Simultaneous determination of sulfasalazine and its metabolites sulfapyridine and N-acetylsulfapyridine in human serum by ion-pair high-performance liquid chromatography using a polymer-based column

An HPLC method is described for the simultaneous and rapid determination of sulfasalazine (salicylazosulfapyridine) and two of its metabolites, sulfapyridine and N-acetylsulfapyridine, in human serum. The range of quantitation is 0.1 to 12 micrograms/mL for sulfasalazine and sulfapyridine and 0.25 to 12 micrograms/mL for N-acetylsulfapyridine. Serum is mixed with acetonitrile containing the internal standard sulfamethazine and the ion-pairing agent tetraethylammonium chloride. The acetonitrile extract is concentrated and analyzed by HPLC, using a new polymer-based column, and detected by UV spectroscopy at 270 nm. This paper is the first both to describe the simultaneous analysis of all three of the compounds from serum and to present sulfasalazine concentration-time data following oral administration to humans.     

An evaluation of Gambusia affinis and Bacillus thuringiensis var. israelensis as mosquito control agents in California wild rice fields

The mosquito control potential of the mosquitofish and Bacillus thuringiensis var. israelensis (Bti) were evaluated in experimental wild rice fields in Lake County, California. Fields were assigned one of six treatment: control, 1.1 kg/ha G. affinis, 3.4 kg/ha G. affinis, Bti only (6 kg/ha Vectobac granules), 1.1 kg/ha G. affinis plus Bti and 3.4 kg/ha G. affinis plus Bti. Gambusia affinis, at both release rates, significantly reduced the mosquito population at densities exceeding 100 fish/minnow trap. Treatments with Bti significantly reduced larval population; however, the populations in the fields without fish rebounded to pretreatment levels within two weeks. In fields stocked with G. affinis and treated with Bti, populations remained low after Bti treatment. Nontarget populations of arthropods were significantly lower in fields stocked with G. affinis than in fields without fish on one or more sampling dates.     

Clinical features of bipolar disorder with and without comorbid diabetes mellitus.

OBJECTIVE: Several papers have reported higher prevalence of diabetes mellitus (DM) type 2 in patients suffering from bipolar disorder (BD). The possible links between these 2 disorders include treatment, lifestyle, alterations in signal transduction, and possibly, a genetic link. To study this relation more closely, we investigated whether there are any differences in the clinical characteristics of BD patients with and without DM. METHOD: We compared the clinical data of 26 diabetic and 196 nondiabetic subjects from The Maritime Bipolar Registry. Subjects were aged 15 to 82 years, with psychiatric diagnoses of BD I (n = 151), BD II (n = 65), and BD not otherwise specified (n = 6). The registry included basic demographic data and details on the clinical course of bipolar illness, its treatment, and physical comorbidity. In a subsequent analysis using logistic regression, we examined the variables showing differences between groups, with diabetes as an outcome variable. RESULTS: The prevalence of DM in our sample was 11.7% (n = 26). Diabetic patients were significantly older than nondiabetic patients (P < 0.001), had higher rates of rapid cycling (P = 0.02) and chronic course of BD (P = 0.006), scored lower on the Global Assessment of Functioning Scale (P = 0.01), were more often on disability for BD (P < 0.001), and had higher body mass index (P < 0.001) and increased frequency of hypertension (P = 0.003). Lifetime history of treatment with antipsychotics was not significantly associated with an elevated risk of diabetes (P = 0.16); however, the data showed a trend toward more frequent use of antipsychotic medication among diabetic subjects. CONCLUSIONS: Our findings suggest that the diagnosis of DM in BD patients is relevant for their prognosis and outcome.     

Predictors of poliomyelitis case confirmation at initial clinical evaluation: implications for poliomyelitis eradication in the Americas.

