Predictors of Clinical Outcomes in Acute Appendicitis: A Retrospective Study.

INTRODUCTION: Acute appendicitis is one of the most common causes of intra-abdominal emergency surgery worldwide. This study was conducted to contribute to global databases by presenting data from our institution, which consist of multi-racial population. We aimed to evaluate the presentation, diagnosis, and management of acute appendicitis and post-operative outcome in our institution and evaluate the risks factors associated with severe complications and prolonged length of stay (LOS). MATERIALS AND METHODS: We performed a retrospective analysis using multivariate regression analysis of all patients who underwent appendectomy (2009-2014) in our institution. The primary outcomes included demographics, presentation, and perioperative management, and the secondary outcomes included risk factors associated with prolonged LOS. RESULTS: Of the 1185 patients, the mean age was 36.4 years, and 940 (79.3%) were male. Majority (98.1%) of patients were ASA (American Society of Anaesthesiologists) 1 or 2. Most of them (83.9%) were from the four racial subgroups (Chinese, Malay, Bangladeshi, and Indian). There was no racial variation in the diagnosis and presentation of disease. The mean duration of symptoms was 1.8 days. The history was commonly a localised or migratory abdominal pain associated with anorexia, nausea, vomiting, and fever. The commonest physical findings were right-sided abdominal tenderness associated with rebound and guarding. About 42.9% of the patients underwent pre-operative CT scan to establish the diagnosis of appendicitis prior to surgery, whilst 57.1% underwent surgery on clinical diagnosis and blood investigation (NWR and CRP). An open appendectomy was performed in 13.2% of the patients. The conversion rate of laparoscopic appendectomy was 4.9% (n = 50). The mean length of hospital stay was 3.6 days. On multivariate Cox regression, patients of Burmese and Thai descent were independently associated with a prolonged LOS. The postoperative morbidity was 5.5%. The 30-day readmission rate was 2.4%. There was no mortality in our study. DISCUSSION: Our study showed that pre-operative diagnosis of acute appendicitis can be made accurately by classical clinical presentation or by imaging. Independent risk factors associated with increased LOS included increased age, male gender, prolonged duration of symptoms pre-admission, fever, generalised tenderness, and prolonged operative time. The effect of race on LOS has been observed in the literature for other surgical procedures. The prolonged LOS found in Burmese and Thai patients contribute to the possibility of intrinsic racial differences in the post-surgery recovery. However, the numbers are small and therefore prone to type I error. Compared to the open approach, the use of laparoscopic appendectomy was associated with shorter LOS. This has similar outcomes to those reported in the literature. CONCLUSION: The identification of risks factors could help surgical team to predict the clinical outcomes and develop risk reduction strategy in post-operative care of these patients.

Surveillance of autoimmune conditions following routine use of quadrivalent human papillomavirus vaccine.

OBJECTIVE: An observational safety study of the quadrivalent human papillomavirus vaccine (HPV4) in women was conducted. This report presents findings from autoimmune surveillance. Design. Subjects were followed for 180days after each HPV4 dose for new diagnoses of 16 prespecified autoimmune conditions. SETTING: Two managed care organizations in California. Subjects. Number of 189,629 women who received ≥1 dose of HPV4 between 08/2006 and 03/2008. OUTCOME: Potential new-onset autoimmune condition cases amongst HPV4 recipients were identified by electronic medical records. Medical records of those with ≥12-month health plan membership prior to vaccination were reviewed by clinicians to confirm the diagnosis and determine the date of disease onset. The incidence of each autoimmune condition was estimated for unvaccinated women at one study site using multiple imputations and compared with that observed in vaccinated women. Incidence rate ratios (IRR) were calculated. Findings were reviewed by an independent Safety Review Committee (SRC). RESULTS: Overall, 1014 potential new-onset cases were electronically identified; 719 were eligible for case review; 31-40% were confirmed as new onset. Of these, no cluster of disease onset in relation to vaccination timing, dose sequence or age was found for any autoimmune condition. None of the estimated IRR was significantly elevated except Hashimoto's disease [IRR=1.29, 95% confidence interval: 1.08-1.56]. Further investigation of temporal relationship and biological plausibility revealed no consistent evidence for a safety signal for autoimmune thyroid conditions. The SRC and the investigators identified no autoimmune safety concerns in this study. CONCLUSIONS: No autoimmune safety signal was found in women vaccinated with HPV4.

Safety of zoster vaccine in adults from a large managed-care cohort: a Vaccine Safety Datalink study.

