Chronic hepatitis B and C co-infection increased all-cause mortality in HAART-naive HIV patients in Northern Thailand.

A total of 755 highly active antiretroviral therapy (HAART)-naive HIV-infected patients were enrolled at a government hospital in Thailand from 1 June 2000 to 15 October 2002. Census dateo f survival was on 31 October 2004 or the date of HAART initiation. Of 700 (92.6%) patients with complete data, the prevalence of hepatitis B virus (HBV) surface antigen and anti-hepatitis C virus (HCV) antibody positivity was 11.9% and 3.3%, respectively. Eight (9.6%) HBV co-infected patients did not have anti-HBV core antibody (anti-HBcAb). During 1166.7 person-years of observation (pyo), 258 (36.9%) patients died [22.1/100 pyo, 95% confidence interval (CI) 16.7­27.8]. HBV and probably HCV co-infection was associated with a higher mortality with adjusted hazard ratios (aHRs) of 1.81 (95% CI 1.30­2.53) and 1.90 (95% CI0.98­3.69), respectively. Interestingly, HBV co-infection without anti-HBc Ab was strongly associated with death (aHR 6.34, 95% CI 3.99­10.3). The influence of hepatitis co-infection on the natural history of HAART-naive HIV patients requires greater attention.

Prophylactic effects of neuroleptics in symptom-free schizophrenics: roles of dopaminergic and noradrenergic blockers.

A clinical trial was undertaken to determine the role of dopaminergic and noradrenergic blockers in the maintenance treatment of remitted schizophrenics. One hundred and six remitted schizophrenic outpatients were treated with one of nine treatments, viz., thioridazine 25 mg or 75 mg, pimozide 2 mg or 6 mg, and their respective combinations, for 1 year in a double-blind controlled study employing a randomized design. The data from a previous study were utilized as a retrospective placebo group. Pimozide prolonged the number of symptom-free days in a dose-dependent manner and did so more markedly than thioridazine. Combined administration of pimozide and thioridazine prolonged the number of symptom-free days to a greater extent than their single administration. However, an inverted U-shaped dose-response curve was obtained with the combined administration of these agents. These data suggest that both the dopaminergic and noradrenergic blocking action of neuroleptics are important in preventing relapse in remitted schizophrenics.

Prophylactic effects of neuroleptics in symptom-free schizophrenics: a comparative dose-response study of timiperone and sulpiride.

Remitted schizophrenic outpatients were prophylactically treated to prevent relapse with three different doses of timiperone or sulpiride for a year in a double-blind controlled study employing a randomized design. Each drug's ability to prevent relapse was by counting the number of subjects with different outcomes (remission, relapse, adverse reactions) during the trial and/or the number of symptom-free days for each patient before any sign of relapse or adverse reactions appeared. Patients were randomly assigned to the following drugs, which were orally administered once every night: placebo; timiperone 1 mg, 3 mg, 6 mg; sulpiride 100 mg, 300 mg, 600 mg. Data from previous studies involving haloperidol and propericiazine were utilized as a retrospective placebo group to compare the characteristics of the four drugs for maintenance treatment of remitted schizophrenic outpatients. Both timiperone and sulpiride increased the number of patients in remission and decreased the number of patients who relapsed, compared with the placebo group. With timiperone, there was an especially marked increase in the number of patients who showed signs of adverse reactions compared with sulpiride. Sulpiride was the only drug that increased the number of dose-dependent symptom-free days. However, both of these drugs significantly increased the number of symptom-free days compared with placebo. By comparing the dose-response curves of four drugs tested in the same fashion, haloperidol and sulpiride were superior to propericiazine and timiperone because they displayed a wider dose range for the maintenance treatment of remitted schizophrenic outpatients.

Scintigraphic detection of hepatic metastases with 131I-labeled steroid in recurrent adrenal carcinoma: case report.

Abdominal scintigraphy using a new 131I-labeled steroid agent was performed on a 40-year-old women proven by surgery to have adrenocortical carcinoma. Considerable accumulations were observed at the sites of liver metastasis. Hepatic scintigraphy and autopsy findings revealed that the accumulation was more marked on the active cancer cells and only slight in the central necrotic tissue. Adrenal scintigraphy is valuable in the study of metastatic hormone-producing adrenal carcinoma.

Sensitivity to chlorpromazine effects on brain function of schizophrenics and normals. A preliminary report.

