A singular case of granulomatous lesions of unknown significance.

The acronym used for granulomatous lesion of unknown significance, (GLUS), was first employed in 1990, to describe epithelioid-cell granulomas occasionally observed in biopsies from liver, lymph-nodes and other tissues without any apparent cause than thorough diagnostic examinations. Authors describe a case of a 51-year-old woman who was admitted to hospital because of fever, nodules in the liver and spleen, skin ulcerative lesions on the legs. The patient had a very long medical history; recurrent fever, liver and spleen enlargement have been lasting since 1975. Laboratory data showed erythrocyte sedimentation rate increase (125 mm 1 hour), anemia, (Hb=8.1 g/dL), an increase of alkaline phosphatase activity (328.4 mU/mL NV=80-275) and also an increase of policlonal gamma-globulins; patient's total proteins was 6.8 g/dL while their gamma-globulins were 29.5%; IgG=2 260 mg/dL (NV=751-1 560 mg/dL), IgM=277 mg/dL (NV=46-230 mg/dL), IgA=405 mg/dL (NV=70-400 mg/dL). One culture of the blood and a needle aspiration specimen of liver nodule was positive for Staphylococcus coagulase negative. This case cannot be regarded as GLUS-syndrome because of the long time duration of the disease and other clinical features. The dramatic, even if transient, liver nodules improvement obtained by Linezolid therapy, and the well-being obtained by prolonged monociclin use, make the authors hypothesize that Staphylococcus coagulase negative could be the etiological agent of this granulomatous clinical picture.

Plasma glucose level decreases as collateral effect of fermented papaya preparation use.

AIM: Fermented Papaya Preparation (FPP) is a natural healthy drug that has been commercially sold in Japan and Philippines. This nutricetive, bio-normalizer product has antioxidant action, inhibitory effect on oxidative DNA damage and tissue injury, being a potent OH scavanger. The wide use of FPP, expecially by elderly people, made us note an unknown collateral effect, i.e., blood sugar level dropping signs especially in the afternoon. The aim of the present work was to scientifically verify the possibility that individuals, who are taking the nutriceutical FPP, might have a decrease of plasma sugar levels. MATERIALS AND METHODS: For this purpose, 50 subjects, divided in two groups, were enrolled. The first group was made of 25 patients: 13 females and 12 males affected by type-2 diabetes mellitus under treatment with the oral antidiabetic drug, glybenclamide. The control group included 25 clinically-healthy subjects: 16 females and 9 males, matching in age. All subjects were given 3 grams of FPP daily, during lunch, for two months. RESULTS: The results of this study confirmed the empirical experience that FPP use can induce a significant decrease in plasma sugar levels in both healthy subjects and type 2 diabetic patients. This hypoglycaemic effect, associated with clinical signs, induced the diabetic patients to reduce the dosage of their antidiabetic oral therapy (in one patient the therapy was really suspended). CONCLUSIONS: In accordance with these results, the FPP administration is suggested as an adjuvant drug to join the oral antidiabetic therapy in type 2 diabetes meltus.

Do hypertension and diabetes mellitus influence the site of atherosclerotic plaques?

BACKGROUND: The concomitant occurrence of atherosclerotic plaques in carotid, coronary and peripheral vessels has been described in a number of studies. A few studies were, on the contrary, done for determining the role of hypertension and/or type 2 diabetes mellitus for the occurrence of the atherosclerotic plaques in different anatomical sites. Moreover these studies deal with atherosclerotic lesions that are generally considered, without differentiating their morphology as a function of the underlying disease, territory, and risk factors. Primary aim of this study is, thus, to verify whether the two most common causes for atherosclerotic disease, i.e., hypertension and type 2 diabetes mellitus, may influence the site of appearance of the atherosclerotic plaque. A second aim is to verify if the anatomical site of the plaque influences plaque morphology and vulnerability. PATIENTS AND METHODS: A retrospective study of 244 patients affected with type 2 diabetes mellitus or hypertension was performed; 114 subjects were affected by moderate-severe and drugs-treated hypertension (Group A); 55 were affected by type 2 diabetes mellitus in treatment with oral antidiabetic drugs (Group B); 75 were diagnosed as affected by the association hypertension and diabetes (Group C). The inclusion criteria were: exhaustive images of the cardiovascular system (coronary angiography, colour Doppler ultrasound of lower limb arteries and carotid arteries, transthoracic Doppler echocardiography ) and a serum lipid profile (total serum cholesterol, HDL-cholesterol, LDL-cholesterol, triglycerides). Three different anatomical sites: carotid axis, ilio-femoral arteries and coronary district, were considered. In each site a plaque lesion-classification was performed to describe the morphology of the plaque. RESULTS: In patients with hypertension, carotid district seems to be the preferential site of onset of atherosclerotic plaques even if a statistical significant association between the two conditions was not found. Statistical evaluation didn't show significant association between different risk factors and coronary district too. On the opposite, a significant association (p < 0.001) between diabetes and the presence of atherosclerotic plaques into lower limb district was found. A very significant association (p < 0.001) between type 2-diabetes and the presence of non-ulcerative plaques was found too. CONCLUSIONS: Our study underlines the relationship between vessel plaques localization and concomitant risk factors for atherosclerosis and suggests a possible difference in plaque morphology and biological behaviour related to different anatomical site.

