Bradycardia associated with intravenous methadone administered for sedation in a patient with acute respiratory distress syndrome

The use of low tidal volumes with permissive hypercapnia in patients with acute respiratory distress syndrome may require heavy sedation to allow them to tolerate mechanical ventilation. Administration of methadone for sedation is an alternative to using other opioids, given its longer elimination half-life and incomplete cross-tolerance with other mu-receptor-active opioids. Methadone appears to have a molecular structure similar to that of verapamil, a calcium channel blocker, and may exhibit similar cardiac properties as well. A 43-year-old man with acute respiratory distress syndrome experienced bradycardia while receiving a continuous infusion of methadone for sedation and mechanical ventilation management. This case report demonstrates that caution is warranted when high dosages of methadone are administered because of its potential cardiac effects.     

Brain imaging: a key to understanding depression

According to the World Development Report 1993 one third of people with a mental illness suffer from a depressive disorder. There is a need for early diagnosis and effective treatment in order to limit the impact on patients' lives. Knowledge gained from brain imaging research may help to improve our understanding and treatment of depression.     

Neuroimaging to predict preclinical Alzheimer's disease

Alzheimer's disease is common in the elderly and causes tremendous distress to patients and their carers. With the advent of newer pharmacological treatments, significant improvement in the early diagnosis of Alzheimer's disease is required. This article examines the usefulness of neuroimaging techniques to predict Alzheimer's disease in prediagnosis individuals.     

Measurement of warfarin in plasma by high performance liquid chromatography (HPLC) and its correlation with the international normalized ratio

The measurement of plasma warfarin is required to investigate non-compliance, resistance to anticoagulation, drug metabolism and pharmacokinetic. Methods so far described are based on extraction of warfarin from plasma followed by reversed-phase HPLC. Extraction is the crucial step and may be performed in liquid- or solid-phase. The latter requires the preparation of columns, which makes the procedure variable. We investigated the suitability of the ready-for-use commercial cartridges for sample preparation. The method displayed between-run CV of 11.8%. Recovery was 99%. The coefficients of correlation between warfarin concentration in 50 patients and weekly dosage or INR were 0.55 (p<0.0001) or 0.25 (p=0.079).     

Neural correlates of tactile prepulse inhibition: a functional MRI study in normal and schizophrenic subjects

Prepulse inhibition (PPI) of the startle reflex refers to the ability of a weak prestimulus, the prepulse, to inhibit the response to a closely following strong sensory stimulus, the pulse. PPI is found to be deficient in a number of psychiatric and neurological disorders associated with abnormalities at some level in the limbic and cortico-pallido-striato-thalamic circuitry. We applied whole-brain functional magnetic resonance imaging to elucidate the neural correlates of PPI using airpuff stimuli as both the prepulse and the pulse in groups of (i) healthy subjects and (ii) schizophrenic patients. Cerebral activation during prepulse-plus-pulse stimuli with stimulus-onset asynchronies of 120 ms was contrasted with activation during pulse-alone stimuli. In healthy subjects, PPI was associated with increased activation bilaterally in the striatum extending to hippocampus and thalamus, right inferior frontal gyrus and bilateral inferior parietal lobe/supramarginal gyrus, and with decreased activation in the right cerebellum and left medial occipital lobe. All activated regions showed significantly greater response in healthy subjects than schizophrenic patients, who also showed a trend for lower PPI. The findings demonstrate involvement of the striatum, hippocampus, thalamus, and frontal and parietal cortical regions in PPI. Dysfunctions in any of these regions may underlie observations of reduced PPI in schizophrenia.     

Mifepristone-misoprostol abortion: a trial in rural and urban Maharashtra,India

As several important policy questions remain regarding the use of medical abortion in developing countries, we investigated the safety, efficacy, and acceptability of mifepristone-misoprostol abortion in the outpatient family planning departments of two urban hospitals and one rural hospital in India. Nine-hundred women (with gestations of < or =63 days in the urban sites and < or =56 days in the rural site) received 600 mg mifepristone followed 48 h later by 400 microg oral misoprostol in the clinic. Four point four percent or fewer urban women and 1.0% rural women were lost to follow-up. Perfect and typical-use failure rates were low at all sites. While rural women reported fewer side effects at all sites, the vast majority of women were satisfied with their medical abortions. Medical abortion can be offered safely, effectively, and acceptably in the outpatient family planning departments of urban and rural hospitals in India.     

Pseutarin C,a prothrombin activator from Pseudonaja textilis venom: its structural and functional similarity to mammalian coagulation factor Xa-Va complex

Several snake venoms contain procoagulant proteins that can activate prothrombin. We have purified pseutarin C, a prothrombin activator from the venom of the Australian brown snake (Pseudonaja textilis). It converts prothrombin to thrombin by cleaving both the peptide bonds Arg(274)-Thr(275) and Arg(323)-Ile(324), similar to mammalian factor Xa. It is a protein complex (approximately 250 Kd) consisting of an enzymatic and a non- enzymatic subunit. These subunits were separated by reverse phase HPLC and their interactions with bovine factor Xa and factor Va were studied. The enzymatic subunit of pseutarin C has an approximately 13 fold higher affinity for bovine factor Va (K(d) of 11.4 nM for pseutarin C enzymatic subunit--bovine factor Va interaction as compared to a K(d) of 147.4 nM for the bovine factor Xa-Va interaction). The non-enzymatic component, however, was unable to activate bovine factor Xa. N-terminal sequence analysis of the catalytic subunit of pseutarin C showed approximately 60% homology to mammalian factor Xa and approximately 78% homology to trocarin, a group D prothrombin activator from Tropidechis carinatus venom. Structural information for the non-enzymatic subunit of pseutarin C was obtained by amino terminal sequencing of several internal peptides. The sequence data obtained indicates that the non-enzymatic subunit of pseutarin C has similar domain architecture like the mammalian factor Va and the overall homology is approximately 55%. Thus pseutarin C is the first venom procoagulant protein that is structurally and functionally similar to mammalian factor Xa-Va complex.     

Prepulse inhibition of the startle response in risperidone-treated patients: comparison with typical antipsychotics

Individuals with schizophrenia are known to show deficits in prepulse inhibition (PPI) of the startle response. PPI refers to a response suppression in reaction to a strong startling stimulus, if preceded briefly by a weak non-startling stimulus and represents a well-established animal model to investigate information processing deficits in schizophrenia. This study examined PPI of the startle acoustic response in schizophrenic patients given typical antipsychotics or a second generation atypical antipsychotic, risperidone, using a naturalistic between-subjects design. Two groups of male schizophrenic patients: (i) stable on a range of typical antipsychotics (n = 20), and (ii) stable on risperidone (n = 10) were tested for PPI (prepulse-to-pulse intervals: 30, 60, and 120 ms, prepulses 15 dB above the background) of the acoustic startle response, and compared with a group of healthy male subjects (n = 20). Patients on typical antipsychotics showed significantly less PPI with 30 and 60 ms prepulse trials than healthy subjects. Risperidone-treated patients did not differ from healthy subjects for PPI with any prepulse trials. Further longitudinal within-subject studies are now required to examine whether risperidone is superior to typical antipsychotics in improving information processing functions, as assessed by PPI of the acoustic startle response, in treatment-responsive male patients with schizophrenia.