The protective effect of alpha-lipoic acid in experimental ovarian ischaemia-reperfusion injury

BACKGROUND: We investigated the effect of alpha-lipoic acid (LA) on reperfusion injury in a rat ovarian torsion-detorsion model. The changes in tissue and plasma levels of malondialdehyde (MDA), end-product of lipid peroxidation, superoxide dismutase (SOD), xanthine oxidase (XO) and nitric oxide (NO), were determined. Ovarian histopathological findings were scored and compared among groups. MATERIALS AND METHODS: Thirty-two female Sprague-Dawley rats were divided into four groups. Sham operation was performed in group I; in group II only ovarian torsion was performed. Group III received intraperitoneal injections of saline, and group IV received LA via intraperitoneal injections (LA group: aqueous solution at 36 mg/kg of body weight per day, saline group: equal volume of saline) 21, nine, and one hour before torsion of the ovary. Rats in the torsion group were killed after 360 degrees clockwise adnexial torsion for three hours, and ovaries were harvested. After three hours of adnexial detorsion, the rats in saline group and LA group were killed and adnexa were surgically removed. RESULTS: Ovarian tissue damage scores were significantly different among groups and were seen to correlate with tissue MDA levels. Ovarian tissue and serum MDA, NO and serum XO levels in the group III were significantly higher than those of the groups I and IV (P<0.05). The serum levels of SOD in the group III were significantly lower than those of the groups I and IV (P<0.05). CONCLUSION: These results suggest that LA pretreatment has beneficial effects in the prevention of ischaemia-reperfusion injury of the ovaries.     

Seronegative Celiac Disease in Patients with Isolated Refractory Dyspepsia and Gastroesophageal Reflux Disease

Background/AimsTo investigate the presence of seronegative celiac disease in patients with isolated refractory dyspepsia and gastroesophageal reflux disease (GERD)-related complaints.MethodsThis was a single-center, prospective study performed at a tertiary care referral hospital. Among 968 consecutive patients, 129 seronegative patients with tissue damage consistent with Marsh IIIa classification or above were included. The patients were divided into two groups dyspepsia (n=78) and GERD (n=51). Biopsies were taken from the duodenum regardless of endoscopic appearance, and patients with Marsh IIIa or above damage were advised to consume a gluten-free diet. The Glasgow Dyspepsia Severity (GDS) score, Reflux Symptom Index (RSI), and Biagi score were calculated at baseline and every 3 months. Control endoscopy was performed every 6 months during follow-up.ResultsThe median follow-up time was 19.9 months (range, 6 to 24 months) in the dyspepsia group and 19.2 months (range, 6 to 24 months) in the GERD group. All the patients were positive for the HLA-DQ2 and DQ8 haplotypes. The differences between the mean GDS scores (14.3±2.1 vs 1.1±0.2, respectively, p<0.05), RSI scores (6.3±0.8 vs 0.7±0.1, respectively, p<0.05), and Biagi scores (3.1±0.4 vs 0.7±0.3 in the dyspepsia group and 2.5±0.4 vs 0.5±0.2 in GERD group) before and after implementation of the gluten-free diet were statistically significant. The decreases in the scores were consistent with improvements in the histological findings. There was no significant correlation between endoscopic appearance and histological examination results (p=0.487).ConclusionsSeronegative celiac disease may be considered in this group of patients. Even if a patient is seronegative and has normal endoscopic findings, duodenal biopsy should be considered.     

Incidence and Impact of Documented Eradication of Breast Cancer Axillary Lymph Node Metastases Before Surgery in Patients Treated With Neoadjuvant Chemotherapy