Reconstruction of a large chest wall defect using greater omentum.

A 56-year-old woman was admitted for treatment of a large carcinoma that involved the chest wall. Fourteen years earlier, she had undergone a radical mastectomy, which was followed by chemotherapy and radiation therapy. The carcinoma was excised and the large anterior chest wall defect reconstructed using Marlex mesh, an omental pedicle flap, and a split-thickness skin graft.

Haemorrheological improvement by pentoxifylline in patients with peripheral arterial occlusive disease.

A group of 25 patients with Stage II peripheral arterial occlusive disease was treated with pentoxifylline ('Trental' 400) for 90 days. Significant changes were observed during treatment in the haemorrheological parameters studied. At the end of treatment, reductions were found compared to basal values in blood viscosity (-10.1%), plasma viscosity (-9.5%), blood fibrinogen (-18.5%), and erythrocyte aggregation (-31.8%); blood filtrability was significantly increased (+41.0%). These positive changes in blood fluidity may be suggestive of beneficial influence of this drug on the clinical condition of claudicants.

Long-term thymopentin treatment in systemic scleroderma.

A study was carried out to investigate whether thymopentin treatment is capable of inducing changes in the immunological status of patients with systemic scleroderma and to compare any such changes with modifications in clinical condition. Nine patients were given thymopentin, 1 ml in 10 ml saline solution, by slow intravenous infusion 3-times weekly for 5 weeks (cycle). The cycles were repeated at 3-month intervals. Treatment duration ranged from 1 to 5 years. Blood samples were drawn at the beginning and at the end of each cycle and the patients' lymphocytic sub-populations were examined. A control group of 9 comparable healthy subjects were similarly tested. Data analysis showed that a statistically significant decrease of CD16+ and CD25+ lymphocytes compared to pretreatment was already apparent at the end of the first thymopentin treatment cycle. An improvement was found in the clinical condition of 7 of the 9 patients at the end of the follow-up period with a significant correction of unbalanced lymphocytic subsets.

Effects of prolonged picotamide therapy on platelet activity in patients with peripheral arterial disease.

An open study was carried out in 14 patients with peripheral arterial disease to investigate the effects of prolonged therapy with picotamide on platelet activity. Patients received daily oral doses of 900 mg picotamide for 1 month, 600 mg per day during the second month and 300 mg per day from the third to the sixth month of the study. Measurements were made before and during therapy of blood coagulation parameters and factors influencing platelet function, i.e. plasma beta-thromboglobulin and serum thromboxane B2. The results showed that there were no significant variations in platelet count, prothrombin time, partially activated thromboplastin time, presence and amount of fibrinogen in blood, and antithrombin III. Examination for fibrinogen degradation products was constantly negative and unaltered during therapy. Although plasma beta-thromboglobulin values did not vary significantly, there was a significant and progressive reduction throughout treatment in serum levels of thromboxane B2.

The relationship between glycated hemoglobin and polymorphonuclear leukocyte leukotriene B4 release in people with diabetes mellitus.

