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Circulating adhesion molecules may have a prognostic significance as markers of endothelial damage. Drugs which inhibit the renin-angiotensin system may be effective in reducing circulating or tissue adhesion molecules, albeit data available are scarce. The aim of the study was to investigate the effects of an angiotensin-converting enzyme (ACE) inhibitor, enalapril and a highly selective angiotensin receptor blocker, candesartan cilexetil, on circulating adhesion molecules in a large sample of patients with non-insulin-dependent diabetes mellitus (NIDDM). The study was comparative, multicenter, randomized and double blind, with two parallel groups.NIDDM patients with a diagnosis of mild (grade 1) essential hypertension were included in the study, at the end of a 2-week placebo run-in period. The primary end-point of the study was to evaluate changes of intercellular adhesion molecule-1 (ICAM-1) plasma levels during treatment. The secondary end-points were: changes in vascular cells adhesion molecule-1 (VCAM-1), von Willebrand factor (vWF), fibrinogen and plasminogen activator inhibitor-1 (PAI-1) circulating levels and of urinary albumin excretion rate (AER) as well; 129 patients were randomized: 66 in the candesartan group and 63 in the enalapril group, 118 of them completed the scheduled 24-week treatment period.Candesartan and enalapril equally reduced circulating level of ICAM-1 and exerted comparable effects on changes of other adhesion molecules and coagulation factors. A similar blood pressure-lowering effect was observed with the two drugs (candesartan: from 148/90 +/- 11/8 to 132/82 +/- 12/7 mmHg, P0.01, enalapril: from 148/91 +/- 12/8 to 131/85 +/- 14/6 mmHg, P0.01). Candesartan was more effective than enalapril in the reduction of albuminuria (P0.05 between treatments), although urinary protein excretion can be considered normal in the majority of patients. The two drugs were comparable in terms of adverse events reported.Candesartan and enalapril showed similar effects on blood pressure and on circulating adhesion molecules. In this study urinary protein excretion was reduced more by candesartan.

Hypertension and non insulin-dependent diabetes mellitus (NIDDM) are well-known risk factors for atherosclerotic disease. Intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) may exert a relevant role in the pathogenesis of atherosclerosis; their prognostic relevance has been recently demonstrated. The aim of the study was to investigate possible inter-relation between circulating adhesion molecule levels, carotid artery structure and endothelial function in 15 patients with NIDDM, as well as in 15 patients with both NIDDM and essential hypertension (NIDDM+EH) compared with 15 normal subjects (NS) and 15 euglycaemic patients with EH, matched for age, sex and body weight. All subjects were submitted to a biopsy of the gluteal subcutaneous fat. Small arteries were dissected and mounted on a micromyograph, and the media-to-lumen (M/L) ratio was then calculated. Carotid artery structure was investigated by Doppler ultrasound. Endothelial function was evaluated by investigation of the flow-mediated dilatation (FMD) of the brachial artery. ICAM-1 and VCAM-1 plasma levels were measured by ELISA. ICAM-1 and VCAM-1 plasma levels were significantly greater and FMD smaller in EH, NIDDM and NIDDM+EH than in NS, but no difference was observed among the three pathological groups. Carotid artery structural changes were more pronounced in NIDDM+EH. No significant difference was observed among NIDDM, EH and NS. The M/L ratio of subcutaneous small resistance arteries was significantly greater in NIDDM+EH than in NIDDM or EH. NS had a smaller M/L ratio than the other groups. Significant correlations were observed between ICAM-1 plasma levels and indices of carotid artery structure in diabetic patients. However, the relations were close only in NIDDM+EH. In conclusion, our data suggest that NIDDM+EH may present more pronounced vascular structural alterations than NIDDM, and that adhesion molecules plasma levels are closely inter-related with carotid artery structural alterations, at least in NIDDM+EH, but not with M/L ratio of small resistance arteries.