OBJECTIVES: The aim of this study was to examine a large cohort of adults who received the zoster vaccine for evidence of an increased risk of prespecified adverse events requiring medical attention. DESIGN: Two self-comparison approaches, including a case-centred approach and a self-controlled case series (SCCS) analysis were used. SETTING: Eight managed-care organizations participating in the Vaccine Safety Datalink project in the United States. SUBJECTS: A total of 193 083 adults aged 50 and older receiving a zoster vaccine from 1 January 2007 to 31 December 2008 were included. MAIN OUTCOME MEASURES: Prespecified adverse events were identified by aggregated International Classification of Diseases, Ninth Revision (ICD-9) codes in automated health plan datasets. RESULTS: The risk of allergic reaction was significantly increased within 1-7 days of vaccination [relative risk = 2.13, 95% confidence interval (CI): 1.87-2.40 by case-centred method and relative rate = 2.32, 95% CI: 1.85-2.91 by SCCS]. No increased risk was found for the following adverse event groupings: cerebrovascular events; cardiovascular events; meningitis; encephalitis; and encephalopathy; and Ramsay-Hunt syndrome and Bell's palsy. CONCLUSIONS: The results of this study support the findings from the prelicensure clinical trials, providing reassurance that the zoster vaccine is generally safe and well-tolerated with a small increased risk of allergic reactions in 1-7 days after vaccination.

[Antitubercular drug treatment failure and HIV infection in Abidjan (Ivory Coast)]. / Echec du traitement antituberculeux et infection due au VIH à Abidjan (Côte d'Ivoire).

A retrospective study from 1989 to 1993 was carried out on eighty patients out of 106 cases of tuberculosis treatment failure; representing 2.2% of persons with active pulmonary tuberculosis followed at the tuberculosis screening center of Abidjan. The rate of HIV seropositivity was 43.7%. At the beginning of the therapy, 80% of HIV-positive and 89% of HIV-negative had diffuse pulmonary lesions (no significant difference: P > 0.05. At the end of second month therapy, 49% of co-infected and 51% of HIV-negative patients showed bacteriological negative sputum. The treatment administered after reporting failure, led to 63% of recovery among the HIV-positive (22/35) and 62% among the HIV-negative (28/45). On the other hand, the rate of patients out of touch was high in both populations; respectively 29% of HIV infected and 31% of HIV-negative spreading the risk of contamination of neighbourhood by probably resistant bacilli.

Deoxyarteannuin B, dihydro-deoxyarteannuin B and trans-5-hydroxy-2-isopropenyl-5-methylhex-3-en-1-ol from Artemisia anuua.

The amorphane sesquiterpenes, deoxyarteannuin B and dihydro-deoxyarteannuin B, were isolated from Artemisia annua and their structures mainly determined by two-dimensional NMR spectoscopic analyses. The irregular monoterpene, trans-5-hydroxy-2-isopropenyl-5-methylhex-3-en-1-ol, was also characterized in the same way, and its structure was confirmed by synthesis from lavandulol. All of these natural products are suggested to be formed by autoxidation reactions. Full assignments of the 1H and 13C resonances for the known natural products epi-deoxyarteannuin B and isoannulide, determined by the same methodology, are also reported.

Contribution of potential EF hand motifs to the calcium-dependent gating of a mouse brain large conductance, calcium-sensitive K(+) channel.

1. The large conductance, calcium-sensitive K(+) channel (BK(Ca) channel) is a unique member of the K(+)-selective ion channel family in that activation is dependent upon both direct calcium binding and membrane depolarization. Calcium binding acts to dynamically shift voltage-dependent gating in a negative or left-ward direction, thereby adjusting channel opening to changes in cellular membrane potential. 2. We hypothesized that the intrinsic calcium-binding site within the BK(Ca) channel alpha subunit may contain an EF hand motif, the most common, naturally occurring calcium binding structure. Following identification of six potential sites, we introduced a single amino acid substitution (D/E to N/Q or A) at the equivalent of the -z position of a bona fide EF hand that would be predicted to lower calcium binding affinity at each of the six sites. 3. Using macroscopic current recordings of wild-type and mutant BK(Ca) channels in excised inside-out membrane patches from HEK 293 cells, we observed that a single point mutation in the C-terminus (Site 6, FLD(923)QD to N), adjacent to the 'calcium bowl' described by Salkoff and colleagues, shifted calcium-sensitive gating right-ward by 50--65 mV over the range of 2--12 microM free calcium, but had little effect on voltage-dependent gating in the absence of calcium. Combining this mutation at Site 6 with a similar mutation at Site 1 (PVD(81)EK to N) in the N-terminus produced a greater shift (70--90 mV) in calcium-sensitive gating over the same range of calcium. We calculated that these combined mutations decreased the apparent calcium binding affinity approximately 11-fold (129.5 microM vs. 11.3 microm) compared to the wild-type channel. 4. We further observed that a bacterially expressed protein encompassing Site 6 of the BK(Ca) channel C-terminus and bovine brain calmodulin were both able to directly bind (45)Ca(2+) following denaturation and polyacrylamide gel electrophoresis (e.g. SDS-PAGE). 5. Our results suggest that two regions within the mammalian BK(Ca) channel alpha subunit, with sequence similarities to an EF hand motif, functionally contribute to the calcium-sensitive gating of this channel.

