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Biomedical subjects

S Raptis

Publications and source records attributed to S Raptis.

At least 37 records · Page 2Linked to original sources

T-cell-rich B-cell lymphoma. Analysis of clinical features, response to treatment, survival and comparison with diffuse large B-cell lymphoma.

OBJECTIVES: Clinical features, response to treatment and survival of T-cell-rich B-cell lymphoma (TCRBCL) patients were compared to those of a similar group of patients with diffuse large B-cell lymphoma (DLBCL). METHODS: Between 1992 and 1999, 10 patients with a diagnosis of TCRBCL were treated in our department. Over the same 7-year period, a group of 65 patients with DLBCL were diagnosed in the same department. Both groups of patients were treated with the same anthracycline-based chemotherapy. RESULTS: A significantly higher percentage of patients with TCRBCL presented with B-symptoms, elevated LDH, bone marrow infiltration and disseminated extranodal involvement compared to patients with DLBCL. TCRBCL patients responded poorly to combination chemotherapy, since only 3 of them achieved complete remission (33%) compared to 48 (75%) patients with DLBCL. All patients with TCRBCL who achieved complete response relapsed within the first 2 years while 65% of patients with DLBCL survive disease free for a median follow-up period of 4 years. The median overall survival for DLBCL patients has not been reached yet, while it was 18 months for TCRBCL patients. CONCLUSIONS: Although the number of patients in our study is small, it seems that patients with TCRBCL present with advanced disease, respond poorly to chemotherapy and display a short disease-free and overall survival compared to patients with DLBCL.

Aged↗

Food-dependent androgen and cortisol secretion by a gastric inhibitory polypeptide-receptor expressive adrenocortical adenoma leading to hirsutism and subclinical Cushing's syndrome: in vivo and in vitro studies.

Aberrant gastric inhibitory polypeptide (GIP) receptor expression in bilaterally hyperplastic adrenals or unilateral adrenal adenomas is a rare form of adrenal hyperfunction. So far, only few cases have been described. In all these cases, cortisol was the predominant steroid released in a food-dependent manner, leading to the development of non-ACTH-dependent Cushing's syndrome. In the present study, we describe a novel case of a GIP receptor-expressive adrenocortical adenomatous nodule, detected incidentally by computed tomography scanning in a 41-yr-old lady with hirsutism but no clinical signs of Cushing's syndrome, on physical examination. Hormonal investigations in morning fasting samples showed slightly elevated androgen levels, low-normal baseline cortisol, normal suppression of cortisol after dexamethasone administration, and ACTH levels that were not suppressed and did stimulate after CRH administration. The elevated urinary free cortisol excretion, in conjunction with an atypical cortisol diurnal rhythm, raised the possibility of an aberrant stimulation of cortisol production by the adrenal tumor. Further studies demonstrated food-dependent secretion of cortisol, which was abolished by prior octreotide administration. Notably, substantial amounts of adrenal androgens were also secreted after food consumption. Removal of the tumor resulted in undetectable cortisol and androgen levels that did not respond to food consumption. Histological examination of the excised tumor revealed an adrenocortical adenomatous nodule originating from the inner zona reticularis, consisting mainly of compact cells. A steroidogenic secretory pattern, indicating the concomitant release of adrenal androgens and cortisol, was also observed in vitro from tumor cells cultured in the presence of GIP. The in vitro secretory response to GIP was higher for the adrenal androgen DHEA, compared with cortisol. The expression of the GIP receptor in tumor cells, but not in the adjacent normal adrenal, was demonstrated by RT-PCR), using specific oligonucleotide probes for this receptor. In summary, we describe a patient with a GIP-expressive cortisol and androgen oversecreting adrenocortical nodule with the unusual presentation of hirsutism and not the typical clinical signs of Cushing's syndrome. It is of note that food intake in this patient provoked a substantial increase in both adrenal androgen and cortisol levels that, together with the histological appearance of this nodule, was compatible with a zona reticularis-derived tumor. Thus, aberrant expression of the GIP receptor does not exclusively involve cells of a zona fasciculata phenotype, as previously reported, but may also occur in other types of differentiated adrenocortical cells.

