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Biomedical subjects

E Malik

Publications and source records attributed to E Malik.

At least 19 recordsLinked to original sources

Therapy-related leukemia: clinical characteristics and analysis of new molecular risk factors in 96 adult patients.

Therapy-related leukemia or myelodysplasia (t-leuk/MDS) is a serious problem that is increasing in frequency. We studied the clinical characteristics of 96 patients (pts) with a mean age of 48 years, and analyzed the molecular parameters that could predispose to t-leuk/MDS. Hematological malignancies were the most common primary (53%), followed by breast and ovarian cancer (30% combined). The mean latency until the development of t-AML was 45.5 months. Median survival was 10 months. Cytogenetics was abnormal in 89% of pts. FLT3 internal tandem duplications were found in six of 41 (14.6%) pts, of whom four had an abnormal karyotype. Analysis of drug metabolism and disposition genes showed a protective effect of the CYP3A4 1*B genotype against the development of t-leuk/MDS, whereas the CC genotype of MDR1 C3435T and the NAD(P)H:quinone oxidoreductase1 codon 187 polymorphism were both noncontributory. Microsatellite instability (MSI) analysis using fluoresceinated PCR with ABI sequence analyzer demonstrated that 41% of pts had high levels of MSI in four or more of 10 microsatellite loci. Immunohistochemistry demonstrated reduced expression of MSH2 and MLH1 in 6/10 pts with MSI as compared to 0/5 of pts without MSI. In conclusion, genetic predisposition as well as epigenetic events contribute to the etiology of t-AML/MDS.

Adaptor Proteins, Signal Transducing↗

A priori implantation potential does not differ in eutopic endometrium of patients with and without endometriosis.

BACKGROUND: In endometriosis, angiogenesis is a crucial step for implantation of the exfoliates. A priori potential to induce angiogenesis by vascular endothelial growth factor (VEGF) expression was compared in eutopic endometrium of patients with and without endometriosis to discriminate the pivotal pathogenic step that differs in endometriosis. METHODS: In an experimental prospective study, endometrium samples were obtained from endometriosis patients (n=10) and from healthy, ovulating women as controls (n=6) undergoing curettage and laparoscopy for benign gynaecological conditions at the Aachen University Hospital, Aachen, Germany. Endometrial fragments were transplanted to the chicken chorioallantoic membrane (CAM) and re-explanted after 0, 24, 48, 72 and 96 h of cultivation for analysis. The main outcome measure was VEGF mRNA expression and protein localisation in endometrial fragments as parameters of angiogenic induction that was quantified by the vessel index. RESULTS: VEGF mRNA expression increased significantly in endometrial fragments of endometriosis and control patients (p<0.05). Protein is expressed in the glands and endometrial stroma. The vessel index is significantly elevated compared with native CAM controls. Endometrial fragments of endometriosis and control patients showed no significant differences in VEGF expression or angiogenic induction. CONCLUSIONS: Eutopic endometrial fragments of patients with and without endometriosis do not differ in their VEGF expression or angiogenic activity in the CAM assay. Implantation is obviously decided by external regulating influences on the exfoliates.

Animals↗

In vitro analysis of modified surfaces of silicone breast implants.

BACKGROUND: Although silicone breast implants are well tolerated, local complications such as capsular contracture occur because of insufficient integration with surrounding tissues. In this study, cell behaviour on hydrophilized silicone breast implant foils was analysed qualitatively and quantitatively under in vitro conditions in order to provoke the desired responses in a defined environment. METHODS: Silicone breast implant foils with different surface modifications were tested after 24 hours, 5 days and 7 days. The following modifications of silicone implant foils were tested: Unmodified silicone, silicone after-graft polymerisation for polyacrylic acid (pAAc), silicone-pAAc-fibronectin adsorptive, silicone-pAAC-fibronectin covalent, positive and negative controls. Experiments were conducted using cell culture with murine mouse fibroblasts L-929. Cytotoxicity assays were carried out in direct and indirect contact with cells grown on the material. For the viability test and qualitative analysis of cell proliferation on different foils, both fluoresceine-diacetate and ethidiumbromide were used and in addition the morphologic description of hemalaun-stained cells were used. Quantitative cell analysis was carried out using XTT after resuspension. RESULTS: Toxic influence on cell cultures could be excluded for coated and uncoated surfaces in contact with dissolved biomaterials. Unmodified silicone surfaces showed poor cell growth in direct contact. We found a gradual improvement of cell morphology, with the spread and proliferation depending on the type of surface modification. Better results were achieved with covalently coupled fibronectin and GRGDS than with pAAc. CONCLUSION: Covalent immobilisation of hydrophobic silicone rubber can improve the initial cell-biomaterial interactions that are required to aid the successful development of tissue-like structures.