OBJECTIVE: To determine the incidence and prognostic significance of documented eradication of breast cancer axillary lymph node (ALN) metastases after neoadjuvant chemotherapy. SUMMARY BACKGROUND DATA: Neoadjuvant chemotherapy is the standard of care for patients with locally advanced breast cancer and is being evaluated in patients with earlier-stage operable disease. METHODS: One hundred ninety-one patients with locally advanced breast cancer and cytologically documented ALN metastases were treated in two prospective trials of doxorubicin-based neoadjuvant chemotherapy. Patients had breast surgery with level I and II axillary dissection followed by additional chemotherapy and radiation treatment. Nodal sections from 43 patients who were originally identified as having negative ALNs at surgery were reevaluated and histologically confirmed to be without metastases. An additional 1112 sections from these lymph node blocks were obtained; half were stained with an anticytokeratin antibody cocktail and analyzed. Survival was calculated using the Kaplan-Meier method. RESULTS: Of 191 patients with positive ALNs at diagnosis, 23% (43 patients) were converted to a negative axillary nodal status on histologic examination (median number of nodes removed = 16). Of the 43 patients with complete axillary conversion, 26% (n = 11) had N1 disease and 74% (n = 32) had N2 disease. On univariate analysis, patients with complete versus incomplete histologic axillary conversion were more likely to have initial estrogen-receptor-negative tumors, smaller primary tumors, and a complete pathologic response in the primary tumor. The 5-year disease-free survival rates were 87% in patients with preoperative eradication of axillary metastases and 51% for patients with residual nodal disease after neoadjuvant chemotherapy. Of the 39 patients with complete histologic conversion for whom nodal blocks were available, occult nodal metastases were found in additional nodal sections in 4 patients (10%). At a median follow-up of 61 months, the 5-year disease-free survival rates were 87% in patients without occult nodal metastases and 75% in patients with occult nodal metastases. CONCLUSIONS: Neoadjuvant chemotherapy can completely clear the axilla of microscopic disease before surgery, and occult metastases are found in only 10% of patients with a histologically negative axilla. The results of this study have implications for the potential use of sentinel lymph node biopsy as an alternative to axillary dissection in patients treated with neoadjuvant chemotherapy.     

Nonoliguric renal failure after transurethral resection of prostate

PURPOSE: To define the relation of nonoliguric renal failure to transurethral resection of the prostate (TURP), its clinical importance, and predictive factors. PATIENTS AND METHODS: The files of 439 patients who had undergone TURP at Hacettepe University School of Medicine, Department of Urology, between January 1991 and 1994 were analyzed. The patients were divided into three groups according to postoperative serum creatinine concentration and the presence of clinical signs and symptoms of TUR syndrome (Group I: patients with preoperative and postoperative creatinine in the normal range; Group II: patients suffering nonoliguric renal failure; and Group III: patients with TUR syndrome). The data of the groups were compared in terms of factors influencing nonoliguric renal failure. RESULTS: The mean postoperative concentrations of sodium, blood urea nitrogen, creatinine, and albumin in Groups II and III were statistically different from those in Group I (P < 0.001). There was a moderate relation between hyponatremia and the occurrence of nonoliguric renal failure (r(s) = -0.56). Capsule perforation increased the risk of nonoliguric renal failure 10.6 fold. All of the patients were managed by a conservative approach, and none of the patients died or progressed to end-stage renal disease. They were all discharged with a mean hospitalization period of 7 days and normal renal function tests. CONCLUSION: Nonoliguric renal failure was thought to be an early step in the pathophysiology of TUR syndrome with acute renal failure. It is an asymptomatic clinical picture that is undiagnosed unless laboratory examinations are performed. A conservative therapeutic approach is enough.     

Epidural neostigmine produces analgesia but also sedation in women after cesarean delivery

BACKGROUND: Intrathecal neostigmine produces analgesia but also nausea, limiting its utility. In contrast, epidural administration of neostigmine has been suggested to produce postoperative analgesia without nausea in nonpregnant patients. The purpose of this study was to examine the dose range for efficacy and side effects of epidural neostigmine in women at cesarean delivery receiving combined spinal-epidural anesthesia. METHODS: After institutional approval and informed consent, 80 patients for elective cesarean delivery were given combined spinal-epidural anesthesia with 8 mg hyperbaric bupivacaine plus 10 microg fentanyl. Patients were randomized to receive either saline or 75, 150, or 300 microg neostigmine (n = 20 per group) in 10 ml saline after cord clamping. Pain, morphine consumption, and side effects were monitored for 24 h. RESULTS: Global pain assessment for the first 24 h was reduced from 5.4 +/- 0.2 in the saline group to 3.0-3.5 +/- 0.3 in the neostigmine groups, dose independently. Correspondingly, global satisfaction with neostigmine was also improved (P < 0.05). Nausea and morphine consumption were similar among groups. Intraoperative shivering and sedation were increased in the 300-microg neostigmine group only (P < 0.05), and postoperative sedation was increased by neostigmine in a dose-independent fashion (P < 0.05). CONCLUSIONS: Epidural neostigmine produced modest analgesia in women after cesarean delivery. In contrast with previous reports, which focused primarily on nausea, these data suggest that epidural neostigmine can also produce mild sedation for several hours. These data suggest a limited role for single bolus-administration epidural neostigmine for analgesia after cesarean delivery. They also support future study of epidural neostigmine for obstetric analgesia.     