For the purpose of quantitative demonstration of the sensitivity to chlorpromazine (CPZ) effects on brain functions of schizophrenics and normal subjects, polygraphic recordings of electroencephalogram (EEG) and electrodermal response (EDR) were performed before and 3 h after oral administration of 25 mg of CPZ: percent time waking EEG (per cent W-EEG) and number per minute of EDR were measured during the resting period and the period of calculation. In 10 normal adult subject, both per cent W-EEG and number of EDR showed remarkable decrease after CPZ administration. In 22 schizophrenics, however, per cent W-EEG showed no significant decrease after CPZ administration. Number of EDR in schizophrenics during the period of calculation did not show any significant decrease. The neural mechanism underlying the lower sensitivity to CPZ effects in schizophrenics was discussed.

Biphasic and long-lasting effect of ceruletide on tardive dyskinesia.

A 55-year-old schizophrenic inpatient with buccolingual dyskinesia was treated with a single dose of ceruletide 0.8 micrograms/kg IM. Time-course effects of the drug were then followed for up to 6 weeks after injection. To assess changes in severity of bucco-lingual dyskinesia objectively, electromyogram (EMG) and microvibration (MV) were recorded. Simultaneously, bucco-lingual dyskinesias were also evaluated by using a five-point rating scale. Before injection of ceruletide, severity of dyskinesia was "moderate" and 3-4 Hz of dyskinetic oral movements were dominant. "Extremely severe" and repetitious gross oral movements (around 1 Hz) were observed within a few minutes after injection and continued for up to 1 h. Thereafter, oral movements tended to decrease, and they disappeared completely 3 weeks after injection. This biphasic and long-lasting effect of ceruletide on tardive dyskinesia might contribute to further understanding of the physio-pathophysiological role of cholecystokinin-like peptides in the brain, and provide a basis for practical treatment of tardive dyskinesia.

Combined treatment of tardive dyskinesia with clonidine and neuroleptics: a follow-up study of three cases for three years.

Three cases of tardive dyskinesia with psychotic symptoms (one presenile psychosis; two schizophrenia) were successfully treated with both clonidine and neuroleptics for 3 years. The dyskinesia abolished or reduced by clonidine returned several months after discontinuation of clonidine. During the follow-up study, it was observed that combining neuroleptics with clonidine was superior to thioridazine, levomepromazine, or sulpiride for controlling the dyskinesia. These findings suggest that noradrenergic involvement is important in tardive dyskinesia and that other subtypes of dyskinesia might exist.

Prophylactic effect of neuroleptics in symptom-free schizophrenics.

Prophylactic effects of psychotropic drugs on 55 schizophrenics in remission were evaluated for 3 years in a double-blind controlled study employing a cross-over design. Patients were randomly assigned to the following drugs orally administered twice a day: placebo; diazepam 15 mg; imipramine 50 mg; chlorpromazine 75 mg; and haloperidol 3 mg. The number of days of remission for each patient was recorded. Since only two patients received all five drug treatments, the data were analyzed using the number of days allocated to the "first assigned drugs" only and the cross-over aspect of the experimental design was disregarded. All patients treated with either the placebo, diazepam or imipramine relapsed within a year. On the other hand, four patients treated with chlorpromazine, or with haloperidol, were in remission for more than 1 year. Fifty percent of the patients relapsed within 16 days with placebo; 88 days with diazepam; 30 days with imipramine; 165 days with chlorpromazine; and 74 days with haloperidol. Within a year, only chlorpromazine significantly prolonged the remission state as compared to placebo and imipramine. At the end of the 3-year trial, both chlorpromazine and haloperidol significantly prolonged the remission state as compared to the other three drugs. These data suggest that neuroleptic treatment for a longer period is vitally important to prevent relapse even in schizophrenics in remission and that such a trial seems an efficient method for investigating the prophylactic effects of neuroleptics.

Effect of ceruletide on tardive dyskinesia: a pilot study of quantitative computer analyses on electromyogram and microvibration.

Seven patients with bucco-lingual dyskinesia were treated with a single dose of ceruletide 0.8 micrograms/kg IM, a potent analogue of cholecystokinin octapeptide. Time-course effects of the drug were then followed up to 6 weeks after injection in the longest case. To assess changes in severity of dyskinesia objectively, electromyogram and microvibration were recorded. These data were subjected to the Fast Fourier Transform and an averaged power spectrum was computed. The effect of ceruletide on dyskinesia within 2 h after injection differed (three cases: inhibitory, two cases: facilitatory, two cases: no effect). It was notable that a long-lasting inhibitory effect of this peptide was observed in two severe irreversible cases. The present findings might contribute to further understanding of the physiopathophysiological role of cholecystokinin-like peptides in the brain and to practical treatment of tardive dyskinesia.

Involvement of the alpha2-adrenergic system in polydipsia in schizophrenic patients: a pilot study.

