Agenesis of the Gallbladder Revisited Laparoscopically

Gallbladder agenesis is an extremely rare disease. Necropsy incidence has been reported to be 0.016%. Failure lo locate the gallbladder at the time of a planned cholecystectomy can be very challenging. We report such a case during a laparoscopic cholecystectomy. The indication for surgery in these patients are complaints of gallbladder symptoms along with a false-positive ultrasound study. During exploration, an abnormal location of the gallbladder has to be excluded. Ectopic gallbladder locations include intrahepatic, lesser omentum, retroperitoneal, retrohepatic, within the falciform ligament, retroduodenal, and retrohepatic areas. Thorough exploration and cholangiography are essential. Embryologically, the gallbladder and cystic duct arise from the caudal portion of the hepatic bud. All of the previously reported cases of gallbladder agenesis have shown an absence of both the gallbladder and cystic duct. We report an embryological oddity wherein a patent cystic duct was found along with an agenetic gallbladder. This is the first case report of this finding, along with this being the first absent gallbladder discovered laparoscopically.     

Clonazepam in the long-term treatment of patients with unipolar depression, bipolar and schizoaffective disorder.

The value of a long-term treatment with clonazepam in the prophylaxis of affective disorder is discussed controversially in the scientific literature. Altogether there are only a few reports on the use of this compound as a mood stabilizer, most of them describing patients suffering from bipolar affective disorder. The aim of this investigation was to evaluate clonazepam as a phase prophylactic medication in affective disorder. We conducted a retrospective chart review in 34 out-patients of our lithium clinic (15 suffering from unipolar depression, 15 from bipolar disorder, four from schizoaffective disorder), who had been treated with clonazepam as a long-term medication. Clonazepam was either given as monotherapy, or as in the case of lithium non-responders, as adjunctive therapy. Patients with unipolar depression had significantly (P=0.026) less depressive episodes after initiation of treatment with clonazepam. Patients with bipolar disorder did not benefit from this therapy. Neither manic/hypomanic phases nor depressive episodes were reduced in this group of patients. Interestingly, clonazepam also reduced affective phases in our four schizoaffective patients on a trend level. Our results indicate that patients with unipolar depression may benefit from a maintenance treatment with clonazepam. Due to methodological limitations our results need to be replicated in controlled double-blind randomized clinical trials.     

Outcome of frozen embryo replacement cycles following elective cryopreservation of all embryos in women at risk of developing ovarian hyperstimulation syndrome

Aim: Our aim was to compare the outcome in subsequent frozen embryo replacement cycles in four groups of patients who had elective cryopreservation of all their embryos because they were considered to be at increased risk of developing severe ovarian hyperstimulation syndrome. Design: Sixty-two (91%) of 68 IVF cycles (68 patients) in which elective cryopreservation of all embryos was performed were analyzed. All patients continued on the GnRH agonist, buserelin, after oocyte recovery until the onset of vaginal bleeding. Frozen embryo replacement occurred in a hormone replacement cycle that started either on day 3 of the withdrawal bleed (group I;N=15) or after serum estradiol levels had fallen to <100 pmol/L (group II;N=16). The other patients commenced a frozen embryo replacement cycle several months later in either a hormone replacement (group III;N=15) or a natural (group IV;N=16) cycle. Results: Two patients developed severe ovarian hyperstimulation syndrome. There were no significant differences among the four groups regarding demographic variables, the dose of hMG used, and the clinical outcome. There was a higher but not significantly different clinical pregnancy rate in group I (26.7%), compared to group II (12.5%), group III (13.3%), and group IV (18.8%). Conclusions: Several options exist for the timing and protocol used for frozen embryo replacement in patients who had elective cryopreservation for the prevention of ovarian hyperstimulation syndrome, none of which was found to be clearly superior in this observational report.Presented at the 1994 Annual Conference of the American Fertility Society.     

Seroepidemiological characterization of a syphilis epidemic in the Republic of the Marshall Islands, formerly a yaws endemic area.

