A to Z: Vitamin A and zinc,the miracle duo

Dietary micronutrients such as vitamins and trace minerals are known modulators of host immune responses against common pathogens. In this respect, vitamin A and zinc have recently received increased attention. Severalin vivo andin vitro studies suggest that vitamin A may be a critical player in the mucosal immune responses in the respiratory and gastrointestinal tracts, particularly in undernourished children. The effect may be mediated primarily by stabilization of the membrane of mucosal epithelial cells, as well as enhanced leukocyte functions. The beneficial effect of vitamin A therapy in reducing measles-associated morbidity and mortality suggests its crucial role in defenses against viral pathogens. Zinc is also known affect leukocyte functions such as phagocytosis and T-lymphocyte-mediated immune responses. However, unlike vitamin A, zinc has been investigated primarily for its effects on bacterial infections. Dietary supplementation or therapeutic treatment with vitamin A and zinc may be a cheap yet effective means of preventing or treating infections in highly susceptible populations. Additional studies, however, are required to better define the types of pathogens and the specific human populations that may benefit from such therapy.     

Intraoperative laparoscopic complications

PURPOSE: The aim of this study was to assess various intraoperative and postoperative complications associated with laparoscopic colorectal surgery. Specifically, the impact of surgical experience and procedure type on complications was analyzed. METHODS: All patients who underwent laparoscopic surgery were analyzed by age, sex, surgical indications, procedure performed, procedure length, intraoperative and postoperative complications, incidence and causes for conversion, duration of postoperative ileus, and length of hospital stay. Patients were classified for type of procedure and chronologically into four consecutive groups. Procedures were also categorized into four different groups: GI, total abdominal colectomies; GII, segmental resections; GIII, diverting procedures; GIV, others (abdominoperineal resection, Hartmann's creation or closure, anterior resection, and rectopexy). RESULTS: Between August 1991 and October 1995, 167 patients of a mean age of 49.6 (15–88) years underwent laparoscopic colorectal procedures. All procedures were electively performed. Common indications for surgery included inflammatory disease in 70 (42 percent), neoplasia in 56 (33 percent), functional bowel disorders in 30 (18 percent), and other forms of colorectal disorders in 11 (7 percent) patients. The most significant variable affecting intraoperative laparoscopic complication rate was surgical experience measured as the time interval during which surgery was performed (P=0.02). Total complication rate decreased from 29 percent during the first period to 11 percent by the second period (P<0.04) and 7 percent during the third period (P<0.005). Thus, the learning curve appeared to have required more than 50 cases to achieve. Moreover, even after performance of 94 (1991–1993) procedures in GI and GIV, these procedures were associated with higher complication rates than were those procedures in GII and GIII (P=0.04). CONCLUSION: Surgical experience and case selection are the most critical variables by which the surgeon can decrease the intraoperative laparoscopic complication rate.     

Prospective comparison of open<Emphasis Type="Italic">vs</Emphasis>. laparoscopic colon surgery for carcinoma

Laparoscopy for colonic diseases began in 1990 and has established a role in benign disease. Early observations and experiences demonstrated feasibility of laparoscopic surgery for a variety of colonic disease processes, but the applicability to colonic carcinoma was unclear. METHODS: In 1990, we began a comparative study of open (OCR)vs.laparoscopic (LCR) approach to colon cancer. The study progressed 65 months, with 224 patients in OCR group and 191 patients in LCR group. Parameters studied are stage, location, length of specimen, number of lymph nodes resected, margins, postoperative course, wound complications, recurrence rates, and immediate and long-term survival. OCR were standardized by one group, and LCR were standardized by a second group. All patients undergoing LCR were given freedom to choose either OCR or LCR, and informed consent was obtained. RESULTS: Equal or greater lymph node retrieval, resections, and distal margins were evident with LCR. Benefits with LCR were shown with shorter hospitalization (5.7vs.9.7 days), less blood loss, less wound problems (1vs.14), and quicker return of bowel function. Survival, recurrence, and death rates were essentially the same. There were no trocar implants in the LCR group. CONCLUSION: After five years, this study shows that laparoscopy does no harm to the patient, offers comparable oncologic resections, and seems to be patient-friendly, with less pain, quicker return of bowel functions, shortened hospitalization, and quicker return to full activity.     