17-alpha-Hydroxyprogesterone↗

Spontaneous remission in myelodysplastic syndrome.

A 73-year-old man was admitted for investigation of pancytopenia. His physical examination was unremarkable and the bone marrow aspirate was compatible with myelodysplastic syndrome (RAEB). Cytogenetic analysis of the bone marrow revealed a trisomy 21. The patient received transfusions of packed red cells, and his condition remained stable for the next 7 months. He was then admitted with a chest infection and was treated with broad-spectrum antibiotics with satisfactory response. During his hospitalization there was a gradual increase in his complete blood count values, which persisted, resulting in a normal peripheral blood after 3 months. A bone marrow aspirate performed at that time revealed normal findings with no karyotypic abnormalities, indicating a spontaneous remission. The patient remained stable for the next 6 months; then he recurred with 20% blasts in his bone marrow and reappearance of trisomy 21 in 42% of the metaphases examined. Several hematologic malignancies with spontaneous remissions have been described to date, but they have generally been short and recurrence is the rule, as in the case described. The role of endogenous cytokines in triggering these spontaneous remissions is under question, as the exact mechanism is unknown.

Aged↗

Relationship of Helicobacter pylori CagA status to gastric cell proliferation and apoptosis.

Despite the fact that the association of Helicobacter pylori with an increased risk of gastric cancer is well documented, the exact mechanisms of this association have not been elucidated. Our aim was to shed some light on these mechanisms by studying the relationship of H. pylori CagA status to gastric cell proliferation and apoptosis, since both play an important role in gastrointestinal epithelial cell turnover and carcinogenesis. We studied fifty patients [32 men, 18 women, median age 39.5 years (range 18-67)], referred for upper gastrointestinal endoscopy, from whom antral biopsies were taken. On biopsy specimens gastritis was estimated by scoring the severity of inflammatory infiltrate, and the presence of atrophy and intestinal metaplasia were also noted. The gastric cell proliferation index (PI) was estimated by AgNOR staining, the epithelial apoptotic index (AI) was measured by special staining for apoptosis, and CagA status was determined serologically by immunoblotting the sera of patients against H. pylori antigens. Thirty-eight (76%) of the 50 patients were H. pylori (positive) and 12 (24%) H. pylori (negative). Among the 38 H. pylori(+) patients, 28 (73.6%) were CagA(+) and 10 (24.6%) CagA(-). In the H. pylori CagA(+) and CagA(-) groups, the PI values [median (ranges)] were 5 (4-7) and 3.7 (3.5-5.5), respectively (P < 0.05). In addition the difference in PI between the H. pylori CagA(+) and H. pylori(-) groups was highly significant (P < 0.001). Concerning apoptosis, in the H. pylori CagA(+) and CagA(-) groups, the values for AI were 1 (1-30) and 5.5 (1-35), respectively (P < 0.05). In addition, the difference in AI between the H. pylori CagA(-) and H. pylori(-) groups, was significant (P < 0.05). We conclude that H. pylori CagA(+) strains induce increased gastric cell proliferation, which is not accompanied by a parallel increase in apoptosis. This might explain the increased risk for gastric carcinoma that is associated with infection by H. pylori CagA(+) strains.

Adult↗

Treatment of anemia in low risk myelodysplastic syndromes with granulocyte-macrophage colony-stimulating factor plus recombinant human erythropoietin.

