A case of silicosis associated with Crohn's disease. Diagnostic and pathogenetic considerations.

A case of silicosis associated with Crohn's disease is reported. Symptoms, radiological and endoscopical findings suggested Crohn's disease in a man, who had worked as ceramist and in whom silicosis was diagnosed four years earlier. The authors, after presenting the clinical and diagnostic features of the patient, discuss the similarity of some pathogenetic features of the two diseases. They hypothesize a common pathogenetic immunological defect in the two diseases, probably caused by inhalation of silica.

Clinical investigation of the effect of ketanserin: a new antihypertensive drug.

The antihypertensive effect of a recently introduced antiserotoninic drug, ketanserin, was examined in a single-blind, placebo-controlled parallel group study in 28 patients with mild to moderate hypertension. Supine and standing blood pressure, electrocardiogram, heart rate and laboratory parameters of liver, kidney and bone marrow functions were checked before and after 3 months of treatment. After 12 weeks' treatment with ketanserin (20-40 mg twice a day), there was a highly significant reduction of both systolic and diastolic blood pressure, as compared to placebo in the supine position (p less than 0.0001/p less than 0.001). In the standing position, the reduction of systolic pressure was more significant than the diastolic pressure (p less than 0.0001/p less than 0.01). Eleven out of 28 hypertensive patients showed electrocardiographic evidence of left ventricular hypertrophy (LVH) according to the ECG criteria of Romhilt and Estes. Although a reduction of the mean point score for LVH as compared to placebo was observed in the ketanserin group, that difference was not statistically significant. These preliminary observations suggest a possible role of ketanserin in the regression of LVH due to essential hypertension.

Evaluation of the therapeutic efficacy and tolerability of levocarnitine propionyl in the treatment of chronic obstructive arteriopathies of the lower extremities: a multicentre controlled study vs. placebo.

The treatment of symptomatic chronic obstructive peripheral arteriopathies is a difficult task since it requires the prolonged administration of drugs which are often unable to correct the various pathogenetic factors reponsible for the disability. The authors, on the basis of recent studies demonstrating the rheological and vasoactive as well as metabolic activities of levocarnitine propionyl, have decided to use this substance in the treatment of arteriopathics affected by intermittent claudication. Levocarnitine propionyl administered orally to 142 arteriopathics affected by intermittent claudication was responsible for a marked increase in initial as well as absolute walking distances. It is particularly important to note that these clinical results were obtained primarily due to the metabolic activities of levocarnitine propionyl.

The therapeutic effect of L-carnitine in patients with exercise-induced stable angina: a controlled study.

An investigation on the therapeutic effect of L-carnitine was performed at three different centres and included two hundred patients, 40 to 65 years of age, with exercise-induced stable angina. In one hundred randomly selected patients the drug was administered orally in daily doses of 2 g in addition to the already instituted therapy, and the effect studied over a 6-month period. Compared with the control group, these patients showed a significant reduction in the number of premature ventricular contractions (PVC) at rest, as well as an increased tolerance during ergometric cycle exercise as demonstrated by an increased maximal cardiac frequency, increased maximal systolic arterial blood pressure and therefore also increased double cardiac product and reduced ST-segment depression during maximal effort. This was accompanied by improvement in cardiac function and resultant performance, as shown by an increase in the number of patients belonging to class I of the NYHA classification and a reduction in the consumption of cardioactive drugs. Laboratory analysis showed an improvement in plasma lipid levels. The authors conclude, after having discussed the particular metabolic mechanisms, that L-carnitine undoubtedly represents an interesting therapeutic drug for patients with exercise-induced stable angina.

Primary neoplasm in vesical diverticulum: comparison of four imaging methods.

In presenting the case of a 61-year-old man with a primary squamous carcinoma in a bladder diverticulum, the authors stress the usefulness of applying all the available modalities of imaging, since it has been found that a bladder diverticulum may harbor a neoplasm more often than a normal bladder.

Steady state pharmacokinetics of idebenone in patients with moderate hepatic impairment.

