In vivo beta-defensin gene expression in rat gingival epithelium in response to Actinobacillus actinomycetemcomitans infection.

BACKGROUND AND OBJECTIVE: Human beta-defensins have been identified in the oral cavity and are predicted to play a role in the defense against pathogenic bacteria. Homologous rat beta-defensins (RBDs) have been identified, but their expression in the oral cavity has not been examined. Therefore, the aim of this study was to investigate the expression of innate immune mediators in the rat gingival epithelium. MATERIAL AND METHODS: Rats were pretreated with antibiotics to depress the normal oral flora, followed by the introduction of Actinobacillus actinomycetemcomitans in their food to allow colonization and the development of periodontal disease. At various time points, animals were killed and the gingival epithelium was extracted. Semiquantitative reverse transcription-polymerase chain reaction was performed to measure RBD and Toll-like receptor (TLR) mRNA levels. RESULTS: Three beta-defensins (RBD-1, -2 and -5) and two TLRs (TLR-3 and -4) are expressed in normal rat gingival epithelium. After the introduction of A. actinomycetemcomitans, RBD-1 and RBD-2 mRNA levels increased for the first week followed by a return to basal levels. No change in TLR mRNA levels was observed. CONCLUSION: The rat model provides a good system for experimental analysis of the innate immune response to periopathogenic bacteria in the oral cavity, as well as the potential role of beta-defensins in the host response to colonization.

Evaluation of the mechanisms of antiepileptic drug-related chronic leukopenia.

Antiepileptic drug (AED)-related chronic leukopenia [white blood cell (WBC) count < 4,000/microliters] is a dilemma, especially when the AED is effective in controlling seizures. We evaluated the possible mechanisms of leukopenia in 7 patients. Mean WBC count was 3,000/microliters with a mean of 42% polymorphonuclear leukocytes (PMN). The AEDs were carbamazepine (CBZ) alone in 1 patient or CBZ combined with phenytoin (PHT), primidone (PRM), phenobarbital (PB) and/or valproate (VPA) in 5 patients; one patient was receiving PHT only. Bone marrow (BM) aspirates and PMN antibody studies using chemiluminescence were normal. Two liver-spleen scans showed mild relative splenomegaly. After exercise, WBC count (n = 7) increased by 54% (SEM 12%), while the WBC counts in controls (n = 5) increased by 52 +/- 16%. Antinuclear antibodies (Hep-2) were absent in 6 patients and positive (1:160) in 1. PMN adhesion to nylon wool was decreased (54 +/- 10% in patients vs. 80 +/- 5% in controls: n = 13, p < 0.005). Our data, particularly the appropriate WBC response to the stress of exercise, and normal BM examinations suggest that continuation of AED therapy when leukopenia is stable and the percentage of PMN is normal is probably safe. Caution should be used if the absolute PMN count is consistently < 1,000/microliters. BM examinations need not be performed routinely for every patient with neutropenia due to AEDs, especially if the leukopenia fluctuates in the range of 2,000-4,000 cells/microliters.

The prolactin response to flutroline hydrochloride in schizophrenic patients.

Flutroline hydrochloride, a gamma carboline manifesting neuroleptic activity, was administered in a double-blind fashion in single daily dosages of 1, 5, 10, 20, and 100 mg to 48 hospitalized schizophrenic patients over a period of four weeks. During this period, weekly evaluations were made of response employing standardized psychiatric ratings. Plasma prolactin (PRL) levels were obtained at the termination of previous neuroleptic medication and at two-week intervals during treatment with the investigational compound. Examination of the initial PRL levels indicated that they could be grouped into those above, within, and below the normal range. Comparisons of these initial levels with those following the administration of flutroline suggested an improved methodology for determining optimal neuroleptic dosage.

Schizophrenia and dialysis.