Biocompatible Materials↗

The diagnostic dilemma of minimal and mild endometriosis under routine conditions.

STUDY OBJECTIVE: To evaluate the reliability of diagnosing minimal and mild endometriosis under routine conditions, and to determine to what extent disease activity is taken into account. DESIGN: Retrospective analysis (Canadian Task Force classification II-2). SETTING: University teaching hospital. INTERVENTION: Laparoscopy. PATIENTS: One hundred eighteen consecutive women with minimal and mild endometriosis undergoing routine surgery between 1994 and 1999. MEASUREMENTS AND MAIN RESULTS: Analytic parameters were the total number of endometriotic lesions; intraoperative description of pigmented, nonpigmented, and nondefined lesions; and number of extirpated lesions and histologic detection rate. In 118 patients, 311 suspected endometriotic lesions were documented. Nonpigmented lesions were reported in only 27% of women. In 51% of surgical reports no importance was attached to disease morphology or activity. Only 1.2 biopsies/patient were taken. The histologic detection rate was 56%. In 49 patients the assumed intraoperative diagnosis was confirmed by histologic examination. CONCLUSIONS: Intraoperative description of endometriotic lesions is inadequate. Little attention is paid to the activity of the illness. There is room for improvement in the number of excisions and histologic detection, and an attempt should be made to find a way out of this diagnostic dilemma.

Adult↗

Laparoscopic management of ovarian dermoid cysts. A series of 83 cases.

We did a retrospective survey of 83 patients who had laparoscopic removal of a benign dermoid cyst in our hospital since 1994. Preoperative transvaginal sonography led to the correct diagnosis in 57 cases (69%). In 59 cases cystectomy with ovarian conservation was performed; spillage of cyst contents occurred in 39 cases (66%). Salpingo-oophorectomy was performed in 24 patients with spillage in 8 cases (24%). The mean tumor size (n=83) was 4.5+/-1.6 cm and 4.9+/-2.8 cm for unspilled and spilled cysts, respectively. The tumor was placed in an endobag in 62 cases. No intra- or postoperative complications occurred. No case of chemical peritonitis was noted.

Adult↗

Prospective evaluation of the systemic immune response following abdominal, vaginal, and laparoscopically assisted vaginal hysterectomy.

BACKGROUND: Alterations in serum levels of cytokine interleukin-6 (IL-6) and acute-phase protein C-reactive protein (CRP) correlate directly with extent of tissue damage and inflammatory reaction. We therefore prospectively compared the postoperative levels of IL-6 and CRP following abdominal (AH), vaginal (VH), and laparoscopically assisted vaginal hysterectomy (LAVH). METHODS: A total of 29 patients were included in the study (10 VH, 10 LAVH, 9 AH). Nine blood samples were taken from each patient at various time points before, during, and after surgery. CRP and IL-6 were measured under standardized conditions using ELISA and turbidometry. RESULTS: Preoperative levels of IL-6 and CRP were low in all three patient groups. There was a significant increase in the IL-6 level in patients undergoing AH at the time of peritoneal closure that reached a maximum 2 h postoperatively and remained significantly elevated for 12 h postoperatively when compared to the IL-6 levels of patients undergoing VH or LAVH (p < 0.05). The levels of the IL-6 time courses differed significantly among the three operative procedures (p = 0.013). In contrast, the levels of the CRP time courses did not differ significantly (p = 0.066); however, CRP expression was elevated 36 h postoperatively in patients undergoing AH, as compared with those undergoing VH. CONCLUSION: Elevated IL-6 levels subsequent to AH may reflect significantly greater tissue damage in these patients than in patients who undergo VH or LAVH. LAVH should therefore be considered in cases that cannot be managed by the vaginal route alone.