Analgesic effects of interpleural bupivacaine with fentanyl for post-thoracotomy pain

OBJECTIVE: The analgesic effect of bupivacaine/fentanyl with epinephrine given interpleurally after thoracotomy was investigated in a randomized placebo and intravenous controlled study. DESIGN: Prospective clinical study. SETTING: University teaching hospital. PARTICIPANTS: Sixty American Society of Anesthesiologists physical status II and III patients scheduled for posterolateral thoracotomy with general anesthesia. INTERVENTIONS: Patients were randomly divided into 4 groups to receive either 0.5% bupivacaine/1.5 microg/kg of fentanyl with 5 microg/mL of epinephrine (n = 15, group IPBF), 0.5 % bupivacaine with 5 microg/mL of epinephrine (n = 15, group IPB), or saline (n = 15, group IPS) in a total volume of 15 to 20 mL in 60 seconds by an interpleural catheter placed at the end of surgery by direct vision. The same volume of bupivacaine 0.25% and 1.5 microg/kg of fentanyl with 5 microg/mL of epinephrine to group IPBF, bupivacaine 0.25% with 5 microg/mL of epinephrine to group IPB or saline to group IPS was injected through the interpleural catheter every 6 hours for 48 hours postoperatively. Intravenous fentanyl (n = 15, group IVF) and interpleural saline groups received 1.5 microg/kg of fentanyl intravenously at the first complaint of pain. All patients also received patient-controlled analgesia (PCA) with fentanyl for 48 hours postoperatively. Metamizol sodium was used as a rescue analgesic. MEASUREMENTS and MAIN RESULTS: Adequacy of pain relief was evaluated with the "Prince Henry Pain Scale" and visual analog pain scale. Fentanyl consumption via PCA and complications were evaluated for 48 hours. Visual analog scale scores were significantly higher in the interpleural saline group at 4 and 12 hours (6.6 +/- 1.2 and 5.0 +/- 2.1, respectively) postoperatively. Significantly more patients in the IPBF group had lower pain scores during coughing and deep breathing. Fentanyl consumption via PCA device was significantly higher in the intravenous fentanyl group (1,069 +/- 96.9 microg) than the interpleural groups (577.3 +/- 72.2 microg, 651.1 +/- 61.9 microg, and 601.0 +/- 22.6 microg in IPBF, IPB, and IPS groups, respectively). CONCLUSION: It is concluded that total fentanyl consumption via PCA decreased in all interpleural groups, but pain during coughing and deep breathing was significantly reduced in only the interpleural bupivacaine/fentanyl with epinephrine group.     

Upper cervical vertebrae movement during intubating laryngeal mask, fibreoptic and direct laryngoscopy: a video-fluoroscopic study

BACKGROUND AND OBJECTIVE: Minimizing cervical vertebrae motion during endotracheal intubation is important in patients with cervical instability. The aim of this study was to compare upper cervical spine extension during endotracheal intubation using three different techniques. METHODS: Duration of intubation and movement of upper cervical vertebrae during endotracheal intubation were compared in 33 patients undergoing lumbar laminectomy. Patients requiring tracheal intubation under general anaesthesia and neuromuscular blockade were randomly allocated into three groups - direct laryngoscopy, intubating laryngeal mask (LM) airway and fibreoptic laryngoscopy. The procedure was recorded by video-fluoroscopy and analysed with computer-assisted measurements. The maximum movement of the C1/C2 and C2/C3 vertebrae during intubation were obtained. Data were analysed using one-way analysis of variance with Bonferroni and Kruskal-Wallis tests. RESULTS: We found statistically significant movement between the first and second, but not between the second and third cervical vertebrae. The mean (+/-SD) movement at C1/C2 was 10.2 +/- 7.3 degrees with direct laryngoscopy, 5.0 +/- 6.3 degrees with LM and 1.6 +/- 3.2 degrees with fibreoptic laryngoscopy. This difference was statistically significant (P = 0.01) between the direct and fibreoptic laryngoscopy groups. The maximum movement at C2/C3 was 2.2 +/- 10.1 degrees with direct laryngoscopy, 3.5 +/- 5.1 degrees with LM and 0.5 +/- 3.2 degrees with fibreoptic laryngoscopy. Duration of intubation was significantly longer in the intubating LM group (P < 0.001). CONCLUSION: We conclude that fibreoptic laryngoscopy is the more suitable intubation technique when cervical spine movement is not desired.     