The aim of this prospective study was to determine whether treatment with a combination of GM-CSF and erythropoietin (rhEpo) can improve the anemia associated with low risk myelodysplastic syndrome (MDS), namely refractory anemia (RA), RA with ring sideroblasts (RAS), and RA with excess of blasts (RAEB) with bone marrow blasts less than 10%. Eligibility criteria included an Hb level of less than 10.5 g/dl for newly diagnosed patients, or symptomatic anemia. GM-CSF was given at a dose of 3 microg/kg s.c. on days 1-2, rhEpo at a dose of 60 U/kg s.c. on days 3-5. No treatment was given on days 6-7. Patients were followed-up with full blood count on a weekly basis. The treatment was repeated for a total of 6 weeks. At that time, if a rise in Hb above 1.5 g/dl had not been achieved, the dose of rhEpo increased to 120 U/kg. Post-treatment evaluation was performed at the completion of 12 weeks. Erythroid response was defined as good (GR), if an increase in untransfused Hb values above 2 g/dl or a 100% decrease in red blood cell transfusion requirements, over the treatment period was observed, while an increase in untransfused Hb values 1-2 g/dl or a >50% decrease in transfusion requirements, were considered as partial response. Responders continued to receive the same treatment until disease progression. Nineteen patients (13 male and six female) with a median age of 69 years were enrolled in the study. The FAB subtypes were: RA one case, RAS eight cases and RAEB 10 cases. Ten of 19 patients (52.6%) responded to the treatment: 7/19 (36.8%) achieved a GR and 3/19 (15.8%) a PR. Six of eight (75%) patients with RAS, one case with RA and 3/10 (30%) of cases with RAEB responded to treatment. Pretreatment serum epo levels were generally low (less than 200 Mu/ml) in responding patients. At the completion of the initial 12 weeks, 8/12 responding patients (5 RAS, 2 RAEB and 1 RA) continued to receive the same treatment. All responding patients with RAS continued to show an erythroid response in a time period from 3 to 24 months, whilst one patient with RA and two with RAEB did not have a continuing response at 2, 4 and 12 months, respectively. The above data suggest that the combination of rhEpo and GM-CSF should be recommended in all cases with RARS. However, the clear indication of this combination for other patients with MDS remains to be determined.

Aged↗

A prospective randomized trial evaluating the haemodynamic role of incompetent calf perforating veins.

AIM: This study was undertaken to determine the haemodynamic effect of incompetent calf perforating veins in patients with uncomplicated varicose veins and long saphenous incompetence. METHODS: Thirty-eight limbs from 35 patients were studied. All patients had uncomplicated varicose veins with both long saphenous and calf perforator incompetence on duplex ultrasonography. Patients were randomized to have incompetent calf perforators ligated or left intact, in addition to saphenofemoral junction ligation, strip of long saphenous vein to knee and stab avulsion of any visible varicosities in the leg. Patients were assessed with air plethysmography pre-operatively and 3 months postoperatively. RESULTS: Superficial venous surgery improved venous volume, venous filling index and ejection fraction in the patient cohort. No significant haemodynamic difference was demonstrated between the two groups of patients who were randomized. CONCLUSIONS: At present, the results of this study do not support the use of routine perforator ligation during superficial surgery for uncomplicated varicose veins.

Adult↗

Extensive apoptosis of bone marrow cells as evaluated by the in situ end-labelling (ISEL) technique may be the basis for ineffective haematopoiesis in patients with myelodysplastic syndromes.

Apoptosis is a gene-directed cellular self-destruction which begins with internucleosomal cleavage of DNA and ends eventually with fragmentation of the nucleus. We have shown that the technique of ISEL of fragmented DNA appears to be an accurate and reliable measurement of the early stages of apoptosis. The present study was undertaken in order to define the incidence of programmed cell death in bone marrow (BM) haematopoietic and stromal cells of myelodysplastic syndromes (MDS). The ISEL technique was employed in 21 BM biopsies of MDS patients. The analysis showed that in 11/21 patients, >70% cells (high score) were undergoing programmed cell death while 5 patients showed up to 1/3 of the biopsy containing apoptotic cells and 2 patients had only few occasional ISEL positive cells. Stromal cells including fat cells, endothelial cells and fibroblasts were frequently in apoptosis in large clusters. Our results indicate that extensive apoptosis of haematopoietic cells documented in BM biopsies of MDS patients may be the explanation for the ineffective haematopoiesis which is the hallmark of these disorders.

Aged↗

Specific signals generated by the cytoplasmic domain of the granulocyte colony-stimulating factor (G-CSF) receptor are not required for G-CSF-dependent granulocytic differentiation.