We have evaluated the effects of an ACE inhibitor, enalapril (ENA) and of an angiotensin II receptor blocker, losartan (LOS), administered either at hypotensive or non-hypotensive dosage, on the cardiac and renal structure of spontaneously hypertensive rats (SHR). Forty-eight rats were included in the study: eight SHR were treated with low-dose (ld, 1 mg/kg/day) ENA; eight with low-dose (ld, 0.5 mg/kg/day) LOS; eight with high-dose (hd, 25 mg/kg/day) ENA; eight with high-dose (hd, 15 mg/kg/day) LOS; while eight Wistar-Kyoto (WKY) and eight SHR were kept untreated (unt). Treatment was given from the 4th to the 12th week of age. Systolic blood pressure (SBP) was measured non-invasively every week. The left ventricular weight to body weight (RLVM) and the left + right kidney weight (RKW) to body weight was measured, and the cardiac and glomerular interstitial collagen content was evaluated using sirius red staining and image analysis. In addition, cardiac metalloproteinases activity (43 kDa MMP, MMP-2, and MMP-9) was evaluated by zymography. A significant reduction in RLVM was observed in SHR given ENA hd or LOS hd. Cardiac collagen was significantly reduced in SHR ENA hd and SHR LOS hd as well as in SHR LOS ld, but not in SHR ENA ld. The 43 kDa MMP collagenase activity was greater in WKY unt compared with SHR unt, being normalized only in SHR ENA hd. The gelatinase activity of MMP-9 showed a trend similar to 43 kDa MMP, but differences between SHR and WKY unt were only of borderline statistical significance. No difference among groups was observed in MMP-2 activity. No significant differences in RKW was observed between groups. However, the collagen content in the glomerular perivascular space was significantly reduced in all treated groups, including those given ld, compared with SHR unt. In conclusion, LOS and ENA showed a similar preventive effect on the increase of RLVM in SHR, but, at least in part, different effects on the extracellular matrix in different organs, being cardiac collagen less sensitive to low dose (ld) ACE inhibition.

Objective Arterial hypertension is frequently associated with the presence of endothelial dysfunction in human subcutaneous small resistance arteries, as evaluated by responses to acetylcholine or bradykinin; however it is not known whether patients with diabetes mellitus show similar alterations. Therefore, we have investigated endothelial function in subcutaneous arteries of normotensive subjects (NT), of patients with essential hypertension (EH), of patients with non-insulin-dependent diabetes mellitus (NIDDM), as well as of patients with both essential hypertension and non-insulin-dependent diabetes mellitus (NIDDM + EH). Patients and methods All subjects were submitted to a biopsy of the subcutaneous fat. Small arteries were dissected and mounted on a micromyograph. The media to lumen ratio (M/L) was calculated. A concentration-response curve to acetylcholine, to bradykinin as well as to the endothelium-independent vasodilator sodium nitroprusside were performed. We also evaluated the contractile response to endothelin-1. Intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule 1 (VCAM-1) plasma levels were also measured. Results The vasodilatation to acetylcholine and bradykinin (but not to sodium nitroprusside) was significantly and similarly reduced in EH, in NIDDM, and in NIDDM + EH compared with NT. The contractile response to endothelin-1 was similarly reduced in EH, in NIDDM and in NIDDM + EH. Plasma ICAM-1 and VCAM-1 concentrations were higher in EH, NIDDM and NIDDM + EH than in NT. Conclusions An evident endothelial dysfunction was detected in patients with NIDDM, and the simultaneous presence of EH did not seem to exert an additive effect. The contractile responses to endothelin-1 were reduced possibly as a consequence of ETA receptor down-regulation.

Background —It is not presently known whether non–insulin-dependent diabetes mellitus (NIDDM) is associated with the presence of structural alterations in small arteries or whether the combination of hypertension and NIDDM may have an additive effect on endothelial dysfunction. Therefore, we investigated subcutaneous small arteries in 12 normotensive subjects (NT group), 18 patients with essential hypertension (EH group), 13 patients with NIDDM, and 11 patients with NIDDM and EH (NIDDM+EH group). Methods and Results —Subcutaneous small arteries were evaluated by a micromyographic technique. The internal diameter, the media-to-lumen ratio, remodeling and growth indices, and the collagen-to-elastin ratio were calculated. Concentration-response curves to acetylcholine, bradykinin, the endothelium-independent vasodilator sodium nitroprusside, and endothelin-1 were performed. The media-to-lumen ratio was higher in the EH, NIDDM, and NIDDM+EH groups compared with the NT group. EH patients showed the presence of eutrophic remodeling, whereas NIDDM and NIDDM+EH patients showed 40% to 46% cell growth. The collagen-to-elastin ratio was significantly increased in the EH and NIDDM+EH groups compared with the NT group. The vasodilatation to acetylcholine and bradykinin was similarly reduced in EH, NIDDM, and NIDDM+EH groups compared with the NT group. The contractile responses to endothelin-1 were similarly reduced in EH, NIDDM, and NIDDM+EH patients. Conclusions —Our data suggest that the effects of NIDDM and EH on small artery morphology are quantitatively similar but qualitatively different and that the presence of hypertension in diabetic patients has little additive effect on small artery morphology and none on endothelial dysfunction.

