Effects of sevoflurane, isoflurane and propofol infusions on post-operative recovery criteria in geriatric patients

We compared the effects of sevoflurane, isoflurane and propofol infusions on postoperative recovery criteria in geriatric patients. Sixty patients aged > 65 years, classified as American Society of Anesthesiologists (ASA) group 1 or 2 and undergoing gynaecological or urological procedures were randomized equally into three groups. Group 1 received 1 minimum alveolar concentration (MAC) sevoflurane in a 50% O2/N2O mixture and group 2 received 1 MAC isoflurane in a 50% O2/N2O mixture. Group 3 received a 50% O2/N2O mixture plus propofol total intravenous anaesthesia (8 mg/kg for the first 30 min, followed by 6 mg/kg for maintenance). Recovery criteria comprising the times to spontaneous eye opening, extubation, response to verbal stimuli and orientation were recorded following the discontinuation of anaesthesia. Recovery times were significantly shorter in groups 1 and 3 compared with group 2. We conclude that sevoflurane and propofol had similar effects on recovery criteria and were associated with a faster recovery than isoflurane.     

Genetic variants in transient receptor potential cation channel, subfamily M 1 (TRPM1) and their risk of albuminuria-related traits in Mexican Americans

BackgroundEvidence for linkage of albuminuria to GABRB3 marker region on chromosome 15q12 was previously reported in Mexican Americans. The objective of this study is to scan a positional candidate gene, Transient Receptor Potential cation channel, subfamily M 1 (TRPM1), for genetic variants that may contribute to the variation in albumin-to-creatinine ratio (ACR).MethodsTo identify the sequence variants, the exons and 2 kb putative promoter region of TRPM1 were PCR amplified and sequenced in 32 selected individuals. Identified variants were genotyped in the entire data set (N = 670; 39 large families) by TaqMan assays. Association analyses between the sequence variants and ACR, type 2 diabetes (T2DM) and related phenotypes were carried out using a measured genotype approach as implemented in the program SOLAR.ResultsSequencing analysis identified 18 single nucleotide polymorphisms (SNPs) including 8 SNPs in the coding regions, 7 SNPs in the promoter region and 3 SNPs in introns. Of the 8 SNPs identified in the coding regions, 3 were non synonymous [Met(1)Thr, Ser(32)Asn, Val(1395)Ile] and one SNP caused stop codon (Glu1375/*). Of the SNPs examined, none of them exhibited statistically significant association with ACR after accounting for the effect of age, sex, diabetes, duration of diabetes, systolic blood pressure and anti-hypertensive medications. However, a SNP (rs11070811) located in the putative promoter region showed a modest association with triglycerides levels (P = 0.039).ConclusionThe present investigation found no evidence for an association between sequence variation at the TRPM1 gene and ACR in Mexican Americans, although it appears to have modest influence on T2DM risk factors.     

Technical Aspects of Laparoscopic Sleeve Gastrectomy in 25 Morbidly Obese Patients

Background Laparoscopic sleeve gastrectomy (LSG) has recently come to be performed as a sole bariatric operation. The postoperative morbidity and mortality are cause for concern, and possibly are related to non-standardized surgical technique. Methods The following is the surgical LSG technique used in 25 morbidly obese patients. Five trocars are used. Division of the vascular supply of the greater gastric curvature is begun at 6–7 cm proximal to the pylorus, proceeding to the angle of His. A 50-Fr calibrating bougie is positioned against the lesser curvature. The LSG is created using a linear staplercutter device with one 4.1-mm green load for the antrum, followed by five to seven sequential 3.5-mm blue loads for the remaining gastric corpus and fundus. The staple-line is inverted by placing a seroserosal continuous absorbable suture over the bougie from the angle of His .The resected stomach is removed through the 12-mm trocar, and a Jackson-Pratt drain is left along the suture-line. Results The mean operative time was 120 minutes, and length of hospital stay was 4 ± 2 days.There were no conversions to open procedures. There were no postoperative complications (no hemorrhage from the staple-line, no anastomotic leakage, no stricture) and no mortality. In 1 patient, cholecystectomy was also done, and in 4, a gastric band was removed. During a median follow-up of 4 months, BMI decreased from 43 ± 5 kg/m² to 34 ± 6 kg/m², and the % excess BMI loss was 49 ± 25%. Conclusions The proposed surgical technique appears to be a safe and effective procedure for morbid obesity.     

Incidence of PTLD in Pediatric Renal Transplant Recipients Receiving Basiliximab, Calcineurin Inhibitor, Sirolimus and Steroids

Pediatric renal transplant recipients were enrolled in a multicenter, randomized, double-blind trial of steroid withdrawal. Subjects received basiliximab, calcineurin inhibitor, sirolimus and steroids. Of 274 subjects enrolled, 19 (6.9%) subjects developed posttransplant lymphoproliferative disorder (PTLD). The relative hazard (RH) for PTLD was 5.3-fold higher in children aged ≤5 versus those >12 years (p = 0.0017). EBV seronegative subjects had a 4.7-fold higher RH compared to EBV positive subjects (p = 0.02). Among EBV donor+/recipient– (D+/R–) subjects, the RH increased by 6.1-fold (p = 0.0001). In a multivariate model, risk factors included recipient age ≤5 years (RH 3.2, 95% CI: 1.1–9.6, p = 0.034) and EBV D+/R– status (RH 7.7, 95% CI: 1.6–35.9, p = 0.010). Of 19 patients with PTLD, 17 are alive with functioning grafts and 2 lost their grafts, 1 of whom subsequently died of recurrent PTLD. This 'robust' immunosuppression protocol was associated with low rejection rates but an unacceptably high incidence of PTLD. The combination of basiliximab, calcineurin inhibitor, sirolimus and steroids resulted in over-immunosuppression in a high-risk pediatric population and we do not recommend its use. Future studies must include routine viral monitoring to permit early identification of viral activity and a protocol driven reduction of immunosuppression aimed at avoiding complications.     

