Effects of humidity and temperature on in vitro dissolution of carbamazepine tablets

The rate and extent of dissolution of various approved marketed carbamazepine (CBZ) tablets exposed to 33, 52, 75, and 97% relative humidities at both room temperature and 40 degrees C, and saturated water vapor at room temperature were compared to fresh unstressed tablets. The dissolution data indicate that exposure of CBZ tablets to high humidity and temperature can have a profound effect on tablet disintegration and dissolution. The dissolution rates of some batches of CBZ products exposed to 97% humidity at 40 degrees C or saturated water vapor at room temperature were drastically reduced in only 6-7 days.     

Localization of C-type natriuretic peptide mRNA in rat hypothalamus

Central or peripheral administration of C-type natriuretic peptide (CNP) affects numerous neuroendocrine systems, including the hypothalamo-pituitary-gonadal, hypothalamo-pituitary-adrenocortical and hypothalamo-neurohypophysial axes. The present report characterizes the distribution of CNP mRNA in hypothalamus, providing the first definition of CNP-containing neuroendocrine circuits. In situ hybridization histochemical analysis revealed high expression of CNP mRNA in the anteroventral periventricular nucleus (AVPv) and in hypothalamic arcuate nucleus (ARC). Hybridization signals of significantly lower intensity were seen in the medial, median and periventricular preoptic area, the supraoptic, dorsomedial, ventral premammillary and lateral mammillary nuclei and in the posterior hypothalamic area. A few scattered CNP mRNA containing cells were visualized in the medial parvocellular paraventricular nucleus, posterior magnocellular paraventricular nucleus and lateral hypothalamic area. In the AVPv and ARC the pattern of CNP mRNA distribution paralleled that of ANP mRNA. The results indicate a distribution of CNP mRNA associated with key neuroendocrine systems, and underscores the potential importance of this novel natriuretic peptide in neuroendocrine regulation.     

Seizures associated with propofol anesthesia

Propofol is a new, fast-acting intravenous (i.v.) anesthetic. Involuntary movements or epileptic seizures have occurred during or after propofol-induced anesthesia in approximately 50 reported cases; a third of the patients have had epilepsy. We report 5 patients with seizures in association with propofol anesthesia. A female epileptic patient developed severe status epilepticus; the other patients with short-lasting seizures had no previous epilepsy. Although propofol has been used in treatment of patients of status epilepticus, the risk of precipitation of epileptic seizures warrants consideration especially when planning anesthesia for epileptic patients.     

Panic disorder in cardiac outpatients

OBJECTIVE: Continuing the long history of interest in the relation of anxiety disorders to cardiovascular function and symptoms, this study investigated the level of anxiety and prevalence of panic disorder in cardiac patients and the possible associations between specific abnormal ECG results and a diagnosis of panic disorder. METHOD: Consecutive patients referred for ambulatory ECG recordings were assessed with the seven anxiety items of the Hospital Anxiety and Depression Scale. Then, 50 patients with scores higher than 8 (the anxious group) were interviewed with the Schedule for Affective Disorders and Schizophrenia--Lifetime Version Modified for the Study of Anxiety Disorders (SADS-LA). RESULTS: Of the 50 anxious patients (26 male and 24 female) interviewed with the SADS-LA, 62% (N = 31) met the DSM-III-R criteria for panic disorder. Patients with panic disorder had a higher mean maximal heart rate and a shorter P-R interval than patients without panic disorder. Unlike the patients without panic disorder, the patients with panic disorder showed no correlation between maximal heart rate and minimal P-R interval. CONCLUSIONS: The rate of panic disorder was high in the patients referred for ECG. Moreover, the prevalence of panic disorder was similar in the patients with and without ECG abnormalities, indicating that in anxious patients the presence of panic disorder does not rule out organic cardiac disease. On the other hand, the higher maximal heart rate and shorter P-R interval of the panic patients may be attributable to hypersensitivity of beta-adrenergic receptors in panic disorder.     

