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Biomedical subjects

I Costea

Publications and source records attributed to I Costea.

At least 19 recordsLinked to original sources
PubMed2005

Combining several polymorphisms of thymidylate synthase gene for pharmacogenetic analysis.

Thymidylate synthase (TS) is an essential enzyme in proliferating cells and an important target for several chemotherapeutics. Several TS gene polymorphisms correlate with variable TS expression: a double (2R) and triple (3R) 28-bp repeat element, a G to C substitution of the 3R allele and a 6 bp variation in 3'UTR. We have previously shown that childhood acute lymphoblastic leukemia (ALL) patients who are homozygous for the 3R allele had reduced event-free survival (EFS) probabilities. Here, we analyzed all three polymorphisms in an extended group of ALL patients (n=259). The effect of the 3R homozygosity on ALL outcome was confirmed (P=0.006), whereas 6 bp polymorphism did not influence EFS when analyzed separately. No significant difference among 3R3R genotype subgroups, as defined by a G to C substitution, was observed. The haplotype analysis revealed the higher frequency of the 3RC/6 bp+ haplotype (P=0.04) and the protective role of the 2R/6b p- (P=0.04). Consequently, homozygosity for the 6 bp- allele appeared to reduce an event-predisposing effect of 3R variant. Although of importance for translation into the clinical practice, these findings need confirmation in larger studies.

Child↗
PubMed2004

Role of polymorphisms in MTHFR and MTHFD1 genes in the outcome of childhood acute lymphoblastic leukemia.

The central role of 5,10-methylenetetrahydrofolate reductase (MTHFR) and methylenetetrahydrofolate dehydrogenase (MTHFD1) in folate metabolism renders polymorphisms in genes encoding these enzymes potential modulators of therapeutic response to antifolate chemotherapeutics. The analysis of 201 children treated with methotrexate for childhood acute lymphoblastic leukemia (ALL) showed that patients with either the MTHFR T677A1298 haplotype or MTHFD1 A1958 variant had a lower probability of event-free survival (EFS) in univariate analysis (hazard ratio (HR)=2.2, 95% confidence interval (CI), 1.0-4.7 and 2.8, 95% CI, 1.1-7.3, respectively). Multivariate analysis supported only the role of the MTHFR variant (HR=2.2, 95% CI, 0.9-5.6). However, the association of both genes with ALL outcome appears to be more obvious in the presence of another event-predisposing variant belonging to the same path of drug action. The combined effect of a thymidylate synthase (TS) triple repeat associated with increased TS levels, with either the MTHFR T677A1298 haplotype or MTHFD1 A1958 allele, resulted in a highly significant reduction of EFS (multivariate HR=9.0, 95% CI, 1.9-42.8 and 8.9, 95% CI, 1.8-44.6, respectively). These results reveal the role of gene-gene interactions within a folate pathway, and how they can correlate with relapse probabilities in ALL patients.

Child↗
PubMed2002

Polymorphism of the thymidylate synthase gene and outcome of acute lymphoblastic leukaemia.

Interindividual variability in response to methotrexate could be caused by variable concentrations of thymidylate synthase. We investigated the possible association between a tandem-repeat polymorphism in the thymidylate synthase promoter, of which a triple repeat is associated with increased expression of thymidylate synthase, and outcome of acute lymphoblastic leukaemia in 205 children treated with methotrexate. We obtained DNA samples from buccal epithelial cells, peripheral blood, or bone marrow in remission, and analysed them for the polymorphism by PCR amplification. Individuals who were homozygous for the triple repeat had a poorer outlook than those with other genotypes (odds ratio 4.1, 95% CI 1.9-9.0, p=0.001). Genotyping of thymidylate synthase might make it possible to individualize treatment for patients with acute lymphoblastic leukaemia.

Child↗
PubMed1998

[The tomographic diagnosis of Basedow's orbitopathy].

The inflammatory and infectious circumstances involving the orbit are known as 'orbitopathies' Considering the progress of immunology and imagistical investigations, it has been proposed a new classification of these entities. This classification divides the orbithopathies in specific and nonspecific. This paper brings up the case of a 65 year old female patient, showing unilateral proptosis with progressive evolution for about one year. The local examination and paraclinical investigations (computerised tomography and thyroid gland scintigram) sustained the diagnosis of Basedow disease. The ophthalmopathy in Basedow disease is a specific orbital involvement. Considering it's high rate of occurrence among the exophthalmic eyes (10%) it rests a severe disease, with a not yet fully understood physiopathology and a controversial treatment. The basedowian ophthalmopathy is, as well, an autoimmune disease, which requires the presence of T lymphocytes at the level of the orbital tissue. The computerised tomography gives us a direct visualisation of the enlarged muscles in hyperthyroidism (the muscles can increase 8 times their normal size), that is why we have to recommend it every time we are facing a patient with proptosis, especially unilateral.