Granulocyte colony-stimulating factor (G-CSF) is the principal growth factor regulating the production of neutrophils, yet its role in lineage commitment and terminal differentiation of hematopoietic progenitor cells is controversial. In this study, we describe a system to study the role of G-CSF receptor (G-CSFR) signals in granulocytic differentiation using retroviral transduction of G-CSFR-deficient, primary hematopoietic progenitor cells. We show that ectopic expression of wild-type G-CSFR in hematopoietic progenitor cells supports G-CSF-dependent differentiation of these cells into mature granulocytes, macrophages, megakaryocytes, and erythroid cells. Furthermore, we show that two mutant G-CSFR proteins, a truncation mutant that deletes the carboxy-terminal 96 amino acids and a chimeric receptor containing the extracellular and transmembrane domains of the G-CSFR fused to the cytoplasmic domain of the erythropoietin receptor, are able to support the production of morphologically mature, chloroacetate esterase-positive, Gr-1/Mac-1-positive neutrophils in response to G-CSF. These results demonstrate that ectopic expression of the G-CSFR in hematopoietic progenitor cells allows for multilineage differentiation and suggest that unique signals generated by the cytoplasmic domain of the G-CSFR are not required for G-CSF-dependent granulocytic differentiation.

Animals↗

Long-term results of femorotibial bypass with vein or polytetrafluoroethylene.

BACKGROUND: This was a retrospective review of the long-term results of femorotibial bypass using autologous vein and polytetrafluoroethylene (PTFE) over 24 years. METHODS: Some 518 patients who underwent 635 femorotibial bypass grafts were studied. Outcome measures analysed included primary and secondary graft patency, limb salvage rates and death. RESULTS: Overall primary and secondary graft patencies were 62 and 67 per cent respectively at 12 months, and 44 and 48 per cent at 24 months. For vein grafts, the primary and secondary patencies were 63 and 66 per cent at 12 months, and 54 and 56 per cent at 24 months. For PTFE grafts, the primary and secondary patencies were 48 and 54 per cent at 12 months, and 31 and 37 per cent at 24 months. Limb salvage and patient survival rates were 81 and 84 per cent at 12 months, and 73 and 74 per cent at 24 months. Primary and secondary graft patencies for vein were significantly better than for PTFE (P = 0.0001). There was no difference in patency between reversed and in situ grafts. CONCLUSION: Femorotibial bypass can produce excellent long-term results. Vein remains the conduit of choice but in the absence of vein acceptable results can be achieved with PTFE.

Adult↗

The effect of a pure antiandrogen receptor blocker, flutamide, on the lipid profile in the polycystic ovary syndrome.

Polycystic ovary syndrome (PCOS) is one of the most common endocrinopathies affecting women of reproductive age; it is associated with hyperandrogenism, hyperinsulinemia, and dyslipidemia. This study was designed to assess the long term effects of a pure androgen receptor blocker, flutamide, on the lipid profile in women with PCOS and to examine the possible mechanisms by which androgens may exert their influence. Seventeen women with PCOS (10 obese and 7 lean) were studied. All subjects received a 12-week course of oral flutamide (500 mg/day). The baseline and posttreatment evaluations included lipid profile, androgen levels, insulin sensitivity, and serum catecholamine determinations. The primary outcome was the change in the ratio of low density lipoproteins (LDL) to high density lipoproteins (HDL). Treatment with flutamide was associated with a significant decrease in the LDL/HDL ratio by 23% (P = 0.005), in total cholesterol by 18% (P < 0.0001), in LDL by 13% (P = 0.002), and in triglycerides by 23% (P = 0.002). Flutamide treatment was also associated with a trend toward an increase in HDL (by 14%; P = 0.14). The effects on lipid profile were found regardless of obesity and were not associated with a change in weight. Furthermore, actions of flutamide on lipid metabolism were not associated with significant changes in circulating adrenaline or noradrenaline, glucose metabolism, or insulin sensitivity. This report has demonstrated for the first time that treatment with the pure antiandrogen, flutamide, may improve the lipid profile and that this effect may be due to direct inhibition of androgenic actions.

Adult↗

Furosemide decreases the sensitivity of glucose transport to insulin in skeletal muscle in vitro.