In 1985, the Pan American Health Organization adopted the goal of eradication of poliomyelitis from the Americas by 1990. Strategies to accomplish this included high vaccination coverage, aggressive outbreak control, and active surveillance for acute flaccid paralysis (AFP). Although the sensitivity of AFP surveillance for detecting paralytic poliomyelitis cases is high, studies have shown the specificity to be low. In 1990, 2497 notified cases of AFP were investigated in the Americas of which 2146 had stool specimens collected. However, only 18 were confirmed as poliomyelitis by isolation of wild poliovirus from stool specimens, 71 were classified as being compatible with poliomyelitis. Cases of AFP due to causes other than poliomyelitis result in extensive but unnecessary outbreak control measures. To predict, at initial clinical evaluation, the likelihood of future confirmation as a case of poliomyelitis, likelihood ratios (LR) were calculated for different combinations of clinical characteristics of AFP cases (249) from Mexico in 1989 and 1990. The best predictors in a child with AFP were proximal muscle involvement which progressed '4 days together with fever at onset of paralysis, and proximal and unilateral involvement with either fever at onset or paralysis which progressed '4 days. The odds would increase by 12 that the child would eventually be confirmed as poliomyelitis (19), based on a stool culture positive for wild poliovirus (95% confidence interval (CI) 2.6-55.9). A guide for use in the field is proposed whereby local health officials, often with little training in neurological evaluation, can predict at initial clinical examination the likelihood that an AFP case will subsequently be confirmed as poliomyelitis.(ABSTRACT TRUNCATED AT 250 WORDS)     

Cellular mechanism of the conduction abnormalities induced by serum from anti-Ro/SSA-positive patients in rabbit hearts.

In this study, IgG fractions from sera of SLE patients with anti-Ro/SSA or anti-Ro/SSA and anti-La/SSB activity were tested in Langendorff preparations of adult rabbit hearts, aiming to reproduce the cardiac manifestations observed in neonatal lupus in an experimental model. The hearts were perfused with normal Tyrode's solution for 30 min, followed by perfusion with Tyrode's containing 0.3 mg/ml of anti-Ro/SSA- (or anti-Ro/La-) positive IgG (nine sera), anti-ribonucleoprotein (RNP)-positive IgG (five sera), or IgG fractions from normal donors (five sera). In one third of the experiments done with anti-Ro/La-positive IgG, heart block was observed. With the remaining fractions, a decrease in heart rate of 17.1% was observed, but normal sinus rhythm was maintained. The IgG fractions with anti-RNP activity (five experiments) and from normal sera (six experiments) reduced heart rates by 12.9 and 3.3%, respectively, but heart block was not observed. To further characterize the cellular mechanisms involved in the conduction disturbances observed in the whole rabbit hearts, we conducted experiments with ventricular myocytes isolated from young rabbit hearts, studied by whole cell patch-clamp technique. In these experiments, the slow inward currents were analyzed during the superfusion of the cell with normal Tyrode's solution and 5 min after superfusion with Tyrode's solution containing 0.3 mg/ml of anti-Ro/SSA- (or anti-Ro/La-) positive IgG (five sera), anti-RNP-positive IgG (three sera), or IgG from normal donors (four sera). Resting and action potential amplitudes were not affected by any of the sera used. The anti-Ro/SSA IgG fraction induced a mean reduction in the peak slow inward current of 31.6%. IgG fractions with anti-RNP activity reduced slow inward current by 4.4%, whereas IgG fractions from normal donors increased this current by 3.3%. IgG-free fractions from sera of patients with anti-Ro/SSA activity did not alter the peak slow inward current. These results show, for the first time, that the presence of anti-Ro/SSA or anti-Ro/SSA and anti-La/SSB antibody activity in IgG fractions from lupus patients' sera can induce cardiac conduction disorders similar to those observed in neonatal lupus.     