Aged↗
PubMed1995

[Secondary hyperparathyroidism].

Secondary (renal) hyperparathyroidism appears in chronic renal failure, sometimes in patients on chronic dialysis. Other causes includes rickets and osteomalacia. These diseases are associated with poor calcium and vitamin D absorbtion from the small bowel. Two patients with chronic renal failure maintained on chronic haemodialysis from two and three years, respectively underwent subtotal parathyroidectomy: removal of three glands and preserving a half of a gland in situ. The diagnosis and surgical indication was made upon clinical (bone pain and severe itching), radiological (demineralisation, ectopic calcifications) and biochemical (hypercalcemia, hyperphosphoremia, increased values of alkaline phosphatases) arguments. Postoperatively the improvement is defined by a return to normal in the clinical, laboratory and radiological parametres. The most appropriate operation for secondary hyperparathyroidism is still unresolved one of two techniques is performed according to the preference of the surgeon: subtotal parathyroidectomy or total parathyroidectomy with autotransplantation of parathyroid fragments into forearm muscle.

Adult↗
PubMedDate not supplied

[A prognostic audit in colorectal cancer: between the clinical realities and the therapeutic principles].

A clinical series of 137 cases of colorectal cancer (98 + 39) was admitted in the IVth Surgical Clinic between 1987-1996 (double compared to the previous decade), consisting of 101 men and 36 women with an average age of 62. The diagnosis was established by physical examination (43 cases, most of them acutely obstructed), completed by biological, radiological and histologic examination of the surgically removed tumours. The pre- and postoperative staging revealed a large number of advanced forms: stage I--6 cases (4.3%), stage II--33 cases (263%), stage III--52 cases (36.5%) and stage IV--46 cases (32.3%). Surgery was performed on 118 patients, the tumours being removed by different types of resections according to location in 81 cases (operative rate of 86.1% and resectability rate of 59.1%, both being higher compared to the previous decade 56.8% of the surgical procedures were palliative and 41 patients (34%) underwent curative resections. The postoperative morbidity and mortality rate was 30.5% and, respectively 4.3% (5 deceased). The long-term survival followed on 44 cases revealed that only 20.3% were alive after 5 years from the operation.

Adult↗
PubMedDate not supplied

[The anatomico-surgical aspects of the lumbar sympathetic network].

Our article yields new statements about macroscopic anatomy of the sympathetic lumbar chain, after the dissection of 480 corpses in a 15 years period. Our observations state new conclusions, with implications in surgical practice, about the function and the vegetative territory of the lumbar sympathetic chain.

Afferent Pathways↗
PubMedDate not supplied

["Spontaneous", "delayed" and "occult" ruptures of the normal and pathologic spleen. Nosologic classification].

The anatomic particularities and the diversity of the splenic pathology determine a wide spectrum of the traumatic lesions of the spleen. The classical acute rupture with consecutive hemoperitoneum and mandatory surgical indication is opposed to the controversial "spontaneous" ruptures of the normal and pathologic spleen and also to the delayed and occult ruptures the lasts of them sometimes minimal or with chronic evolution. A series of eight cases all males with ages between 40-77 years is presented in order to exemplify all these entities. There are underlined the variety of etiologic conditions, the difficulties of the diagnosis which impose an insistent anamnesis and clinical examination (searching even a "trivial" trauma) completed with ultrasonography and CT scan which are preferred to radionuclide scan of arteriography and finally peritoneal lavage after punction, laparoscopy and even laparotomy. Splenectomy--often laborious--was effective in all our patients (obviously only temporary for the cases with nonhodgkin malignant lymphoma and respectively with splenic metastasis from a renal carcinoma). In some situations--especially in children--the conservative treatment can be considered.

Adult↗
PubMedDate not supplied

[Hyperfunctional parathyroid carcinoma].