The effects of the diuretic furosemide on the sensitivity of glucose disposal to insulin were investigated in rat soleus muscle in vitro. At basal levels of insulin, the rates of 3-O-methylglucose transport, 2-deoxyglucose phosphorylation and lactate formation were not affected significantly by furosemide (0.5 mmol/l). However, furosemide significantly decreased these rates at physiological and maximal levels of insulin. The contents of 2-deoxyglucose and glucose 6-phosphate in the presence of furosemide were not significantly different from those in control muscles at all levels of insulin studied. It is concluded that furosemide decreases the sensitivity of glucose utilization to insulin in skeletal muscle by directly inhibiting the glucose transport process.

3-O-Methylglucose↗

Early administration of somatostatin and efficacy of sclerotherapy in acute oesophageal variceal bleeds: the European Acute Bleeding Oesophageal Variceal Episodes (ABOVE) randomised trial.

BACKGROUND: Sclerotherapy is widely used for acute variceal bleeding, although in emergencies bleeding makes it difficult to obtain the clear view required for safe and effective treatment. We investigated whether early administration of somatostatin would improve the efficacy of sclerotherapy. METHODS: In this double-blind, prospective trial, patients who had cirrhosis with upper-gastrointestinal bleeding were randomly assigned natural somatostatin (6 mg per 24 h) or placebo for 120 h. In addition, intravenous bolus doses of somatostatin (250 micrograms) or placebo were injected after the start of the infusion, before emergency endoscopy or sclerotherapy, and when active bleeding was observed. The primary endpoint was treatment failure, defined as the occurrence during the infusion period of at least one of: excess transfusion of blood products, haematemesis, haemodynamic instability, need for rescue therapy, or death. FINDINGS: 205 patients were enrolled: 101 received somatostatin and 104 received placebo. Treatment failed in 35 somatostatin and 57 placebo recipients (p = 0.004); death or use of rescue therapy occurred in nine and 19 patients, respectively (p = 0.05). The mean quantity of blood products transfused over 120 h (adjusted for baseline haemoglobin) was 2.64 (SD 0.35) units in the somatostatin group versus 3.62 (0.35) units in the placebo group (p = 0.05). At endoscopy, active bleeding from oesophageal varices was less frequent (27 vs 42 patients, p = 0.012) and the sclerotherapy procedure was easier (2.8 vs 4.7 cm, p = 0.0027) in the somatostatin than in the placebo group. INTERPRETATION: Early administration of natural somatostatin continued for 120 h, combined with additional bolus injections, is more effective than placebo in the overall control of acute variceal haemorrhage in patients with cirrhosis undergoing sclerotherapy.

Double-Blind Method↗

Coronary microcirculation evaluation with transesophageal echocardiography Doppler in type II diabetics.

Evaluation of coronary microvascular function can be obtained through coronary flow reserve measurements. The aim of this study was to evaluate the coronary microvascular function by using transesophageal-Doppler echocardiographic assessment of coronary flow reserve. The study included 32 normotensive patients with type II diabetes mellitus (group A) of short duration (6.1+/-3.8 years) aged 55.4+/-9.4 years and 14 healthy volunteers matched for age, gender and BMI (group B). No patients had clinical evidence of coronary artery disease and all of them produced a negative recent stress ECG test. Excluded from the study were patients with anemia, left ventricular hypertrophy, arrhythmia, congenital, or acquired structural heart disease. All subjects underwent transesophageal-Doppler echocardiography. Satisfactory coronary blood flow velocity recordings could be obtained from the initial segment of the left anterior descending coronary artery in healthy volunteers and in 27 patients at baseline and 2 min after dipyridamole infusion (0.56 mg/kg, for 4 min). In the remaining 5 patients no satisfactory recordings were available. The indexes of coronary flow reserve, i.e. the ratios of dipyridamole over basal maximum and mean diastolic velocities were calculated. Dipyridamole/rest maximal coronary reserve (Table 3) was 1.946+/-0.743, while this ratio for the mean diastolic velocity was 1.969+/-0.805 in group A. The respective values for group B, were 2.811+/-0.345 (P=0.000 vs. group A) and 2.914+/-0.303 (P=0.000 vs. group A). Thus, the increase in coronary flow reserve although present in both groups, it was more impressive in the normal group. Multiple regression logistic analysis of: age, sex, smoking, glucosylated hemoglobin, duration of diabetes and type of therapy, did not show any correlation of these parameters with the above ratios. This study shows that coronary flow reserve, as measured with transesophageal echocardiography-Doppler, is severely impaired in normotensive patients with type II diabetes, with relatively short duration of the disease.