Cytokines in combination with chemotherapy for advanced renal carcinoma--the importance of patient selection

An outpatient regimen of interferon-alpha (IFN-alpha), interleukin-2 (IL-2) and 5-fluorouracil (5-FU) was previously reported to have significant activity (response rate 48.6%) in patients with advanced renal cell carcinoma (RCC). The patient group reported were generally of good performance status (PS), had undergone previous nephrectomy and would be considered of good prognosis with respect to response and survival after treatment with IL-2. The characteristics of patients with RCC referred to specialist units in the UK differ from that patient group in that many patients present with metastatic disease, are of poor PS and are considered unfit for nephrectomy. We tested the three drug regimen in a representative patient group of 55 patients who had: median PS of 1 (range 0-2); median time from diagnosis to treatment of 2.7 months (0.2-113); and median number of sites of disease 3 (1-5). 22/55 had not had prior nephrectomy and 31 were considered of poor risk, 15 moderate risk and only 9 of good risk. Treatment consisted of an 8 week cycle of IFN-alpha 6 MU/m2 day 1 weeks 1 and 4 and thrice weekly weeks 2-3 and 9 MU/m2 thrice weekly, weeks 5-8. IL-2 20 MU/m2 days 3-5, weeks 1 and 4 and 5 MU/m2 thrice weekly weeks 2-3. 5-FU 750 mg/m2 day 1 of weeks 5-8. There were no complete responses (CR), 9 (17%) partial responses (PR) and 13 patients (24%) had stable disease. Sixteen patients withdrew early from treatment and were not evaluable for response. Amongst 25 evaluable patients who had undergone nephrectomy the response rate was 32% (95% CI: 14-50%). Only 1 response was seen in patients who had not undergone nephrectomy. Survival was predicted by PS, nephrectomy, number of sites of metastasis and risk group. Most patients experienced significant toxicity of grade I/II but few grade III/IV toxicities were seen as compared to intravenous IL-2 regimens. These data are part of a large data set that has been submitted for publication in The British Journal of Urology. The regimen has been shown to have activity but this is seen predominantly in patients of good PS, with prior nephrectomy and limited sites of disease. Patients of poor risk are likely to experience significant toxicity without benefit and should be offered alternative palliative therapies.     

A comparison between epidural anaesthesia using alkalinized solution and spinal (combined spinal/epidural) anaesthesia for elective caesarean section

In a double-blind investigation, 40 women undergoing elective lower segment caesarean section were randomly divided into two groups. Group I (n = 20) received spinal anaesthesia with 2.0 ml hyperbaric 0.5% bupivacaine using a single space combined spinal epidural technique. Group II (n = 20) received epidural anaesthesia with a local anaesthetic mixture consisting of 0.5% bupivacaine plain 10 ml and 2% lignocaine plain 10 ml to which was added 0.1 ml of adrenaline 1 in 1000 and 2 ml of 8.4% sodium bicarbonate. The mean onset times of sensory block to T4 and grade 3 motor blockade were 7.9 min and 9.5 min respectively in the spinal group, compared to 13.1 min and 16.3 min in the epidural group. These differences were both significant (P < 0.05). There was no difference between the two groups in the quality of analgesia or the incidence of hypotension and nausea. The relatively rapid onset of the pH adjusted epidural solution may provide an attractive alternative to spinal anaesthesia. Moreover, this study underlines the important role of pH adjusted epidural solutions in parturients progressing to emergency caesarean section with epidural catheters previously inserted for labour analgesia.     

Influence of alpha-tocopherol and ascorbic acid on pan masala induced genomic damage. An in vitro experiment

Pan masala is a dry complex mixture of areca nut, catechu, lime, cardamon, unspecified flavouring agents etc., with (PMT) or without tobacco (pm). We have previously reported genotoxic potential of tobacco, areca nut and pan masala per se. An antigenotoxic effect of alpha-tocopherol (AT) and ascorbic acid (AA) against the PM/PMT induced genotoxic on Chinese hamster ovary (CHO) cells have been studied using chromosone aberration (CA) assay. AT and AA, per se, had no effect on CA frequency at the concentrations used in the present study. The short-term treatment of AT with aqueous extracts of PM/PMT yielded lower frequencies of CA as compared to the cultures treated with aqueous extracts of PM/PMT alone. However, a statistically significant reduction in CA frequency was observed with continuous treatment only. AA had no statistically significant protective effect except for continuous treatment with 10 ug/ml AA against the aqueous extract of PMT. The results indicate the possible use of AT to reduce the risk of oral cancer among PM/PMT chewers.     

"False inhibition" of demand pacemaker due to leakage of fluid into the pacemaker lead socket

"False inhibition" of a demand pacemaker usually occurs with a microfracture of the lead system resulting in a galvanic potential at the site of the fracture or with sensing of myopotential with exercise. An increase in the slope of the leading half edge of the pulse contour is generally considered diagnostic of lead fracture. We report the case of a patient in whom "false inhibition" at rest and an increase in the slope of the leading half edge of the pulse contour were caused by leakage of fluid into the pacemaker lead socket.     