Acute-Phase Reaction↗

Vascular endothelial growth factor mRNA in eutopic and ectopic endometrium.

OBJECTIVE: To evaluate changes in expression levels of vascular endothelial growth factor (VEGF) mRNA in human endometrial explants in a chicken chorioallantoic membrane model of endometriosis. DESIGN: Experimental prospective study. SETTING: University hospital. PATIENT(S): Endometrial biopsy samples were obtained from healthy, ovulating women undergoing elective surgery. INTERVENTION(S): Endometrial fragments were placed on the chicken chorioallantoic membrane and removed for analysis after 0, 24, 48, and 72 hours. MAIN OUTCOME MEASURE(S): Expression of different VEGF mRNA splice variants was tested. Expression of VEGF(165) mRNA was assessed by using competitive polymerase chain reaction and normalized to expression of the housekeeping gene human glyceraldehyde 3-phosphate dehydrogenase (GAPDH) mRNA. RESULT(S): After 0, 24, 48, and 72 hours of incubation, all grafts expressed VEGF(121), VEGF(145), VEGF(165), and VEGF(189) mRNA. Expression of VEGF(165) mRNA increased up to 10-fold at 24 to 72 hours compared with precultivation values. CONCLUSION(S): Levels of VEGF(165) mRNA in endometrial grafts increase after implantation on chicken chorioallantoic membrane. Hypoxic induction of VEGF mRNA expression in endometrial cell cultures has been reported previously. Induction of VEGF expression might indicate relative hypoxia of the specimen due to insufficient vascularization. Expression of VEGF may assist in vascularization of endometrial explants after retrograde menstruation.

Animals↗

Reproductive outcome of 32 patients with primary or secondary infertility and uterine pathology.

We did a retrospective study on 102 patients who had a laparoscopy and a hysteroscopy during investigations for primary or secondary infertility. 32 of the 102 patients had uterine pathology. Seven of them had septate uteri, eight had uterine synechiae, another six had uterine fibroids, four had a bicornuated uterus, while the remaining had either a combination of all or other uterine anomalies. After surgical treatment of these conditions ten women conceived and five pregnancies including one twin pregnancy resulted in term deliveries.

Adult↗

Fluorescence diagnosis of endometriosis using 5-aminolevulinic acid.

BACKGROUND: The diagnosis of nonpigmented endometrial lesions by simple laparoscopic visualization is difficult and often inaccurate. We therefore sought to establish a new and more accurate method to visualize these nonpigmented peritoneal changes caused by endometriosis. METHODS: A total of 37 patients received 30 mg 5-aminolevulinic acid/kg body weight 10 to 14 hs prior to surgery. Laparoscopy was then performed using a D-light system (Storz, Tuttlingen, Germany). The findings were evaluated first in the white-light mode; the D-light system was then activated, and all areas of fluorescence were documented. Multiple specimens were obtained by biopsy. RESULTS: The sensitivity of the fluorescence diagnosis in detecting endometriosis in nonpigmented areas and normal-looking peritoneum is 100%, with a specificity of 75%. Diagnosis by simple visualization under white illumination has a sensitivity of only 69% and a specificity of 70%. Occult areas of endometriosis were discovered using fluorescence diagnosis. CONCLUSIONS: Our findings suggest that fluorescence diagnosis using 5-aminolevulinic acid is feasible and can improve the diagnosis of endometriosis in nonpigmented and occult endometrial lesions. Fluorescence diagnosis is a promising new tool in the diagnosis of endometriosis.

Aminolevulinic Acid↗

Laparoscopic management of tubo-ovarian abscesses: retrospective analysis of 60 cases.