The parathyroid cancer is mentioned in literature with an incidence of 0.5-5% in the etiology of the primary hyperparathyroidism. The authors present the case of a 45 year old female with diagnosis of "primary hyperparathyroidism" based on clinical, ultrasonographic and biochemical investigations. A right superior adenoma of 3 x 2 x 1 cm (150 mg) has been found and extirpated. The histological examination showed an adenoma with predominant "chief" cells. Three years after surgery the patient had a recurrence of the clinical and hypercalcemie syndrome (with more severe damages). The surgical reexploration showed the right thyroid lobe with a nodular aspect and in its inferior pole a enlarged parathyroid gland of one cm size was found. An en-block exeresis including the right thyroid lobe with isthmus as well as the mentioned lesion and the half of left superior parathyroid, the left inferior one together with retrosternal fat tissue have been performed. Frozen sections completed by paraffin examination established the diagnosis of hyperfunctioning parathyroid carcinoma. We have emphasize the issues that could suggest the initially preoperative true diagnosis: the large size of excised adenoma and the relatively quick recurrence of the phenomena of parathyroid hyperfunction. The surgical principles and strategies in the treatment of parathyroid cancer are also discussed.

Carcinoma↗
PubMedDate not supplied

[Upper digestive hemorrhage, physiopathologic and therapeutical considerations].

The study is based on the analysis of 158 patients admitted in the "Fourth Clinic of Surgery" with diagnosis of "Upper Digestive Haemorrhage" (U.D.H.) between 1998-2002, emphasising the importance of the physiopathological chains induced by the ulcer bleeding; 119 cases (76%) were diagnosed with gastro-duodenal ulcer, 20 with portal hypertension (20%), 14 subjects were with gastric carcinoma (8.8%) and 5 with miscellaneous etiologies so called "rare circumstances" of U.D.H. (two patients with Idiopathic Thrombocytopenia, one case with Dieulafoy gastric ulceration and two subjects with Haemorrhagic Gastritis). All the patients were admitted in the first moment in the Intensive Care Unit where haemostasis were successfully obtained with drug therapy adapted to the physiopathological changes induced by bleeding, in the majority of cases with light bleeding (8 cases, 5.4%) or medium bleeding (139 patients, 87.4%); only in 9 subjects (6%) with severe haemorrhage surgery was indicated (posterior bulbar ulcer in which the surgical haemostasis was necessary). In 88 patients (55%) surgery was performed as an elective procedure--74 from them had haemorrhagic gastric or duodenal ulcers with a medium amount of bleeding and 14 observations for gastric carcinoma with a chronic bleeding. In most all the cases the postoperative evolution was in good terms. Two observations with severe U.D.H. due to rupture of esophageal varices occurred on hepatic cirrhosis were out of therapeutical proof (1.2% deaths from all the admitted patients with U.D.H.).

Adult↗
PubMedDate not supplied

[Antibiotic prophylaxis in surgery for colorectal cancer].

The prophylactic use of antibiotics in the purpose of decreasing the frequency and severity of surgical infections is still controversial. The practical need of defining the concept of antibiotic prophylaxis gave rise to numerous polemics in the literature. This paper presents a retrospective study on 103 cases whom diagnostics were colon and rectum cancer, that were operated in the IV-th Surgical Clinic in 1993-2002 period; at these patients was done antibiotic prophylaxis local and systemic before, during and after operating. This method made possible the registration of a minimum number of cases with surgical infection (7 cases, representing only 7% of the operated patients): a case (1%) with peritoneal collection (needing the surgical evacuation of this collection) and in 6 cases, parietal superficial infections, which imposed the prolong of drainage for almost 7 days. Starting from the basic principles of antibiotic therapy, this paper aims at outlining practical guidelines for a judicious antibiotic prophylaxis.

Anti-Bacterial Agents↗
PubMedDate not supplied

[Total parathyroidectomy with forearm graft in tertiary hyperparathyroidism].

Autonomic and persistent hypersecretion of PTH is a frequent and tormenting complication of the patients with chronic renal dialysis for end stage renal disease (ESRD). In these cases, surgery remains a therapy option with real effects on clinical status of patients, especially in perspective of a renal transplant. The authors present the case of a patient with tertiary hyperparathyroidism for which a total parathyroidectomy followed by autotransplantation of small glandular fragments in forearm muscles was performed. The postoperative clinical and immunological statuses were favorable with the disappearance of pruritus and osteoartralgia with improvement of psychic behavior and normalization of calcium blood level. Considering the parathyroidectomy as a palliative stage in the treatment of ESRD, the authors discussed a hierarchy system of both indications and surgical alternatives to be considered in this condition. In well selected cases this surgical method represents an attractive and easy possibility to control and later adjustment of the hyperfunction of remained parathyroid tissue, avoiding in this way a very risky intervention.