The annual numbers of reported cases of syphilis in the Republic of the Marshall Islands (RMI) increased from none in 1983 to more than 600 in 1989, suggesting a large outbreak of syphilis. Much of the increase resulted from expanded serological screening. The apparent outbreak of syphilis, therefore, may have been partly the result of increased surveillance or, since the RMI was formerly a yaws endemic area, possibly due to a resurgence of yaws. To address this problem and better characterize the epidemic, we analysed results from a 1989/90 Ministry of Health Services mass serological screening on Majuro Atoll, the main population centre. Serum specimens from 9160 people (86% of residents aged 15-44 years) on Majuro were screened with the rapid plasma reagin (RPR) card test; we repeated the RPR and performed a confirmatory microhaemagglutination assay for Treponema pallidum-specific antibodies (MHA-TP) on a sample of serum specimens. To estimate the seroprevalence of syphilis, we also tested a sample of RPR nonreactive specimens by MHA-TP. Among people less than 45 years of age, total (11.5%) and high-titre (5.2%) seropositivity rates were highest in the 20-24 year age group, as was MHA-TP seroprevalence (15.9%). These results suggested that a large outbreak of syphilis was responsible for the observed seroreactivity. Cumulative incidence modelling and comparisons with the results of a previous serosurvey conducted in 1985 suggested that the duration of the syphilis epidemic was approximately 10 years and that incidence had not increased appreciably since 1985.     

Capsaicin cough sensitivity in allergic asthmatic patients increases during the birch pollen season.

BACKGROUND: A change in neural responsiveness may occur as the result of allergic inflammation in the lower airways as well as in the upper airways. In the lower airways, capsaicin cough sensitivity is known to reflect sensory neural reactivity. OBJECTIVE: The aim of this study was to establish whether allergic inflammation changes airway neural sensory reactivity during prolonged allergen exposure. METHODS: Ten nonsmoking patients with birch pollen-allergic asthma performed a capsaicin inhalation challenge twice, once in the off-pollen season and once during the pollen season. The number of coughs and symptoms induced by capsaicin were recorded and compared with those of healthy control subjects. RESULTS: The response to capsaicin, expressed as number of coughs, increased in a dose-dependent manner during both tests. Before the season, the response was similar to that of healthy control subjects, but during the pollen season, the reactivity was significantly increased. Variations in forced expiratory volume in 1 second were not significant before and after each challenge, and values did not change during the pollen season as compared with the winter season. CONCLUSIONS: Sensory reactivity in allergic asthmatic patients may be increased during prolonged allergen exposure as during the pollen season. This finding suggests that allergic inflammation in the lower and/or upper airways may trigger neurogenic mechanisms of significant clinical importance.     

Evaluation of peripheral blood involvement of mantle cell lymphoma by fluorescence in situ hybridization in comparison with immunophenotypic and morphologic findings.

Mantle cell lymphoma is non-Hodgkin's B-cell lymphoma characterized by the t(11;14)(q13;q32) translocation. Peripheral blood involvement of mantle cell lymphoma is usually associated with a poor prognosis and therefore, its identification is clinically important. In this study, we performed cyclin D1/IgH-probe fusion fluorescence in situ hybridization analysis on 223 peripheral blood samples: 185 from 125 mantle cell lymphoma patients, and 38 normal controls. The cutoff values for the test were established using normal controls. Flow cytometry on peripheral blood and corresponding bone marrow samples was used to evaluate this test. In all, 26% of the 185 peripheral blood samples and 27% of the 161 corresponding bone marrow samples were flow cytometry positive for mantle cell lymphoma. The mean numbers of single and- double-fusion signals and the mean number of CD5/CD19-positive cells, absolute blood lymphocyte count, and white blood cell count were significantly higher in peripheral blood and corresponding bone marrow samples with mantle cell lymphoma-positive flow cytometry. Double-fusion signals were more specific than single-fusion ones. Fluorescence in situ hybridization was far more likely to be positive for mantle cell lymphoma when the peripheral blood and the corresponding bone marrow samples had positive flow cytometry results or morphology (P<0.01). Our study indicates that cyclin D1/IgH-fusion fluorescence in situ hybridization analysis could be used to determine the presence and character of circulating mantle cell lymphoma cells in peripheral blood, thus enhancing our ability to evaluate leukemic mantle cell lymphoma and minimum residual disease.     