The kinetics of idebenone (45 mg twice daily p.o.) in 6 Caucasian chronic hepatopathic patients without portal hypertension were studied. The pharmacokinetic parameters were evaluated both for single (day 1) and multiple (day 10) administrations. These 6 patients showed a first order bi-compartimental kinetic curve for idebenone and for its metabolites, superimposable on the curves obtained from healthy volunteers. The C(max) parameters, tmax and bioavailability confirm the absence of accumulation. On day 12, 48 h after the last administration (performed on day 10), there was no evidence of residual drug. One of these patients was being treated with diuretics (chlorthalidone) and with perfusion fluids, including 5% glucose, and no interference was shown between the two drugs. There is no evidence of any particular side effect or alteration of the haematochemical parameters that could be thought to be drug related. This study confirms that idebenone at the dose of 90 mg/day p.o. administered to hepatopathic patients does not cause accumulation or toxicity.

Steady-state pharmacokinetics of idebenone in patients with moderate renal impairment.

Idebenone (45 mg twice daily) was administered to 7 patients with moderate renal impairment (creatinine clearance 21-40 ml/min) for 10 days. Standard pharmacokinetic parameters were computed on day 1 (single administration) and on day 10. On day 1 the mean of the maximum plasma concentration values (C(max)) was 364 ng/ml (standard deviation (S.D.) 100); time to C(max) (t(max)) was in the range of 1-2 h for 6 patients and 12 h for the remaining patient: the mean was 3 h (S.D. 3.99); the mean area under the plasma concentration vs. time curve (AUC) was 3005 ng h/ml (S.D. 1152). On day 10 the mean C(max) was 531 ng/ml (S.D. 355.3), the mean t(max) was 0.07 h (S.D. 0.19), the mean AUC was 3167 ng/ml (S.D. 2944) and the mean elimination half-life (t(1/2)) was 4.9 h (S.D. 1.1). Idebenone metabolites (QS-4, QS-6 and QS-10) showed a kinetic profile similar to the parent compound, with pharmacokinetic parameters comparable to idebenone for QS-4 and lower than idebenone for QS-6 and QS-10. Idebenone was metabolized and easily excreted and no accumulation was observed for the compound and its metabolites. No significant modification of the biohumoral indexes and vital signs and no adverse reactions were observed.

Clinical efficacy of picotamide in long-term treatment of intermittent claudication.

The clinical efficacy of picotamide was investigated in a randomized, double-blind, placebo-controlled study in patients with peripheral occlusive arterial disease of the lower limbs at functional stage II of the Fontaine classification. Forty patients with a history of claudication for at least six months were admitted to the study and were given either 3 x 300 mg tablets of picotamide (20 subjects) or three identical placebo tablets (20 subjects) for six months. The two groups of patients were similar in regard to clinical features and potential risk factors. At the end of treatment painfree walking distance and systolic ankle-arm pressure ratio improved more in the picotamide than in the placebo group (p = 0.05). Systolic ankle pressure curves, determined before and after the six-month treatment, showed a positive trend to a higher postexercise ankle pressure and a faster return to the preexercise levels in the picotamide group; however, the difference was not statistically significant. Laboratory monitoring revealed a slight prolongation of bleeding time, a significant decrease in arachidonic acid-induced platelet aggregation, and an enhanced fibrinolysis with absence of interference with hemostasis in the picotamide group. One patient in the placebo group developed a major cardiovascular event (angina pectoris) during the study. These results indicate that picotamide is an effective drug that may modify the natural course of intermittent claudication and associated vascular problems.

Evaluation of the clinical efficacy of idebenone in patients affected by chronic cerebrovascular disorders.

This study evaluated the efficacy and tolerability of idebenone, a new neuroactive drug, in 33 patients aged from 50 to 80 years. They were affected by chronic cerebrovascular disease (CCVD) and their last cerebrovascular accident had taken place at least 3 months prior to enrollment. All these subjects presented a score within the range of the following psychometric scales: Hamilton Scale for Depression <24; Hachinski Dementia Score >/=18 and < 25; Mini Mental State >/=16 and

Long-term safety and efficacy of picotamide, a dual-action antithromboxane agent, in diabetic patients with carotid atherosclerosis: a 6-year follow-up study.

