Effects of malathion subchronic exposure on rat skeletal muscle glucose metabolism

Regarding the widespread use of organophosphorous pesticides (OP) especially malathion in environment and reported cases of muscle disturbances in human and animal, the present work was undertaken to explore effects of malathion subchronic exposure on rat leg skeletal muscle glucose metabolism by measuring key enzymes of glycogenolysis and glycolysis. Malathion was administered through food for 4 weeks at concentrations of 100, 200, and 400ppm to rats. Activities of enzymes including glycogen phosphorylase (GP), hexokinase (HK), and phosphofructokinase-1 (PFK) were measured in skeletal muscle homogenate of exposed rats. Levels of glucose and insulin were measured in blood. Four weeks administration of malathion at doses of 200 and 400ppm increased blood glucose concentrations to 44.4 and 60.6% of control, respectively. Malathion at doses of 200 and 400ppm increased blood insulin concentration to 36.6 and 143.2% of control, respectively. Malathion at doses of 100, 200, and 400ppm increased muscle PFK activity to 40.4, 53.5, and 83.1% of control, respectively. Malathion at doses of 400ppm increased skeletal muscle GP to 91.6% of control. Skeletal muscle HK was not influenced by malathion treatment. It is concluded that malathion influences muscle glycogenolysis and glycolysis as well as secretion of insulin from pancreas which all may explain diabetic potential of malathion.     

Laparoscopic versus open appendectomy: a prospective randomized double-blind study

SUMMARY BACKGROUND DATA: The value of laparoscopy in appendicitis is not established. Studies suffer from multiple limitations. Our aim is to compare the safety and benefits of laparoscopic versus open appendectomy in a prospective randomized double blind study. METHODS: Two hundred forty-seven patients were analyzed following either laparoscopic or open appendectomy. A standardized wound dressing was applied blinding both patients and independent data collectors. Surgical technique was standardized among 4 surgeons. The main outcome measures were postoperative complications. Secondary outcome measures included evaluation of pain and activity scores at base line preoperatively and on every postoperative day, as well as resumption of diet and length of stay. Activity scores and quality of life were assessed on short-term follow-up. RESULTS: There was no mortality. The overall complication rate was similar in both groups (18.5% versus 17% in the laparoscopic and open groups respectively), but some early complications in the laparoscopic group required a reoperation. Operating time was significantly longer in the laparoscopic group (80 minutes versus 60 minutes; P = 0.000) while there was no difference in the pain scores and medications, resumption of diet, length of stay, or activity scores. At 2 weeks, there was no difference in the activity or pain scores, but physical health and general scores on the short-form 36 (SF36) quality of life assessment forms were significantly better in the laparoscopic group. Appendectomy for acute or complicated (perforated and gangrenous) appendicitis had similar complication rates, regardless of the technique (P = 0.181). CONCLUSIONS: Unlike other minimally invasive procedures, laparoscopic appendectomy did not offer a significant advantage over open appendectomy in all studied parameters except quality of life scores at 2 weeks. It also took longer to perform. The choice of the procedure should be based on surgeon or patient preference.     

Use of serum bicarbonate measurement in place of arterial base deficit in the surgical intensive care unit

HYPOTHESIS: Serum bicarbonate (HCO(3)) measurement may accurately and reliably be substituted for the arterial base deficit (BD) assay in the surgical intensive care unit (ICU). DESIGN: Retrospective criterion standard analysis. SETTING: Surgical ICU in a tertiary care facility. PATIENTS: Consecutive sample of non-trauma-related surgical ICU admissions from January 1996 to January 2004 with simultaneously obtained serum HCO(3) and arterial BD levels. MAIN OUTCOME MEASURES: Correlation between HCO(3) and BD at admission and during the ICU stay; predictive value of serum HCO(3) for significant metabolic acidosis and ICU mortality. RESULTS: The study included 2291 patients with 26 063 sets of paired laboratory data. The mean +/- SD age was 52 +/- 16 years and mean ICU stay was 5.8 +/- 9.8 days. There were 174 ICU deaths (8%). Serum HCO(3) levels showed significant correlation with arterial BD levels both at admission (r = 0.85, R(2) = 0.72, P<.001) and throughout the ICU stay (r = 0.88, R(2) = 0.77, P<.001). Serum HCO(3) reliably predicted the presence of significant metabolic acidosis (BD > 5) with an area under the receiver operating characteristic curve (AUC) of 0.93 at admission and 0.95 overall (both P<.001), outperforming pH (AUC, 0.80), anion gap (AUC, 0.70), and lactate (AUC, 0.70). The admission serum HCO(3) level predicted ICU mortality as accurately as the admission arterial BD (AUCs of 0.68 and 0.70, respectively) and more accurately than either admission pH or anion gap. CONCLUSIONS: Serum HCO(3) provides equivalent information to the arterial BD and may be used as an alternative predictive marker or guide to resuscitation. Low HCO(3) levels should prompt immediate metabolic acidosis evaluation and management.     

Does autoantigen administration inhibit recurrence of type 1 diabetes in transplanted islets?

Type 1 diabetes is a chronic disease with a subclinical prodromal period resulting from autoimmune destruction of pancreatic beta-cells. At the time of clinical symptoms of diabetes, the majority of islets have irreversibly been destroyed. Thus, the only cure for type 1 diabetes is pancreas (or islet) transplantation. To reach this goal, both allograft rejection and recurrent autoimmunity must be overcome. These have partly been achieved at the cost of lifelong immunosuppression, however, the risk to benefit ratio for immunosuppressive drugs to insulin usage remains obscure. To eliminate the need for immunosuppression, several tolerance induction protocols have been developed which particularly target alloimmune responses, whereas no tolerance induction protocol that particularly prevents the recurrence of autoimmunity has been suggested. It is hypothesized that autoantigen-based interventions may inhibit the recurrence of type 1 diabetes in transplanted pancreas (or islets) through the induction of specific tolerance to beta-cell autoantigens.     

