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Biomedical subjects

M Hayran

Publications and source records attributed to M Hayran.

At least 19 recordsLinked to original sources

Diarrhea in neutropenic patients: a prospective cohort study with emphasis on neutropenic enterocolitis.

BACKGROUND: Although diarrhea is a frequent complication in neutropenic patients, its true incidence, risk factors and clinical course have not been investigated prospectively. PATIENTS AND METHODS: The study was carried out at Hacettepe University Hospital for Adults and involved patients over 16 years of age. Patients with malignant diseases who were neutropenic on admission or who became neutropenic during their stay in the wards between January 2001 and February 2003 were included. They were monitored daily until discharge, exitus, or recovery from neutropenia-whichever occurred earlier-to monitor the presence of diarrhea and other infections. RESULTS: A total of 317 neutropenic episodes in 215 patients were followed. Diarrhea was observed in 18.6% episodes, and the incidence of NEC was 3.5%. The etiology in 27% episodes of diarrhea could not be identified. The use of anthracyclines and mitoxantrone increased the incidence of diarrhea. Prior use of penicillin derivatives plus beta-lactam inhibitors and N-imidazoline derivatives was associated with decreased incidence of diarrhea. CONCLUSIONS: Diarrhea is a common complication in neutropenic patients. Not only specific conditions like NEC, but also nonspecific diseases like parasitosis may be the cause of diarrhea in this patient population.

Adult↗

Appropriate analysis and presentation of data is a must for good clinical practice.

Good Clinical Practice (GCP) is defined as an international ethical and scientific quality standard for designing, conducting, monitoring, auditing, analyzing and reporting trials that involve the participation of human subjects. This paper focuses mainly on the issues that need attention at the time of statistical analysis and reporting of results. Findings from a review of published articles in Turkey are also presented. The types of variables, the distributions of variables, the number of groups compared, the dependency structure among these groups and the primary goal of the analysis determine the appropriate method to be selected for the statistical analysis. The review of a stratified sample of research articles from 60 journals published in 1992 in Turkey revealed that in 56% of the cases the statistical methods were improper or inadequate. In 15% of the articles the authors failed to select an appropriate design for the proposed aim mentioned in the manuscript. Despite the recent improvements, the necessity and the value of performing and presenting research according to the international standards remains to be assimilated better by Turkish investigators.

Clinical Trials as Topic↗

In vivo use of all-trans retinoic acid prior to induction chemotherapy improves complete remission rate and increases rhodamine 123 uptake in patients with de novo acute myeloid leukemia.

All-trans retinoic acid (ATRA) is used in the treatment of acute promyelocytic leukemia. Because ATRA has effects (increase in apoptosis, suppression of bcl-2), it has also been used for the treatment of other French-American-British (FAB) subtypes of acute myelogenous leukemia (AML). To find out the in vivo and in vitro effects of ATRA in AML, we analyzed 37 patients with de novo AML. Twenty-seven patients received ATRA before remission-induction (RI) treatment (ATRA group). Results were compared to a control group (10 patients) that received induction without ATRA during the same time period. Bone marrow or peripheral blood samples were collected from all patients on d 0 and 4. The immunphenotype, myeloperoxidase (MPO), reac tion and the efflux uptake of rhodamine 123 (Rh123) were analyzed on myeloblasts in these samples. In the myeloblasts from patients treated with ATRA, the uptake of Rh123 was increased significantly (p = 0.026) from d 0 to d 4, and all other parameters remained unaltered. ATRA administration increased the complete remission (CR) rate (88%, 22/25 vs 55%, 5/9) significantly (p = 0.042). Logistic regression analysis revealed that ATRA administration was the important factor in CR, among other potential factors including age, white blood count, bcl-2 expression, and the uptake and efflux of Rh123 (p = 0.05). Estimated disease-free survival and overall survival were similar between these two groups (43% vs 37.5% and 51.2% vs 37.5%, respectively). In conclusion, ATRA treatment prior to RI treatment may improve the CR rate in patients with de novo AML, which seems to be related to its beneficial effect on multidrug resistance.

Acute Disease↗

A retrospective review of 228 episodes of infective endocarditis where rheumatic valvular disease is still common.

