Malignant hyperthermia

Malignant hyperthermia refers to covert myopathies, which do not affect the individual during daily life activities, but may lead to life-threatening tachycardia, rigor, labile blood pressure and most importantly high-grade temperature when exposed to general anaesthesia. This conditions is mimicked by thyroid storm, neuroleptic malignant syndrome, phaeochromocytoma and sepsis. We present a presumptive case of malignant hyperthermia.     

Calcium-supplemented daptomycin Etest strips for susceptibility testing on Iso-Sensitest agar

OBJECTIVE: Iso-Sensitest agar (ISA), which is recommended by the BSAC for routine susceptibility testing of staphylococci and enterococci, contains insufficient calcium for testing daptomycin. Isotonic agar supplemented with 50 mg/L calcium has been advocated, but is not routinely available in many laboratories. We evaluated a daptomycin Etest that incorporates a constant level of calcium throughout the daptomycin gradient, designed to give an appropriate concentration around the strip during testing, as an alternative for susceptibility testing on ISA. METHODS: Ninety-one isolates of Staphylococcus aureus (45 methicillin-susceptible, 46 methicillin-resistant) and 90 enterococci (47 Enterococcus faecalis, 43 Enterococcus faecium) were tested. Daptomycin Etest MICs were determined on ISA, whereas agar dilution MICs were determined in parallel on Isotonic agar supplemented with calcium to 50 mg/L as a control. RESULTS: The agar dilution and Etest MIC ranges of daptomycin for S. aureus were 0.25-1 mg/L (mode 0.5 mg/L), and 0.125-2 mg/L (mode 0.25 mg/L), respectively. The corresponding MIC values for enterococci were 0.25-4 mg/L (mode, 1 mg/L) and 0.125-4 mg/L (mode, 2 mg/L). For staphylococci, 86% of the Etest MIC results were within one dilution of the agar dilution values, and for enterococci, 90% of the Etest MIC results met these criteria. When results from the two methods were not identical, there was a tendency for the Etest MIC values to be lower than the agar dilution values. CONCLUSIONS: This study shows that calcium-supplemented daptomycin Etests on ISA are an accurate and convenient alternative to calcium-supplemented Isotonic agar.     

Iloprost inhibits superoxide formation and gp91phox expression induced by the thromboxane A2 analogue U46619, 8-isoprostane F2alpha, prostaglandin F2alpha, cytokines and endotoxin in the pig pulmonary artery

Since the roles of thromboxane A2 (TXA2), prostacyclin (PGI2) and 8-isoprostane F2alpha in mediating vascular O2*- formation and its relation to adult respiratory distress syndrome (ARDS) is unknown, the effects of these eicosanoids on the expression of gp91phox (catalytic subunit of NADPH oxidase) and O2*- release from cultured pig pulmonary artery (PA) segments, PA vascular smooth muscle cells (PAVSMCs) and PA endothelial cells (PAECs) were investigated. PA segments, PAVSMCs and PAECs were incubated with the TXA2 analogue, U46619, (+/-LPS, tumour necrosing factor-alpha (TNF-alpha) or IL-1alpha), 8-isoprostane F2alpha and+/-iloprost (a stable PGI2 analogue) for 16 h. The formation of superoxide dismutase-inhibitable O2*- was then measured spectrophotometrically and gp91phox expression assessed using Western blotting. In parallel experiments, whole PA segments were treated with LPS, TNF-alpha and IL-alpha after which time TXA2, PGI2, PGF2alpha and 8-isoprostane F2alpha formation was measured using enzyme-linked immunoassays. U46619, PGF2alpha and 8-isoprostane F2alpha promoted the formation of O2*- in PA segments, PAVSMCs and PAECs, an effect inhibited by diphenyleneiodonium and apocynin (both NADPH oxidase inhibitors) and upregulated the expression of gp91phox in PAECs and PAVSMCs. These effects were augmented by LPS, TNF-alpha and IL-1alpha but inhibited by iloprost. Under identical incubation conditions, IL-1alpha, LPS and TNF-alpha all induced an increase in the formation of TXA2, PGF2alpha and 8-isoprostane F2alpha but reduced the concomitant formation of PGI2. These data demonstrate that LPS and cytokines influence the relative balance of TXA2, PGI2, PGF2alpha and 8-isoprostane F2alpha in pig PA, which in turn alter NADPH oxidase expression and O2*- formation. These novel findings have implications in devising effective strategies for treating ARDS.British Journal of Pharmacology (2004) 141, 488-496. doi:10.1038/sj.bjp.0705626     