BACKGROUND: The laparoscopic management of tubo-ovarian abscesses (TOA) was evaluated. The study sought to answer the following question: Does operative laparoscopy with only incision of the abscess cavity and lavage (organ-preserving treatment) improve intraoperative and postoperative safety and long-term prospects of fertility as compared with laparoscopic salpingectomy or salpingo-oophorectomy (ablative treatment)? METHODS: A retrospective chart review of 60 patients with TOA undergoing laparoscopic treatment in combination with broad-spectrum antibiotics from 1994 to 1998 was performed. Patients not wishing to have children underwent salpingectomy or salpingo-oophorectomy, whereas patients wishing to remain fertile were treated by means of an organ-preserving procedure. To investigate the operative and reproductive outcome, patients were interviewed by telephone. RESULTS: Of 60 women with TOA, 25 were treated laparoscopically, preserving the internal genital organs, and 35 underwent ablative treatment. Apart from one postoperative readmission because of lower pelvic pain in the organ-preserving group, there were no operative complications or serious systemic sequelae. In contrast, there was a significantly higher incidence of intraoperative and postoperative complications when ablative treatment was performed: one intestinal perforation requiring subsequent laparotomy, four serosal lesions, two lesions of the greater omentum, two lacerated collaterals of the internal iliac artery, one postoperative fever higher than 38 degrees C for 2 days, two bowel obstructions, one thrombosis of the upper leg, and one thrombosis of the lower leg. There were no significant differences between the two patient groups in body mass index, duration of pelvic pain, laboratory findings at admission, ultrasonic assessment of abscess size, and the extent of the abscess at laparoscopy. CONCLUSIONS: When laparoscopic treatment of TOA is performed, organ-preserving treatment should be chosen irrespective of the patient's age or desire to have children because of the risk of complications.

Abscess↗

Subjective evaluation of the therapeutic value of laparoscopic adhesiolysis: a retrospective analysis.

BACKGROUND: Adhesions are believed to be one of the principal causes of chronic pelvic pain. Although there may be some discrepancy between the degree of adhesions and the severity of the symptoms, surgical adhesiolysis is still considered to be useful for the relief of pain. METHODS: A total of 187 patients who underwent laparoscopic adhesiolysis at the Medical University of Ulm, Germany, within a 2-year period were asked to rank their discomfort on a visual pain scale before surgery and up to 1 1/2 years postoperatively. RESULTS: In this retrospective study, we found that nearly one-third of patients suffered from functional irritations that were either ameliorated or completely relieved by laparoscopic adhesiolysis. When other causes of chronic pain (such as endometriosis) are excluded, the results show that most patients benefited from laparoscopic adhesiolysis. CONCLUSIONS: It appears that laparoscopic adhesiolysis is an effective therapeutic measure to relieve chronic pelvic pain. Therefore, adhesiolysis should be performed in all patients with chronic or intermittent pain, and a complete lysis of adhesions should be planned. However, since pelvic pain may have organic or functional causes other than adhesions, complete adhesiolysis in patients with persistent pelvic pain may be of only limited importance.

Adult↗

Fluorescence diagnosis of endometriosis on the chorioallantoic membrane using 5-aminolaevulinic acid.

The chorioallantoic membrane (CAM) is a useful model for the fluorescence diagnosis of experimentally induced endometriosis. In our experimental setup 75.7% of the histologically examined tissue preparations were viable and only 24.3% showed signs of necrosis on the CAM after various periods of incubation. Best results were obtained when grafting to the CAM was performed between days 7 and 9 and when implants were left on the CAM for 3-5 days (P < 0.05). We were able to demonstrate that 5-aminolaevulinic acid (ALA) is stored selectively in ectopic endometrium. The subsequent fluorescence of the endometrium shows a rapid increase that reaches a peak after 10-14 h which can be clearly differentiated from the weaker fluorescence of grafted normal peritoneum and fimbriae (P < 0.01).

Adult↗

Laparoscopic management of ovarian tumors.