Forearm↗
PubMedDate not supplied

[Bulbantrectomy with truncal vagotomy in the surgical treatment of duodenal ulcer].

Duodenal ulcer benefits of very efficient medical treatment. In currently medical practice exist many cases with complicated duodenal ulcer (by stenosis or penetration in neighbor organs like pancreas or biliary tract or painful forms etc.) to which surgical treatment is necessary. Based on the retrospective study of 116 patients operated between 1991-2002 years for gastric or duodenal ulcer, this paper demonstrates that bulbantrectomy associated with bilateral truncal vagotomy (63.7% of cases) is the best surgery in the treatment of duodenal complicated ulcer or resistant to the medical procedures. Provided by correct indication, the intervention is the most pathogenic, offering the best immediate and long term postoperative results. If the bulbantrectomy is contraindicated (critical general status, etc.), the alternative is a bilateral truncal vagotomy associated with a drainage procedure: pyloroplasty (6.9% of cases) or gastroenterostomy. When the vagotomy are contraindicated or cannot be correctly performed, a large gastrectomy (29.3% of cases) followed by gastroduodenal (preferable) or gastrojejunal anastomosis are practiced.

Adult↗
PubMedDate not supplied

[Minimally invasive approach of the cervical endocrine glands].

Improved preoperative functional and topographic diagnostic techniques and availability of intra-operative hormone monitoring, stimulated the introduction of video-assisted minimally invasive operations in parathyroid and thyroid surgical pathology. The first cases of such pathology operated on in our clinic are presented. The first one is a 62 year old man with renal hyperparathyroidism consecutive to a chronic renal insufficiency and hemodialysis from five and three years respectively. The technique of a minimally invasive gapless resection of all four "adenomised" parathyroid glands using laparoscopic and classic instruments is described. Fragments of one gland are implanted in the left forearm musculature. The second case was a 48 year old woman with a three cm diameter right toxic adenoma. With a lateral 15 mm incision, dissociation of the musculature and adequate moving of the retractors the excision of the thyroid nodule was done in 25'. The video-assisted minimally invasive approach allows magnification and adequate identification and removal of endocrine secreting tissues in thyroid and parathyroid pathology. The authors believe that these techniques represent a feasible and attractive alternative to conventional surgery.

Adenoma↗
PubMedDate not supplied

[The evaluation of the teratogenesis and embryotoxicity of the pharmaceutical product Boicil tablets. I. The effect of the pharmaceutical product Boicil tablets on fertilization and implantation in rats and mice].

The teratogen action of Boicil tablets was studied in two animal species, rats and mice, the prefertilization and implantation stages being the main interest. Three generations of animals were followed up. The active powder suspended in distilled water (0.1 ml/10 g for mice and 1 ml/100 g for rats) was administered per os in a single dose, prepared on spot and in two doses, 2 mg/kg body weight and 20 mg kg body weight, respectively. The administered doses were equivalent to the daily maximum therapeutic dose prescribed in humans (110 mg active principle). The first gestational day was determined differently in the two species. For estimating the effect on prefertilization, Boicil tablets was administered for 5 days before making and for its effects on the number of implantations during the first 3 gestational days. The two parameters under investigation were within normal limits and all newborn animals followed up for three generations did not present pathological microscopic and gross alterations or somatic malformations. It was concluded that Boicil tablets is not teratogenic.

Abnormalities, Drug-Induced↗
PubMedDate not supplied

[The evaluation of the teratogenesis and embryotoxicity of the pharmaceutical product Boicil tablets. II. The effect of the pharmaceutical product Boicil tablets on early embryogenesis, organogenesis and the fetus in 3 successive generations of rats and mice].

The effect of Boicil tablets on early embryogenesis (the first 3 gestational days), organogenesis (the 10th, 11th and 12th gestational days) and fetus (the 18th and 19th gestational days) by its intraamniotic administration was followed up in three successive generations of mice and rats. Two doses were used (2 mg/kg body weight and 20 mg/kg body weight), estimated in relation with the maximum therapeutic daily dose in man, being administered in a single dose, per os. No inborn malformations or somatic abnormalities were recorded both in mothers and in their descendents for three successive generations. It is concluded that Boicil tablets is not teratogenic.

Abnormalities, Drug-Induced↗