Cutaneous manifestations in relation to immunologic parameters in a cohort of primary myelodysplastic syndrome patients.

BACKGROUND: Cutaneous lesions in myelodysplastic syndrome (MDS) may be specific or not and may reveal bone marrow transformation. Our purpose was to investigate in a cohort of 84 MDS patients the correlation of cutaneous findings with immunologic parameters and prognostic features of MDS in order to clarify their potential clinical significance. MATERIALS AND METHODS: We studied a cohort of 84 newly diagnosed MDS patients in order to assess the cutaneous findings present at the time of diagnosis and during 1 to 3 years of follow-up. We described the clinical variety of cutaneous findings ascertained by histology. We also looked for any association between the group of MDS patients with skin manifestations and MDS subtype, immunologic and prognostic features highlighting transformation to acute leukaemia. RESULTS: Twenty-one patients presented cutaneous manifestations: 1 patient developed leukaemia cutis, 6 patients photosensitivity not associated with autoimmune disease, 3 prurigo nodularis, 2 Sweet's syndrome, 6 leucocytoclastic vasculitis, 2 ecchymoses and purpura associated with preexisting relapsing polychondritis, 1 patient subcutaneous nodules associated with Wegener's granulomatosis and 1 patient with malar rash and oral ulcers associated with preexisting systemic lupus erythematosus. Adjusted for age and gender, the presence of skin findings constitutes a significant predictor of the high-risk MDS subgroup (odds ratio, 3.59; 95% confidence interval, 1.18-10.92). Hypergammaglobulinemia was significantly higher in the MDS subgroup with skin manifestations (P = 0.03). CONCLUSION: Most MDS patients with cutaneous manifestations belong to the high-risk MDS subgroup and present hypergammaglobulinemia. Early biopsy of skin lesions in myelodysplasia is indicated.

A case of ovarian sarcoidosis mimicking malignancy.

We present a case of systemic sarcoidosis with ovarian and peritoneal involvement. The atypical clinical presentation of the disease has lead to a problem of the differential diagnosis with ovarian cancer. A 72-year-old female was admitted because of low grade fever, fatigue and dilatation of the abdomen. Clinical and laboratory evaluation of the patient revealed moderate right pleural effusion, ascites, diffuse ovarian infiltration, presence of enlarged intraabdominal lymph nodes and a substantially high value of serum CA 125. Histological examination after laparotomy was indicative of ovarian sarcoidosis.

Hematological malignancies are associated with a lower interferon-a blocking activity than solid tumors.

UNLABELLED: Interferon (IFN) and especially IFN-alpha exhibit clinical anti-tumor activity against various types of malignant diseases. Natural inhibitors to various cytokines and IFNs have been documented in vitro as well as in vivo. IFN inhibitors have been implicated for the ineffectiveness of IFN treatment in malignant neoplasias. The aim of this study was to investigate the incidence of the IFN inhibiting activity in serum from patients with haematological malignancies versus patients with solid tumours, as an effort to explain, just in part, the different response of these patients to IFN treatment. PATIENTS AND METHODS: Ninety patients with a clinically evident solid tumour and forty-six patients with haematological malignancies were included in the study. Serum samples from all patients were collected before any treatment and stored at -70 degrees until use. Controls sera were selected from 50 apparently healthy blood donors. Interferon-inhibiting activity as well as endogenous IFN-like activity were determined in all serum samples in a cell line highly sensitive to IFN. RESULTS: There was no endogenous IFN-like activity in any of the patients' group or controls' group. Sera from patients with haematological malignancies exhibited IFN-blocking activity at a lower percentage (21.7%) in comparison to sera from patients with solid tumours (56.6%, P<0.001), but at a significantly higher percentage in comparison to sera from controls (P<0.01). CONCLUSIONS: The fact that IFN inhibitors were detected at a significantly lower percentage in sera from patients with haematological malignancies versus patients with solid tumours, could explain in part the better response of the haematological malignancies to IFN treatment.

Effects of buflomedil on early carotid atherosclerosis in Type 2 diabetic patients.

