Reye-like syndrome resulting from novel missense mutations in mitochondrial medium- and short-chain l-3-hydroxy-acyl-CoA dehydrogenase

Medium- and short-chain l-3-hydroxy-acyl-CoA dehydrogenase (M/SCHAD) deficiency is a recessively inherited disorder of fatty acid oxidation. Currently, only four patients from three families have been reported in the literature. All these patients presented with hypoglycemia associated with hyperinsulinism (HI). This association suggests that there is a role for M/SCHAD in regulating the pancreatic secretion of insulin. We present a fifth patient whose presentation was similar to Reye syndrome, a feature in common with most of the previously recognized disorders of fatty acid oxidation but with no clinical evidence of HI. Sequencing of the HAD1 gene on chromosome 4 revealed compound heterozygosity for two novel missense mutations, 170A>G, resulting in D45G, and 676T>C, resulting in Y214H. The mutant enzymes were expressed and subjected to kinetic analysis. Y214H has no detectable activity, whilst D45G, which resides in the cofactor-binding pocket, has an altered K(m) for NADH (96 microM versus 24 microM for the wild-type). This represents the first kinetic M/SCHAD mutant, which explains the high residual activity in skin fibroblasts. The lack of obvious HI in this patient may be related to the high residual activity and indicates that HI associated with M/SCHAD deficiency may only be present with complete deficiency. The spectrum of M/SCHAD phenotype should be broadened to include acute liver disease.     

Spine growth precedes synapse formation in the adult neocortex in vivo

Dendritic spines appear and disappear in an experience-dependent manner. Although some new spines have been shown to contain synapses, little is known about the relationship between spine addition and synapse formation, the relative time course of these events, or whether they are coupled to de novo growth of axonal boutons. We imaged dendrites in barrel cortex of adult mice over 1 month, tracking gains and losses of spines. Using serial section electron microscopy, we analyzed the ultrastructure of spines and associated boutons. Spines reconstructed shortly after they appeared often lacked synapses, whereas spines that persisted for 4 d or more always had synapses. New spines had a large surface-to-volume ratio and preferentially contacted boutons with other synapses. In some instances, two new spines contacted the same axon. Our data show that spine growth precedes synapse formation and that new synapses form preferentially onto existing boutons.     

Variation among state-level approaches to addressing alcohol abuse in opioid treatment programs

In view of their role in licensing opioid treatment programs (OTPs), state opioid treatment authorities (SOTAs) are in a unique position to influence how OTPs address their patients' alcohol abuse. Using data from a telephone survey of SOTAs from the District of Columbia and states that have at least one OTP (n = 46), this study examines the extent to which SOTAs address alcohol abuse in their respective state policies and guidelines for OTPs. Findings indicate that 27 states have overall measures on how to address patients' problematic alcohol use, 23 states require or recommend alcohol education to be provided to all patients, and 17 states have stipulations that address specific actions to be taken if patients present at daily dosing under the influence of alcohol. Although SOTAs generally rate alcohol of at least moderate importance in formulating regulations, many of their policies and guidelines do not deal with various alcohol-related services and issues.     

Recurrence rates associated with incompletely excised low-risk nonmelanoma skin cancer

Background: Reported recurrence rates for transected nonmelanoma skin cancer (NMSC) vary widely, and few studies have addressed recurrence of tumors followed clinically or treated with nonsurgical modalities.
Methods: Retrospective review of dermatopathology records from January 1999 to January 2005 was conducted to identify biopsies or excision specimens with histologically transected basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) which were not subsequently excised. Patient and tumor characteristics associated with recurrence were analyzed in a subgroup of patients with predominantly 'low-risk' and/or minimally transected NMSCs. Prospective follow up was performed through March 31, 2008. Data was analyzed with Chi-square and Fishers exact tests and multivariate logistic regression.
Results: Of 376 transected NMSCs, 27 (7.2%) recurred, including 20 (9%) of 223 BCCs and 7 (4.6%) SCCs in situ of 153 SCCs. The overall recurrence rate of the 124 minimally transected NMSCs was even lower (5.6%). Multivariate logistic regression identified three significant predictors of recurrence: tumor location on the head and neck (p = 0.041), tumor size (p = 0.00741) and superficial subtype of BCC (p = .035).
Conclusions: Although surgical excision of NMSC remains the standard of care, observation or nonsurgical treatment may be acceptable in many cases of incompletely excised low-risk or minimally transected NMSCs.     