Two hundred and twenty-eight episodes of infective endocarditis in adult patients (mean age 36 years) were reviewed retrospectively. There were 183 episodes (80%) of native valve, 15 (7%) early prosthetic valve and 30 (13%) late prosthetic valve endocarditis. The most common predisposing factor was rheumatic valvular disease (65%). None of the patients were intravenous drug users. According to the Duke criteria, the number of definite, probable and rejected episodes were 121 (53%), 94 (41%) and 13 (6%), respectively. Additional minor criteria increased the number of definite endocarditis to 82%. The Duke criteria are not primarily intended to influence treatment decisions but are helpful in standardising research activities. The choice of the level of sensitivity or specificity of the criteria may be adjusted according to the aim of the study and prevalence of disease in a particular area. More sensitive criteria may be valuable in those countries where the prevalence of rheumatic valvular disease is still high.

Adolescent↗

Impact of radiotherapy on normal brain tissue: semi-automated quantification of decrease in perfusion.

PURPOSE: We attempted to ascertain the impact of Co-60 conventional external radiotherapy (cRT) on the perfusion of normal brain tissue in relation to the radiation doses delivered to the tumors in patients with primary brain tumors. MATERIALS AND METHODS: After surgery 18 patients (pts) were due to undergo cRT with a total dose of 5400- 6400 cGy. All the patients had a Tc-99m-HMPAO SPECT study prior to cRT (basal), 15th and 30th days of cRT as well as 1 (in 6 pts), 3 (in 9 pts), and 6 (in 3 pts) months after cRT. For quantitative evaluation, the entire set of transverse slices were divided into 4 regions as frontal, parietal, occipital and temporal regions by means of a computer software program. Semi-automated quantification was performed on a total of 1392 regions in 87 studies to determine left to right ratios. An interregional difference of at least 10% was considered abnormal. RESULTS: After elimination of tumor sites, 80 normal brain regions showed decreased perfusion after cRT. The percent decrease in perfusion was (mean 22.5+/-9.9) significantly higher in areas irradiated with doses > 3000 cGy (p < 0.05). CONCLUSION: cRT has adverse effects on the perfusion of normal brain tissue for doses > 500 cGy. Our findings justify treating patients with small and limited lesions with stereotactic radiotherapy in order to minimize the adverse effects of cRT on normal tissues.

Adolescent↗

Analysis of a mini-outbreak of methicillin-resistant Staphylococcus aureus in a surgical ward by using arbitrarily primed-polymerase chain reaction.

In November 1995, an increase was noticed in the number of methicillin-resistant Staphylococcus aureus (MRSA) isolates from a surgical ward at Hacettepe University Hospital. All MRSA isolates obtained from clinical specimens in this ward (14 MRSA isolates from wound cultures of 10 patients) were collected prospectively for 10 weeks. Surveillance cultures were taken from ward personnel (nose cultures from 4 physicians, 7 nurses, 1 secretary, 1 waiter), 2 surgical dressing containers and 1 nebulizer. MRSA was isolated from one of the surgical dressing containers, the nebulizer and nose cultures of 3 physicians, 3 nurses and the ward secretary. Arbitrarily primed polymerase chain reaction (AP-PCR) analysis showed that most MRSA isolates belonged to 2 major clones (pattern A, pattern B). Pattern A was the most frequent one and was present in 4 clinical isolates, surgical dressing container-1. Pattern B was identified in 3 clinical isolates and nose culture of physician-3. AP-PCR analysis revealed that this mini-MRSA outbreak was caused by contamination of surgical dressing container with MRSA and nasal MRSA carriage in ward staff. AP-PCR seems to be a valuable typing method for analysis of nosocomial MRSA outbreaks because of its simplicity and rapidity.

Adolescent↗

Treatment results and prognostic factors in inoperable carcinoma of the cervix treated with external plus high dose brachytherapy.

Patients with inoperable carcinoma of the cervix treated with external plus high dose rate brachytherapy (HDRB), between 1988 and 1995 were evaluated retrospectively. According to stage, 5 year survival rates were 67.3% in stage IIb and 52.6% in stage III (P = 0001) and disease free survival (DFS) rates were 54.0% in stage IIb and 43.9% in stage III (P = 0.01). The following parameters were studied: age; stage; external beam dose; brachytherapy dose; total dose to point A; tumor mass; tumor response rate; bilateral or unilateral invasion of parametria in stage IIb; and bilateral or unilateral invasion of pelvic wall in stage IIIb; and the existence of hydronephrosis. The only significant parameter of 5 year survival and local control was tumor mass (P = 0.003).

