[Significance of "minor" genetic mutations in hereditary hemochromatosis: 2 case reports]. / Significato delle mutazioni genetiche "minori" nell'ambito dell'emocromatosi ereditaria: a proposito di due casi clinici.

We describe a case of homozygosity due to the substitution of aspartic acid with histidine at position 63 of the protein encoded by the gene (known as HFE) associated with hereditary hemochromatosis. Liver biopsy did not disclose stainable iron accumulation; serum ferritin was elevated (639 ng/mL), while the transferrin saturation index was within the normal range (38.1%). As the patient was affected by chronic hepatitis C virus, the high serum ferritin could be attributed to this disease, a frequent occurrence. We also describe a case of heterozygosity for both the substitution of tyrosine with cysteine at position 282 and the substitution of histidine to aspartic acid at position 63 (so-called "compound heterozygosity"). The patient had the typical biochemical abnormalities of iron overload: transferrin saturation index of 53.1% and elevated serum ferritin (658 ng/mL). The removal of > 5 g of iron by phlebotomies did not precipitate iron deficiency. Although the patient refused to undergo liver biopsy, clinical evidence alone enabled a diagnosis of hemochromatosis. These two cases concord with the present scientific orientation, i.e.: 1) homozygosity for the major mutation is associated with the phenotypical (clinical) picture of hemochromatosis, but compound heterozygosity also determines significant iron metabolism abnormalities; 2) homozygosity for the minor mutation does not appear to determine important phenotypical abnormalities.

Nephrotic syndrome from 5-ASA for ulcerative colitis? Complicated by carcinoma of the colon and sclerosing cholangitis.

A patient with nephrotic syndrome had been treated with mesalazine for ulcerative colitis, and also had a carcinoma of the colon and sclerosing cholangitis. This seemingly unrelated series of complications gives us the opportunity to review the problem of nephropathy in ulcerative colitis.

Italian multicenter study on the safety and efficacy of coenzyme Q10 as adjunctive therapy in heart failure. CoQ10 Drug Surveillance Investigators.

Digitalis, diuretics and vasodilators are considered the standard therapy for patients with congestive heart failure, for which treatment is tailored according to the severity of the syndrome and the patient profile. Apart from the clinical seriousness, heart failure is always characterized by an energy depletion status, as indicated by low intramyocardial ATP and coenzyme Q10 levels. We investigated safety and clinical efficacy of Coenzyme Q10 (CoQ10) adjunctive treatment in congestive heart failure which had been diagnosed at least 6 months previously and treated with standard therapy. A total of 2664 patients in NYHA classes II and III were enrolled in this open noncomparative 3-month postmarketing study in 173 Italian centers. The daily dosage of CoQ10 was 50-150 mg orally, with the majority of patients (78%) receiving 100 mg/day. Clinical and laboratory parameters were evaluated at the entry into the study and on day 90; the assessment of clinical signs and symptoms was made using from two-to seven-point scales. The results show a low incidence of side effects: 38 adverse effects were reported in 36 patients (1.5%) of which 22 events were considered as correlated to the test treatment. After three months of test treatment the proportions of patients with improvement in clinical signs and symptoms were as follows: cyanosis 78.1%, oedema 78.6%, pulmonary rales 77.8%, enlargement of liver area 49.3%, jugular reflux 71.81%, dyspnoea 52.7%, palpitations 75.4%, sweating 79.8%, subjective arrhytmia 63.4%, insomnia 662.8%, vertigo 73.1% and nocturia 53.6%. Moreover we observed a contemporary improvement of at least three symptoms in 54% of patients; this could be interpreted as an index of improved quality of life.

Italian multicenter study on the safety and efficacy of coenzyme Q10 as adjunctive therapy in heart failure (interim analysis). The CoQ10 Drug Surveillance Investigators.

Digitalis, diuretics, and vasodilators are considered standard therapy for patients with congestive heart failure, for which treatment is tailored according to the severity of the syndrome and the patient profile. Apart from the clinical seriousness, heart failure is always characterized by an energy depletion status, as indicated by low intramyocardial ATP and coenzyme Q10 levels. We investigated safety and clinical efficacy of coenzyme Q10 (CoQ10) adjunctive treatment in congestive heart failure, which had been diagnosed at least 6 months previously and treated with standard therapy. A total of 2500 patients in NYHA classes II and III were enrolled in this open noncomparative 3-month postmarketing drug surveillance study in 173 Italian centers. The daily dose of CoQ10 was 50-150 mg orally, with the majority of patients (78%) receiving 100 mg/day. Clinical and laboratory parameters were evaluated at the entry into the study and on day 90; the assessment of clinical signs and symptoms was made using from two- to seven-point scales. Preliminary results on 1113 patients (mean age 69.5 years) show a low incidence of side effects: 10 adverse reactions were reported in 8 (0.8%) patients, of which only 5 reactions were considered as correlated to the test treatment. After 3 months of test treatment the proportions of patients with improvement in clinical signs and symptoms were as follows: cyanosis 81%, edema 76.9%, pulmonary rales 78.4%, enlargement of the liver area 49.3%, jugular reflux 81.5%, dyspnea 54.2%, palpitations 75.7%, sweating 82.4%, arrhythmia 62%, insomnia 60.2%, vertigo 73%, and nocturia 50.7%.(ABSTRACT TRUNCATED AT 250 WORDS)