Two distinct pathways of immuno-modulation improve potency of p53 immunization in rejecting established tumors

The p53 gene product is overexpressed by almost 50% of cancers, making it an ideal target for cancer immunotherapy. We previously demonstrated rejection of established p53-overexpressing tumors without stimulating autoimmunity by immunization with modified vaccinia Ankara-expressing murine p53 (MVAp53). Tumor rejection was enhanced through antibody-mediated CTL-associated antigen 4 (CTLA-4) blockade. We examined the role of synthetic oligodeoxynucleotides (ODN) containing unmethylated cytosine-phosphate-guanine (CpG) motifs (CpG ODN) in enhancing MVAp53-mediated tumor rejection. CpG ODN with MVAp53 resulted in tumor rejection in BALB/c mice bearing poorly immunogenic 11A-1 murine mammary carcinomas or Meth A sarcomas and C57Bl/6 mice bearing MC-38 colon carcinomas. The effect was similar to that seen in tumor-bearing mice treated with MVAp53 along with CTLA-4 blockade. Monoclonal antibody depletion experiments demonstrated that the adjuvant effects of CpG ODN and CTLA-4 blockades were CD8 dependent. CpG ODN were partially natural killer cell dependent and ineffective in Toll-like Receptor 9(-/-) and interleukin 6(-/-) mice, whereas CTLA-4 blockade was partially CD4 dependent and functional in Toll-like Receptor 9(-/-) and interleukin 6(-/-) mice. In addition, when administered with MVAp53, both adjuvants enhanced p53-specific cytotoxicity and demonstrated an additive effect when combined. The combination of CpG ODN and CTLA-4 blockade worked synergistically to reject palpable 11A-1 and MC-38 tumors. These experiments demonstrate the potential for augmenting MVAp53-mediated antitumor immunity using CpG ODN and CTLA-4 blockade. This cell-free immunotherapy approach is a candidate for evaluation in cancer patients.     

Effect of hypothyroidism and its treatment on the IGF system in infants and children

We performed a study on infants and children with hypothyroidism to determine the effect of hypothyroidism and its correction on components of the IGF system. A total of 35 patients were subdivided into four groups based on age and severity of the disease. Serum concentrations of immunoreactive IGF-I, free IGF-I, IGFBP-2 and IGFBP-3 were measured before and after treatment and compared to controls matched for age, sex and puberty. Baseline total IGF-I (TIGF-I) concentrations were significantly lower prior to treatment in the infants with severe hypothyroidism and increased significantly after thyroxine therapy. Baseline free IGF-I (FIGF-I) concentration was significantly lower prior to treatment in infants with severe hypothyroidism when compared to controls but did not increase significantly after treatment. In infants with severe and compensated hypothyroidism, IGFBP-3 concentrations prior to treatment were lower when compared to controls. These concentrations increased during treatment. Baseline IGFBP-2 levels did not differ from the control values in both these groups but decreased significantly after correction of the hypothyroidism. Although these changes appeared to occur with thyroxine therapy, multiple regression analysis suggested that age was a more important determinant of the changes observed in these parameters than serum thyroxine concentration. In children with acquired hypothyroidism no difference in any of these parameters was noted between hypothyroid patients and controls. TIGF-I increased significantly on thyroxine therapy, but the difference was small. No significant differences were noted in other measured parameters with thyroxine therapy. In older children with compensated hypothyroidism no significant differences were noted in any of the measured parameters in the pretreatment, post-treatment and control groups. In conclusion, although changes appear in TIGF-I, IGFBP-3 and IGFBP-2 in infants with congenital hypothyroidism when they are treated with thyroxine, age appears to be the more important determinant of these changes than does thyroxine concentration. In older children with acquired hypothyroidism, TIGF-I and FIGF-I levels were not significantly lower than in age- and sex-matched controls. After treatment only TIGF-I levels increased.     