In order to evaluate polymorphonuclear leukocyte (PMN) activity in diabetes mellitus, leukotriene B4 (LTB4) levels were measured in sixty patients, 31 affected with Type 1 diabetes mellitus and 29 affected with Type 2 diabetes mellitus. The LTB4 levels (12.1+/-0.2 pg/100 microl) in diabetic patients were higher compared to those of the control group (7.9+/-0.1 pg/100 microl) (P < 0.001), and remained significantly higher (P < 0.001) (12.8+/-0.2 pg/100 microl) than in the control group (11.0+/-0.2 pg/100 microl) after stimulation with calcium ionophore. A significant and positive correlation between glycated hemoglobin and LTB4 was demonstrated (P < 0.001, r = 0.80). This study demonstrates that in diabetic patients there is a PMN activation and that this activation is correlated to glycated hemoglobin level.

Internal bile diversion--a new model for the study of cholesterol metabolism.

Biliary diversion in different ways has been studied as a prevention against induced hypercholesterolemia in experimental animals. A new model for the study of cholesterol metabolism is described in dogs in this paper. The technique consists in ligation and division of the common bile duct and interposition of an isoperistaltic loop of jejunum between the gallbladder and urinary bladder. This technique is free of complications such as diarrhea, infection, and peptic ulceration that are seen in other biliary diversion models, and it is tolerated well by the animals. This requires further study for its effectiveness in the prevention of experimental hypercholesterolemia and subsequent development of arteriosclerosis.

ET-1 plasma levels during cold stress test in sclerodermic patients.

Endothelial cell injury in blood vessels of small arteries and capillaries is considered the primary event in the pathogenesis of systemic sclerosis (SSc). Because endothelin-1 (ET-1) is mainly released in the site of endothelial cell damage, thereby inducing a potent vasoconstriction, it was our intention to study ET-1 release in a group of SSc patients during a cold pressor test (CPT). Twelve SSc patients and a control group of 10 healthy subjects underwent CPT. Blood samples for ET-1 assay were collected at 90 and 180 seconds of exposure to cold stress. Heart rate and blood pressure were recorded at the same intervals. A capillaroscopic examination was performed in both groups before and after CPT. We observed significantly higher levels of plasma ET-1 in SSc patients compared with those of the control group at baseline (P=0.007) and at 90 (P=0.006) and 180 seconds (P=0.03) of CPT. During the test, the capillaroscopic examination showed a dramatic worsening of the vascular picture that was parallel to the increase in ET-1 plasma levels. This suggests that higher ET-1 plasma levels can have a part in the acute vascular reactivity of SSc patients undergoing CPT.

Failure of intestinal lymphatic block to prevent experimental hypercholesterolemia.

Intestinal lymphatic blockade was produced in dogs by ligating the individual lymphatics and then obturating them with an acrylic solution. Despite meticulous technique a complete and lasting lymphatic block could not be produced. Extensive collateral channels developed via the omental, the colonic, the renal and the retroperitoneal lymphatics. Some of the vessels recanalized. Absorptions studied using C-14 octanoic and H-3 oleic acid suggested that although the lymphatic blockade was partially successful in lowering the content of oleic and octanoic acid in the lymph, direct lymphovenous transport compensated for the lymphatics' obstruction. The cholesterol values of the lymph blocked dogs were not lower than those of the controls. Intestinal lymphatic obstructions does not appear to be a practical approach to the prevention or treatment of hypercholesterolemia.

[Relationship among VIP plasma levels, esophageal dysfunction, and microcirculation in systemic sclerosis]. / Rapporti fra livelli plasmatici di VIP, disfunzione esofagea e del microcircolo in corso di sclerosi sistemica.

BACKGROUND: Recent studies suggest that esophageal dysmotility occurring in systemic sclerosis might be caused by neurotransmitter levels decrease. The aim of the present study is to value VIP plasma levels, and to relate them with the pressure of the inferior esophageal sphincter (IES) and the capillaroscopy score in a group of patients affected by Systemic Sclerosis (SSc). METHODS: Eleven subjects affected by SSc (eight male and three female, age from 30 to 72 years old) have been studied through esophageal manometry, capillaroscopy and VIP plasma levels evaluation. Fifteen healthy volunteers, as control group, have been enlisted. RESULTS: Our results show a decrease of VIP plasma levels in patients with SSc compared with control group. The difference between two groups has statistical significance (p < 0.01). Capillaroscopy has shown remarkable microcirculatory impairment and the esophageal manometry proved a decreased IES pressure. The scores of capillaroscopy, VIP plasma levels and pressures of IES have been compared and it has been observed that there is a relationship between VIP plasma level and pressure of IES. CONCLUSIONS: VIP plasma levels decrease enhances the role of the autonomic disorder in SSc and may contribute to produce the alteration of vascular tone as well as the gastroenteric musculature dysfunction.