Enhanced activity of a large conductance, calcium-sensitive K+ channel in the presence of Src tyrosine kinase.

Large conductance, calcium-sensitive K(+) channels (BK(Ca) channels) contribute to the control of membrane potential in a variety of tissues, including smooth muscle, where they act as the target effector for intracellular "calcium sparks" and the endothelium-derived vasodilator nitric oxide. Various signal transduction pathways, including protein phosphorylation can regulate the activity of BK(Ca) channels, along with many other membrane ion channels. In our study, we have examined the regulation of BK(Ca) channels by the cellular Src gene product (cSrc), a soluble tyrosine kinase that has been implicated in the regulation of both voltage- and ligand-gated ion channels. Using a heterologous expression system, we observed that co-expression of murine BK(Ca) channel and the human cSrc tyrosine kinase in HEK 293 cells led to a calcium-sensitive enhancement of BK(Ca) channel activity in excised membrane patches. In contrast, co-expression with a catalytically inactive cSrc mutant produced no change in BK(Ca) channel activity, demonstrating the requirement for a functional cSrc molecule. Furthermore, we observed that BK(Ca) channels underwent direct tyrosine phosphorylation in cells co-transfected with BK(Ca) channels and active cSrc but not in cells co-transfected with the kinase inactive form of the enzyme. A single Tyr to Phe substitution in the C-terminal half of the channel largely prevented this observed phosphorylation. Given that cSrc may become activated by receptor tyrosine kinases or G-protein-coupled receptors, these findings suggest that cSrc-dependent tyrosine phosphorylation of BK(Ca) channels in situ may represent a novel regulatory mechanism for altering membrane potential and calcium entry.

Novel phenylpropanoids and lignans from Illicium verum.

Nine new phenylpropanoids (2-7, 10, 12, and 14) and two compounds representing novel structural classes of 7-O-8' and 7-O-8'.8-O-7' lignans (8 and 9, respectively) have been isolated from Illicium verum and their structures established by two-dimensional NMR. Most of these compounds appear to be biogenetically derived from threo-anethole glycol: relative stereochemistries for some members of this series were established by NOESY; absolute stereochemistries of others were determined by formation of Mosher esters.

Abietane diterpenes from Illicium angustisepalum.

Twelve novel (1, 2, 4, 5, 7-14) and two known (3, 6) abietane diterpenes and have been isolated from the aerial parts of Illicium angustisepalum. These diterpenes are unusual in that they are oxygenated at the axial C-19 position of the gem-dimethyl group rather than the equatorial C-18 position.

Juvenile scleroderma: report of a case.

Scleroderma is a rare connective tissue disease in children. A 12-year-old boy suffered from progressive increasing skin tension with erythematous changes in his left leg for a period of 3 months. This limited the range of motion in his left first and second metatarsophalangeal joints. A skin biopsy showed hypertrophic collagen bundles with atrophic skin appendages and lymphocytic infiltration. Based on the clinical manifestations and typical histopathologic findings, juvenile linear scleroderma was diagnosed. He was successfully treated with a short course of oral prednisolone in addition to long-term therapy with D-penicillamine and a topical emollient.

Generation of cytotoxic T lymphocytes from peripheral blood.

