Reproducibility of angiotensin converting enzyme inhibitor induced cough: A double-blind randomised study

1 The reproducibility of angiotensin converting enzyme inhibitor induced cough was examined in a double-blind cross over study in patients previously shown to have exhibited this side effect.

2 Ninety-seven patients who had experienced angiotensin converting enzyme inhibitor cough within the last 2 years were challenged with enalapril 20 mg daily for 4 weeks to establish eligibility. Eighty-eight of 97 (91%) patients experienced a repeat of their cough symptoms. Sixty-four patients entered the double-blind part of the study where they were treated with enalapril 20 mg and a renin inhibitor for up to 4 weeks in random order. These periods were separated by a minimum 4 week placebo wash out.

3 Of 59 evaluable patients who received enalapril a second time, 37 (62.7%) experienced cough again. Of 62 patients on the renin inhibitor 16 (25.8%) experienced cough, however as it was not equi-efficacious to enalapril no valid comparison could be made.

4 Angiotensin converting enzyme inhibitor cough is not reproducible within patients, as other factors are involved in the aetiology. Objective testing with blinded assessment together with symptom reporting, would give a more accurate measure of the incidence, and mechanism of this side effect.

     

Monocytes in active multiple sclerosis: intact regulation of HLA-DR density in vitro despite decreased HLA-DR density in vivo

HLA-DR expression on circulating monocytes varies as a function of disease activity in patients with multiple sclerosis (MS), a putative immunopathological demyelinating disorder. Specifically, monocytes isolated from subjects with active MS exhibit reduced HLA-DR antigen density, and immunoregulatory aberrations such as impaired T lymphocyte-mediated suppression correlate strongly with this quantitative defect. To address the mechanism underlying this phenomenon, we compared in vitro regulation of HLA-DR by interferon beta (IFN beta), interferon gamma (IFN gamma), and lipopolysaccharide (LPS) in monocytes from patients with stable and active MS and normal individuals. Interferon-gamma and LPS enhanced monocyte expression of HLA-DR equally in both MS patient groups, suggesting that underexpression of HLA-DR in active MS was not explained by impaired in vivo monocyte responsiveness. Furthermore, interferon regulation of HLA-DR in normals and stable MS subjects was indistinguishable, indicating that aberrant interferon-mediated regulation of class II major histocompatibility complex (MHC) on circulating monocytes does not appear to be a characteristic of the MS disease state.     

Comparison between short- and long-term haloperidol administration on somatostatin and substance P concentrations in the rat brain

Neuroleptics influence a variety of putative neurotransmitters in the basal ganglia, including somatostatin and substance P. Most studies have been performed in animals after only 3 or 4 weeks of neuroleptic administration and have seldom examined the effects of withdrawal. To understand better the effects of haloperidol on neuropeptide systems, the effects of short-term (3 weeks) and long-term (8 months) administration, as well as withdrawal from long-term administration of haloperidol, on somatostatin and substance P concentrations were examined in the rat. Short-term haloperidol significantly decreased the concentrations of somatostatin in the caudate-putamen, nucleus accumbens, and ventral tegmental area, and decreased the concentration of substance P in the substantia nigra and the nucleus accumbens. However, long-term administration only decreased the concentration of somatostatin in the nucleus accumbens. In addition, a slight reduction in the concentration of substance P in the medial prefrontal cortex was detected after long-term treatment. After withdrawal from long-term haloperidol administration the concentrations of these peptides did not differ from control values in any of the brain regions examined. These results confirm that dopamine receptor blockade can affect the somatostatin and substance P systems in the basal ganglia and indicate that during long-term administration (8 months) tolerance develops to some of the effects that are observed after shorter (3 weeks) treatment periods.     

Growth hormone releasing activity by intranasal administration of a synthetic hexapeptide (hexarelin)

OBJECTIVE Hexarelin is a new synthetic growth hormone releasing peptide. We have tested the efficacy of intranasal (i.n.) administration of hexarelin to stimulate plasma GH and have compared this to the intravenous (i.v.) administration of the peptide. PATIENTS Ten children with familial short stature (FSS) aged 5·5-15·5 years and two known GH deficient patients aged 24 and 28 years without GH treatment. METHODS All 12 subjects were submitted to i.v. (1 μg/kg) and i.n. (20 μg/kg) hexarelin tests with a one-week interval between tests. Blood samples for GH, TSH, fT4 and T3 were obtained at 0, 15, 30, 60, 90 and 120 minutes. The hormone determinations were made by standard radio-immunoassays (RIA). RESULTS Both the i.n. and i.v. administration of hexarelin induced a large GH response, the mean (±SD) being 72·2± 35·5 mU/l for the i.n. test and 79·6 ± 53·0 mU/l for the i.v. test. The peak GH in the i.v. test occurred at 15–30 minutes and in the i.n. test between 30 and 60 minutes. The GH deficient patients showed no GH response In either test. Plasma TSH decreased in the FSS children from a mean (±SD) of 1.0 ± 0·26 to 0·64±0 2 mU/l (P<0 005) during the i.n. test and from 1·0±0·3 to 0·7±0·3mU/l (P> 0 05) during the I.v. test. In the isolated GH deficient patient, plasma TSH decreased from 1·06±0·38 mU/l to 0·86±0·17 during the i.v. test and from 1·60±0·01 to 1·11±0·06mU/l during the i.n. test. There were no significant changes in plasma fT4 or T3 in any of the tests. CONCLUSIONS The synthetic hexapeptide hexarelin is a potent pituitary GH stimulator when administered intra-nasally. The GH response was similar to that observed after intravenous hexarelin. Simultaneously, there was a significant decrease in plasma TSH but the concentrations remained in the normal range. These findings appear to be of theoretical and practical relevance to the investigation and management of short children.     

