Valproate treatment of panic disorder and lactate-induced panic attacks.

Several lines of evidence suggest that the anticonvulsant drug valproate may have antipanic properties: (1) It enhances gamma-aminobutyric acid activity in the brain; (2) it has anxiolytic effects in animal models of anxiety; and (3) it has been reported to be effective in panic disorder in several preliminary studies; however, valproate has not been studied in the prevention of lactate-induced panic attacks. Sixteen patients with panic disorder underwent a lactate infusion followed by a 28-day treatment period with valproate and subsequent rechallenge with lactate. Response was measured by change in panic attack frequency and Hamilton Anxiety Scale (HAS) scores and by the ability of valproate to block lactate-induced panic on rechallenge. Of the 14 patients completing the 28-day trial, 10 (71%) experienced a greater than 50% reduction in the weekly frequency of panic attacks. Six (43%) had complete remission. HAS scores dropped significantly from a baseline mean of 30.8 +/- 9.4 (SD) to 12.6 +/- 7 after 4 weeks of treatment. Valproate blocked reinduction of panic symptoms on lactate rechallenge in 10 (83%) of 12 patients who had initially experienced panic symptoms on initial infusion. The significant reduction in spontaneous panic attacks and the blockade of lactate-induced panic symptoms by valproate support earlier studies suggesting that the drug may be an effective treatment for panic disorder.

High-performance liquid chromatographic analysis of clorazepate dipotassium and monopotassium in solid dosage forms.

Methodology for the quantitative determination of clorazepate dipotassium and monopotassium in solid dosage forms was developed. Clorazepate was resolved from its degradation products, making the analysis specific and stability indicating. Analytical separation was performed on a octadecylsilylated silica column. Clorazepate was extracted from the dosage forms with 0.04% NaOH and chromatographed with aqueous 0.005 M tetra-n-butylammonium ion (pH 7.5)- acetonitrile (70:30) as the eluent. The analysis was completed in approximately 20 min with a precision of less than 2.4% RSD.

An anatomical radiolucency of the cervical spine.

A radiolucency in the cervical spine consistently seen on panoramic dental radiographs has been investigated. It was found to arise from the axis and be caused by a combination of its unique morphology and the oblique angle of incidence of the X-ray beam in the first part of its rotation.

Oral manifestations of Crohn's disease without demonstrable gastrointestinal lesions.

The literature relating to oral manifestations of Crohn's disease is reviewed and a case is reported in which clinical and histopathologic features of oral Crohn's disease are present without demonstrable gastrointestinal lesions. It is suggested that it is reasonable to make a firm diagnosis of the condition on this evidence alone and to monitor the patient for subsequent gastrointestinal symptoms, so that treatment can be instituted at an early stage.

Systematic correction procedures in vocational-skill training of severely retarded individuals.

Seventy severely retarded adults were taught a vocational assembly-skill task involving a difficult visual--motor discrimination. Comparisons of relative effects on trials-to-criterion were made among two types of verbal-correction procedures (general: "try another way" and specific: "flat side in") and three types of systematic physical-correction procedures (gesture, physical prompt, and repeated practice). Reliable differences in effects occurred only between the three systematic physical-correction procedures, with repeated practice the most effective, physical prompts next, and gestures the least effective. The results were interpreted as demonstrating the efficacy of trainer-related training procedures in relation to stimulus-related strategies, as well as relative efficacy among trainer-related correction procedures.

Vocational skill assessment of severely mentally retarded adults.

The Trainee Performance Sample, a vocational skills assessment instrument, was revised to enhance content validity and utility in making vocational skill learning placements for severely retarded individuals. The Trainee Performance Sample employs a process measurement approach; i.e., each of the 30 test items (a variety of benchwork tasks) includes both training and correction procedures within the item. To some extent, the examinee's ability to benefit from various training strategies is measured. Psychometric analyses demonstrated that the revised Trainee Performance Sample meets standard test development criteria. Thus, a dynamic approach to vocational skills assessment of severely retarded individuals--one that involves training while testing--has been shown to have both utility and psychometric adequacy.

Expression of xenobiotic metabolizing enzymes in tumours of the urinary bladder.

The cytochromes P450, epoxide hydrolase and glutathione S-transferases are several of the major groups of enzymes involved in the metabolism of xenobiotics and these enzymes may have a role in influencing the response of tumours to anti-cancer drugs. In this study the cell specific expression of individual xenobiotic metabolizing enzymes has been investigated using immunohistochemistry in primary transitional cell tumours of the urinary bladder. The cytochromes P450 CYP1A, CYP2C and CYP3A, were present in 68, 28 and 68% of tumours respectively and the expression of CYP1A correlated with bladder tumour grade (P = 0.03). Epoxide hydrolase was identified in 84% of tumours while the alpha, mu and pi forms of glutathione S-transferase were expressed in 56, 72 and 52% of tumours respectively. In normal bladder epoxide hydrolase and glutathione S-transferase pi were the main enzymes expressed while there was no expression of CYP2C.

The immunohistochemical localization of drug-metabolizing enzymes in prostate cancer.

The major groups of enzymes involved in activating and detoxifying therapeutic drugs, not least several anti-cancer drugs, include the cytochromes P450 (P450s), epoxide hydrolase, and glutathione S-transferases (GSTs). The expression of these enzymes in malignant tumours is one possible mechanism of anti-cancer drug resistance. This study has investigated the presence, cellular localization, and distribution of drug-metabolizing enzymes in prostate cancer. The P450 subfamilies CYP1A, CYP2C, and CYP3A were present in 63, 25, and 61 per cent of tumours, respectively. Epoxide hydrolase was identified in 96 per cent of tumours. GST-alpha and GST-mu were expressed in 29 and 41 per cent of tumours, respectively, while there was no immunoreactivity for the pi form of GST. The absence of GST-pi in prostate cancer contrasts with the frequent expression of GST-pi observed in other types of malignant tumour. In non-neoplastic prostatic epithelium, there was expression of CYP1A, CYP2C, epoxide hydrolase, and the different forms of GST, while there was no apparent immunoreactivity for CYP3A.

Biophysical and biological activity of a synthetic 8.7-kDa hydrophobic pulmonary surfactant protein SP-B.

We have synthesized pulmonary surfactant apoprotein SP-B peptides by solid-phase chemistry and demonstrated their ability to enhance the surface-active properties of synthetic lipid mixtures. The synthetic peptides were reactive with antiserum generated against the native bovine surfactant peptide. Both peptides conferred surfactant-like properties to synthetic lipid mixtures as assessed by a Wilhelmy balance and pulsating bubble surfactometer. Likewise, mixtures of synthetic SP-B peptides and lipid restored compliance of isolated surfactant-deficient rat lungs. This work demonstrates the utility of SP-B as a functional component of pulmonary surfactant mixtures for treatment of respiratory distress syndrome or other disorders characterized by surfactant deficiency.