Correlates of death anxiety in Pakistan

To ascertain the effect of gender, age, and religiosity on death anxiety, 132 participants were interviewed using Templer Death Anxiety Scale and Collett-Lester Fear of Death Scale (CLS). Women, older participants, and less religious participants were found to be more scared of their impending death. Gender effect was more pronounced, however, on the CLS. Women and less religious people reported to experience greater anxiety than their respective counterparts about different dimensions of death, for example, the shortness of life, total isolation of death, fear of not being, and disintegration of body after dying. The findings of the current work indicate that the general predictors of death anxiety, gender, age, and religiosity reported in Western, predominantly Christian samples also hold in an Eastern, Muslim sample.     

Itemized bill: novel method to audit the process of laparoscopic cholecystectomy

One of the recurring obstacles to the successful completion of a medical audit cycle is the unavailability of accurate and complete information. This is particularly evident in the review of clinical processes, where the hand-written medical record is the source of information. We have attempted to bypass this information deficit by using information recorded primarily for financial transactions, using the itemized bill. The study was conducted in two parts. Initially information recorded as an itemized bill for the in-hospital process of laparoscopic cholecystectomies over a one-year period was analyzed. Areas for change in practice were identified, and recommendations were developed. These recommendations were presented to a multidisciplinary group consisting of consultants, residents, and nursing staff involved in caring for these patients. A clinical pathway was developed and implemented from these recommendations. One year after introduction, a review of the clinical pathway was undertaken using the same methodology. The in-hospital process consisted of 23 charge categories according to the itemized bill. Of these, 8 accounted for 95% of the total charge. The surgeons fee and the anesthesiologists fee accounted for 34% of the total; medical/surgical supplies, 20%; operating theater time, 17%; pharmacy, 7%; radiology, 5%; laboratory, 7%; and ward, 4%. Areas were identified in the latter 6 categories for change. Review of practice 1 year after implementation of the changes showed that a large number of recommendations were in place. We describe a new method for auditing the processes of medical care, using the itemized bill to adapt and use information primarily recorded for financial purposes.     

Surgical wound infection surveillance in general surgery procedures at a teaching hospital in Pakistan

BACKGROUND: A surveillance system was established at the Aga Khan University Hospital in Karachi, Pakistan, to determine surgical wound infection (SWI) rates, trends, and risk factors; and to compare rates with those reported by the National Nosocomial Infection Surveillance (NNIS) system of the Centers for Disease Control and Prevention. METHODS: Surveillance was performed from January 1997 to December 1999. Risk categorization was on the basis of the NNIS system. P <.05 was set for statistically significant difference between groups. Data were analyzed using the Epi-Info software (version 6.04, CDC, Atlanta, Ga). RESULTS: Overall SWI rates for the NNIS risk categories 0, 1, 2, and 3 were 1.9%, 3.7%, 6.7%, and 5.1%, respectively. SWI rate in 0 risk category decreased from 3% in 1997 to 1.1% in 1999 (P =.06). Multivariate analysis showed that SWI rates were higher after mastectomy (odds ratio [OR] 4.28, 95% confidence interval [CI] 1.8-10), hernia repair (OR 3.28, 95% CI 1.6-6.7), gastrointestinal resection (OR 2.2, 95% CI 0.88-5.9), skin procedures (OR 1.97, 95% CI 0.89-4.3), appendectomy OR 0.57, 95% CI 0.20-1.60, and miscellaneous procedures (OR 3.6, 95% CI 1.6-7.7), as compared with cholecystectomy. Other risk factors were contaminated type of operation (OR 2.6, 95% CI 1.2-5.5), and duration of operation exceeding the NNIS standard of "T" hours (OR 2.6, 95% CI 1.7-4). CONCLUSION: The SWI rates at the Aga Khan University Hospital are higher than the NNIS standards. There was a downward trend in the SWI rates during the surveillance period. A decrease in the duration of surgical procedures could further reduce the risk.