Effects of desflurane and isoflurane on hepatic and renal functions and coagulation profile during donor hepatectomy

We compared the effect of two inhalation anesthetics desflurane and isoflurane on postoperative hepatic and renal functions as well as coagulation profiles in living donors undergoing right hepatectomy. This study was performed on 80 patients who were randomly allocated to group D (desflurane, n = 40) or group I (isoflurane, n = 40) after Faculty Ethics Committee approval. After induction, isoflurane or desflurane was used with air/oxygen for anesthetic maintenance. The isoflurane or desflurane concentration was set at one minimum alveolar concentration (MAC). Remifentanil was infused for analgesia as well as cisatracurium. Aspartate aminotransferase (AST), alanine aminotransferase (ALT), international normalized ratio (INR), albumin, total bilirubin, blood urea nitrogen, creatinine, platelet count, and hemoglobin levels were analyzed preoperatively at end of the operation, and on postoperative days (PODs) 1, 2, 3, 5, 7, and 30. Both AST and ALT differed significantly and continually except on POD 30. AST showed significant elevations from the end of the operation to POD 2 and ALT, from the end of the operation to POD 5 in group I compared with group D. INR was significantly higher from the end of the operation to POD 3 in group I and to POD 2 in group D. At the end of the operation as well as on POD 1 and POD 2, INR was significantly increased in group I compared with group D. Albumin level was significantly lower at the end of the operation in both groups, but it was not different. No patient developed hepatic or renal failure. Our study showed better postoperative hepatic tests and INR using desflurane than isoflurane at equivalent doses of 1 MAC in living donors undergoing right hepatectomy.     

[18F]Fluciclatide in the in vivo evaluation of human melanoma and renal tumors expressing αvβ3 and αvβ5 integrins

Purpose

[¹⁸F]Fluciclatide is an integrin-targeted PET radiopharmaceutical. α_vβ₃ and α_vβ₅ are upregulated in tumor angiogenesis as well as on some tumor cell surfaces. Our aim was to use [¹⁸F]fluciclatide (formerly known as [¹⁸F]AH111585) for PET imaging of angiogenesis in melanoma and renal tumors and compare with tumor integrin expression.

Methods

Eighteen evaluable patients with solid tumors ≥2.0 cm underwent [¹⁸F]fluciclatide PET/CT. All patients underwent surgery and tumor tissue samples were obtained. Immunohistochemical (IHC) staining with mouse monoclonal antibodies and diaminobenzidine (DAB) was applied to snap-frozen tumor specimens, and additional IHC was done on formalin-fixed paraffin-embedded samples. DAB optical density (OD) data from digitized whole-tissue sections were compared with PET SUV_{80% max}, and Patlak influx rate constant (K _i) data, tumor by tumor.

Results

Tumors from all 18 patients demonstrated measurable [¹⁸F]fluciclatide uptake. At the final dynamic time-point (55 min after injection), renal malignancies (in 11 patients) demonstrated an average SUV_{80% max} of 6.4?±?2.0 (range 3.8 – 10.0), while the average SUV_{80% max} for metastatic melanoma lesions (in 6 patients) was 3.0?±?2.0 (range 0.7 – 6.5). There was a statistically significant difference in [¹⁸F]fluciclatide uptake between chromophobe and nonchromophobe renal cell carcinoma (RCCs, with SUV_{80% max} of 8.2?±?1.8 and 5.4?±?1.4 (P?=?0.020) and tumor-to-normal kidney (T/N) ratios of 1.5?±?0.4 and 0.9?±?0.2, respectively (P?=?0.029). The highest Pearson's correlation coefficients were obtained when comparing Patlak K _i and α_vβ₅ OD when segregating the patient population between melanoma and RCC (r?=?0.83 for K _i vs. melanoma and r?=?0.91 for K _i vs. RCC). SUV_{80% max} showed a moderate correlation with α_vβ₅ and α_vβ₃ OD.

Conclusion

[¹⁸F]Fluciclatide PET imaging was well tolerated and demonstrated favorable characteristics for imaging α_vβ₃ and α_vβ₅ expression in melanoma and RCC. Higher uptake was observed in chromophobe than in nonchromophobe RCC. [¹⁸F]Fluciclatide may be a useful radiotracer to improve knowledge of integrin expression.