Loss of endogenous androgen receptor protein accelerates motor neuron degeneration and accentuates androgen insensitivity in a mouse model of X-linked spinal and bulbar muscular atrophy

Human Molecular     

Trans-perineal implantation of radio-opaque treatment verification markers into the prostate: an assessment of procedure related morbidity, patient acceptability and accuracy.

On-line imaging of prostate markers can be used to compensate for errors in radiation delivery. This study assessed the patient acceptability and morbidity associated with the trans-perineal route of implantation. A minority experienced acute pain or bleeding. Placement was accurate in all but one subject. An operator related learning curve exists. Although this is an invasive procedure most patients found it acceptable. Implementation for routine clinical practice is feasible.     

Investigation of focal hepatic lesions: Is tomographic red blood cell imaging useful?

Noninvasive diagnosis of cavernous hemangioma of the liver is an important step in the investigation of patients with focal hepatic lesions since biopsy may result in life-threatening hemorrhage. To determine the diagnostic accuracy of 99m-technetium red blood cell (^99mTc-RBC) imaging with tomography, 50 patients with various types of focal liver lesions were studied. Thirty-two patients had 45 hemangiomas and 7 other benign lesions while 18 patients had either primary (n=8) or secondary (n=10) hepatic malignancies. Tomographic imaging identified 12 more hemangiomas than planar imaging, improving sensitivity from 53% to 80%, and was found most useful for detection of smaller lesions (mean size, 2.1 cm). Specificity for hemangiomas was 100% with all lesions greater than 1.9 cm showing the characteristic scintigraphic pattern of blood-pooling on delayed images. There was excellent agreement between 2 independent observers concerning interpretation of tomographic images (89% for the hemangioma group and 100% for other patients). Therefore^99mTc-RBC scintigraphy with tomography is an accurate diagnostic technique in the investigation of cavernous hemangiomas. Its major value resides in its ability to distinguish hemangiomas from other types of hepatic pathology.

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Resumen El diagnóstico no invasivo del hemangioma cavernoso del hígado es un paso de importancia en el proceso de investigación de pacientes con lesiones hepáticas focales, puesto que la biopsia puede resultar en hemorragia de consecuencias potencialmente fatales. Con el objeto de determinar la certeza diagnóstica de la tomografía con glóbulos rojos marcados con tecnecio 99m, se estudiaron 50 pacientes con varios tipos de lesiones hepáticas focales. Treinta y dos pacientes presentaron 45 hemangiomas y 7 lesiones benignas, en tanto que 18 pacientes presentaron neoplasias malignas primarias (n=8) o secundarias (n=10). Las imágenes tomográficas obtenidas por este método lograron identificar 12 hemangiomas más, en comparación con imágenes convencionales, aumentando la sensibilidad de 53% a 80%, y demostró ser de máxima utilidad para la detección de las lesiones más peque¯nas (tamaño promedio, 2.1 cm). La especificidad para los hemangiomas fue 100%, con todas las lesiones mayores de 1.9 cm exhibiendo el patrón centelleográfico característico de estancamiento sanguíneo en las imágenes tardías. Se encontró excelente correlación entre 2 observadores independientes en la interpretación de las imágenes tomográficas (89% para el grupo de pacientes con hemangiomas y 100% para el resto de los pacientes). En consecuencia, la escintigrafía con glóbulos rojos marcados con^99mTc aparece como una técnica certera en el diagnóstico de los hemangiomas cavernosos. Su mayor valor reside en su habilidad para diferenciar los hemangiomas de otra clase de patología.

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Résumé Le diagnostic non invasif d'hémangiome caverneux du foie est une étape importante dans l'investigation des patients ayant des lésions hépatiques focales, puisque la biopsie risque de se résoudre par une hémorrhagie menaçant le pronostic vital. Pour définir la précision diagnostique de la tomoscintigraphie après marquage des hématies au technetium 99m (^99mTc), on a étudié 50 patients ayant des types différents de lésions focales du foie. Trente-deux patients avaient 45 hémangiomes et 7 lésions bénignes tandis que 18 patients avaient des tumeurs hépatiques malignes soit primaires (n=8) soit secondaires (n=10). L'imagerie tomographique a identifié 12 hémangiomes de plus que l'imagerie planaire, améliorant la sensibilité de 53% à 80% et s'est avérée très utile pour détecter les lésions plus petites (taille moyenne, 2.1 cm). La spécificité pour les hémangiomes était de 100% pour toutes les lésions dépassant 1.9 cm montrant les caractères scintigraphiques typiques d'accumulation de sang sur les images retardées. Il y a eu concordance totale entre 2 observateurs indépendents sur l'interprétation des images tomographiques (89% pour le groupe des hémangiomes et 100% pour les autres patients). Voilà pourquoi la scintigraphie^99mTc avec tomographie est une technique de diagnostic précis dans l'investigation des hémangiomes caverneux. Sa valeur essentielle est sa capacité de distinguer les hémangiomes des autres types de pathologie hépatique.