The application of population pharmacokinetic analysis to large scale clinical efficacy trials

Summary Results have been presented that demonstrate the ability to conduct population pharmacokinetic analysis as a component of clinical efficacy and safety trials. This method of analysis offers the potential to determine the pharmacokinetics of a drug in the actual patients receiving medication and to evaluate relationships between pharmacokinetics and drug action. However, active involvement in the protocol design, and data collection process are required to ensure the quality of the resultant data set.     

Regional differences in evoked dopamine efflux in brain slices of rat anterior and posterior caudate putamen

Summary Fast cyclic voltammetry using carbon fibre microelectrodes in rat brain slices, was used to investigate regional differences in electrically-evoked dopamine (DA) efflux at 10 different sites in the anterior caudate putamen (aCPu) and 10 sites in the posterior caudate putamen (pCPu). For each site DA overflow was evoked by both single pulse (1P) stimulation and by trains of 25 pulses applied at a frequency of 50 Hz (25P/50 Hz). Peak DA efflux evoked by 1P was about 58% greater in the aCPu (0.19 mol/l DA) than in the pCPu (0.12 mol/l DA), but showed no mediolateral variation in either region. Peak DA efflux evoked by 25P/50 Hz relative to 1P efflux also varied between the two regions; the aCPu contained predominantly low ratio (25P/50 HZ: 1P) sites ranging from 1.47 to 3.71, whereas in the pCPu these ratios were higher, ranging from 2.73 to 9.40, and were particularly high in the dorsomedial region of the pCPu. Efflux detected in low ratio sites of the aCPu showed little dependence on the frequency (10 to 500 Hz), or the number of pulses (5 to 20) in a train. By contrast DA efflux evoked in high ratio sites of the pCPu responded in a pulse and frequency dependent manner, the maximum ratio (approximately 8 times 1P) being at 20P/20 Hz. Interestingly the frequency response relationship obtained in the pCPu resembled the profile observed in the nucleus accumbens (NAc).Voltammetric evidence and experiments with selective reuptake blockers indicated that only DA was measured in our studies and 5-HT did not significantly contribute to the frequency dependent pattern of efflux detected in high ratio sites of the pCPu, where striatal 5-HT concentrations are highest. Experiments with the selective D₂ receptor antagonists metoclopramide or (–)sulpiride revealed that under our experimental conditions, DA efflux in the aCPu was not modulated by DA autoreceptor activation. By contrast, autoreceptor modulation did occur in high ratio sites of the pCPu at stimulations lasting longer than approximately 1000 ms.These observations support the concept that the caudate putamen is heterogeneously organised with respect to the frequency characteristics of evoked DA release. The factors controlling frequency dependent release under these conditions may be a function of A10 innervation, since high ratio release sites occur in areas where the density of such innervation is greatest, for example, the dorsomedial pCPu. This is supported by the observation that high ratio release sites are also found in the NAc, which receives dopaminergic fibres predominantly from an A10 region. However, the involvement of different regionally distributed transmitters acting on presynaptic receptors involved in the regulation of dopamine release, or differences between nerve terminals in striosomes and matrix, cannot be excluded. Send offprint requests to S. J. Trout at the above address     

Predictive value of Doppler ultrasonography in renal transplantation

During a 17-month period, 268 Doppler sonography studies were performed on 46 consecutive renal transplant patients. There were 35 episodes of acute rejection in 10 patients, 8 episodes of delayed function and 47 episodes of high cyclosporine levels (greater than 800 ng/dl by TDX method) in 21 patients. Defining an abnormal resistive index (RI) as greater than 0.8 or a 20% increase above baseline, the test has a specificity of 99% and a sensitivity of 94% in the 1st month post-transplant and had an overall predictive value of 99%. Episodes of high cyclosporine levels ranging from 800 to 1650 ng/dl did not correlate with a high RI except in one circumstance with concurrent acute rejection. Within the 1st month post-transplant, only 1 false-negative study occurred. An additional 8 false-negative studies occurred beyond 1 month post-transplant. Patients with delayed function are separated into three groups based on the Doppler ultrasounds: Group I, patients with an accelerated acute rejection with high RI (N = 2); Group II, patients with true ischemic acute tubular necrosis with normal RI (N = 2); and Group III, patients with possible immunologically-mediated delayed function with intermediate RI between 0.6 and 0.8 (N = 4). Doppler ultrasound is a useful ancillary test to confirm the clinical suspicion of acute rejection. Since high cyclosporine levels do not cause an increase in RI, Doppler ultrasound may help to avoid confusion between acute rejection and cyclosporine toxicity. Additionally, this test may offer insight into the cause of early post-transplant renal dysfunction.