BACKGROUND: Cytotoxic T lymphocytes (CTL) have been shown to be useful for adoptive immunotherapy in malignancy. Traditional sources for CTL, such as tumor-infiltrating lymphocytes, have limitations. It would therefore be useful to develop a method of generating antitumor CTL from a renewable source such as peripheral blood. METHODS: DBA/2 mice were injected intradermally in the abdominal wall with the murine tumor PHS-5 and killed 14 days later. Peripheral blood lymphocytes were harvested and cultured with 20 units/ml interleukin-2 and autologous tumor-stimulator cells treated with mitomycin C. Cultures were split when greater than 2 x 10(6) cells/well, fed every 3 days and stimulated weekly. RESULTS: Lymphocytes expanded greater than 130,000-fold during 8 weeks. Specific cytotoxicity was shown with 51Cr release assay. Withdrawal of repeated stimulation with autologous tumor resulted in failure of cells to expand in culture and loss of cytotoxicity. In vivo administration showed marked reduction of 10-day liver metastases, indicating therapeutic efficacy. CONCLUSIONS: These data demonstrate a successful animal model of adoptive immunotherapy with CTL generated from peripheral blood lymphocytes.

Isolation and characterization of a 50 kDa testosterone-binding protein from Pseudomonas testosteroni.

A testosterone-binding protein (Mr = 50,500) has been isolated from the Gram-negative bacterium Pseudomonas testosteroni. The protein was partially purified by a combination of ion exchange chromatography and chromatofocusing. Final purification was achieved by electroelution of the 50 kDa protein from SDS-polyacrylamide gels. Following renaturation from a diluted solution of guanidine-HCl, specific binding of [3H]testosterone to the purified protein was observed. The native protein has a pI of 6.8. It appears to contain 428 amino acids, 39% of which are hydrophobic. There is only one cysteine residue. Both chymotrypsin and V8 protease were used to produce peptide maps of the protein for use in future identification. The first 10 amino acids situated at the N-terminal of the protein were Ser-Pro-Phe-Asp-Leu-Arg-Pro-Leu-Ser-Gly. Testosterone binding to the protein was saturable at approximately 3.8 nmol/mg protein; the binding constant was approximately 25 nM. Unlabelled testosterone, androstenedione, 5 alpha-dihydrotestosterone and 5 beta-dihydrotestosterone were able to compete for [3H]testosterone bound to the protein; 17 beta-estradiol also competed for [3H]testosterone but to a lesser degree. Neither progesterone nor desoxycorticosterone competed for the testosterone-binding site. Binding of testosterone to the protein was stable at pH's ranging from 5.5 to 9.0 and at various temperatures ranging from 4 to 30 degrees C. The protein was unable to metabolize testosterone in either the presence or absence of the cofactor NAD.

Regression of pituitary microadenoma during and following bromocriptine therapy: persistent defect in prolactin regulation before and throughout pregnancy.

During 5 years of clinical, endocrinologic, and radiologic observations in a woman with a microprolactinoma treated medically with bromocriptine for 29 months, serial hypothalamic-pituitary studies revealed a defect in lactotrope function after prolactin (PRL) concentrations and ovulation were restored to normal. This defect persisted throughout a spontaneously conceived pregnancy in which the PRL, estradiol, and progesterone levels were subnormal, while, the dehydroepiandrosterone sulfate levels were normal and estriol concentrations were elevated. Levels of the beta subunit of human chorionic gonadotropin (hCG) were close to and slightly above the normal ranges. These observations are consistent with a role for PRL, interacting with hCG, in the control of estrogen and progesterone secretion by the fetoplacental unit. Lactation was initiated and maintained post partum. Pituitary function and PrL responses to suckling suggested improved lactotrope function 22 to 25 months after withdrawal of bromocriptine. The impaired lactotrope function, therefore, did not preclude normal implantation, pregnancy maintenance, onset of parturition, fetal development, and lactation.

Prolactin, estradiol, and thyroid hormones in umbilical cord blood of neonates with and without hyaline membrane disease: a study of 405 neonates from midpregnancy to term.

Concentrations of prolactin (PRL), estradiol (E2), thyroxine (T4), triiodothyronine (T3), and reverse T3 in umbilical cord blood were measured by radioimmunoassay in neonates with (n = 60) and in a control group without (n = 345) hyaline membrane disease. Mean levels of all hormones assayed were not significantly different between the two groups at various stages of gestation. In the control group, gestational age correlated positively with PRL and inversely with reverse T3, whereas birth weight correlated positively with PRL, T4, and T3, but inversely with reverse T3 levels. Thus, larger, more mature neonates tended to have higher cord levels of PRL, T4, T3 and lower concentrations of reverse T3. The data also suggest that, in the premature neonate, various obstetric complications and exposure in utero to beta-mimetic drugs and glucocorticoids may be important determinants of the concentrations of E2 and thyroid hormone in cord blood.

