Cytotoxicity of (2,2':6',2'-terpyridine)platinum(II) complexes to Leishmania donovani, Trypanosoma cruzi, and Trypanosoma brucei

A range of (2,2':6',2'-terpyridine)platinum(II) complexes are shown to possess antiprotozoal activity in vitro against Leishmania donovani, Trypanosoma cruzi, and Trypanosoma brucei,the causative organisms of tropical diseases leishmaniasis and trypanosomiasis. The best compounds caused 100% and 78% inhibition of growth of the intracellular amastigote forms of L. donovani and T. cruzi, respectively, at a concentration of 1 microM and 100% inhibition of growth of the bloodstream trypomastigote forms of T. brucei at a concentration of 0.03 microM. The results obtained with complexes in which the fourth ligand to platinum(II) is capable of being substituted with a substitution inert hydroxyethanethiolate complex are compared. The ammine complexes show high antiprotozoal activity suggesting that the trans influence of the 2,2':6',2'-terpyridine ligand has a profound effect on the ease of displacement of the fourth ligand in (2,2':6',2' -terpyridine)platinum(II) complexes, although nonbonded interaction between the ammine ligand and the 6 and 6' ' hydrogens probably also weakens the ligation to Pt(II).     

Elderly suicide, mental health professionals, and the clergy: a need for clinical collaboration, training, and research

This article addresses the need for improved clergy-mental health professional collaboration in the assessment and treatment of elderly suicide. Millions of older adults with personal problems seek the counsel of clergy. A recent Gallup survey found that elders are more willing to turn to their clergy than their medical doctor or a mental health specialist for help when a friend is contemplating suicide (Gallup Organization, 1992). Elder suicide prevention presents the mental health and religious communities with unique opportunities to work together in the best interests of those they serve.     

Metabolic and neuroanatomical correlates of barrel-rolling and oculoclonic convulsions induced by intraventricular endothelin-1: a novel peptidergic signaling mechanism in visuovestibular and oculomotor regulation?

The neuroactive peptide endothelin-1 has receptors distributed abundantly among subdivisions and nuclei of the visuovestibular and oculomotor systems. In previous work, we and others described the convulsive manifestations resulting from central injection of this neuropeptide, including nystagmus, oculoclonus, exophthalmos, tonic hindlimb extension, and a generalized repetitive motor disturbance called barrel-rolling. We applied the quantitative, autoradiographic [¹⁴C]deoxy-glucose method to examine the hypothesis that visuovestibular and oculomotor structures would become metabolically stimulated when endothelin was introduced into the brain via the ventricular system in conscious rats. Since previous work had demonstrated that hypermetabolic responses to endothelin in other neural systems were inhibited by an antagonist of neuronal calcium L-type channels, nimodipine, we further tested whether the increased function of vestibulooculomotor nuclei whose metabolic activity was sensitive to endothelin could be altered following nimodipine pretreatment via the ventricle. A single unilateral injection of endothelin (9 pmol in 3 l saline) into a lateral ventricle provoked significantly increased rates of glucose metabolism in 22 of 39 individual anatomical structures of the visuovestibular and oculomotor systems. Among those affected were the superficial stratum of the caudal superior colliculus (+25%), the optic tract bilaterally (+ 35 to 43%), the oculomotor cranial nerve nuclei (III, IV, VI; range of +21 to 47%), and the medial terminal nucleus of the accessory optic tract which harbors dense fields of endothelin binding sites (bilateral increase of +70 to 96%). Several other nuclei involved in the proprioceptive and visuovestibular disturbance caused by endothelin displayed increased metabolic activity, including the cuneate, gracile, sensory trigeminal, and prepositus hypoglossal nuclei, the vestibular subnuclear system, and the cerebellar flocculus. Identification of hypermetabolic responsivity to endothelin in these structures provides further information on the anatomical substrates mediating the behavioral phenomenology of endothelin-induced motor convulsions which involve the paroxysmal participation of the extraocular muscles and motor control systems producing barrel-rolling convulsions. Nimodipine pretreatment inhibited both the convulsive activity and the cerebral hypermetabolic responses to intraventricular endothelin. The results indicate that the neural systems sensitive to intraventricular endothelin become functionally active via a calcium-mediated process that may involve the neuropeptide as an intrinsic signaling molecule.     