Role of treatment alliance in the clinical management of bipolar disorder: stronger alliances prospectively predict fewer manic symptoms

The strength of the treatment alliance between patients and their clinicians may play a unique role in the management of bipolar disorder. However, few empirical studies have examined the alliance in bipolar disorder or its effects on patient outcomes. This study investigates variables associated with a strong treatment alliance in bipolar disorder, and the prospective effects of treatment alliance on patients' mood symptoms and treatment attitudes. Participants were 58 longitudinally followed individuals with Bipolar I disorder. We found that alliance ratings covaried with depressive symptoms, such that alliance strength increased as depressive symptoms decreased, and stronger alliances were associated with more social support. Tests of temporal association indicated that stronger alliances predicted fewer manic symptoms 6 months later. Stronger alliances also predicted less negative attitudes about medication and less of a sense of stigma about bipolar disorder. Thus, a strong treatment alliance may help to reduce manic symptoms over time. It may be that a strong treatment alliance encourages patients' greater acceptance of bipolar disorder and psychopharmacological interventions, and thus contributes to improved medication adherence and clinical outcomes. Considered in sum, these findings suggest that the treatment alliance is an integral component of the long-term management of bipolar disorder.     

Effect of treatment with the Molecular Adsorbents Recirculating System on arterial amino acid levels and cerebral amino acid metabolism in patients with hepatic encephalopathy

Background: Liver failure is associated with low concentrations of branched‐chain amino acids and high concentrations of most other amino acids. In this study the effect of treatment with the Molecular Adsorbents Recirculating System (MARS) on arterial amino acid levels and cerebral amino acid metabolism was examined in patients with severe hepatic encephalopathy. Methods: The study included seven patients with hepatic encephalopathy from fulminant hepatic failure (FHF) and five patients with hepatic encephalopathy from acute‐on‐chronic liver failure (AoCLF). Cerebral blood flow and cerebral arteriovenous differences in amino acids were measured before and after 6?h of treatment with MARS. Results: During MARS treatment, the total arterial amino acid concentration decreased by 20% from 8.92?±?7.79?mmol/L to 7.16?±?5.64?mmol/L (P?P?Conclusions: MARS treatment tends to normalize the arterial amino acid concentrations in patients with hepatic encephalopathy. Even though the overall reduction in plasma amino acids and improvement in amino acid dysbalance may well be beneficial, it was not accompanied by any immediate improvement in cerebral amino acid metabolism in patients with FHF or AoCLF.     

Problems to discuss with cancer patients in palliative care: a comprehensive approach

This study presents a comprehensive overview of the problems patients experience in a palliative phase of cancer. A two-step qualitative method was used: in-depth interviews with patients and relatives (N=9 patients+7 relatives), followed by interviews (N=31patients+15 relatives) using a checklist to confirm and complete the picture. Quality of life and quality of care domains were addressed. Patients experienced problems in all of these palliative care domains, although individual patients may have experienced only a few problems. Fatigue, feelings of futility, reluctance to accept help, fear of suffering and the fear that help would not be available if needed, were common problems. Communication problems arose when a grudge against a GP had remained, or because one family member tried to spare the other a confrontation with his/her feelings of fear or grief. A comprehensive checklist of relevant problems is presented.     

Benefit of a Second Opinion for Lung Cancer: No Metastasis to the Kidney but a Synchronous Primary Renal Neoplasm

Background

The finding of a renal mass on imaging is suggestive of metastatic non-small cell lung cancer in the presence of a lung tumor but can also have another origin.

Case Report

We describe the case of a patient diagnosed with stage IV lung cancer based on a renal metastasis. A second opinion including review of histopathological data and additional imaging followed by lung surgery and cryoablation of the kidney lesion revealed two tumors of different origins, non-small cell lung cancer and a renal cell carcinoma.

Discussion

The presence of a renal mass diagnosed on a CT scan in a patient with lung cancer is not always synonymous with metastatic disease. Confirmation of diagnosis by tissue sampling is mandatory, especially if a synchronous primary tumor is possible.Key words: Non-small cell lung cancer, Second opinion, Renal cell carcinoma, Diagnosis/treatment, Metastatic disease, Synchronous primary tumor     

Changes in hepatic perfusion after administration of hydroxyethyl starch in intensive care patients assessed using color-coded Doppler sonography

Using color-coded Doppler sonography (CCDS), changes in the resistance index of the hepatic artery (HA-RI) and in the velocities of the hepatic artery, portal and splenic vein (HA-V, PV-V, SV-V) were measured after administration of hydroxyethyl starch (HES) in 50 intensive care patients. PV-V and SV-V increased, whereas HA-V and HA-RI remained unchanged. CCDS is suitable to assess liver perfusion in intensive care patients. Since HES enhances splanchnic perfusion, its application improves hepatic perfusion in intensive care patients.