Today, osteitis fibrosa cystica is seldom present in primary hyperparathyroidism while it is mainly observed in uraemic osteodystrophy. We describe the case of a 54-year-old woman who was found to have huge bone cysts due to osteitis fibrosa cystica in the long bones. A parathyroid adenoma was identified and removed. Coeliac disease and Turner syndrome were diagnosed. Metabolic bone disease due to secondary hyperparathyroidism is common in coeliac disease; however, osteitis fibrosa cystica has not yet been described.

Ten patients (mean age, 49 ± 14 years) with heterozygous familial hypercholesterolemia who had high levels of lipoprotein (Lp)(a) (>30 mg/dl) and were receiving chronic treatment with simvastatin were treated with six capsules a day of fish oil for 4 weeks. Each 1-gm fish oil capsule contained almost 850 mg of omega-3 fatty acids with a ratio of eicosapentaenoic acid:docosahexaenoic acid of 1:1; the total daily dosage of omega-3 fatty acid was 5.1 gm/day. After 2 and 4 weeks of fish oil supplementation, mean serum Lp(a) levels did not change significantly (baseline, 67 ± 29 mg/dl; week 2, 68.3 ± 35 mg/dl; week 4, 60.6 ± 26 mg/dl). Triglyceride levels decreased by 23% after 2 weeks (from 1.355 ± 0.38 mmol/L to 1.05 ± 0.35 mmol/L) and by 33% after 4 weeks (to 0.91 ± 0.18 mmol/L) ( P P

Structural alterations of subcutaneous small resistance arteries are associated with a worse clinical prognosis in hypertension and noninsulin-dependent diabetes mellitus (NIDDM). However, no data are presently available about the effects of antihypertensive therapy on vascular structure in hypertensive patients with NIDDM. Therefore, we have investigated the effect of an angiotensin-converting enzyme inhibitor, enalapril, and a highly selective angiotensin receptor blocker, candesartan cilexetil, on indices of subcutaneous small resistance artery structure in 15 patients with mild hypertension and NIDDM. Eight patients were treated with candesartan (8 to 16 mg per day) and 7 with enalapril (10 to 20 mg per day) for 1 year. Each patient underwent a biopsy of the subcutaneous fat from the gluteal region at baseline and after 1 year of treatment. Small arteries were dissected and mounted on a micromyograph and the media-to-internal lumen ratio was evaluated; moreover, endothelium-dependent vasodilation to acetylcholine was assessed. A similar blood pressure-lowering effect and a similar reduction of the media-to-lumen ratio of small arteries was observed with the 2 drugs. Vascular collagen content was reduced and metalloproteinase-9 was increased by candesartan, but not by enalapril. Changes of circulating indices of collagen turnover and circulating matrix metalloproteinase paralleled those of vascular collagen. The 2 drugs equally improved endothelial function. In conclusion, antihypertensive treatment with drugs that inhibit the renin-angiotensin-aldosterone system activity is able to correct, at least in part, alterations in small resistance artery structure in hypertensive patients with NIDDM. Candesartan may be more effective than enalapril in reducing collagen content in the vasculature.