Adult↗

The significance of the bone marrow biopsy pattern in chronic lymphocytic leukemia: a prognostic dilemma.

Although bone marrow biopsy pattern (BMBP) has long been suggested to be an independent prognostic factor in chronic lymphocytic leukemia (CLL), conflicting reports continue to appear in the literature. To investigate this issue we retrospectively reviewed 70 CLL patients who had undergone bone marrow biopsy at the time of diagnosis in a multivariate Cox regression analysis together with other prognostic factors. There were 51 (72.8%) males and 19 (27.2%) females with a median age of 60 years (range, 38-77). The median follow-up time was 24 months (range, 1-76), and median survival was 44 months. Thirtyfour patients (48.6%) had diffuse and 36 patients (51.4%) had nondiffuse BMBP (14 nodular, 11 interstitial, and 11 mixed). The median survival for diffuse and nondiffuse BMBP groups were 17 and 53 months, respectively (P= 0.05). Sixteen patients (22. 9%) had stage A, 28 (40.0%) stage B, and 26 (37.1%) stage C disease according to the Binet system, and four patients (5.7%) had low-risk, 39 (55.7%) intermediate-risk, and 27 (38.6%) high-risk disease according to the modified Rai staging system. The difference between the median survivals of patients in different stages was statistically significant (P < 0.0001). The BMBP and staging systems that are thought to be significant predictors of prognosis were used to build a multivariate Cox proportional hazard model. BMBP was not found to add additional information to the prognostic value of the staging systems. Our results underline two points: first, the significance of BMBP must be investigated in multivariate analysis including the stage, and second, BMBP is not a dynamic prognostic parameter, it is an index of tumor burden and does not add any prognostic information beyond that provided by clinical stage.

Adult↗

Comparison of meropenem with amikacin plus ceftazidime in the empirical treatment of febrile neutropenia: a prospective randomised multicentre trial in patients without previous prophylactic antibiotics. Meropenem Study Group of Turkey.

Eighty three patients with neutropenia and cancer were randomised to receive either 1 g meropenem tds or amikacin 15 mg/kg single dose daily plus ceftazidime 2 g tds. No prophylactic antibiotics were allowed before entry to the trial. Seventy seven patients were available for analysis. Infection was microbiologically or clinically documented in 53 episodes (69%). The overall success rate without adjustment was 49% in monotherapy, 37.5% in the combination group. These rates were increased to 65% and 56%, respectively when secondary infection episodes requiring a different class of chemotherapy were taken into account. Median duration for defervescence was 3 days in successfully treated patients in both groups. Only minor reversible side effects were noted in both treatment arms. Meropenem monotherapy seemed as effective and safe as amikacin plus ceftazidime for the empirical treatment of neutropenic cancer patients with fever.

Adult↗

Sucralfate in the prevention of radiation-induced oral mucositis.

Radiotherapy-induced mucositis decreases the quality of life by impairing eating, swallowing, and talking and by disturbing sleep. Mucositis may also predispose to local and systemic infections and may cause interruption of radiotherapy course. We studied the efficacy of sucralfate suspension in the prevention and management of oral mucositis and pain during radiotherapy in a double-blind, placebo-controlled, randomized, prospective trial. Twenty-eight patients with head and neck cancer were included in the study. The patients were randomized to use either sucralfate mouth washing (n = 18) or placebo washing (n = 10) during irradiation. Oral mucositis and symptoms were assessed by the same physician using Radiation Therapy Oncology Group Acute Radiation Morbidity Scoring criteria. All patients developed varying degrees of radiation-induced mucositis. Grade 4 mucositis was not encountered in any patient. One patient had grade 1, seven patients grade 2, and two patients grade 3 mucositis in placebo group. In sucralfate group, nine patients each had grade 1 and grade 2 with no grade 3 mucositis. Patients in the sucralfate group experienced significantly lower degree of mucositis than placebo group (p < 0.05). Sucralfate mouth washing is beneficial in decreasing the intensity of radiation-induced mucositis and oral discomfort. It is cheap, easy to administer with no serious side effect, and may be routinely used in patients receiving head and neck radiotherapy.

Double-Blind Method↗

Reduced incidence of the somnolence syndrome after prophylactic cranial irradiation in children with acute lymphoblastic leukemia.