Fibrolamellar carcinoma of the liver in a child: ultrastructural and immunohistologic aspects

We describe a fibrolamellar carcinoma of the liver in a 12-year-old girl and review the literature concerning the occurrence of this distinct hepatic neoplasm in children up to the age of 16 years. The results of our electron microscopic and immunohistologic studies suggest that some cells of this tumor exhibit neuroendocrine differentiation. This finding has important theoretical implications relative to the tumor's histogenesis and practical implications with respect to the search for tumor markers of clinical usefulness and possibly for therapy.     

Deregulation of cell proliferation by polycyclic aromatic hydrocarbons in human breast carcinoma MCF-7 cells reflects both genotoxic and nongenotoxic events.

Polycyclic aromatic hydrocarbons (PAHs), such as benzo[a]pyrene (BaP), are carcinogens suggested to be involved in development of human cancer. Several recent studies have reported that PAHs can activate estrogen receptors (ER), either directly or indirectly by producing estrogenic metabolites. We hypothesized that the activation of ER by PAHs or their metabolites could induce cell proliferation in estrogen-sensitive cells. In the present study, we found that two PAHs, benz[a]anthracene (BaA) and BaP, can stimulate proliferation of human breast carcinoma MCF-7 cells at concentrations 100 nM and higher. This effect was ER-dependent, because it was blocked by the pure antiestrogen ICI 182,780. Although both PAHs partially inhibited S-phase entry and DNA synthesis induced by 17beta-estradiol, they stimulated S-phase entry when applied to MCF-7 cells synchronized by serum deprivation. This was in contrast with model antiestrogenic aryl hydrocarbon receptor ligand, 2,3,7,8-tetrachlorodibenzo-p-dioxin, which fully suppressed S-phase entry. BaP, which is a strong mutagen, was found to induce p53 tumor suppressor expression, a partial S-phase arrest and at higher concentrations also cell death. Pifithrin-alpha, a synthetic inhibitor of p53 activity, abolished both S-phase arrest and apoptosis induced by genotoxic PAHs, and it potentiated the proliferative effect of BaP. Thus, both genotoxic and nongenotoxic events seem to interact in the effects of BaP on cell proliferation. Taken together, our data indicate that both BaA and BaP can stimulate cell proliferation through activation of ER. The proliferative effects of these carcinogenic compounds might contribute to tumor promotion in estrogen-sensitive tissues.     

Epithelioid sarcoma. Flow cytometric study of DNA content and regional DNA heterogeneity.

The DNA content and regional DNA heterogeneity in correlation with clinicopathologic parameters and patient survival were investigated in epithelioid sarcoma. Such neoplasms preponderantly manifest diploid DNA content and a remarkably stable intratumoral and intertumoral DNA content. Small tumor size (less than 5.0 cm) and low S-phase fraction (less than 5%) were significant prognostic factors in this study. Ploidy status, mitotic rate, age, and postsurgical treatment were not significantly correlated with survival.     

The effects of menstrual phase and nicotine abstinence on nicotine intake and on biochemical and subjective measures in women smokers: a A preliminary report

Nicotine intake, menstrual and smoking withdrawal symptomatology, and baseline cortisol and MHPG were assessed in nine women smokers under conditions of ad lib smoking and overnight abstinence in three menstrual phases (early follicular, mid-to-late follicular, and late luteal). A trend towards higher nicotine intake p <0.100 was observed in the mid-to-late follicular phase. Although me menstrual symptomatology was not significantly elevated during the smoking abstinence condition overall, abstinence appeared to prevent the normal reduction in symptomatology during the mid-to-late follicular phase that occurred under conditions of ad lib smoking. Menstrual and withdrawal symptoms were highly correlated, and both were most pronounced during the late luteal/abstinence condition. The smoking-specific item “craving” reflected this pattern, though in attenuated form, suggesting that the observed exacerbation of withdrawal symptomatology was not simply due to generalized dysphoria, as queried in both instruments. MHPG was significantly elevated in the late luteal phase, whereas cortisol was significantly higher during ad lib smoking than during abstinence and tended to be highest in the mid-to-late follicular phase. Further investigation will be needed to determine the functional significance of these findings for understanding and treating smoking in women.