Intravenous labetalol for the control of hypertension following repair of coarctation of the aorta

Paradoxical hypertension is a relatively common complication of surgical repair of coarctation of the aorta. An early phase of systolic hypertension has been ascribed to elevated levels of norepinephrine. Activation of the renin-angiotensin system from sympathetic stimulation has been implicated in a later phase of systolic and diastolic hypertension that can result in mesenteric arteritis. The use of a rapidly acting, titratable intravenous alpha- and beta-adrenergic blocker, such as labetalol hydrochloride, addresses both of these neurohormonal mechanisms. In the intravenous form, it would appear to be an excellent choice for the management of early postoperative hypertension and it can be converted to the oral form in cases of persistent hypertension. We report for the first time the use of labetalol in two young patients for the control of paradoxical hypertension following coarctation repair.     

Aberrant hormone production from ovarian neoplasms: Strategies for diagnosis and therapy

Syndromes involving peptide or nonsex steroid hormone secretion due to aberrantly located tumors are rare. We report a collected series of 16 patients with ectopic hormone production from ovarian neoplasms, including 3 patients recently encountered at our institution as well as 13 additional cases identified in the recent literature. These tumors included 2 insulin-producing ovarian carcinoids, 1 ACTH-producing pituitary adenoma within a benign ovarian cystic teratoma, 2 cortisol-producing ovarian neoplasms, 8 gastrin-producing ovarian cystadenomata or cystadenocarcinomata, and 3 thyroxine-producing ovarian strumal carcinoids. All patients presented with syndromes of hormone excess. Only 62% of all tumors were localized preoperatively. Following ovarian resection, 87% of patients remained disease-free with a median follow-up period of 1.5 years. In addition to ovariectomy, 8 additional unnecessary ablative procedures were performed in 7 patients. These included distal pancreatectomy, pancreaticoduodenectomy, adrenalectomy, total gastrectomy, selective vagotomy, and subtotal thyroidectomy. Failure to localize the ovarian neoplasm preoperatively was associated with a significantly higher risk of subsequent unnecessary ablative procedures. Because of the potential for the ovary to act as a source of aberrant hormone secretion, we recommend complete preoperative evaluation of the pelvis in female patients presenting with nonlocalizable endocrine tumors.

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Resumen Los síndromes relacionados con la secreción de péptidos o de hormonas esteroideas no sexuales por tumores de ubicación aberrante ocurren infrecuentemente. En este artículo reportamos una serie de 16 pacientes con producción hormonal ectópica por neoplasmas ováricos, la cual incluye 3 pacientes vistos recientemente en nuestra institución y 13 identificados en la literatura médica de los últimos años. El grupo incluye 2 carcinoides ováricos productores de insulina, 1 adenoma pituitario productor de ACTH, 2 neoplasmas ováricos productores de cortisol, 8 cistadenomas o cistadenocarcinomas ováricos productores de gastrina, y 3 carcinoides ováricos estrumales productores de tiroxina. Todas las pacientes se presentaron con síndromes de exceso hormonal. En sólo el 62% de los tumores se pudo establecer la ubicación anatómica en la fase preoperatoria. Después de realizada la resección del ovario, 87% de las pacientes permanecieron libres de enfermedad en el período de seguimiento, que fue de 1.5 años en promedio. Además de la resección ovárica, se practicaron otros 8 procedimientos adicionales innecesarios en 7 pacientes. Estos incluyeron pancreatectomía distal, pancreatoduodenectomía, adrenalectomía, gatrectomía total, vagotomía selectiva, y tiroidectomía subtotal. La falla en la localización preoperatoria del neoplasma ovárico apareció asociada con un riesgo aumentado de ulteriores procedimientos quirúrgicos innecesarios. En vista de la potencialidad del ovario de actuar como fuente de secreción hormonal aberrante, nosotros recomendamos una completa evaluación de la pelvis en las pacientes femeninas en quienes se diagnostiquen tumores endocrinos no localizables.