Open-trial reports of substantial clinical improvement in most schizophrenic patients on hemodialysis for their psychiatric condition prompted the present study to determine the efficacy of hemodialysis under double-blind, controlled conditions. Fifteen schizophrenic outpatients were randomly assigned to either a real-sham or sham-real dialysis treatment sequence. Presented in detailed, graphic form, results of repeated measurement and other analyses of symptom and behavioral data collected initially, at crossover, and at the end of treatment revealed no differential effects between real and sham dialysis. These results provide important experimental evidence of the lack of therapeutic efficacy of hemodialysis in schizophrenia.

The therapeutic efficacy of hemodialysis in schizophrenia.

Prompted by previous reports of substantial clinical improvement in most schizophrenic patients given hemodialysis for their psychiatric condition, we studied the efficacy of hemodialysis in 15 schizophrenic outpatients, under double-blind, controlled conditions. The patients were randomly assigned to either a real-sham or sham-real sequence of dialysis treatment. Results of repeated measurement and other analyses of data on symptoms and behavior that were collected before study treatment, at crossover, and at the end of treatment revealed no difference between the effects of real and sham dialysis. These results provide important experimental evidence of the lack of therapeutic efficacy of hemodialysis in schizophrenia.

Flutroline in the treatment of the schizophrenic patient.

As an introduction into a clinical study of one of a new group of compounds having neuroleptic potential, the background and characteristics of the gamma carbolines, particularly flutroline, are cited in the general context of a review of the use of antipsychotic drugs in psychiatry. In the four-week double-blind trial involving dosages of 1, 5, 10, 20 and 100 mg, 48 hospitalized schizophrenic patients were given the tryptoline derivative flutroline on a once-a-day basis. Outcome criteria obtained weekly, including the incidence of side effects, standardized psychiatric ratings, and clinical global impressions of psychopathology, indicated that flutroline was a safe and effective antipsychotic drug. Data suggested that dosages of 20 mg and above offered the best potential for optimal clinical effectiveness.

Viloxazine and the depressed schizophrenic--methodological issues.

A pilot study of a small group of schizophrenic patients manifesting symptoms of a depressive nature was treated in a double-blind study in which viloxazine or a placebo was administered in combination with either chlorpromazine or haloperidol. There appeared to be no difference between the viloxazine-treated group and the placebo-treated group, although the study raised some question as to the adequacies of the dosage utilized since there was an absence of any apparent side effects. In view of these issues concerning the clinical merit of the combination, this obviously requires further investigation.

A comparison of dopamine receptor blocking assay with plasma drug levels of haloperidol in schizophrenic patients.

A comparison of a chemical analytic technique (gas chromatography/mass spectrometry) with that of the dopamine receptor blocking assay in a study involving seven schizophrenic patients being administered a fixed dosage of haloperidol (20 mg) demonstrated a high degree of correspondence in the quantification of the plasma levels of the neuroleptic.

The dopamine radioreceptor assay--a clinical application.

The counterbalanced design in a bioequivalent study of haloperidol indicated an absence of any clinical difference between a new 20-mg dosage form and two 10-mg tablets of haloperidol (Haldol). This impression was supported by the absence of any significant behavioral changes during the four weeks when either form of the once-a-day fixed dose of 20 mg haloperidol was administered. This impression was substantiated by experiences with the dopamine receptor blocking assay, since results with this procedure also indicated the lack of any significant difference in the plasma neuroleptic equivalence of either dosage form. On the basis of present findings the assay would appear to offer promise for clinical application in the adjusting of the dosage of neuroleptic drugs, as well as in the monitoring of drug usage.

The treatment of perceptual disturbances in schizophrenia with naloxone hydrochloride.

The authors treated 12 schizophrenic patients who had overt hallucinatory symptoms with intravenously administered naloxone hydrochloride, a narcotic antagonist purported to have antihallucinatory properties. They found no evidence of the effectiveness of naloxone in preventing hallucinations over that of placebo when administered in a randomized, double-blind fashion.

Antidepressant drug therapy in psychotic depression.