A monitoring, feedback, and triggering system for reproducible breath-hold MR imaging

OBJECTIVE: To evaluate the diagnostic accuracy and clinical usefulness of high-resolution transvaginal duplex Doppler ultrasound in postpartum and post-abortion patients with excessive hemorrhage who are suspected of having residual trophoblast. METHODS: Forty-eight women with excessive hemorrhage referred for possible residual trophoblastic tissue were evaluated by transvaginal duplex Doppler ultrasonography. Based on two-dimensional imaging, the patients were divided prospectively into groups: women who had an empty uterus with a normal uterine cavity, those with a pure endometrial fluid collection and no echogenic foci, those who had a mixed endometrial fluid collection with foci of echogenicity, and those with intracavitary heterogeneous material with mixed echo patterns of fluid and solid components. In each group, Doppler studies were performed and the resistance index (RI) was calculated. The two-dimensional patterns and Doppler results were correlated with clinical and pathologic follow-up. RESULTS: Twenty-eight subjects had a normal uterine cavity and seven had a pure endometrial fluid collection; all were treated conservatively and none showed later clinical evidence of residual trophoblastic tissue. In 13 women, residual trophoblast was strongly suggested from the images of two-dimensional ultrasonography: Five showed an endometrial fluid collection with some echogenic foci, and eight exhibited intracavitary mixed echogenic material. All underwent curettage, and residual trophoblastic tissue was found in ten of the 13. The mean (+/- standard deviation) RI to flow in the myometrial arteries was 0.54 +/- 0.15 in women without residual trophoblast and 0.35 +/- 0.1 in those with residual trophoblastic tissue (P < .01). CONCLUSION: Our experience suggests that transvaginal duplex Doppler ultrasonography is an effective noninvasive method for evaluating patients with excessive postpartum and post-abortion hemorrhage who are suspected of having residual trophoblastic tissue. Its use enhances the positive preoperative diagnosis of residual trophoblastic tissue and may reduce unnecessary curettage procedures.     

Relative involvement of protein kinase C and of the estrogen receptor in the cytotoxic action of a population of triphenylethylenes on MCF7 cells as revealed by correspondence factorial (CF) analysis

A multivariate statistical method, correspondence factorial (CF) analysis, was used to examine the correlations among the protein binding and cell proliferation effects of a series of 36 di- and triphenylethylenes (DPEs and TPEs). The analysis was applied to a study which measured their competition for estradiol binding to cytosol estrogen receptor (ER), their influence on protein kinase C (PKC) activity under different conditions of enzyme activation, their ability to promote the growth of a breast cancer cell line and to inhibit growth at high concentrations (cytotoxicity). The CF analysis revealed several levels of correlation. First, it distinguished those molecules within the population that stimulated rather than inhibited PKC activity. Second, it made apparent a strong correlation between cytotoxicity and inhibition of Ca++ and phosphatidylserine-dependent PKC activity, which was most marked when the enzyme had been activated by diacylglycerol indicating that PKC inhibition under physiological conditions might contribute to the overall cytotoxicity of these compounds. Third, a lower level of correlation was established between competition for ER binding and cytotoxicity. Taken together, the results suggest that MCF7 cells might be most sensitive to a cytotoxic effect of TPEs (via PKC and other targets) when they at the same time decrease estrogen-stimulated proliferation via an ER-mediated antiestrogenic effect.     

Further delineation of spondylo-meta-epiphyseal dysplasia, short limb-abnormal calcification type, with emphasis on diagnostic features

Further delineation of a generalized bone dysplasia which we call spondylo-meta-epiphyseal dysplasia, short limb-abnormal calcification type is presented. This dwarfing condition has several serious complications, with the most common cause of death being spinal cord damage secondary to atlantoaxial instability. It is a heritable condition with an autosomal recessive mode of transmission. Radiologic diagnostic criteria are developed on the basis of studies in 8 patients with the oldest being between 4 and 5 years old. The condition is clinically and radiographically apparent neonatally or in early infancy, and it is probable that all or almost all affected individuals will come to medical attention in the age range screened by this study.     

