Percutaneous Hepatic Perfusion With Filtered Melphalan for Localized Treatment of Metastatic Hepatic Disease: A Risk Assessment.

Regional therapies for metastatic liver disease have garnered interest in recent years due to technological advances in drug delivery. A percutaneous hepatic perfusion (PHP) using a newly developed generation 2 (GEN2) filtration system was designed to mitigate systemic toxicity and cardiovascular risk associated with hepatic blood filtration during hepatic artery infusion of the chemotherapy drug melphalan. The GEN2 system was evaluated in healthy swine, and plasma samples were assessed for clinical chemistry, melphalan toxicokinetics (TK), inflammatory cytokines, catecholamines, hematological, and cardiac biomarkers. Cardiovascular safety was assessed by echocardiography, electrocardiogram, and telemetry. Toxicology parameters included clinical signs, body weight, gross pathology, and histopathology. There were no treatment-related deaths associated with the PHP procedure with GEN2 filtration, and all animals survived to scheduled necropsy. Assessment of the pharmacokinetic/TK plasma concentrations of melphalan demonstrated that the GEN2 filter was able to extract melphalan from blood with high efficiency and reduce melphalan exposure in the systemic circulation. The hemodynamic, immunosuppressive, immunotoxic, cardiotoxic, and histopathologic effects of melphalan were limited. The significant hemodynamic challenge imposed by filtration resulted in a compensatory tachycardia with supranormal left ventricular function, although no wall motion abnormalities were detected and left ventricular function remained normal. Catecholamines decreased and then quickly rebounded during washout. Transient and reversible effects of treatment on cardiac enzymes, catecholamines, and cytokines and reversible hemodynamic effects without cardiac damage indicated that PHP with melphalan was not cardiotoxic or immunotoxic under the conditions tested, due to high efficiency of the filtration system limiting exposure of melphalan to the systemic circulation.

Myxedema coma in a patient with Down's syndrome.

INTRODUCTION: hyroid dysfunction is common in Down's syndrome, most common being hypothyroidism. Longstanding, untreated hypothyroidism can lead to myxedema coma. METHODS: Here we report a patient with Down's syndrome who presented with myxedema coma. DISCUSSION: The three essential elements for the diagnosis of myxedema coma include altered mental status, defective thermoregulation and a precipitating event or illness; all of these were present in our patient. Also, very high TSH, low T3 and T4, and the rapid response to the treatment with levothyroxine confirmed the diagnosis. CONCLUSION: Patients with Down's syndrome should have regular screening for thyroid dysfunction.

Intra- and interrater reliabilities of the Myotonometer when assessing the spastic condition of children with cerebral palsy.

The purposes of this study were to assess intra- and interrater reliabilities by novice users of the Myotonometer (Neurogenic Technologies, Inc., Missoula, MT), a portable electronic device that quantifies muscle tone (stiffness) and paresis, in assessing children with cerebral palsy. Two raters used the Myotonometer to assess the biceps brachii and medial gastrocnemius muscles of 10 children with spastic-type cerebral palsy. Muscles were measured in a relaxed state and during a voluntary isometric contraction. Intraclass correlation coefficients and repeatability coefficients were calculated for each muscle and for each condition (relaxed and contracted). Intrarater reliabilities ranged from 0.82 to 0.99 (biceps brachii muscles) and 0.88 to 0.99 (medial gastrocnemius muscles). Interrater reliabilities ranged from 0.74 to 0.99 (biceps brachii muscles) and 0.84 to 0.99 (medial gastrocnemius muscles). Repeatability coefficients indicated a 98% level of agreement between raters across all conditions. Novice users of the Myotonometer, with few exceptions, had high to very high intra- and interrater reliabilities for measurements of the biceps brachii and medial gastrocnemius muscles of children with spastic-type cerebral palsy.