Imipramine and phenelzine were ineffective in the treatment of five primary unipolar depressives with delusions, even when plasma levels of imipramine and desmethylimipramine or activity of platelet monoamine oxidase suggested that an adequate dose of drug had been given. Four patients went on to receive ECT and all responded well. Five non-delusional patients responded satisfactorily to the antidepressant drug given. Nine out of ten subjects were women. Non-delusional patients showed some placebo response. ECT is considered to be the treatment of choice in the acute phase of delusional depression in women.

MDA-assisted psychotherapy with neurotic outpatients: a pilot study.

Ten neurotic patients (five males and five females) were treated over a period of 2 to 6 months (mean, 4.1) as outpatients. The study allowed for a maximum of 75 hours of psychotherapy (mean, 51.55 hours). During the course of treatment, two to four (mean, 3.5) administrations of MDA (3,4-methylenedioxyamphetamine) were employed as adjunctive aids in an effort to enhance the psychotherapeutic process. The mean duration of the drug sessions was 8 hours (range, 6 to 14 hours). The first administration of MDA took place when, in the therapist's judgment, sufficient rapport had been established with the patient. All patients received an initial dose of 75 mg of MDA; subsequent dosage was allowed to range up to 200 mg. On these occasions, the drug appeared to be well tolerated with no serious side effects or complications observed. Psychometric assessments were obtained pre- and post-treatment, employing the Minnesota Multiphasic Personality Inventory (MMPI), Wittenborn Psychiatric Rating Scales (WPRS), and Brief Psychiatric Rating Scale (BPRS). In addition, follow-up evaluations were obtained 6 months after the termination of therapy by the use of the MMPI, WPRS, BPRS, and a Social History Questionnaire (SHQ) which had also been administered before treatment was initiated. Clinically, the impression was obtained that psychotherapy and the adjunctive use of MDA appeared to facilitate improvement in these patients. This impression was substantiated by significant reductions in scores on the psychometric assessments measuring depression, anxiety, and obsessive-compulsive traits. The meaures evaluating the sense of well-being and self-actualization also were encouraging. Although some of the patients were not as responsive as others, there were no observations to suggest that the condition of any of these patients had become worse.

Rapid detoxification of the narcotic addict with naloxone hydrochloride. A preliminary report.

Parenteral (0.2--2.0 mg) and oral (500 mg) doses of naloxone hydrochloride were administered to 29 parolees showing evidence of increasing opiate use while participating in an aftercare abstinence program. The naloxone was found to be capable of inducing withdrawal symptoms, the intensity of which being a function of the amount of naloxone administered and of the level of physical dependence. Some patients (38%) showed a "detoxification effect" characterized by a positive abstinence reaction to initial naloxone administrations but a negative reaction to subsequent administrations. All of the 29 subjects, however, returned to illicit heroin use within several days following their release from the treatment unit. the potential of naloxone as a rapid detoxification tool is discussed in counterpoint to the apparent lack of potential the procedure has as a means of attenuating opiate-seeking behavior.

Contingent naloxone treatment of the narcotic addict: a pilot study.

In a community-based abstinence program, 108 chronic heroin abusers, paroled from Maryland correctional institutions, were administered the narcotic antagonist, naloxone, in escalating 500 mg dosages to a daily maximum dosage of 2,000 mg when either urine analysis indicated narcotic drug use or unexcused absences led to the suspicion of narcotic intake. Dosage was then continued at the maximum level until the record again indicated abstinence. This approach was regarded as such a distinct departure from customary antagonist administration that a pilot investigation of its effectiveness was undertaken. Six month outcome data on all patients were constrasted with those of an historical comparison group previously treated in the same clinic without naloxone administration. Both groups were equivalent on all criminal history, demographic, and prognostic variables. The group receiving contingent naloxone administration showed a significantly lower institutionalization rate (8%) than that for the reference sample (37%). Complete abstinence rates were also in favor of the naloxone group (38 vs. 12%).