Characterization of the chicken and quail homologues of the human gene responsible for the X-linked Kallmann syndrome

The human KAL gene, responsible for the X-linked Kallmann syndrome, was isolated previously. Southern blot analysis using human cDNA probes detected cross-hybridization with DNA from several organisms, including chicken and quail. The entire coding sequences of chicken and quail KAL cDNAs were determined. A comparison of these cDNAs with the human KAL cDNA reveals an overall identity of 73 and 72%, respectively. This results in 76 and 75% identity at the protein level. The highest conservation was found in the WAP four-disulfide core motif and in two of the four fibronectin type III repeats reported in the human protein. These results further support the hypothesis that the KAL protein is an extracellular matrix component with anti-protease and adhesion functions.     

Interleukin 10 (IL-10) upregulates functional high affinity IL-2 receptors on normal and leukemic B lymphocytes

Interleukin 10 (IL-10) has recently been shown to induce normal human B lymphocytes to proliferate and differentiate into immunoglobulin (Ig)-secreting cells. Herein, we show that IL-10 also promotes DNA synthesis and IgM production by anti-CD40 activated B cell chronic lymphocytic leukemia (B-CLL). Most strikingly, IL-2 and IL-10 were found to synergize to induce the proliferation and differentiation of B-CLL cells. This synergy between IL-2 and IL-10 was also observed with normal B cells which proliferated strongly and secreted large amounts of IgM, IgG, and IgA. The observed synergy is likely to be due to the IL-10-induced increase of high affinity IL-2 receptors on both normal and leukemic B cells. This increase of high affinity receptor is associated to an increase of Tac/CD25 expression that can be detected by flow cytometric analysis. Taken together, these results indicate that IL-10 permits anti-CD40 activated B cells to respond to IL-2 through an induction of high affinity IL-2 receptors. This effect of IL-10 may partly explain how T cells, which activate B cells in a CD40-dependent fashion, induce B cell proliferation and differentiation mostly through IL-2.     

Two structural adaptations for regulating transmitter release at lobster neuromuscular synapses

The distal accessory flexor muscle (DAFM) in the lobster (Homarus americanus) walking leg consists of 5 muscle fiber bundles. All five bundles, one proximal, one distal, and 3 medial, are innervated by one excitatory and one inhibitory motor neuron. Both neurons release more transmitter on the distal bundle than on the proximal bundle. The aim of our studies was to investigate the structural basis of this differentiation. Thin sections cut at 50 microns intervals showed a similar number of excitatory synapses on the two bundles. Freeze-fracture views of excitatory synapses showed that synapse size, active zone number per synapse, and intramembrane particle density in the postsynaptic membrane are similar proximally and distally. Active zones at synapses on the distal bundle are larger and contain about 50% more large intramembrane particles, which are thought to include the voltage-gated Ca2+ channels that couple the action potential to transmitter release, than their counterparts on the most proximal bundle. This difference in channel number appears to produce a disproportionate increase in the probability of transmitter release sufficient to account for most of the proximal-distal disparity in the amplitude of the excitatory postsynaptic potential. In contrast, staining the inhibitor for antibodies to the inhibitory neurotransmitter, GABA, showed that it forms more varicosities on the distal bundle than on the proximal bundle. Because most of the synapses are located in the varicosities, differences in synapse number likely regulate the proximal-distal disparity in the amount of inhibitory transmitter released. Therefore, the regional differentiation in the amount of transmitter released in the DAFM appears to be based on two distinct mechanisms. In the inhibitor, transmitter release appears to be regulated differentially by differences in synapse number. In the excitor, transmitter release appears to be regulated differentially from a similar number of synapses by differences in active zone structure.