BACKGROUND: An increased thickness of the carotid artery wall is thought to be a sign of early atherosclerosis. We have investigated the effect of early treatment with buflomedil on the prevention of the arterial wall thickening. METHODS: Eighty patients with Type 2 diabetes were studied. Oral buflomedil (600 mg once daily) was administered for 12 months in 42 patients randomly selected, while 38 received no treatment. The two groups were matched for age, sex, body mass index (BMI), duration of diabetes and glycaemic control. Arterial wall thickness was measured as the mean of the maximum intima media thickness (IMT) in 8 carotid segments measured by B-mode ultrasound. RESULTS: Blood pressure and lipid levels remained unchanged in the two studied groups while no difference was found in metabolic control between them. The IMT increase over 12 months was 0.04 mm in the buflomedil group whereas in that without buflomedil it was 0.10 mm. CONCLUSIONS: We conclude that buflomedil treatment may be useful in decreasing the progression rate of arterial wall thickness.

Ca(2+)-Mg(2+)-ATPase activity and ionized calcium in Type 2 diabetic patients with neuropathy.

Ca(2+)-Mg(2+)-ATPase is an important regulator of intracellular calcium concentration and therefore, of erythrocyte deformability. We have investigated the possible relationship between Ca(2+)-Mg(2+)-ATPase activity (ATPase) and ionized calcium (Ca(2+)), in diabetic patients with peripheral neuropathy. A total of 104 Type 2 diabetic patients (57 neuropathic and 47 non-neuropathic) and 25 non-diabetic subjects were studied. After an overnight fast, blood was taken for Ca(2+)-Mg(2+)-ATPase activity, Ca(2+), Mg(2+), PTH and HbA(1c). The neuropathy study group had significantly lower levels of ATPase, 6.6 (95% CI, 5.6-7.7) nmol/mg/min compared to controls 7. 1 (6.2-8.3) nmol/mg/min, P<0.001 and to diabetic patients without neuropathy 7.0 (6.0-8.1) nmol/mg/min, P<0.001. The study group had also lower levels of Ca(2+) (0.89+/-0.18 mmol/l vs. control 1.08+/-0. 24 mmol/l, P<0.01 and non-neuropathic 0.98+/-0.27 mmol/l, P<0.05) and Mg(2+) (0.73+/-0.13 mmol/l vs. control 0.81+/-0.14 mmol/l, P<0. 05), despite similar PTH levels. In diabetic subjects, no correlation was found between ATPase or Ca(2+) with glucose, HbA(1c), age or duration of diabetes. We conclude that in patients with diabetic neuropathy there are abnormalities of Ca(2+)-Mg(2+)-ATPase activity and Ca(2+). This provides further support for the role of microangiopathy in the pathogenesis of neuropathy.

Progression of carotid atherosclerosis and the role of endothelin in diabetic patients.

An increased thickness of the carotid artery wall is thought to be a sign of early atherosclerosis. Since vascular endothelium is the site of formation of several substances, we have investigated the rate of progression of carotid atherosclerosis and the contribution of endothelin (ET-1), lipid peroxides [measured as thiobarbituric acid reacting species (TBARS)] and 6-keto-Prostaglandin-F1A (6-keto-PG-F1A) at baseline and after 30-months. Fifty patients with Type 2 diabetes without evidence of macroangiopathy, hypertension, proteinuria or proliferative retinopathy, and 27 healthy, non-diabetic persons were studied. Arterial wall thickness was measured as the mean of the maximum intimal-medial thickness (IMT) in 16 carotid segments by b-mode ultrasound. The IMT values was significantly increased in diabetic subjects (at baseline: 1110 +/- 310 microm, after 30 months: 1260 +/- 280 microm, p < 0.01), but not in control subjects (1100 +/- 280 microm, 1200 +/- 290 microm, respectively). At baseline time both groups had similar levels of ET-1, TBARS and 6-keto-PG-F1A. In 30-months follow-up, the ET-1 level 8.0 pmol/l (5.8-10.7) was significantly elevated in diabetic subjects, compared with the level at baseline time 7.43 pmol/l (4.8-11.1) p < 0.01. No significant differences were found in the other examined parameters in the studied groups. Although insulin levels remained unchanged in the two studied groups, in 30 months follow-up, the insulin level in the diabetic subjects, 92.4 +/- 35.1 pmol/l was significantly elevated compared with those of control subjects 76.0 +/- 31.0 pmol/l, p < 0.05. In conclusion, endothelis is the main associate of the change of IMT value over 30 months in diabetic patients, in whom the extent of atherosclerosis was significantly greater than in control subjects.

Plasma levels of endothelin and early carotid atherosclerosis in diabetic patients.