We have evaluated the effects of different doses of an angiotensin-converting enzyme (ACE) inhibitor, enalapril (ENA) and of an angiotensin II type 1 receptor blocker olmesartan (OLM), on extracellular matrix of the heart, kidney, aorta and mesenteric artery of spontaneously hypertensive rats (SHR). Forty SHR and eight Wistar-Kyoto controls (WKY) were included in the study. Eight SHR were treated with high-dose OLM 15 mg/kg per day, eight with high-dose ENA 25 mg/kg per day, eight with low-dose OLM 1 mg/kg per day and eight with low-dose ENA (2 mg/kg per day). Eight SHR and eight WKY were kept untreated as controls. Treatment was from age 4 to 12 weeks. Systolic blood pressure (SBP) was measured non-invasively every week. The left ventricular weight to body weight (RLVM) was measured, and the cardiac, aortic and glomerular interstitial collagen content was evaluated using Sirius red staining and image analysis. Mesenteric small arteries were dissected and mounted on a micromyograph, and the media:lumen ratio (M/L) was calculated. Collagen subtypes were evaluated by polarized light microscopy. The SHR treated with high-dose OLM or ENA showed a normalization of SBP. The RLVM was significantly increased in untreated SHR compared with untreated WKY, whereas significantly lower values were observed in the groups of SHR treated with high-dose OLM or ENA. A significant increase in cardiac and glomerular collagen content was observed in untreated SHR. Both high- or low-dose OLM and ENA normalized collagen content in the heart and the kidney. Both high-dose OLM and high-dose ENA normalized M/L ratio; however, OLM proved to be more effective than ENA in normalizing collagen pattern. In fact, aortic collagen content was normalized by both high-dose and low-dose OLM, but only by high-dose ENA. In conclusion, both OLM and ENA were significantly and equally effective in the prevention of cardiac and renal damage in SHR, whereas OLM was more effective than ENA in terms of effects on vascular extracellular matrix.

Today, osteitis fibrosa cystica is seldom present in primary hyperparathyroidism while it is mainly observed in uraemic osteodystrophy. We describe the case of a 54-year-old woman who was found to have huge bone cysts due to osteitis fibrosa cystica in the long bones. A parathyroid adenoma was identified and removed. Coeliac disease and Turner syndrome were diagnosed. Metabolic bone disease due to secondary hyperparathyroidism is common in coeliac disease; however, osteitis fibrosa cystica has not yet been described.

BACKGROUND AND AIM: Increased vascular resistance is a hallmark of hypertension and involves structural alterations, which may entail smooth muscle cell hypertrophy or hyperplasia, or qualitative or quantitative changes in extracellular matrix (ECM) proteins. Since the renin-angiotensin-aldosterone system modulates these changes, we investigated the effects of 8 weeks of treatment with an angiotensin-converting enzyme (ACE) inhibitor, ramipril (RAM), or a dual ACE and neutral endopeptidase (NEP) inhibitor, MDL-100240 (MDL), on mesenteric small artery structure and ECM proteins in mRen2-transgenic rats (TGRs), an animal model of hypertension with severe cardiovascular damage. MATERIALS AND METHODS: Thirty-five 5-week-old rats were included in the study: six TGRs received RAM; five TGRs RAM + the bradykinin receptor inhibitor, icatibant; six TGRs, MDL; and five TGRs MDL + icatibant, while eight TGRs and five normotensive Sprague-Dawley controls were kept untreated. Mesenteric small arteries were dissected and mounted on a micromyograph. The media-to-lumen ratio (M/L) was then calculated. Vascular metalloproteinase (MMP) content was evaluated by zymography. RESULTS: In untreated TGRs severe hypertension was associated with inward eutrophic remodelling of small arteries. Both RAM and MDL prevented the increase in blood pressure and M/L and decreased MMPs. Icatibant blunted the effect of MDL on BP, M/L and MMPs. CONCLUSIONS: Changes in collagenase activity induced by ramipril and MDL are associated with prevention of small artery structural alterations in TGRs. Furthermore, MDL-induced enhancement of bradykinin could play a role in both the prevention of vascular structural alterations and in the stimulation of MMPs.

Structural alterations of small resistance arteries in patients with essential hypertension (EH) are mostly characterized by inward eutrophic remodeling. However, we have observed the presence of hypertrophic remodeling in patients with renovascular hypertension, as well as in patients with noninsulin-dependent diabetes mellitus, suggesting a relevant effect of humoral growth factors on vascular structure. Growth hormone may stimulate in vitro proliferation of vascular smooth muscle cells. However, no data are presently available about small artery structure in acromegalic patients. Therefore, we have investigated the structure of subcutaneous small arteries in 12 normotensive (NT) subjects, in 12 EH subjects, and in 9 acromegalic patients (APs). All subjects underwent biopsy of the subcutaneous fat; then, small resistance arteries were dissected and mounted on a micromyograph. The normalized internal diameter, media thickness, media-to-lumen ratio, the media cross-sectional area together with remodeling, and growth indices were calculated. Demographic variables were similar in the three groups, except for blood pressure. The media-to-lumen ratio was significantly greater in EH and AP, compared with NT. No difference was observed between EH and AP. The media cross-sectional area was significantly greater in AP compared with EH and with NT. The calculation of remodeling and growth index suggests the presence of eutrophic remodeling in EH (growth index 0%) and of hypertrophic remodeling in AP (growth index 40%). In conclusion, our data suggest the presence of hypertrophic remodeling of subcutaneous small resistance arteries of AP, probably as a consequence of growth-stimulator properties of IGF-1.