[Systemic sclerosis after a long-term follow-up]. / Riflessioni sulla sclerosi sistemica dopo un follow-up a lungo termine.

The authors suggest some remarks on the aetiopathogenesis of systemic sclerosis through a critical review of a group of 51 patients affected by this disease for many years. In this paper the authors report their previous studies regarding the correlation of immunological response, both cell-mediated and humoral, hemocoagulative aspects and haemorheological changes. From the results of immunological studies, the authors report a long-term treatment with an immunomodulating drug: thymopentin. Moreover they report a recent work about the connection among stressor event, production of endothelin-1 (ET-1) and serum levels of some stress hormones such as possible pathogenetic factors of Raynaud's phenomenon and of scleroderma. This work ends with a proposal of a pathogenetic scheme that, even if it doesn't exclude an infective pathogenesis, considers stress as a factor able to switch on a series of psycho-neuro-immunoendocrinological reactions that can support, through the activation of lymphocytes, fibroblastic proliferation and finally fibrosis.

Vulvar lymphatics as demonstrated by vital dyes and lymphangiography.

Human and animal studies have demonstrated that vital dye technics can delineate vulvar lymphatic patterns, which vary from those occurring clinically because dye particles may traverse unblocked channels. Lymph blockage can change these patterns to those seen clinically. Deep pelvic nodes are seldom seen on foot lymphangiography, and the vulvar technic does not appear clinically feasible. Normal unblocked spread is over or under the mons, bilaterally into the pelvis through the obturator foramen, or the Space of Retzius. Blockage by pressure, disease or deformity changes this to a clinical pattern where the lymphatic pathways approach the perianal or the deep external pudendal basins, going laterally to the thigh and then to the deep femoral nodes, here to take the "usual" pathway. Spread is invariably bilateral, with the greatest dispersion not necessarily on the homologous side.

[Evaluation of C3c, C4 and C1-esterase inhibitor (C1-INH) during unstable angina]. / Valutazione del C3c, del C4 e dell'inibitore della C1q-esterasi (C1-INH) in corso di angina instabile.

BACKGROUND: The complement system plays an important role in the physiopathology of acute myocardial infarction (AMI) taking part in myocardial damage and reperfusion injury. The aim of this study is to investigate the plasmatic levels of some complement components (C3c, C4 and C1-INH) during unstable angina (C1-INH) and their different concentrations in relation to the different myocardial areas affected by ischemia. METHODS: The plasmatic levels of C1-INH, C3c and c4 in 30 patients affected by unstable angina, and those of 22 clinically healthy subjects (control group) were evaluated (Nefelometer Behering). The patients were divided into four groups according to the different myocardial area affected by ischemia (anterior, antero-lateral, lateral or inferior ischemia), RESULTS: No statistically significant differences were found in plasmatic levels of C3c, C4 and C1-INH between the group of patients and the control group. There is a statistically significant difference between the C1-INH levels of the patients with inferior ischemia and the plasmatic concentrations of the whole patients' group (p<0,01), the control group (p<0,01) and the group of patients with lateral ischemia (p<0,02). CONCLUSIONS: There seems to be a different activation of the complement system during unstable angina, in relation to the different myocardial area affected by ischemia.

[Lipoprotein (a) and plasminogen in atherosclerosis]. / Lipoproteina (a) e plasminogeno nella malattia aterosclerotica.

The aim of this study was to evaluate plasma levels of lipoprotein (a) [LP(a)] and plasminogen in patients affected with atherosclerotic disease and to understand the mutual relationships. Eighty-four patients affected with atherosclerosis were examined and divided as follows: group I, 24 patients with peripheral arteriopathy; group II, 40 patients with ischemic heart disease (myocardial infarction and/or angina pectoris); group III, 20 patients with multi-infarct dementia; group IV (control group) with 20 healthy young subjects. The results show that Lp(a) plasma levels, in atherosclerotic patients, are higher than 30 mg/dl, while the plasminogen levels are lower than 80 mg/dl. There is an inverse correlation between these two data. Moreover, a different behaviour of Lp(a) and plasminogen rate related to age of patients, to number of atherosclerotic lesions or to acuteness of ischemic heart disease, was observed.