An increased thickness of the carotid artery wall is thought to be a sign of early atherosclerosis. Since plasma endothelin concentrations were released from vascular endothelial cells, we have investigated the possible relationship between endothelin 1 (ET-1) and arterial wall thickness. Ninety-eight patients with Type 2 diabetes without evidence of macroangiopathy, hypertension, proteinuria or proliferative retinopathy, and 50 non-diabetic subjects were studied. After an overnight fast, blood was taken for ET-1, glucose, HbA1c, lipids, insulin and C-peptide. Arterial wall thickness was measured as the mean of the maximum intimal-medial thickness (IMT) in 16 carotid segments by B-mode ultrasound. ET-1 levels were significantly elevated in diabetic patients with IMT>1100 microm, 8.3 pmol/l (5.2-12.9) compared with control subjects, 7.6 pmol/l (5.0-11.0), p<0.01 and with diabetic subjects with IMT<500 microm, 7.43 pmol/l (4.8-11.1), p<0.01. The diabetic (IMT>1100 microm) study group had also significantly higher levels of insulin, 102.8 +/- 46.4 pmol/l vs control subjects, 77.5 +/- 32.4 pmol/l, p<0.01. In diabetic subjects, no correlation was found between ET-1 and IMT with glucose, HbA1c, lipids, age or duration of diabetes, respectively. We conclude that ET-1 levels are elevated in Type 2 diabetic patients with increased IMT. Thus providing further support for the role of endothelin in atherosclerosis.

Detection of interferon inhibitors or antagonists in gastrointestinal malignancies.

BACKGROUND/AIMS: The aim of this study was to investigate the IFN-inhibiting activity in sera from patients with gastrointestinal malignancies, exerted in a variety of cellular types, as well as to elucidate the determinants of cellular sensitivity to such IFN-inhibitors. METHODOLOGY: Sera from 16 patients with gastric cancer and 18 with colon cancer were tested, while sera from 37 healthy blood donors were used as controls. All serum samples, collected before any kind of treatment, were tested for IFN-blocking and endogenous IFN-like activity. These activities were determined by assaying the inhibition of the vesicular stomatitis virus specific cytopathic effect in three cell lines: A549 cells, intestine 407 and Chang liver cells. RESULTS: There was no endogenous IFN in any of the serum samples of patients or controls. Concerning the IFN blocking activity of serum, there was no significant difference between gastric and colon cancer, while a marked variability was prominent depending on the cell line used. 76.4% of serum samples exerted IFN-blocking activity in the A549 cells, 47.05% in the Int-407 cell line and 32.3% in the Chang Liver cells. No control sample had IFN-blocking activity in any of the cell lines tested. CONCLUSIONS: The results support a cytokine and cytokine inhibitors network, mediating pathophysiological events at the cellular level as well as the whole organism. The limited responsiveness of many neoplasias, including digestive system cancer, to IFN treatment might be due to the presence of IFN inhibitors in the patient's serum.

Interferon-inhibiting activities in sera of patients with lung cancer.

A differential pattern of sera exhibiting interferon-inhibiting activity in cases of histologically confirmed lung cancer patients have been observed. The sera distribution was dependent on the clinical entity and the cell line specificity used measuring IFN-inhibition. Although either small cell lung cancer (SCLC) or non small cell lung cancer (NSCLC) sera exhibiting in a high percentage (80 and 75% respectively) such an activity, in any of the 3 lines tested, the ratio of sera exerting inhibition in each cell line was different. Such cell specific systems could be of prognostic/predicting value for effective therapeutic schedules of specific clinical entities.

Effect of fosinopril sodium on early carotid atherosclerosis in diabetic patients with hypertension.

An increased thickness of the carotid artery wall is thought to be a sign of early atherosclerosis. We have investigated the effects of fosinopril sodium in asymptomatic diabetic hypertensive subjects on the 12-month progression of arterial wall thickness. Forty non-insulin-dependent diabetics with hypertension and without hyperlipidemia were studied. After a 4-week run-in-diet phase, oral fosinopril sodium was administered (20 mg once daily) to 20 patients randomly selected, while 20 subjects were treated only with diet. The two groups were matched for age, sex, body mass index (BMI), duration of diabetes and glycemic control. Arterial wall thickness was measured as the mean of the maximum intimal-media thickness (IMT) in 16 carotid segments by B-mode ultrasound. The IMT increase over 12 months was 4.3% in the fosinopril sodium group vs 15.1% in subjects with diet. We conclude that fosinopril sodium treatment may be useful in decreasing the progression rate.