Animal studies have suggested the involvement of the adrenergic system in drinking behavior. The present study investigated the involvement of the alpha2-adrenergic system in the polydipsia of patients with chronic schizophrenia by use of an alpha2 agonist and an antagonist. Four patients with schizophrenic disorders accompanied by intermittent hyponatremia and polydipsia were the subjects of, and completed, this study. Drinking behavior was assessed by calculating the percent of maximum weight gain [PMWG: (maximum diurnal weight - standard weight) x 100/standard weight]. Standard weight was defined as body weight after 8 h of water restriction. Clonidine (75, 150, and 225 mg/day) increased the PMWG in a dose-dependent manner in the four subjects. In contrast, in three of the subjects, mianserin (30, 60, and 90 mg/day) decreased PMWG, and the severe polydipsia disappeared almost completely. These findings indicate clearly that the alpha2-adrenergic system is involved in the drinking behavior of schizophrenic patients. Mianserin appears to be clinically useful in treating such patients with polydipsia.

Prophylactic effect of neuroleptics in symptom-free schizophrenics: a comparative dose-response study of haloperidol and propericiazine.

Remitted schizophrenic outpatients were treated in order to prevent relapse with three doses of haloperidol or propericiazine for 1 year in a double-blind controlled study employing a randomized design. The drug's ability to prevent relapse was evaluated by counting the number of symptom-free days for each patient before any sign of relapse or over-dose appeared. Patients were randomly assigned to the following drugs orally administered once per day at night: placebo; haloperidol 1 mg, 3 mg, and 6 mg; propericiazine 10 mg, 30 mg, and 60 mg. Serum prolactin levels in each patient were estimated by radioimmunoassay. All patients treated with placebo relapsed within 1 year and the relapse rate with placebo was significantly higher than with any dose of the two neuroleptics. Haloperidol increased the number of symptom-free days in a dose-dependent manner. Propericiazine at 10 mg and 30 mg also increased the number of symptom-free days dose-dependently but at 60 mg, the number decreased. It appears that propericiazine shows an inverted U-shaped dose-response curve. Prolactin levels were elevated dose-dependently by both drugs but failed to show a significant correlation with the number of symptom-free days. The present results indicate that haloperidol is superior to propericiazine from the viewpoint of the wider "therapeutic window" in maintenance treatment and antidopaminergic properties of neuroleptics, wherein it is important to prevent relapse even in remitted schizophrenics.

A new method of intrathecal PO2, PCO2, and pH measurements for continuous monitoring of spinal cord ischemia during thoracic aortic clamping in pigs.

BACKGROUND: Impaired spinal cord circulation during thoracic aortic clamping may result in paraplegia. Reliable and fast responding methods for intraoperative monitoring are needed to facilitate the evaluation of protective measures and efficiency of revascularization. METHODS: In 11 pigs, a multiparameter PO2, PCO2, and pH sensor (Paratrend 7, Biomedical Sensors Ltd, United Kingdom) was introduced into the intrathecal space for continuous monitoring of cerebrospinal fluid (CSF) oxygenation during thoracic aortic cross-clamping (AXC) distal to the left subclavian artery. A laser-Doppler probe was inserted into the epidural space for simultaneous measurements of spinal cord flux. Registrations were made before and 30 minutes after clamping and 30 and 60 minutes after declamping. The same measuring points were used for systemic hemodynamic and metabolic data acquisition. RESULTS: The mean CSF PO2 readings of 41 mm Hg (5.5 kPa) at baseline decreased within 3 minutes to 5 mm Hg (0.7 kPa) during AXC (P < .01). Spinal cord flux measurement responded immediately in the same way to AXC. Both methods indicated normalization of circulation during declamping. Significant (P < .01) changes were also observed in the CSF metabolic parameters PCO2 and pH. CONCLUSIONS: In this experimental model of spinal ischemia by AXC, online monitoring of intrathecal PO2, PCO2, and pH showed significant changes and correlated well with epidural laser-Doppler flowmetry (P < .01).

Treatment of tardive dyskinesia with ceruletide.

1. Seven patients with TD were treated with a single dose of ceruletide 0.8 microgram/kg i.m. 2. EMG and MV were recorded, and the average power spectrum was computed. 3. Effect of ceruletide on TD within 2 hr after injection was varied (3 cases: inhibitory, 2 cases: facilitatory, 2 cases: no effect). 4. Two patients with severe TD, who showed improvement after a single administration, received repeated administration of ceruletide (0.6 microgram/kg i.m.) and their TD symptoms were recorded on videotape for blind consensus ratings. In both patients ceruletide caused a marked decrease in severity of TD, and the effects lasted for several weeks. 5. The present findings might contribute to further understanding of the role of CCK in the brain and to the treatment of TD.

Naloxone attenuates drinking behavior in psychiatric patients displaying self-induced water intoxication.