Rheological leukocyte indexes in diabetes mellitus type II.

Eleven healthy volunteers were examined, as well a thirty-five diabetic subjects divided into three groups according to the presence or absence of macro-microvascular complications and according to whether or not these complications were chronic. The results of our study show a marked unfavorable in cell rheology in the diabetic subjects, as studied using the St. George filtrometer. In particular, polymorphonuclear (PMN) cells, in the diabetic subject showed a substantial decreases in viscosity and elasticity, reflected by decreased IrFr and increased CR values. These changes were most marked in the group of diabetics with acute vascular events, i.e., AMI and stroke. Rheological indexes studied appeared to be independent from the simultaneous blood glucose level.

[Sodium channels and multiple sclerosis]. / Canali del sodio e sclerosi multipla.

Multiple Sclerosis is a chronic demyelinating disease of the central nervous system of undetermined etiology. Damage of myelinated fibers leads to block of conduction of impulses. In myelinated axons sodium channels are expressed at high density and they play a very important role in the conduction of nervous impulse. In myelinated fibers affected by Multiple Sclerosis substantial variations of sodium channels pattern occurs. These variations can help to explain pathophysiological and clinical aspects of Multiple Sclerosis and open a new way to approach and, probably, treat this disease.

[A five year follow-up of an HHV-8 related lymphoma in an HIV-negative elderly patient]. / Follow-up a 5 anni di un caso di Linfoma Primitivo delle cavità correlato all'HHV-8, in un paziente anziano HIV negativo.

Primary Effusion Lymphoma (PEL) associated with the Human Herpes Virus 8 (HHV-8), is a rare type of non-Hodgkin lymphoma. It mainly strikes HIV-positive men. Five-year follow-up of a case of PEL HHV-8 related in HIV negative elderly man, is described. The patient was admitted to our Department for dyspnea, thoracic pain and persistent slight temperature. Chest radiography showed a left pleural effusion. Cytomorphological, immunohistochemical and molecular assays performed on pleural fluid, demonstrated the presence of a PEL HHV-8 related, in absence of Epstein-Barr virus (EBV) infection in the tumour cells. Serologic test for HIV (ELISA) resulted negative. Chest TC, taken after thoracentesis, showed marked thickening of diaphragmatic pleura. Because patient's age and general conditions, no chemotherapy was performed. Five years after diagnosis, clinical examination and chest tomographyshowed resolution of the described syndrome; particularly chest TC showed complete disappearance of diaphragmatic pleura thickening. This biological behaviour is unusually for PEL: medical literature shows that this lymphoma has a very poor prognosis; this case-report suggests, as already proposed from some authors, that PEL, in HIV-negative EBV-negative patients, is a distinct clinical entity, with a different clinical behaviour.

[Circadian rhythm of serum levo-carnitine: parameters]. / Ritmo circadiano della levo-carnitina sierica: parametri ritmometrici per programmare una eventuale cronoterapia.

OBJECTIVE: The present study investigates the circadian rhythm (CR) of levo-carnitine (L-c) in systemic venous blood, in order to detect rhythmometric parameters that can be used for programming an eventual chronoterapy with such a molecule. MATERIALS AND METHODS: The L-c CR was investigated in 10 clinically healthy subjects (5 M; 5 F; mean age: 26.02 +/- 1.11 yrs), who were diurnally active and nocturnally resting. Blood samples were taken at 06:00; 08:00; 12:00; 18:00; 20:00; 24:00, not juxtaposed to breakfast, lunch and dinner. The serum concentrations of L-c were assayed via a spectrophotometric method. RESULTS: A nychtohemeral variability in circulating levels of L-c was observed, with a peak in the afternoon. Such a intradiem variability was validated to have the properties of a significant CR (MESOR = 33.37 mumol/l with a SEM of 1.19 mumol/l; amplitude = 6.31 mumol/l with 95%CL ranging from 3.58 mumol/l to 9.69 mumol/l; acrophase at 15:52 h:min with 95%CL ranging from 13:28 h:min to 17:00 h:min). CONCLUSIONS: It is important to remark that the validation of a CR for the systemic serum levels of L-c was obtained in diurnally-active/nocturnally resting subjects. Such validated rhythmometric properties are parameters that can be used for programming an eventual chronotherapy, considering that the molecule L-c is used for treating its various types of primary and secondary deficiency.