Combretastatin A4-camptothecin micelles as combination therapy for effective anticancer activity

Cancer is a major worldwide health problem, for which chemotherapy is a common treatment option. However drug toxicity and the development of resistance to chemotherapy are two main challenges associated with the traditional anticancer drugs. Combined pharmacological therapy based on different mechanisms might be an effective strategy in cancer treatment, and could exhibit a synergistic therapeutic efficacy. Herein, we aim to combine combretastatin A4 (CA4) and camptothecin (Cpt) chemically into a codrug through two hydrophilic linkers utilizing click chemistry to improve their water solubility and anticancer activity. The synthesized amphiphilic structure could self-assemble into a micelle structure as confirmed by atomic force microscopy (AFM) and dynamic light scattering (DLS), which showed a high stability and improved water solubility at pH 7.4, with a low critical micelle concentration (CMC) value of 0.9 mM. Moreover, in vitro hydrolysis was observed upon incubation of the hybrid compound with an esterase enzyme, which suggested a complete disassembly into the starting active drugs. Finally, cytotoxicity studies on HeLa cancer cells showed that the codrug demonstrated an enhanced (five fold) cytotoxicity as compared with the free drugs. In addition the combination index (CI) was <1, which suggests a synergistic activity for the codrug. Moreover, the tested concentrations of the codrug were not significantly cytotoxic to a noncancerous fibroblast cell line. The imaging of HeLa cells treated with FITC-loaded micelles showed a rapid internalization. In conclusion, the codrug of CA4 and Cpt might be a potential novel anticancer drug as it demonstrated a synergistic cytotoxic activity that might spare noncancerous cells.

Novel CA4-TEG-triazole-TEG-Cpt (codrug 9) was synthesized and self-assembled into a micelle structure that showed a great synergistic anticancer activity on HeLa cancer cells without affecting the viability of 3T3 normal cells.     

Genetic fieldwork for hereditary prostate cancer studies

The success of a genetic family study depends on the recruitment of a sufficient number of unaffected family members. We present our experiences from interviews performed in two family studies, a genetic family study of prostate cancer (PC) and a medical, anthropological, qualitative study. In the genetic family study, 949 PC patients were contacted, and 29% responded. Response rates were higher (44%) among subjects contacted by health providers participating in the study, compared to only 18% of those contacted by letter. Thirty-six pedigrees were ascertained. On average, each family had 3.3 affected relatives. Average age at time of diagnosis was 61.9 years in the probands. 58% of the families reported additional cancers. Breast cancer was reported in 12 families; colon cancer was the second most reported cancer, followed by lung, stomach, and throat cancers. Beliefs about the inheritance of PC were explored with 20 participants. The parental origin of the proband's PC in each family did not significantly affect participants' beliefs about the inheritance of PC. 95% agreed that PC could be inherited from a father to a son. Participants thought that a mother (n = 12) or daughter of a patient (n = 11) could not give PC to their sons. This misperception of the inheritance of PC can result in (1) an underreporting of PC cases in a kindred, and (2) healthy men underestimating their risk of developing PC when the disease runs in the mother's family. Thus health educators and genetic counselors might consider these findings when teaching patients and their relatives about hereditary PC.     

The use of esmolol and magnesium to prevent haemodynamic responses to extubation after coronary artery grafting

BACKGROUND AND OBJECTIVE: The haemodynamic responses during extubation can cause complications after open-heart surgery. In this study, we aimed to examine the effect of esmolol and magnesium before extubation on these haemodynamic responses. METHODS: Following the approval of local Ethics Committee, 120 patients having coronary artery bypass grafting with extubation in the intensive care unit were included in the study. Patients were allocated to receive esmolol 1 mg kg-1 (group I, n = 40), magnesium 30 mg kg-1 (Group II, n = 40) or normal saline (Group III, n = 40). Study medication was administered as a 20-min infusion in a volume of 20 mL. Patients were extubated just after termination of the infusion. Heart rate, blood pressure and central venous pressure were recorded prior to drug administration, before extubation, during extubation and 1 min after extubation. RESULTS: Heart rate was lower in Group I than in Groups II (P < 0.05) and III (P < 0.001) and lower in Group II than in Group III (P < 0.05) during extubation. It was also lower in Group I than in Group III (P < 0.05) after extubation. Systolic blood pressure was lower in Group I than in Groups II and III (P < 0.001) during extubation. Diastolic blood pressure was higher in Group III than in Groups I and II during extubation (P < 0.001) and after extubation (P < 0.05). Mean arterial pressure was lower in Group I than in Groups II and III (P < 0.001) during extubation, lower in Group II than in Group III (P < 0.05) during extubation and lower in Group I than in Group III (P < 0.05) after extubation. CONCLUSION: We found that using esmolol before extubation following coronary artery bypass graft surgery prevents undesirable haemodynamic responses while magnesium reduces undesirable haemodynamic responses but does not prevent them.