A 66-year-old woman affected by sinus histiocytosis with massive lymphadenopathy (Rosai-Dorfman disease) is described. She presented with renal and ovarian masses. Percutaneous fine-needle aspiration was performed. Histologic specimens showed numer ous histiocytes that contained lymphocytes or plasma cells in their cytoplasm. Strong reac tivity for histiocyte-associated antigens was diffusely present in these cells. She was treated with prednisone and cyclophosphamide; a partial remission was obtained. Int J Surg Pathol 2(4) :329-332, 1995

Background— The presence of structural alterations in the microcirculation may be considered an important mechanism of organ damage; however, it is not currently known whether structural alterations of small arteries may predict fatal and nonfatal cardiovascular events. Methods and Results— One hundred twenty-eight patients were included in the present study. There were 59 patients with essential hypertension, 17 with pheochromocytoma, 20 with primary aldosteronism, 12 with renovascular hypertension, and 20 normotensive patients with non-insulin-dependent diabetes mellitus. All subjects were submitted to a biopsy of subcutaneous fat. Small resistance arteries were dissected and mounted on an isometric myograph, and the tunica media-to-internal lumen ratio (M/L) was measured. The subjects were reevaluated after an average follow-up time of 5.4 years. Thirty-seven subjects had a documented fatal or nonfatal cardiovascular event (5.32 events/100 patients per year). In the subcutaneous small arteries of subjects with cardiovascular events, a smaller internal diameter and a clearly greater M/L was observed. Our subjects were subdivided according to the presence of an M/L greater or smaller than the mean and median values observed in the whole population (0.098) or mean value +2 SD of our normal subjects (0.11). Life-table analyses showed a significant difference in event-free survival between the subgroups. Cox’s proportional hazard model, considering all known cardiovascular risk factors, indicated that only pulse pressure ( P =0.009) and M/L ( P Conclusions— Our results strongly indicate a relevant prognostic role of structural alterations in small resistance arteries of a high-risk population.

Background Vascular structural alterations in small resistance arteries of patients with essential hypertension (EH) are mostly characterized by inward eutrophic remodeling. In fact, no difference in the smooth muscle cell volume (CV) between normotensive subjects (NT) and essential hypertensive patients was observed. However, experimental models of hypertension with chronic infusion of agonists of adrenergic receptors were characterized by the presence of smooth muscle cell hypertrophy or hyperplasia. Recently, we have observed the presence of vascular smooth muscle cell hypertrophy in patients with renovascular hypertension. Objective The aim of the study to investigate the structural characteristics of subcutaneous small resistance arteries of NT, of EH, and of patients with phaeochromocytoma (Phaeo). Patients and methods Thirty Phaeo, 30 NT and 30 EH were included in the study. A biopsy of subcutaneous fat was taken from all subjects. Small resistance arteries (relaxed diameter 160–280 μm) were dissected and mounted on a micromyograph and the media : lumen ratio was calculated. In nine Phaeo, nine NT and 13 EH the cell volume was measured by an unbiased stereological principle, the ‘disector’ method. Results No difference in smooth muscle cell volume was observed between groups. However, inward remodeling in Phaeo was less marked than in EH, although the increase in media : lumen ratio was similar compared with NT. However, the lack of changes in media cross-sectional area, compared with NT, suggest that there has been little hypertrophy, the changes observed thus being eutrophic. Conclusions Our data show, based on a reasonably large sample, that a pronounced activation of the adrenergic system is not associated with vascular smooth muscle cell hypertrophy or hyperplasia in humans. It is therefore possible that adrenergic mechanisms may have a relevant role in the development of eutrophic remodeling in small vessels.

The problem of heart failure (HF) has become a topic of great interest. Until recently, the use of beta-blockers in patients with HF was considered as a contraindication. Times have changed and the contraindicated drug is now an advised and preferred one to be used in HF patients with certain advised recommendations for its use in a safe and beneficial way. Still we need to emphasize the benefits of these agents in order to achieve more application in HF patients. Here we try to stress the proved beneficial effects of beta-blockers by major studies in HF patients, and to supply the reader with practical information regarding the use of these agents with a look at the frequency of using them and the possible reasons behind their underuse. The files of heart failure patients admitted to 1st Internal Department in the University Hospital in Bratislava in the period between January and December 1997 were checked to show the magnitude of using beta-blockers in them. Among 150 patients admitted during the above mentioned period only 30 patients (20%) received beta-blockers. It seems that beta-blockers have to be used in all patients with HF with reduced ejection fraction unless a real contraindication exists, but the actual data shows that beta-blockers are still underused. (Tab. 2, Ref. 30.)