Evaluation of a clinical recovery score after general anesthesia.

A clinical recovery score (CRS) assessing recovery after general anesthesia was compared with the Digit-Symbol Substitution Test (DSST), Trieger Test (TT), a patient-completed visual analogue scale for alertness (VAS), and an independent observer's evaluation of recovery. The CRS included ratings of the following parameters: activity, respiration, circulation, consciousness, ambulation, color, and nausea and vomiting. Forty patients requiring the removal of three or four third molars participated in the study. All patients received the same general anesthetic technique. Each patient was evaluated by the five methods preoperatively, on admission to the recovery room, and at 15-min intervals until discharge. The four recovery tests (CRS, DSST, TT, VAS) were evaluated using chi 2 analysis to determine if there was any overall difference among the tests using the observer's determination of home readiness as the standard for discharge. The CRS was significantly more in agreement with the observer's determination than were the paper and pencil tests. The recovery tests were also evaluated with regard to instances of early dismissal or prolonged retention of the patient, again using the observer's determination as the "gold standard." The CRS was the only recovery test devoid of early dismissals. We conclude that the CRS provides a valid, simple measure of recovery that can be readily used in offices providing outpatient anesthesia and in studies measuring clinical recovery from anesthesia or sedation.     

Total anomalous pulmonary venous connection to the left vertical vein. A plain-film sign useful in early diagnosis.

Total anomalous pulmonary venous connection to the left vertical vein often may be recognized on the plain postero-anterior chest radiograph by the characteristic supracardiac shadow. This "snowman sign" is useful in older patients but rarely is apparent in infancy. In such young patients the authors have discovered a density anterior to the trachea on the lateral chest radiograph. This finding is present prior to the appearance of the snowman sign and should prove useful in the early diagnosis of this anomaly, facilitating prompt, appropriate treatment. Five representative cases are tabulated and developmental and clinical aspects are reviewed.     

13Carbon mixed triglyceride breath test and pancreatic enzyme supplementation in cystic fibrosis

Children with cystic fibrosis have variable degrees of exocrine pancreatic insufficiency which, if untreated, is the main cause of fat malabsorption. The impact of pancreatic enzyme supplementation on fat digestion was measured in 41 children with cystic fibrosis, 11 healthy controls, and five children with mucosal diseases by a non-invasive test of intraluminal lipolysis using 13carbon (13C) labelled mixed triglyceride (1,3-distearyl, 2[13C] octanoyl glycerol). The children with cystic fibrosis without pancreatic supplements had a median (range) 13C cumulative percentage dose recovered over six hours (cPDR) of 3.1% (0-31.7), the controls 31.0% (21.8-41.1), and the subjects with mucosal disease 27.8% (19.7-32.5). In 23 subjects with cystic fibrosis the usual dose of pancreatic enzyme supplements increased the cPDR to a median of 23.9% (0-45.6), and twice the usual dose of enteric coated microspheres increased the cPDR to 31.1% (11.1-47.8). There was no significant difference between the median cPDR of normal controls and children with mucosal disease, but there was a highly significant difference between these groups and children with untreated cystic fibrosis. Thirteen children with cystic fibrosis had no 13C recovery in their breath without enzymes and 10 showed marked increases with regular enzymes. In eight children doubling the dose of enzymes caused no or minimal improvement. The mixed triglyceride breath test offers a simple, non-invasive way of assessing the need for pancreatic enzyme supplementation in children with cystic fibrosis and could be used to optimise treatment.