A prospective double blind randomized trial comparing two different dose schedules of continuous steroid coverage during prophylactic cranial radiotherapy (CRT) in leukemic children was conducted to find out the optimum dose to be prescribed to reduce the incidence of Somnolence Syndrome (SS). Between April 1994 and February 1996, 32 patients with acute lymphoblastic leukemia received CRT of 18 Gy in 10 fractions. Patients were randomized to receive oral dexamethasone of 2 or 4 mg/m2 during radiotherapy. The diagnosis of SS was made clinically based on symptoms of somnolence. All patients were followed for a minimum of 8 months. The overall incidence of SS was 40%. The development of SS was steroid dose dependent. In low dose steroid arm the incidence of SS was 64.3% (9/14), compared to 17.6% (3/17) in high dose arm with statistically significant difference (P = 0.008). The median time to development of SS was 4 weeks. The most common symptom of SS was drowsiness followed by anorexia, headache, nausea, vomiting, decreased activity, irritability, fever and ataxia, respectively. The duration of symptoms ranged from 2 to 14 days. The development of SS was not related to the presence of acute reactions, age at the time of CRT and sex. In all cases the symptoms subsided completely and spontaneously. Our results suggest that steroid coverage at a dose of 4 mg/m2 during CRT reduces the incidence of SS. However, a multicentric prospective randomized trial is needed to determine the role and the optimal dose of steroid.

Adolescent↗

Circulating intercellular adhesion molecule-1 and E-selectin levels in gastric cancer.

A diversity of adhesive interactions occur between the cancer cell and host extracellular matrix which potentiate neoplastic expansion and metastatic dissemination. In miscellaneous malignant diseases, tumour progression has been observed to be associated with alterations in adhesion molecule expression. Recently, circulating soluble intercellular adhesion molecules have been identified. In this study, serum levels of soluble intercellular adhesion molecule-1 (sICAM-1) and soluble E-selectin (sE-selectin) were determined in patients with gastric cancer. The study group consisted of 27 patients with previously untreated gastric adenocarcinoma. Four patients had stage II, two patients stage III and 21 patients stage IV disease according to the TNM classification. Nineteen patients had distant metastasis. The sera obtained from 18 healthy volunteers served as controls. Serum sICAM-1 and sE-selectin concentrations were determined by enzyme-linked immunosorbent assay (ELISA). In addition, we also studied other tumour-associated antigens, i.e. CEA and CA 19-9. Serum sICAM-1 levels were significantly increased in patients with gastric cancer (P < 0.0001). However, sE-selectin levels did not differ from the controls. sICAM-1 concentrations were also significantly higher in patients with distant metastasis and peritoneal spread (P = 0.0045 and P = 0.0157 respectively), whereas sE-Selectin levels were elevated only in patients with peritoneal metastasis (P = 0.033). Serum concentrations of sICAM-1 and sE-selectin correlated with CEA levels (P = 0.0013 and P = 0.003 respectively). Elevated levels of sE-selectin were associated with poorer prognosis (P = 0.0099), whereas sICAM-1 had no significant impact on survival. Our results suggest that increased sICAM-1 serum levels may reflect widespread disease and contribute directly to the progression of gastric cancer. Further investigation of the molecular mechanisms of adhesive tumour-host interactions may lead to a better understanding of the natural history of gastric cancer.

Adult↗

Correlation of in vitro fluconazole susceptibility with clinical outcome for severely ill patients with oropharyngeal candidiasis.

We investigated the correlation between in vitro susceptibility to fluconazole and clinical response in severely ill patients with oropharyngeal candidiasis treated with fluconazole. The study included 48 adult patients, of whom 23 were neutropenic (absolute neutrophil count, < 500/mm3). Forty-eight isolates (20 Candida albicans, 12 Candida krusei, 10 Candida kefyr, 3 Torulopsis glabrata, and 3 Candida tropicalis) were tested for susceptibility to fluconazole with use of the macrodilution method of the National Committee for Clinical Laboratory Standards. A strain was considered to be susceptible to fluconazole if the MIC was < or = 8 micrograms/mL and resistant if the value was > or = 64 micrograms/mL. All but one of the resistant strains were C. krusei isolates. Species of causative Candida, persistent neutropenia, and susceptibility to fluconazole were significant predictors of clinical response by univariate analysis. Logistic regression analysis indicated that the only significant factor was the species of Candida isolates, validating the recently recommended MIC breakpoint and the correlation between clinical outcome and in vitro antifungal susceptibility.

Adult↗