride treatment led to a greater improvement compared to the haloperidol group. The different effectiveness of treatment could be explained by the different hyperprolactinemic potency. The therapeutic efficacy of neuroleptics suggests also that hyperactivity of dopaminergic transmission is involved in the pathophysiology of hysterical neurotic symptoms.

Adult↗

Lipoprotein(a) in cirrhosis. A new index of liver functions?

Over the last few years, lipoprotein(a) [Lp(a)] levels have been investigated because clinical studies have related it to increased cardiovascular and cerebrovascular risk. Although it is known that serum Lp(a) concentrations are controlled genetically, little is known about its metabolism. We studied changes in the lipid profile and Lp(a) values in 57 patients (34 males and 23 females) affected by cirrhosis of the liver subdivided into Child's classes in order to assess whether this lipoprotein is sensitive to reduced liver protein synthesis. The patients presented with low total cholesterol, normal HDL-cholesterol (HDL-c), LDL-cholesterol (LDL-c), triglycerides, apoprotein A1 (Apo-A1) and apoprotein B100 (Apo-B100) concentrations, while Lp(a) concentrations seemed elevated. Grouping the patients into Child's classes revealed that all the lipid parameters investigated reduced as the disease progressed. Lp(a) reduced significantly between Child's Classes I and II and seems to be correlated with the severity of cirrhosis and the clinical worsening of the patients' conditions. These findings suggest that Lp(a) is not only an index of atherosclerosis risk, but also plays a role in monitoring liver functions.

Aged↗

[Role of interleukin 6 in hepatocellular carcinoma].

Interleukin 6 (IL-6) is a pleiotropic cytokine which possesses a broad spectrum of action in diverse pathological conditions. It is mainly produced and metabolised in the liver where it carries out one of its best known actions in the mediation of the acute phase response. We studied its behaviour in hepatocellular carcinoma to evaluate its clinical prognostic role. We determined serum IL-6 concentrations in 39 patients with hepatocarcinoma (27 males and 12 females) and 25 healthy controls (15 males and ten females). Our results showed a significant increase in serum IL-6 concentrations in hepatocarcinoma subjects compared with controls (P < 0.005) and an elevated positive correlation (r = 0.616) between IL-6 and size of the hepatocarcinoma. Our study demonstrated that IL-6 is able to influence hepatocarcinoma progression by acting as an autocrine tumoral growth factor and depleting immune surveillance.

Adult↗

Electrophysiological alterations in hepatic encephalopathy detected by brain mapping.

Analogical electroencephalogram has been used to study electric alterations in the brain during liver encephalopathy. We adopted digital technique brain mapping to study the electric background activity in the brain and to evaluate the diagnostic and prognosis usefulness of this technique compared with the methods routinely used in this disease. We studied 18 patients with liver cirrhosis and varying degrees of liver encephalopathy and 7 healthy control subjects to assess correlation between the severity of encephalopathy and abnormal electric activity in the brain, and to detect the main differences between the brain mapping findings obtained in the two groups. The findings revealed an overall reduction in the rhythm, increased amplitude and anomalous distribution of the waveforms in the cirrhotic patients. Although similar results have already been reported, brain mapping furnished prompt and more easily visualised findings. Moreover, brain mapping facilitated detailed analysis of wave amplitude, frequency and topographic location indicating that this technique is a valid tool in diagnosing brain disorders.

Brain Mapping↗

Interleukin-6 in hepatitis C cirrhosis.

Interleukin-6 (IL-6) is a pleiotropic cytokine involved in numerous diseases but the correlation between liver fibrosis and IL-6 role is not clear. We studied IL-6 levels in 50 HCVAb+ patients with liver cirrhosis (grouped into A, B and C, Child classes) and in 27 healthy control subjects. IL-6 serum levels were significantly increased in the former (p < 0.005) suggesting that IL-6 stimulates and sustains liver fibrosis. In cirrhotic subjects, the rise in IL-6 serum levels is due to impaired hepatic clearance of this cytokine, while its production remains steady.

Adult↗

[Erythropoietin in hepatocellular carcinoma].