Alpha-(phenylselenenyl)acetophenone derivatives with glutathione peroxidase-like activity. A comparison with ebselen.

Here we describe a new class of organoselenium compounds possessing glutathione peroxidase-like activity. The parent compound, alpha-(phenylselenenyl)acetophenone (PSAP), increased the rate of reaction of glutathione with H2O2, tert-butylhydroperoxide, cumene hydroperoxide, linoleic acid hydroperoxide and dilinoleyl lecithin hydroperoxide by 7.0, 25.1, 34.1, 19.1 and 8.4-fold, respectively, as assessed by the oxidized glutathione (GSSG) reductase enzyme assay. Direct assay of the removal of hydrogen peroxide and glutathione from reaction mixtures confirmed the peroxidase-like activities of these selenoorganic compounds, but indicate that the conventional coupled GSSG reductase assay may be unsuitable for the assessment of the catalytic capacity of PSAP and Ebselen. One possible mechanism of catalysis by PSAP involves an initial oxidation at selenium. Thiol may then react with the selenoxide to yield a selenium (II) compound, H2O and a disulfide. Compounds derived from PSAP may provide potential selenium-based anti-inflammatory agents.     

Effect of chronic neonatal morphine and naloxone on sensorimotor and social development of young rats

Chronic morphine treatment of newborn Long-Evans rat pups between 3-26 days of age (thrice daily starting with 0.5 mg/kg, increased daily by 0.5 mg/kg to 10 mg/kg) led to lags of 1 to 3 days in physical development (body weights and eye opening times) and motor coordination (catalepsy test, grasping, swimming). Chronic naloxone treatment (5 mg/kg administered thrice daily from day 3-26), in contrast, led to modest gains in development on a number of measures (body weights, vaginal opening). Morphine animals also lagged behind controls and naloxone-tested animals in social behaviors, such as homing and play. Chronic naloxone did not block or retard social development; in fact naloxone-treated animals exhibited more rapid acquisition of homing behavior than controls.     

On the role of Ca2+ in the toxicity of alkylating and oxidizing quinone imines in isolated hepatocytes

The cytotoxicity of acetaminophen (paracetamol) has been shown to be associated with a disruption of intracellular Ca2+ homeostasis caused by the interaction of its metabolite N-acetyl-p-benzoquinone imine (NAPQI) with hepatocyte thiols [Moore, M., et al. (1985) J. Biol. Chem. 260, 13035-13040]. Inasmuch as NAPQI can both covalently bind to thiols and oxidize thiols, we investigated the effects of two dimethylated analogues of NAPQI, one of which (2,6-dimethyl-NAPQI) primarily binds to thiols and the other of which (3,5-dimethyl-NAPQI) primarily oxidizes thiols. Of the three compounds, 2,6-dimethyl-NAPQI decreased protein thiols to the greatest extent and also inhibited hepatocyte plasma membrane Ca(2+)-ATPase to the greatest extent. The 3,5-dimethylated analogue decreased protein thiols to the least extent and inhibited the plasma membrane Ca(2+)-ATPase to a lesser extent. The cytotoxicity of all three compounds was preceded by a sustained elevation in cytosolic Ca2+ as compared to the transient rise caused by the alpha-agonist phenylephrine. Again, the 2,6-dimethyl analogue was the most potent of the three compounds. The thiol reagent dithiothreitol (DTT), which reversed the inhibition of the Ca(2+)-ATPase and the rise in cytosolic Ca2+, also protected against cytotoxicity. Agents that are known to inhibit either Ca(2+)-dependent proteases or phospholipases significantly delayed the onset of cytotoxicity caused by NAPQI and its analogues. Our results suggest that both arylation and oxidation of protein thiols may result in the elevation of cytosolic Ca2+ and in cytotoxicity and that arylation of critical thiol groups appears to be the more lethal reaction.