Age Factors↗

Codon 12 ras mutations in patients with myelodysplastic syndrome: incidence and prognostic value.

To determine the prevalence of activated rasoncogenes (N-ras, Harvey-ras Kirsten-ras), DNA derived from peripheral blood of 51 patients with myelodysplastic syndrome (MDS) was investigated. The method was based on the polymerase chain reaction (PCR) technique to amplify DNA, followed by restriction fragment length polymorphism (RFLP) analysis. Among the French-American-British (FAB) subtypes, N-ras mutations were found in two patients with refractory anemia with excess of blasts (RAEB), in one patient with refractory anemia with excess of blasts in transformation (RAEB-t), and in two patients with chronic myelomonocytic leukemia (CMML). MDS patients with a mutation at codon 12 of the N-ras gene showed shorter survival duration than other MDS patients of the same FAB subtypes, although these findings proved to be not statistically significant (P > 0.1). Interestingly, all but one patient with N-ras mutation developed acute myelogenous leukemia (AML). In conclusion, the presence of mutation at codon 12 of the N-ras gene might serve as a negative prognostic factor at diagnosis of MDS.

Adult↗

Anterior, posterior, or laparoscopic approach for the management of adrenal diseases?

BACKGROUND: At the advent of laparoscopic adrenalectomy it seemed timely to us to assess the advantages and the overall results of the different techniques that are currently used in an approach to adrenalectomy. PATIENTS AND METHODS: Between 1984 and 1995, 165 patients underwent adrenalectomy. Eighty-six patients (37 men and 49 women with a mean age of 46.4 years) underwent adrenalectomy via the anterior approach, 61 patients (18 men and 43 women with a mean age of 43.8 years) underwent posterior extraperitoneal adrenalectomy, and 18 patients (8 men and 10 women with a mean age of 48.7 years) underwent anterior laparoscopic adrenalectomy. For statistical analysis of the different comparisons between the groups we used the t test for independent samples, the Wilcoxon test, chi-square, and one way analysis of variance. RESULTS: There was no operative mortality. The morbidity was 13.9% in the anterior approach, 9.8% in the posterior approach, and 0% in the laparoscopic approach. The mean operating time for unilateral adrenalectomy was 155.3 min (range 75 to 315) for the anterior approach, 108.6 min (range 60 to 195) for the posterior approach and 116.1 min (range 75 to 180) for the laparoscopic approach. For bilateral adrenalectomy the mean operating time was 165 min for the anterior and 178 min for the posterior approach. The average diameter of tumors resected anteriorly was 8.07 cm (range 2.5 to 20), posteriorly was 5.25 cm (range 0.5 to 14), and laparoscopically was 4.03 cm (range 2 to 6.5). The mean length of postoperative hospitalization for patients undergoing unilateral adrenalectomy was 8 days (range 2 to 25) for the anterior approach, 4.5 days (range 1 to 11) for the posterior approach, and 2.2 days (range 1 to 5) for the laparoscopic approach. Patient controlled analgesia lasted 3.4 days for those operated anteriorly, 2.3 days for those operated posteriorly, and 1.08 days for those that underwent laparoscopic adrenalectomy. CONCLUSIONS: The laparoscopic approach to the adrenal promises the safest and least painful operation with shorter in-hospital stay and the best cosmetic and long-term results. The posterior approach is the fastest of all and a better overall operation than the anterior approach that should only be reserved for removing very large adrenal tumors and when concomitant intra-abdominal procedures, that can't be handled laparoscopically, are anticipated.

Adolescent↗