BACKGROUND: Laparoscopy can be used with minimal operative morbidity to evaluate adnexal masses. We report our experience with the endoscopic approach to the diagnosis and treatment of ovarian tumors. In particular, we describe 11 patients who incidentally underwent laparoscopy and in whom the ovarian masses were found to be malignant. METHODS: Between September 1994 and September 1996, 292 patients with 316 ovarian tumors were treated laparoscopically in the Department of Obstetrics-Gynaecology, University of Ulm. We assessed vaginal ultrasonography, clinical assessment, the tumor marker CA 12-5, and the intraoperative low-power magnification for their value in predicting the final diagnosis in all laparoscopically treated ovarian tumors. RESULTS: From a total of 292 patients with ovarian tumors, 11 were diagnosed, intraoperatively or after final histologic examination, as having a malignant or borderline ovarian tumor. All applied pre- and intraoperative diagnostic procedures were by themselves too unreliable to exclude early stages of ovarian carcinoma exactly. CONCLUSIONS: On the basis of the present findings, we are tempted to conclude that laparoscopic surgery is justified in the management of ovarian tumors. Even with an accurate preoperative selection of suitable patients for laparoscopic surgery, the presence of an undetected ovarian carcinoma cannot be entirely excluded.

Adult↗

Laparoscopic extirpation of an aplastic ectopic uterus in a patient with Mayer-Rokitansky-Küster-Hauser syndrome.

The Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome comprises the combined hypoplasia of the vagina and the uterus. In recent years, variable anomalies of the development of the Mullerian duct [as classified by the American Fertility Society (AFS)] have been operated on by the laparoscopic approach. We describe here a laparoscopic extirpation of an aplastic ectopic uterus in a patient found to have a hypoplastic vagina and ectopic uterus attached to the right pelvic wall. The uterus was linked to a normotopic right Fallopian tube and right ovary which were covered with endometriosis and adhesions. While the uterine vessels and the round ligament could be demonstrated on the right side, these structures were missing on the contralateral left side of the uterus. However, a normal tube and ovary were present on the left pelvic wall. Although not explicitly described in the AFS classification, this constellation most likely corresponds to the AFS classification stage Ie.

Abnormalities, Multiple↗

[Complications after 106 laparoscopic hysterectomies].

At our hospital in Hamburg 106 patients underwent laparoscopic hysterectomies. 92 patients had no complications, but 6 had major and 10 minor ones. As major complications occurred: one vesico-vaginal fistula, one uretero-vaginal fistula, one ureter injury, one lesion of the small intestine and two bladder injuries. As minor complications could be found: six urinary tract infections, one anemia (Hb 7,1 g/dl) and one febrile morbidity. The overall complication rate is 13.2%.

Adult↗

Influence of vaginal versus abdominal hysterectomy on perioperative glucose metabolism.

The aim of this study was to investigate the metabolic effects of abdominal versus vaginal hysterectomy with specific regard to perioperative glucose metabolism. Fourteen patients received either abdominal (AH, n = 7) or vaginal hysterectomy (VH, n = 7). Hepatic glucose production was measured before and 2.5 h after the operation by stable isotope technique ([6,6-2H2]-glucose). Metabolic substrates (glucose, lactate, nonesterified fatty acids [NEFA], beta-hydroxybutyrate) and hormones (insulin, glucagon, cortisol, catecholamines) were determined pre-, intra-, and postoperatively. VH induced a higher postoperative glucose concentration than the abdominal approach (VH, 148 +/- 25 mg/dL; AH, 111 +/- 16 mg/dL; P < 0.05). Since postoperative enhancement of hepatic glucose production was comparable in both groups, glucose clearance was lower after the vaginal procedure (VH, 1.7 +/- 0.3 mL.kg-1.min-1; AH, 2.1 +/- 0.3 mL.kg-1.min-1; P < 0.05). NEFA, beta-hydroxybutyrate, and catecholamines similarily increased after surgery. Cortisol levels were more increased after VH (VH, 80 +/- 26 micrograms/dL; AH, 37 +/- 14 micrograms/dL; P < 0.001). Lactate, glucagon, and insulin concentrations did not change perioperatively. The more pronounced hyperglycemic response to VH was due to lower peripheral glucose use caused by higher postoperative cortisol values. The mechanisms responsible for this marked cortisol enhancement after the vaginal operation as well as the clinical significance for patients with preexisting impaired carbohydrate tolerance, however, remained unclear and warrant further investigation.

3-Hydroxybutyric Acid↗