The aim of our study was to investigate contractile responses to endothelin-1 in the presence or absence of selective blockers of ET(A) or ET(B) receptors in subcutaneous small resistance arteries of normotensive subjects and of patients with essential hypertension.Twenty-four subjects (eight normotensives aged 50 +/- 4 years, and 16 with essential hypertension aged 53 +/- 4 years) were included in the study. All subjects were submitted to a biopsy of the subcutaneous fat. Small resistance arteries (internal diameter 160-280 microm) were dissected and mounted on a micromyograph as a ring preparation (Mulvany's technique). The media-to-lumen ratio was calculated. A concentration-response curve to endothelin-1 was then performed in the presence or absence of FR 139317, (a selective blocker of ET(A) receptors) or of BQ 788, (a selective blocker of ET(B) receptors).The media-to-lumen ratio was lower in normotensives compared with those subjects with essential hypertension (0.08 +/- 0.02 vs. 0.12 +/- 0.05, p0.01). The vasoconstriction induced by endothelin-1 was greater in normotensives than in patients with essential hypertension. In normotensives, almost all the vasoconstriction induced by endothelin-1 was blocked by the addition of FR 139317, while in subjects with essential hypertension the effect was smaller. The selective blocker of ET(B) was devoid of effect in both groups.The vasoconstrictor effect of endothelin-1 in small resistance arteries of normotensive subjects and, in part, also in hypertensive patients is mediated by ET(A) receptors, while ET(B) receptors play a minor role, if any. It is, however, possible that a vasoconstrictor effect mediated by ET(B) receptors located on vascular smooth muscle cells may be masked by the simultaneous stimulation of endothelial ET(B) receptors which may induce a vasodilation mediated by nitric oxide.

The problem of heart failure (HF) has become a topic of great interest. Until recently, the use of beta-blockers in patients with HF was considered as one of the contraindications which were taught to medical students as realities with a strict policy to avoid them in HF patients. Times have changed and the contraindicated drug is now an advised and preferred one to be used in HF patients with certain advised recommendations for its use in a safe and beneficial way. Even though the use of beta-blockers in HF patients is an important and necessary step towards an optimal treatment of these patients as most of the big studies have proved, still we need to emphasize these benefits in order to achieve more application of these agents in HF patients. Here we analyse the major studies which used beta-blockers in HF patients. It seems that beta-blockers have to be used in all patients with HF with reduced ejection fraction unless a real contraindication exists as they bring up a great benefit towards decreasing mortality and morbidity.

Eosinophilic gastroenteritis is a rare disease; clinical features depend on which intestinal layer is involved. In our report a 70-year-old woman presented with intestinal subocclusion and ascites. Endoscopic biopsies of gastric mucosa were negative. Ultrasound guided percutaneous fine-needle biopsy showed muscle infiltration by eosinophils of muscle layer of the stomach and jejunum. Muscular and serosal disease are usually diagnosed only by laparotomy or laparoscopy.

A 62 years old man was admitted to hospital because of fever; a small superficial hepatic nodule was showed by ultrasonography. Blood cultures grew Salmonella enteritidis. Cefotaxime was administered for ten days. Fever promptly disappeared but one week later recurred with abdominal and back pain. Cultures grew again Salmonella enteritidis. Biopsy of the hepatic nodule showed hepatocarcinoma. Computed abdominal tomography showed a paraaortic mass. Angiography demonstrated hematoma communicating with the aortic lumen. The patient underwent revascularization of the involved aortic tract and resection of the hepatic nodule. Histology showed suppurative aortic endarteritis and a well-differentiated hepatocellular carcinoma with a large area of suppurative necrosis. The recovery of Salmonella species as of any uncommon bacteria from blood should warrant a through research of underlying disease, especially cancer.