Hemopoietic alterations may occur during tumoral diseases, determining anemia. In most cases, serum EPO levels were lower than normal values. Hepatocellular carcinoma (HCC), one of the most frequent malignancies world-wide, is often characterized by mild anemia and increased serum EPO levels. We studied 30 HCC patients and 20 healthy subjects. We found that HCC patients presented higher serum EPO levels than healthy controls. In HCC patients, there was a significant inverse correlation between serum EPO levels and red blood cell count or hemoglobin levels. We postulated that the elevated serum EPO levels observed in these patients may be due to reduced hepatic clearance of EPO, and to the influence of cytokine-mediated inflammatory factors.

Aged↗

Lipoprotein(a) concentration in patients with chronic active hepatitis C before and after interferon treatment.

Patients with chronic active hepatitis C show low lipoprotein(a) (Lp[a]) values. We studied the changes in Lp(a) levels caused by treatment with interferon in 24 patients (9 men and 15 women; mean age, 56.8 +/- 7.3 years) affected by chronic active hepatitis C. Fifteen healthy subjects (6 men and 9 women; mean age, 57.4 +/- 10.3 years) were used as controls. All of the patients with chronic hepatitis C were treated with intramuscular interferon, 3 million units 3 times per week for 6 months. These patients had lower baseline serum Lp(a) concentrations than the controls (4.8 +/- 3.8 mg/dL vs 13.4 +/- 10.3 mg/dL, respectively; P = 0.0007). A significant increase in Lp(a) levels (6.6 +/- 7.2 mg/dL; P = 0.05) occurred after 6 months of treatment in patients with chronic active hepatitis C. Only complete responders presented a significant increase in Lp(a) values (P = 0.01). We believe that increased Lp(a) levels represent an expression of improved liver functions.

Aged↗

Erythropoietin in healthy elderly subjects.

The effects of aging on erythropoiesis and the factors regulating it are not well known. Erythropoietin (Epo) is a specific growth factor for the erythroid line and is mainly produced by the kidney. As data on the effects of aging on Epo are discordant we studied serum Epo concentrations in a group of apparently healthy subjects divided into age classes in order to evaluate age-related modifications and correlations with hemoglobin (Hb) and red blood cells (RBC). Our results revealed that Epo values were correlated with age. Epo was higher in the over 65 years age classes than observed in control subjects. We believe that the elevated Epo values in the latter age class may be required to maintain Hb and RBC within normal range.

Journal Article↗

Successful aging in centenarians: myths and reality.

The term "successful aging" appeared in the first issue of "The Gerontologist" in 1961. During the successive years, this expression has changed its meaning. Nowadays, successful aging means "absence of diseases and disabilities, maintenance of high levels of physical and cognitive abilities, preservation of the social and productive activities". It has become a common opinion that the centenarians may represent the prototypes of the successful aging. This motivated our work to study the clinical, psychical, and functional aspects in a centenarian group, verifying the real autonomy, instrumental capacities, and working abilities. Our study pool consisted of 602 centenarians, who were also subjects of then epidemiological studies of the Italian Multicenter Studies on Centenarians (IMUSCE). All subjects underwent a clinical-anamnestic evaluation, cognitive-functional tests by means of the mini mental state examination (MMSE), the independence index in activities of daily living (ADL), the instrumental activities of daily living (IADL) scale. The centenarians were classified in three groups, according to the criteria elaborated previously by us, based on their psychophysical status and autonomy, as follows. Group A: centenarians in good health status; Group B: centenarians in an intermediate health status. Group C: centenarians in bad health status. Group A represented 20.0% of the total pool, Group B amounted to 33.4%, and the Group C was 46.6%. The centenarians of Group A presented normal ADL values, and 47.9% of them were autosufficient in all functions; 5.7% of them were independent in all IADL items. These data confirm that the centenarians of Group A are free of invalidating chronic diseases, are autonomous, maintain good physical and cognitive capacities, however, have not maintained any social or productive activities. Therefore, they cannot be considered as prototypes of successful aging.

Activities of Daily Living↗

Correlation between the bone mass, psychometric performances, and the levels of autonomy and autosufficiency in an elderly Italian population above 80 years of age.