Regulation of ovarian follicular and luteal function during treatment with exogenous gonadotropins in anovulatory infertility.

The dosage, duration of treatment, and plasma hormone levels were analyzed statistically between and within groups of treatment cycles with (n = 46) and without (n = 10) ovulation. A significant difference was observed in the dosage of human menopausal gonadotropins (hMG) over various days of treatment, but not in the mean dosage of hMG and human chorionic gonadotropin (hCG) administered per cycle. Follicle-stimulating hormone (FSH):luteinizing hormone (LH) ratios, prolactin (PRL) levels, and the magnitude and the duration of the estradiol response were greater in the ovulatory cycles. Additionally, in the ovulatory cycles, the dose of hMG correlated with the plasma levels of estradiol, FSH, and LH, while in the anovulatory cycles, hMG dosage correlated only with the LH concentrations. After administration of hCG, the mean plasma concentrations of its beta subunit peaked within 1 day and remained detectable for up to 10 days thereafter. In the ovulatory cycles, the mean progesterone level was maximal 6 days following hCG administration. In these cycles, luteal phase progesterone levels correlated positively with the preovulatory estradiol and inversely with concentrations of the beta subunit of hCG. The data demonstrate that, in contrast to anovulatory follicles, ovulatory follicles were exposed to a relative "dominance" of FSH over LH, with higher concentrations of estradiol and PRL for several days before hCG was administered. Apart from hMG dosage, the endogenous discharge of LH appeared to be an important determinant of the ovarian response. A single 10,000 IU dose of hCG was adequate for inducing ovulation and maintaining luteal function.

Human chorionic gonadotropin, estradiol, progesterone, prolactin, and B-scan ultrasound monitoring of complications in early pregnancy.

In a prospective study of women in the first trimester who were at risk for recurrent abortion, data from 20 pregnancies with normal outcomes were contrasted with those of 9 pregnancies that aborted spontaneously between 7 and 12 weeks. In pregnancies in which an embryo was present before abortion, the mean concentrations of human chorionic gonadotropin beta-subunit (hCG-beta) were low with a steady decline in progesterone levels, whereas estradiol (E2) and prolactin concentrations approximated those in normal pregnancies. With growth disorganization, mean hCG-beta, E2, and progesterone levels were significantly lower than normal. In 87.5% of embryopathic pregnancies, conclusive evidence of this disorder was obtained with ultrasound monitoring. Subnormal levels of hCG-beta, E2, and progesterone were observed in 88.9, 100, and 57.1%, respectively. The karyotype was abnormal in 80% of embryopathic pregnancies successfully cultured. The normal production of E2 appeared dependent on the presence of the embryo in the first trimester of pregnancy. Endocrine failure of the trophoblast and/or the corpus luteum in embryopathic pregnancy is suggested by diminished hCG-beta and progesterone concentrations. Serial ultrasound scanning and hormone assay, particularly of hCG-beta and E2, may be useful in assessing pregnancy at risk for recurrent abortion. However, because subnormal hormone levels may occur relatively late in the clinical course of embryopathic gestation, ultrasound scanning may yield more useful results as compared with hormone assay. Further studies are required to define more clearly the mechanisms of endocrine failure in embryopathic pregnancy.

A possible role for prolactin in the control of human chorionic gonadotropin and estrogen secretion by the fetoplacental unit.

The effects of prolactin (PRL) on fetoplacental function were studied by measuring the beta subunit of human chorionic gonadotropin (hCG-beta), estradiol (E2), progesterone (P), and PRL concentrations throughout seven pregnancies in a control group (N = 6 women) and in three pregnant women with prolactinomas, who were receiving bromocriptine. In one of the latter, estriol (E3) was also assayed. Long-term suppression of PRL was associated with augmentation of hCG-beta at the first-treimester peak and in late pregnancy. Concomitant augmentation of E3 (in late gestation) and possibly E2, but not P, levels was also observed. This effect on hCG appeared dependent on PRL rather than the dopaminergic effect of bromocriptine. Short-term drug induced alterations in PRL (over 3 hours) during early pregnancy did not result in significant changes in hCG-beta or steroid concentrations. In each control pregnancy, a significant negative correlation (p less than 0.05) was observed between hCG-beta and PRL, while a significant positive correlation between the latter and E2 concentrations in these women was also demonstrated. Apart from its effect on lactation, osmoregulation, and gonadal and adrenal function, a further role for PRL during reproduction appears to be in the control of hCG and estrogen secretion in the fetoplacental unit.