Familial hypercholesterolemia is associated with premature coronary heart disease. In patients with familial hypercholesterolemia, monotherapy with hydroxymethylglutaril coenzyme. A reductase inhibitors rarely achieves the goal of desirable low-density lipoprotein levels. Epidemiological studies suggest that populations with a high dietary intake of marine n3 fatty acids are protected against coronary heart disease. Hepatic synthesis and secretion of very low density lipoproteins are reduced during fish oil supplementation while other effects on lipid and lipoprotein metabolism are controversial. Fourteen patients affected by familial heterozygous hypercholesterolemia on chronic treatment with simvastatin were enrolled in a double blind, placebo controlled, randomized crossover trial that evaluated the effect of fish oil ethyl ester (Esapent, 5.1 g/day) on lipid and lipoprotein serum concentrations. Total cholesterol, low density lipoprotein cholesterol, high density lipoprotein cholesterol, triglycerides, apoprotein B, apoprotein AI, lipoprotein (a) did not show any significant variation during the four week treatment period with fish oil ethyl ester. The present data suggest that the possible favourable influence of fish oil on the progression of atherosclerosis in these high-risk patients might involve mechanisms which are different from lipid metabolism.

A case of acute inflammatory myopathy associated with the use of pravastatin, a new hydrophilic 3-hydroxy-3 methylglutaril coenzyme A reductase inhibitor, is reported. The patient, a 69-year-old man was affected by non-insulin-dependent diabetes mellitus and hypertension. He assumed pravastatin (20 mg/day) because of hypercholesterolemia. He was admitted with acute myopathy of the lower limbs which resolved in a few days after pravastatin discontinuation. A previously unknown hypothyroidism, probably due to chronic autoimmune thyroiditis, was evidenced. Muscle biopsy (left gastrocnemius) revealed a perimysial and endomysial inflammatory infiltrate with a prevalence of CD4+ lymphocytes. While lovastatin and simvastatin have been associated with toxic myopathy, pravastatin-associated myopathy could represent a distinct, inflammatory entity.

The influence of nutrient absorption, caloric content, and diet on lipoprotein (a) [Lp(a)] concentration is uncertain. To our knowledge, there are no reports on Lp(a) behavior in malabsorption. Serum lipids and Lp(a) concentrations were evaluated in 17 celiac patients (5 male and 12 female patients; age range, 1-24 years) when the diagnosis was established and after a 3-month gluten-free diet. Mean total and low-density lipoprotein cholesterol did not show significant change, while mean high-density lipoprotein cholesterol rose and triglycerides decreased significantly after the diet. The Lp(a) concentration remained unchanged in all patients (median values, 35 mg/L before and 40 mg/L after the diet). Our results suggest that, in our patients, the lipoprotein profile was influenced by the gluten-free diet, while the Lp(a) concentration was not modified.

Alterations of the lipid profile are a well known phenomenon in thyroid dysfunction. Thyroid hormones regulate lipid metabolism through various mechanisms, but a key role is played by the LDL receptor pathway. Thyroid hormone influence on Lipoprotein (a) (Lp[a]) metabolism is unknown; therefore we studied Lp(a) concentrations in a group of 29 hypothyroid patients with post-surgical hypothyroidism and in a group of 14 hyperthyroid subjects with Graves' disease before and after the thyroid function was normalized by treatment. In hypothyroid patients total and LDL-cholesterol markedly decreased after T4 treatment (342 +/- 78 mg/dl before and 193 +/- 46 mg/dl after; 225 +/- 72 mg/dl before, 111 +/- 43 mg/dl after respectively, p < 0.001). Also HDL-cholesterol and triglycerides decreased (from 75 +/- 22 mg/dl to 56 +/- 18 mg/dl and from 182 +/- 87 mg/dl to 112 +/- 42 mg/dl respectively, p < 0.001). Lp(a) showed minor but not significant variations (median values 80 mg/l before 55 mg/l after treatment, p: N.S.). In hyperthyroid patients total and LDL-cholesterol increased after methimazole treatment (from 148 +/- 49 mg/dl before to 254 +/- 67 mg/dl after and from 87 +/- 38 mg/dl before to 178 +/- 51 mg/dl after, p < 0.001). HDL-cholesterol increased (from 39 +/- 9 to 50 +/- 15, p < 0.01) while triglycerides were unchanged. Lp(a) levels slightly rose (median values 57 mg/l before 84 mg/l after treatment, p < 0.05). These data suggest that the influence of thyroid hormones on Lp(a) metabolism is of minor entity and probably does not operate through the LDL receptor pathway.