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Résumé Les syndromes concernant la sécrétion d'hormones peptidique ou stéroïde nonsexuelle due à des tumeurs ectopiques sont rares. Nous rapportons une série de 16 patientes avec une production d'hormone ectopique provenant de néoplasmes ovariens, comprenant 3 patientes récemment soignées dans notre établissement ainsi que 13 cas supplémentaires relevés dans la littérature récente. Ces tumeurs comprennent 2 tumeurs carcinoïdes ovariennes productrices d'insuline, 1 adénome hypophysaire producteur d'ACTH à l'intérieur d'un tératome cystique ovarien bénin, 2 néoplasmes ovariens producteurs de cortisol, 8 cystadénomes ou cystadénocarcinomes ovariens producteurs de gastrine, et 3 carcinoïdes ovariens strumaux producteurs de thyroxine. Toutes les patientes avaient des syndromes d'hyperproduction hormonale. Soixante-deux pour cent seulement des tumeurs avaient été localisées en préopératoire. Après ovariectomie, 87% des patientes étaient apparamment sans récidive avec un suivi médian d'un an et demi. Cependent, outre l'ovariectomie, 8 interventions supplémentaires non nécessaires ont été accomplis chez 7 patientes. Celles-ci comprenaient: pancréatectomie distale, duodénopancréatectomie, surrénalectomie, gastrectomie totale, vagotomie sélective, et thyroïdectomie subtotale. L'impossibilité de localiser le néoplasme ovarien en période préopératoire était associée à un risque notoirement plus grand de faire une résection inutile. Compte tenu de la possibilité pour l'ovaire de se comporter en producteur de sécrétion ectopique d'hormone, nous recommandons un examen complet préopératoire du bassin chez les femmes se présentant avec des tumeurs endocrines non localisables.

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Presented at the International Association of Endocrine Surgeons in Toronto, Ontario, Canada, September, 1989.     

Geriatric heart failure, depression, and nursing home admission: an observational study using propensity score analysis.

OBJECTIVE: Heart failure (HF) and depression are both common in older adults, and the presence of depression is known to worsen HF outcomes. For community-dwelling older adults, admission to a nursing home (NH) is associated with loss of independent living and poor outcomes. The objective of this study was to examine the effect of depression on NH admission for older adults with HF. METHODS: Using the 2001-2003 National Hospital Discharge Survey datasets, the authors identified all community-dwelling older adults who were discharged alive with a primary discharge diagnosis of HF. The authors then identified those with a secondary diagnosis of depression. Using a multivariable logistic regression model, the authors then determined probability or propensity to have depression for each patient. The authors used propensity scores for depression to match all 680 depressed patients with 2,040 nondepressed patients. Finally, the authors estimated the association between depression and NH admission using bivariate and multivariable logistic regression analyses. RESULTS: Patients had a mean (+/- standard deviation) age of 79 (+/- 8) years, 72% were women, and 9% were blacks. Compared with 17% nondepressed patients, 25% depressed patients were discharged to a NH. Depression was associated with 50% increased risk of NH admission (unadjusted relative risk [RR]: 1.50; 95% confidence interval [CI]: 1.28-1.74). The association became somewhat stronger after multivariable adjustment for various demographic and care covariates (adjusted RR: 1.60; 95% CI: 1.35-1.68). CONCLUSION: In ambulatory older adults hospitalized with HF, a secondary diagnosis of depression was associated with a significant increased risk of NH admission.     