Plasma cholesterol and triglycerides in heroin addicts.

We examined total cholesterolemia, triglyceridemia, high density lipoproteins- (HDL) cholesterolemia, apolipoproteins A1 and B, body mass index, albuminemia and alanine aminotransferase in 60 heroin addicts. After comparing 23 control subjects with the heroin addicts the result was that the latter have significantly lower mean values of total cholesterolemia and of HDL-cholesterolemia and higher values of triglyceridemia. They also have significantly higher prevalences of cases of hypocholesterolemia and of hypo-HDL-cholesterolemia. Within the addict group there is no linear correlation between total cholesterolemia and body mass index; there is, however, an inverse linear correlation between total cholesterolemia and alanine aminotransferase. Therefore, the alterations found in the lipid pattern of heroin addicts are not due to malnutrition but hypothetically to liver diseases which are frequent in these patients.

A case of arthropathy and hypothyroidism during recombinant alpha-interferon therapy.

Late side effects of alpha-interferon therapy include some autoimmune diseases, such as thyroiditis. We present the case of a patient with severe chronic active hepatitis and hepatitis-C-virus positivity, who during alpha-interferon therapy developed an autoimmune thyroiditis and at the same time arthropathy with some characteristics of rheumatoid arthritis (several articular stations simultaneously affected, involvement of the hand joints and morning stiffness).

Contraceptive methods in the McCune-Albright syndrome.

We describe the case of a woman with McCune-Albright syndrome who had a pathological bone fracture while being treated with an oral contraceptive. In this syndrome the bone lesions contain estrogen and progesterone receptors. The possibility of progression of the bone lesions during pregnancy is well-known. We judge the use of oral contraceptives to be dangerous in this syndrome; the affected women must be orientated towards alternative contraceptive methods.

PIP: The authors describe the case of a woman with McCune-Albright syndrome who suffered a pathological bone fracture while being treated with an oral contraceptive (OC). In this syndrome, the bone lesions constrain both estrogen and progesterone receptors. The possibility of progression of these bone lesions during pregnancy is well-documented. The authors judge the use of OCs to be dangerous in this syndrome, and thus, the women affected by it must be directed to alternative contraceptive methods.

Chronic neutrophilic leukemia: description of a new case with karyotypic abnormalities.

A further case of chronic neutrophilic leukemia (CNL) is reported. On karyotype analysis of the bone marrow aspirate, all of the examined cells showed trisomy of chromosome 9 and partial deletion of the long arms of chromosome 20. This anomaly has never before been reported in CNL, and it could be directly associated to the disease.

[Value of some biological variables for the diagnosis of alcoholism in a hospital population]. / Valore di alcune variabili biologiche per la diagnosi di alcoolismo in una popolazione ospedaliera.

279 male patients consecutively admitted to a medical ward were interviewed about their drinking habits using a CAGE-like questionnaire and were subdivided into teetotallers, normal-, borderline-, heavy-drinkers. The mean values of the following laboratory tests resulted significantly different in heavy drinkers compared with the others: mean cell volume, gamma-glutamyl-transpeptidase, serum urea (BUN), SGOT, SGPT, total bilirubin. No significant difference was found for triglycerides, uric acid, albumin and gamma-globulins. Sensitivity, specificity, predictive values of positive test and negative test, "goodness" were calculated for each of the 6 above-mentioned tests. Each of them had a linear correlation (inverse for BUN, direct for the others) between amount of alcohol intake and level of the test.

Bile lipid composition and haemostatic variables in a case of high density lipoprotein deficiency (Tangier disease).

A 62-year-old man with clinical and biochemical findings consistent with homozygous Tangier disease is presented. Widespread atherosclerosis was present. Bile lipid analysis showed a low molar percentage of cholesterol with a low saturation index. The data suggest that high density lipoprotein cholesterol may act as a preferential precursor of biliary cholesterol. Coagulation and platelet studies indicated that the patient's platelets were hyper-responsive to aggregating agents and produced an increased amount of thromboxane B2. A platelet storage pool deficiency was also found.