1. The present study was performed to examine the effect of naloxone on drinking behavior in three schizophrenic inpatients with psychosis, intermittent hyponatremia, and polydipsia. 2. Their body weight were checked five times daily and the maximum weight gain during a day was chosen as an index of their polydipsia. 3. After control recording for six weeks, a daily naloxone (0.6 mg) injection series was performed once every two weeks for three series (six weeks). Withdrawal of this drug for six weeks resulted in weight gain recovering to control level. 4. The present study showed that naloxone seems to be a potential treatment for psychiatric patients displaying self-induced water intoxication and that endogenous opioid systems are involved in the compulsive drinking behavior of this syndrome.

Transient and intermittent oral dyskinesia appearing in a young woman ten days after neuroleptic treatment.

A 22-year-old woman was admitted to our hospital because she showed psychomotor excitement and signs of schizophrenia following psychological stress. Nine days after neuroleptic medication, she could not eat and exhibited high fever, diaphoresis, excessive salivation, and severe extrapyramidal signs with cogwheel rigidity and resting tremor of the upper extremities. The next day, bucco-linguomasticatory dyskinesia, which is quite similar to tardive dyskinesia, appeared. The dyskinesia lasted intermittently for 6 days. The present case shows that buccolingual dyskinesia can occur even after early neuroleptic exposure in certain patients.

Life-threatening dysphagia following prolonged neuroleptic therapy.

We report the cases of two patients with complaints of dysphagia following long-term neuroleptic therapy. Esophageal contrast radiography revealed that one patient suffered disruption of the normal swallowing activity of the pharyngoesophagus due to tardive dyskinesia. Her dysphagia disappeared following changes in her neuroleptic medications and the administration of clonazepam. The other patient demonstrated severe rabbit syndrome involving the glossopharynx. This 3-Hz rhythmic movement disorder resolved following injection of an anticholinergic agent. Thereafter, the addition of oral trihexyphenidyl to her medication regimen improved her dysphagia. It should be emphasized that the differential diagnosis of neuroleptic-associated dysphagia subtypes is important because therapeutic strategies differ depending on the subtype of this life-threatening illness.

Prevalence of and risk factors for respiratory dyskinesia.

We explored the prevalence of respiratory dyskinesia (RD), diagnosed objectively using a spirograph, and the major risk factors for tardive dyskinesia (TD) and RD. A total of 258 inpatients treated with neuroleptics was interviewed, and TD was evaluated using the Abnormal Involuntary Movement Scale (AIMS). Movement of the chest and respiratory regularity were assessed on clinical examination. Spirographs of patients with suspected RD were recorded, and RD was diagnosed based on spirographic data and the concurrence of two investigators. The prevalence of TD in this study was 22.1% (57 of 258). Aging and organic brain damage (OBD) were confirmed as risk factors; female gender, mood disorders, and the duration of neuroleptic exposure were not. Ten of 28 patients suspected of having RD were diagnosed with RD on the basis of persistent respiratory irregularities without other physiologic causes. The overall prevalence of RD was 3.9% (10 of 258) and was 17.5% (10 of 57) among the TD patient population. Four of these patients complained of dyspnea, and three demonstrated grunting. RD was more highly associated with aging and OBD than with TD itself. The identification of risk factors for RD is not only helpful in planning prophylactic strategies, but also facilitates the understanding of the pathogenesis of this syndrome.

Clonidine therapy for tardive dyskinesia and related syndromes.

Twenty-nine patients with tardive dyskinesia (n = 20) or related syndromes [spontaneous dyskinesia (n = 3), levodopa-induced dyskinesia (n = 3), tardive dystonia (n = 3)] were treated with clonidine. Clinical effects of this drug were observed for up to 4 years. Seventy-five percent of patients showed at least moderate improvement, and in 50% of patients, full resolution occurred. In most cases, patients received concomitant medications, including neuroleptics and benzodiazepines. Two patients received clonidine alone, and dyskinesia was only minimally improved; however, when bromocriptine was added, prompt improvement occurred on this combined regimen. On the basis of these findings, we suggest that not only receptor supersensitivity of dopaminergic neurons but also involvement of noradrenergic neurons is important in the pathophysiology of tardive dyskinesia and related syndromes.

Respiratory dyskinesia: a variety of clinical forms differentially diagnosed by using a spirograph.

Four cases of respiratory dyskinesia were investigated by using a spirograph before and after biperiden injection. The abnormal respiratory patterns in four cases appeared to be in two types and these abnormalities were abolished after biperiden injection. The present study showed that respiratory dyskinesia could be defined more clearly by using a spirograph and these results are useful for the diagnosis of patients with respiratory discomfort while undergoing neuroleptic drug treatment.