A prospective evaluation of changes in neuropsychological and liver function tests following transjugular intrahepatic portosystemic stent-shunt

Background/Aims: This study was designed to assess changes in: (a) neuropsychological tests, measures of memory, quality of life and scores for anxiety and depression; (b) liver function tests; and (c) the relationship between these following transjugular intrahepatic portosystemic stent-shunt.Methods: Twenty-nine patients undergoing transjugular intrahepatic portosystemic stent-shunt for recurrent variceal haemorrhage, 12 matched patients with cirrhosis and variceal haemorrhage manage with variceal band ligation and 16 normal controls were studied. Patients in any of the groups who were clinically encephalopathic were excluded from the study. Serial changes in the conventional liver function tests and Indocyanine green clearance, and psychometric function (Hospital Anxiety Depression Scale, Rivermead Behavioral Memory Test, Quality of Life and the memory and reaction sub-tests of the Cambridge Automated Neuropsychological Test Assessment Battery) were measured prior to and 1, 3, 9 and 15 months following transjugular intrahepatic portosystemic stent-shunt.Results: Over a mean follow up of 9.1 months in the transjugular intrahepatic portosystemic stent-shunt group (range 3–28), one patient (3%) developed clinically detectable encephalopathy. Sixty-seven percent of patients with cirrhosis showed evidence of subclinical encephalopathy as compared with the control population. Significant deterioration occurred in the reaction sub-tests of the Cambridge Automated neuropsychological Test Assessment Battery in patients, both in the transjugular intrahepatic portosystemic stent-shunt group and the controls with cirrhosis, during follow up. Transjugular intrahepatic portosystemic stent-shunt was followed by significant deterioration in levels of anxiety and psychological component of the quality of life. The Rivermead Behavioural Memory Test and the memory sub-test of the Cambridge Automated Neurpsychological Test Assessment Battery did, however, improve significantly at 1 and 15 months after transjugular intrahepatic portosystemic stent-shunt, respectively. Serum alanine aminotransferase, bilirubin and indocyanine green clearance deteriorated significantly following transjugular intrahepatic portosystemic stent-shunt (p<0.001, p<0.001 and p<0.0001, respectively). Significant correlation was observed between changes in the indocyanine green clearance and changes in the complex and simple reaction time subtests of the Cambridge Automated Neuropsychological Test Assessment Battery (r=0.6 and r=0.66, respectively).Conclusions: The results of this study showed that about 67% of patients with cirrhosis were subclinically encephalopathic and that temporary deterioration occurred in the Cambridge Automated Neuropsychological Test Assessment Battery during follow up, both in patients having transjugular intrahepatic portosystemic stent-shunt and in the controls with cirrhosis. These parallel the changes in the liver function tests and indocyanine green clearance. Temporary deterioration was also observed in the Quality of Life and Hospital Anxiety Depression Scale in the transjugular intrahepatic portosystemic stent-shunt group, although the measures of memory improved. Further studies should address the biochemical mechanisms of these changes and the role of prophylactic measures.     

Ziprasidone, Diazepam, or the Combination for Prevention of Cocaine Toxicity in a Mouse Model

Background Acute cocaine poisoning is a common problem in the United States. Sedation with benzodiazepines is the standard treatment, but animal studies have suggested that ziprasidone is also protective.
Objectives To assess whether the combination of these two medications would offer more protection than either treatment alone.
Methods This was a randomized, blinded, placebo-controlled trial in CF-1 mice. The authors administered intraperitoneal injections of 2 mg/kg diazepam (group D), 4 mg/kg ziprasidone (group Z), the same dose of both drugs (group DZ), or saline 15 minutes before intraperitoneal administration of 105 mg/kg cocaine (an estimated lethal dose to 70%). The number of animals with seizures and apparent lethality over the following 30 minutes was recorded.
Results All treatments increased survival relative to placebo (relative risk: D = 2.6, Z = 2.3, DZ = 2.9) and decreased seizures (relative risk: D = 0.5, Z = 0.3, DZ = 0.02).
Conclusions This study suggests that diazepam and ziprasidone have efficacy for preventing lethality from cocaine poisoning in an animal model but that the combination offers little addition to either therapy alone. However, the combination may be more effective for prevention of cocaine-induced seizures.     