This study was aimed at evaluating the correlation between bone mineral density (BMD) and the psychophysical health status in an elderly study population (62 subjects, mean age 84+/-5 years, 21 males and 41 females), institutionalized (Group A) in various structures of Pozzallo, a marine locality of the Ragusa Province in Sicily. BMD was measured by using ultrasonography of the calcanear area (T-score, Z-score, stiffness). The alterations of the cognitive and affective spheres as well as the levels of autonomy and autosufficiency were estimated by means of psychometric scales like mini-mental state examination (MMSE), geriatric depression scale (GDS), activities of daily living (ADL) and instrumental activities of daily living (IADL). Other biological, social and health-related factors, such as age, sex, body weight and height, nutritional and drug-taking habits, physical activity and previous pathologies, were also considered. These variables were compared to those obtained in a similar, but non-institutionalized controls (Group B) of 63 subjects (mean age 85+/-2 years, 27 males and 36 females), being similar in number and age distribution, frequenting the Geriatric Day Center of the same locality. Statistical analysis revealed significant differences between Groups A and B: the BMD was considerably lower, but also the cognitive and affective performances were strongly reduced in Group A. These findings can be attributed to decreased psychosensorial stimuli and lost interest of the patients in Group A, resulting in a lower physical activity, accompanying the depressive state, and may represent the first signs of a decreased intellectual performance, which can later be transformed into dementia. The functional abilities and the levels of autonomy are also reduced, risking the loss of autosufficiency. Also, the drug usage was different in Group A: more sedative-hypnotics and anticoagulants were consumed. As regards the polymorbidities, arterial hypertension and consequent chronic renal failure, hepatopathies and thyreopathies were most frequent, these latter two being more frequent in the Group A.

Journal Article↗

Alendronate reduces the daily consumption of insulin (DCI) in patients with senile type I diabetes and osteoporosis.

The use of Alendronate for the treatment of senile diabetes with osteopenia or osteoporosis is a common practice today, although the reasons for the success of this treatment are not completely understood. We investigated 40 elderly female patients, over 70 years of age, divided in two Groups (A and B) 20 cases of each, with insulin-dependent senile diabetes and fair metabolic balance, with an average disease duration of 30 +/- 4 years. They all had osteoporosis shown by the mean T-score of bone mineral densitometry. The Groups were treated as follows, Group A with 10 mg/day of Alendronate per os, with morning fasting plus a supplementation of calcium and vitamin D3, while the Group B received only calcium and vitamin D3 per os. Bone mineral density (BMD) expressed in mg/cm2, and in terms of T-score and Z-score at the spine (L1-L4) was monitored over time after 12 and 24 months, using dexa technique with a Lunar DPX densitometer. Moreover, the variation of daily consumption of insulin (DCI) of all the study population was calculated 12 and 24 months after the start of treatments. The data of Group A showed an improvement of osteoporosis, as evidenced by the increase of BMD at both times of measurement, accompanied by a significant reduction in the DCI (-21.6% by the 12th month, and -36.2% by the end of the observation period). In the Group B only small, statistically insignificant changes were observed in both the BMD and DCI. The most plausible explanation of reduction of DCI in Group A seems to be that Alendronate has improved the clinical symptoms of osteoporosis (pain, rigidity, and reduction of movements) through its action on the bone mass recovery and slowing down the bone turnover and under these conditions the diabetic patients improved their own physical performance. The better and more extensive movements certainly produced a reduction in the DCI, since a correct and adequate physical activity does contribute to an improved glucose metabolism.

Journal Article↗

The prevalence of various arrhythmias in normotensive and hypertensive elderly patients.

The prevalence of the most frequent arrhythmias was studied in a geriatric day hospital. Patients older than 65 years have been considered, of them 118 were normotensive and 56 hypertensive subjects. Comparison of the two groups revealed no statistically significant difference either in the frequency of occurrence or in the type of arrhythmias. Dividing the hypertensive patients in the Lown's classes, only those of class 3 or over displayed a considerably higher frequency of arrhythmias than the normotensive subjects. The results demonstrate the age-dependent increase of the prevalence of arrhythmias in general, and the increased occurrence of complex ventricular types in the hypertensive subjects.

Journal Article↗