Reduced haloperidol does not interfere with the antipsychotic activity of haloperidol in the treatment of acute schizophrenia.

The aim of this study was to investigate the effect of reduced haloperidol, the main metabolite of the antipsychotic drug haloperidol, on psychopathology improvement and extrapyramidal adverse effects in acute schizophrenia. The steady-state pharmacokinetics of reduced haloperidol was studied. Serum concentrations of reduced haloperidol (C(RH)) and haloperidol (C(H)) were measured in an open clinical trial over 6 weeks of treatment in 57 acutely schizophrenic patients. Psychopathology was measured by the Brief Psychiatric Rating Scale and several subscales. The assay of extrapyramidal adverse effects was conducted by means of the Extrapyramidal Symptom Rating Scale. A significant serum concentration-therapeutic effect relationship (SCTER) of haloperidol of the same data has been demonstrated. In our study, the influence of the metabolite reduced haloperidol on the antipsychotic activity of haloperidol was analysed by means of regression analysis of the residuals of the SCTER of haloperidol with C(RH). In addition, the steady-state pharmacokinetics of reduced haloperidol and direct relationships between C(RH) and the metabolite ratio C(RH)/C(H) with psychopathology improvement and extrapyramidal adverse effects were investigated. Reduced haloperidol was not found to interfere with the antipsychotic action of the parent drug. Patients with elevated C(RH) or elevated metabolite ratio C(RH)/C(H) did not show consistently lower clinical improvements compared with the fitting curve of the SCTER of haloperidol and therefore no significant relationship between C(RH) and the residuals of the SCTER of haloperidol was detected. Furthermore, no significant result was found in the analysis of the direct relationships of C(RH) and C(RH)/C(H) with clinical variables which, for example, indicate decreased outcome with increased C(RH). In contrast, because of the pharmacokinetic dependence of C(RH) and C(H), a trend for a bisigmoidal relationship with C(RH) emerged for some outcome variables which was traced as an epiphenomenon from the bisigmoidal SCTER of the parent drug (e.g. change of hostility after 3 weeks). No relationship of reduced haloperidol with extrapyramidal adverse effects could be detected. It is concluded that serum concentrations of reduced haloperidol are of minor value for the interpretation of data of therapeutic drug monitoring of haloperidol in patients with acute schizophrenia. Reduced haloperidol does not act as a 'false neuroleptic'.     

Age-Specific Native Hawaiian Mortality: A Comparison of Full, Part, and Non-Hawaiians

PURPOSE OF THE PAPER: The purpose of this paper is to test if the previously identified disparity in mortality rates among full Hawaiians, part Hawaiians, and non­Hawaiians in the state of Hawaii has continued into the 1990s. SUMMARY OF METHODS UTILIZED: Based on Hawaii vital records and population data, standardized age­specific mortality rates by cause and 95% confidence intervals were estimated. PRINCIPAL FINDINGS: The most striking finding was the significant differences in mortality rates in four age strata ­­ 45­54, 55­64, 65­74, and 75­84 ­­ with mortality rates highest for full Hawaiians, lowest for non­Hawaiians, and intermediate for part Hawaiians. CONCLUSIONS: Findings suggest that Native Hawaiians continue to be at greater risk of death compared with non­Hawaiians, with full Hawaiians at greatest risk. RELEVANCE TO ASIAN PACIFIC ISLANDER AMERICAN POPULATIONS: Asian and Pacific Islander Americans have been called the model minority. These data provide evidence that Native Hawaiians, especially full Hawaiians, have dramatically higher mortality rates than non­Hawaiians and merit special attention.     

Radiation doses of yttrium-90 citrate and yttrium-90 EDTMP as determined via analogous yttrium-86 complexes and positron emission tomography

Yttrium-90 is used for palliative therapy for the treatment of skeletal metastases, but because it is a pure - emitter, data on the pharmacokinetics and radiation doses to metastases and unaffected organs are lacking. To obtain such data, the present study employed yttrium-86 as a substitute for⁹⁰Y, with detection by positron emission tomography (PET). The study compared the properties of two different⁸⁶Y complexes —⁸⁶y-citrate and⁸⁶Y -ethylene diamine tetramethylene phosphonate (EDTMP) — in ten patients with prostatic cancer who had developed multiple bone metastases (the ten patients being divided into two groups of five). Early dynamics were measured up to 1 h post injection (p.i.) over the liver region, followed by subsequent whole-body PET scans up to 3 days p.i. Absolute uptake data were determined for normal bone, bone metastases, liver and kidney. Radiation doses were calculated according to the MIRD recommendations. Based on the pharmacokinetic measurements of the distribution of the⁸⁶Y complexes, it was possible to calculate radiation doses for the bone metastases and the red bone marrow delivered by complexes containing⁹⁰Y. In 1 cm³ of bone metastasis, doses of 26±11 mGy/MBq and 18±2 mGy/MBq were determined per MBq of injected⁹⁰Y- citrate and⁹⁰Y- EDTMP, respectively. The doses to the bone marrow were 2.5±0.4 mGy/MBq for⁹⁰Y- citrate and 1.8±0.6 mGy/MBq for⁹⁰Y-EDTMP.⁸⁶Y and PET provide quantitative information applicable to the clinical use of⁹⁰Y. This method may also be useful for the design of other⁹⁰Y radiopharmaceuticals and for planning radiotherapy dosages.     