In a controlled, randomized, 6-year trial the safety and efficacy of picotamide, a dual-action antithromboxane agent, were assessed in 50 patients with type 2 diabetes mellitus at increased risk of thrombotic vascular events. The patients were randomized to two groups of equal size and received 900 mg picotamide daily or placebo. After phase I (double-blind; years 1 - 2), patients receiving placebo were treated, if necessary, with antiplatelet drugs (aspirin, ticlopidine) while members of the other group continued to receive 600 mg picotamide daily. In the course of the study 21 vascular events occurred: 16 in the group receiving placebo (fatal myocardial infarction, n = 7; non-fatal stroke, n = 3) and five in the group receiving drug (fatal myocardial infarction, n = 2) (P < 0.005; Fisher's exact test). One patient (placebo group) died of malignant disease. During the initial double-blind phase a total of nine vascular events was observed (six and three in the groups receiving placebo and drug, respectively). Picotamide treatment was well tolerated and no major side-effects were observed during the study periods.

[Diabetes and atherosclerosis: a follow-up echographic study of atherosclerotic carotid lesions]. / Diabete ed aterosclerosi: studio ecografico evolutivo delle lesioni aterosclerotiche carotidee.

A two years follow up on 105 diabetic patients and 50 normal subjects was carried out by high resolution real time echotomography, aiming to evaluate the prevalence and the evolutionary trends of carotid atherosclerotic plaques. The prevalence of atherosclerotic lesions was higher in diabetic patients than in normal subjects, and the most part of them showed an "intermediate" echographic pattern, minimal stenosis and regular surface. The results of the two years follow up indicate that the "soft" and the "hard" plaque types were those showing a more significant progression toward to the "mixed" type. "Hard" and "mixed" plaques, particularly those showing irregular surface, resulted most associated with higher degree of vessel stenosis. Four diabetic patients experienced three minor and one major ischemic events during the follow up; however all the patients had shown plaques with "intermediate" pattern, regular surface, and no signs of vessel stenosis progression. Further studies, performed for longer period of time with a higher number of patients are needed to evaluate the evolutionary trends of carotid plaques in diabetic patients and their relationship with clinical ischemic events.

POEMS syndrome: an Italian case with diagnostic and therapeutic implications.

A young Italian patient with a multisystem disorder and a solitary osteosclerotic bone lesion is described. His clinicopathological situation involved sensory-motor polyneuropathy, organomegaly, endocrine dysfunction, skin alterations, edema of the lower limbs and generalized lymphadenopathy. These features were consistent with the diagnosis of POEMS syndrome, reported primarily in Japanese patients. M components were not found in this patient's serum or urine. Bone marrow biopsy showed only a slight plasma cell infiltrate; histological study of the sural nerve evidenced a mixture of both axonal degeneration and segmental demyelinization. Lymph node biopsy revealed peculiar pathological changes resembling those of type II Castleman-like disease. A wide bone defect with osteosclerotic margins and trabeculation was evidenced in the right ilium. The relationship of these findings to plasma cell dyscrasias is discussed. After prednisone and local radiotherapy failed, the patient was treated with human recombinant interferon for 18 months. After three months of therapy he has experienced remarkable improvement of his neurological symptoms and almost complete recovery of organomegaly and lymphadenopathy. These improvements have continued to the present.

Socioeconomic status and hypertension in children of two state schools in Naples, Italy: preliminary findings.

Most epidemiologic studies have shown a relationship between high blood pressure and socioeconomic status in childhood. Systolic and diastolic pressure were measured in 296 schoolboys and 338 schoolgirls aged 10 to 13 years. The presence of known and suspected risk factors for hypertension was evaluated by a standardized questionnaire consisting of two sections: one completed by the subjects and another by their parents. Descriptive analysis showed a lack of association between socioeconomic background, parental educational levels and childhood hypertension, a relatively strong association between a sedentary style of life and hypertension (p less than 0.001) and a statistically significant influence of maternal or paternal history of hypertension or diabetes in the sample studied (p less than 0.05). However, when all the variables were assessed by multiple correspondence analysis, two nuclei of schoolchildren were delimited. One was composed of hypertensive children with family histories of hypertension and/or diabetes mellitus who lead sedentary lives, live in large dwellings with a low crowding index and whose parents are better educated. The second nucleus was composed of normotensive subjects with opposite characteristics. The data obtained indicate that there may be a relationship between blood pressure in children and the socioeconomic status and educational level of their parents and suggest that these factors may have an impact on the child's blood pressure at a relatively young age.