Early development of neurophysiological processes involved in normal reading and reading disability: a magnetic source imaging study

This longitudinal study examined the development of the brain mechanism involved in phonological decoding in beginning readers using magnetic source imaging. Kindergarten students were assigned to 2 groups: those who showed mastery of skills that are important predictors of proficient reading (low-risk group) and those who initially did not show mastery but later benefited from systematic reading instruction and developed average-range reading skills at the end of Grade 1 (high-risk responders). Spatiotemporal profiles of brain activity were obtained during performance of letter-sound and pseudoword naming tasks before and after Grade 1 instruction. With few exceptions, low-risk children showed early development of brain activation profiles that are typical of older skilled readers. Provided that temporoparietal and visual association areas were recruited into the brain mechanism that supported reading, the majority of high-risk responder children benefited from systematic reading instruction and developed adequate reading abilities.     

Emergence of methicilllin resistant Staphylococcus aureus (MRSA) associated with wound infections

In a hospital setting antimicrobial resistant organisms especially Methicillin resistant Staphylococcus aureus (MRSA) has emerged as an important variable influencing patients' outcome and overall resource utilisation. The present study was undertaken to find out the proportion of MRSA and other organisms and their antimicrobial resistance pattern in admitted cases with postoperative wound infections. A total of 50 wound swabs were collected irrespective of age and sex of the patients from National Institute of Traumatology and Orthopaedics Rehabilitation (NITOR). The laboratory work was performed in the department of microbiology of National Institute of Cardiovascular Diseases (NICVD). Isolation, identification and susceptibility testing was done according to the guideline of the National Committee for Clinical Laboratory Standards (NCCLS, 1998). Out of the 50 samples 34 yielded growths of which 15 had growth of single organism and 19 had mixed growth of 2 to 3 organisms. Four different types of organisms were identified. Highest percentage was Escherichia coli 55.9%, followed by Pseudomonas sp. 52.9%, Proteus sp. 38.2%, and Staphylococcus aureus 17.6%. Of the 6 isolates of S aureus 5 (83.3%) were MRSA. Therefore it can be concluded that MRSA is existing in the hospital premises of NITOR, which can endanger the life of many. This study emphasises that susceptibility testing of all clinical isolates is essential to reduce the morbidity, mortality and longer duration of hospital stay. In addition proper management of the cases can decrease the spread of multiple drug resistant organisms in the community.     

Flunisolide HFA for the treatment of asthma: an old friend reformulated

The environmental mandate to eliminate the production of ozone-depleting products including chlorofluorocarbon (CFC) propellants has encouraged much needed research into improving modes of delivery of inhaled corticosteroids and enhancing drug deposition. Consequently, flunisolide CFC, an inhaled corticosteroid with a proven track record in the treatment of asthma, has been reformulated using a hydrofluoroalkane (HFA) as a propellant and is now awaiting FDA approval. Flunisolide HFA is a solution aerosol, unlike flunisolide CFC which is a suspension aerosol. As a solution aerosol, flunisolide HFA has a smaller mean particle size than flunisolide CFC. In addition, the built-in spacer included in the flunisolide HFA inhaler acts to reduce ex-actuator particle size; the smaller particle size of flunisolide HFA results in an improved deposition profile. Flunisolide HFA has substantially more lung deposition and much less oropharyngeal deposition than flunisolide CFC. Limited information is currently available on the clinical performance of flunisolide HFA. A single dose-response study has been performed in adults and in children comparing multiple doses of flunisolide HFA and flunisolide CFC. These studies indicate that flunisolide HFA is effective in controlling asthma. No unusual safety concerns have been noted, although further studies are needed to determine the long-term systemic effects of flunisolide HFA.     

Masking of 13C urea breath test by proton pump inhibitors is dependent on type of medication: comparison between omeprazole, pantoprazole, lansoprazole and esomeprazole

BACKGROUND: The need to withhold acid suppression therapy while awaiting urea breath test results is a common clinical problem in symptomatic patients. It is unclear at present if the dose or type of proton pump inhibitor or the type of test meal govern the apparent masking effect of proton pump inhibitors on the urea breath test. AIM: To prospectively evaluate Helicobacter pylori detection rates during treatment with four different proton pump inhibitors, utilizing a high-dose citric acid-based 13C urea breath test. METHODS: Patients positive for Helicobacter pylori by urea breath test were randomized to receive either omeprazole 20 mg/day, pantoprazole 40 mg/day, lansoprazole 30 mg/day or esomeprazole 40 mg/day for 14 days. A repeat breath test was performed on day 14 of treatment. RESULTS: One hundred and seventy-nine patients, mean age 45.8 +/- 16.8, completed the study. Treatment with omeprazole or pantoprazole prior to urea breath test (UBT) was associated with low false negative results, while lansoprazole and esomeprazole caused clinically unacceptable high false negative rates (pantoprazole 2.2% vs. lansoprazole 16.6%, P = 0.02, vs. esomeprazole 13.6%, P = 0.05; omeprazole 4.1% vs. lansoprazole 16.6%, P = 0.05). CONCLUSIONS: Proton pump inhibitor-induced false negative results on high-dose citric acid based urea breath test vary with the type of proton pump inhibitor used. Selection of the appropriate test meal and proton pump inhibitor may allow symptomatic individuals to continue their proton pump inhibitors prior to performing a urea breath test.