Ketamine for analgosedative therapy in intensive care treatment of head-injured patients

Summary Ketamine was supposed to be contra-indicated in head injured patients although it possesses numerous advantages over other commonly used analgosedative drugs. Referring to these potential advantages and the lack of definitive data about its effect upon ICP, CPP or neurological development, we conducted a prospective study in which moderate or severely head injured patients (n=35) were prospectively allocated to receive treatment either with a combination of ketamine and midazolam or fentanyl and midazolam. The initial dose was 6.5 mg/kg/day midazolam, 65 mg/kg/day ketamine or 65 g/kg/day fentanyl and was later adjusted due to clinical requirements for a period of 3 to 14 days. Comparably high dosages of detamine have been found necessary (104 mg/kg/day).Four patients from the ketamine group (n=17) and 5 from the control group (n=18) were withdrawn during treatment due to persistent ICP above 25 mm Hg, countermeasured by barbiturate coma. Two more patients were withdrawn due to development of cardiovascular arrest (ketamine group) and multi organ failure. A comparison of the remaining patients revealed a lower requirement of catecholamines (significant on first day, p<0.05), an on average 8 mm Hg higher cerebral perfusion pressure and a 2 mm Hg higher intracranial pressure in the fentanyl group. Enterai food intake was better in the study group. The outcome was comparable in both groups with or without inclusion of withdrawn patients.     

Development of a new controlled-release formulation of chlorpheniramine maleate using in vitro/in vivo correlations

Development of a controlled-released formulation of chlorpheniramine maleate is described, using in vitro/in vivo correlates, according to a process that has been termed "biorelevant dissolution". The process begins with simulations using several possible input rates combined with known disposition parameters of chlorpheniramine maleate. Based on desired plasma concentrations, an input rate is selected for further development which consists of a combination of clinical bioequivalence studies and further in vitro testing and simulations. The method is designed to reduce the requirements for trial and error clinical bioequivalence testing of a new controlled-release formulation.     

Anthralin derivatives--inhibition of 5-lipoxygenase--antipsoriatic efficacy.

Inhibition of 5-lipoxygenase by anthralin (1) and 41 derivatives is determined: the acids 38 and 39, the lactones 40-42 and 9-anthrone (8) are the most potent inhibitors, the lactone 41 reaching the efficacy of nordihydroguaiaretic acid (NDGA). The results were correlated with the hydrophilic/lipophilic balance of the test compounds and their clinical efficacy as far as known. There is no correlation between the "minimum structure" of Krebs and Schaltegger concerning antipsoriatic activity and the inhibitory effects against 5-lipoxygenase.     

Efficacy of "high-intensity" blue-light and "standard" daylight phototherapy for non-haemolytic hyperbilirubinaemia

We report our clinical experience with phototherapy in 3802 infants; 3629 were exposed to "standard" daylight phototherapy and 173 to "high-intensity" blue-light phototherapy. High-intensity blue-light phototherapy was twice as effective as standard daylight phototherapy in decreasing bilirubin concentrations. No failures occurred with high-intensity phototherapy compared with an overall failure rate of 1.84/1000 with daylight lamps; these cases were transferred to high-intensity phototherapy with prompt response. Rebound after cessation of phototherapy was greater in those exposed to high-intensity blue light with a significantly greater number requiring a second exposure. However, the incidence was still low. No third exposure was required in any infant. Nursing of infants under high-intensity blue light was more difficult and inconvenient as was clinical monitoring. The light also caused more stress on the nursing and medical personnel. However, the infants tolerated both types of phototherapy equally well. High-intensity blue-light phototherapy would seem to be the treatment of choice for infants with rapidly increasing or very high bilirubin levels, as well as in those not responding adequately to daylight phototherapy.     

Determination of the spread of epidural anesthesia. A comparison between pin-prick and a new method using a metallic roller]

A new method (metal roller) for testing the spread of analgesia in regional anesthesia is introduced. The possible advantages of testing with a metal roller (cold sensation) in comparison to the pinprick method are investigated and discussed to determine whether loss of cold-sensation is comparable to loss of pinprick-sensation and thus reliable in clinical practice. METHOD AND MATERIAL. Spread of analgesia was tested with both the metallic roller and the conventional pinprick method in 40 patients (20 epidural and 20 spinal blocks), and pain perception or cold perception were compared. RESULTS. In epidural as well as in spinal anesthesia, similar levels of loss of pain perception and cold perception were found. DISCUSSION. Testing the spread of analgesia after nerve bock by the pinprick method is sometimes unpleasant for the patient. The metal roller is not unpleasant, and the possible danger of contamination or pinprick pain is virtually impossible because physical integrity is preserved and the feeling of "cold" is not harmful.     

Glutaric aciduria type I

Summary Serial CT findings in an infant with glutaric aciduria type I (GA-I) are reported. The major CT features were dilatation of the insular cisterns, regression of the temporal lobes, with bat wings dilatation of the Sylvian fissures and hypodensity of the lenticular nuclei. CT changes preceded the onset of symptoms by 3 months. An improvement in the temporal lobe atrophy was seen after a period of treatment, coinciding with marked clinical improvement. A peculiar feature was the presence of external hydrocephalus, which diverted the attention from manifestations of the primary disease and thus consitituted a diagnostic pitfall. The delineation and recognition of the characteristic radiologic manifestations of GA-I are essential for allowing an adequate radiologist/clinican interaction in diagnosing this inborn error of metabolism.