Solubility of neurofibrillary tangles and ultrastructure of paired helical filaments in sodium dodecylsulphate

Summary Temporal cortex from 14 cases of Alzheimer-type dementia and 6 cases of Down's syndrome, all selected for severe Alzheimer pathology, was homogenised in distilled water, NaOH, or sodium dodecylsulphate (SDS) containing 0.1% -mercaptoethanol. The homogenates were stained with Congo red, and the neurofibrillary tangles and plaque cores were counted under crossed-polarisation microscopy. The number of tangles and plaque cores in the water-treated extracts was not related to age, sex, postmortem interval or duration of dementia. The number of tangles after extraction in SDS or NaOH, as a percentage of tangles in water-treated extracts, was 57±25 (mean±SD) for 1% SDS, 43±17 for 5% SDS and 37±22 for 0.2 M NaOH. Plaque cores were essentially insoluble in all three agents. The percentage of tangles insoluble in 1% SDS did not correlated with age or post-mortem interval but decreased with increasing duration of dementia. Enhanced tangle solubility with increasing duration of dementia suggests that the nature of tangles changes with time; one possibility is that this reflects transformation of intracellular to extracellular tangles. Paired helical filament (PHF) length and the number of repeats per PHF were measured in electron micrographs of PHF prepared with and without treatment by 1% SDS. There was no significant multimodality of PHF length to suggest that PHF broke at regular intervals. The mean repeat length (PHF length/number of repeats) was greater for PHF isolated in the presence of 1% SDS than in its absence, showing that SDS affects ultrastructure by untwisting PHF. An untwisting process may also occur in vivo producing the straight filaments found, together with PHF, in tangles and neurites.Supported by Miss E. Buchan (to the MRC Brain Metabolism Unit) and the British Foundation for Age Research and the Wellcome Trust (to P. A. M. Eagles). S. Hussey was in receipt of an MRC Partnership Award.     

Incidence of intraglomerular platelets in steroid sensitive nephrotic syndrome.

Renal biopsies from 44 patients with steroid sensitive nephrotic syndrome were examined with respect to the content of their intraglomerular platelets and compared with 18 normal control patients and with 51 patients with membranous glomerulonephritis and the nephrotic syndrome. The results suggested that platelet activity was not involved in the pathogenesis of steroid sensitive nephrotic syndrome; in the active phase of the number of platelets in glomeruli is lower than that of normal controls, and this may be associated with increased sensitivity to aggregating agents as part of the nephrotic syndrome. After steroid treatment and disappearance of proteinuria, the number of intraglomerular platelets rises to normal values.     

c-Myc is essential for vasculogenesis and angiogenesis during development and tumor progression

c-Myc promotes cell growth and transformation by ill-defined mechanisms. c-myc(-/-) mice die by embryonic day 10.5 (E10.5) with defects in growth and in cardiac and neural development. Here we report that the lethality of c-myc(-/-) embryos is also associated with profound defects in vasculogenesis and primitive erythropoiesis. Furthermore, c-myc(-/-) embryonic stem (ES) and yolk sac cells are compromised in their differentiative and growth potential. These defects are intrinsic to c-Myc, and are in part associated with a requirement for c-Myc for the expression of vascular endothelial growth factor (VEGF), as VEGF can partially rescue these defects. However, c-Myc is also required for the proper expression of other angiogenic factors in ES and yolk sac cells, including angiopoietin-2, and the angiogenic inhibitors thrombospondin-1 and angiopoietin-1. Finally, c-myc(-/-) ES cells are dramatically impaired in their ability to form tumors in immune-compromised mice, and the small tumors that sometimes develop are poorly vascularized. Therefore, c-Myc function is also necessary for the angiogenic switch that is indispensable for the progression and metastasis of tumors. These findings support the model wherein c-Myc promotes cell growth and transformation, as well as vascular and hematopoietic development, by functioning as a master regulator of angiogenic factors.