Cardioversion and the digitalized patient

Previous studies have reported lower intelligence for cyanotic than for acyanotic children with congenital heart disorders, a finding attributed to the degree of hypoxemia present. Several important variables have not been examined consistently, however, including coexisting neurologic or genetic disorders, definitive surgery, degree of sickness, age at testing sex and social class. The present study examined the relation of these variables to obtained intelligence measures for 82 consecutively admitted children, excluding children with abnormal neurologic examinations and those having received definitive surgery. Consistent with earlier reports, intelligence quotients for the acyanotic children (112.81 +/- 14.52 mean +/- SD) were significantly higher (t = 2.60; p = 0.006) than for the cyanotic group (103.50 +/- 15.81). Although sex, race and social class were not significantly different between the 28 cyanotic and the 54 acyanotic children, the cyanotic children were significantly sicker (x2 = 9.12; p = 0.005) and younger (t = 4.10; p = 0.001). However, when young and old children and the degree of sickness within cyanotic and acyanotic groups were compared, no significant differences were found. These findings demonstrate that intelligence differences between cyanotic and acyanotic children persist when the effect of neurologic abnormalities and definitive surgery is removed and remain despite the severity of sickness or child's age at testing.     

The use of monoamine oxidase inhibitors as adjuncts in the treatment of hypertension and angina pectoris

The newer monoamine oxidase inhibitors have clinical actions in hypertension and angina pectoris similar to those of iproniazid but appear to produce less frequent side effects. Some of the side effects suggest that in addition to amine oxidase inhibition, they may also have a ganglionic blocking action.

The amine oxidase inhibitors are effective and useful in the clinical management of refractory cases of angina pectoris even though they may not alter the electrocardiogram significantly. Since the relief of chest pain also is accompanied frequently by a sense of well-being, cautioning the patient against over-exertion is advisable. Some of the amine oxidase inhibitors are also worthy of a trial in resistant cases of hypertension. However, they should be employed cautiously in these selected cases since their long term effects, even in moderate dosage, on liver and cardiac function are not known.     

Microvesicles derived from mesenchymal stem cells: Potent organelles for induction of tolerogenic signaling

The adult bone contains a number of distinct populations of stem cells, including haematopoietic stem cells, mesenchymal stem cells, endothelial progenitor cells and fibrocytes. While haematopoietic stem cells are required to provide a lifelong supply of blood cells it is thought that the other populations of stem cells play a role in tissue regeneration and potentially disease. The chemokine CXCL12 is produced constitutively in the bone marrow and, acting via CXCR4, is critical in maintaining HSPCs in a quiescent state and retaining all subsets of stem and progenitor cells in the bone marrow environment. The cytokine G-CSF, used clinically to mobilize haematopoietic stem cells for bone marrow transplants, activates the sympathetic nervous system and bone marrow macrophages to reduce the expression of CXCL12 by bone marrow stromal cells, thereby promoting the exit of haematopoietic stem cells from the bone marrow. Understanding the molecular mechanisms underlying G-CSF stimulated mobilization has led to development of CXCR4 antagonists as fast acting mobilizing agents for haematopoietic stem cells. Evidence now suggests that CXCR4 antagonists can similarly mobilize distinct subsets of progenitor cells, namely the endothelial progenitor cells and mesenchymal stem cells, but this requires conditioning of the bone marrow with VEGF rather than G-CSF.     

Refining indications for contemporary surgical treatment of renal cell carcinoma metastatic to the pancreas

Background:

The pancreas is a rare location for metastatic disease, with only 2–11% of all pancreatic tumours being of non-primary origin. It is also uncommon for renal cell carcinoma (RCC) to metastasize to the pancreas (1–3% of cases) and, when it does, it typically occurs substantially after index nephrectomy. It is not known whether all pancreatic metastases need be resected because today''s chemo- and biological therapies are increasingly effective in controlling advanced disease.

Methods:

Six patients with a variety of symptoms are discussed. Four patients presented with recurrent gastrointestinal bleeding, ranging from occult to life-threatening in severity.

Results:

The four patients with gastrointestinal bleeding had RCC metastases that had eroded into the duodenum and were successfully controlled by palliative pancreaticoduodenectomy or completion pancreatectomy. The other two patients were treated using different chemotherapeutic or biological agents.

Conclusions:

Renal cell carcinoma metastases to the pancreas typically occur long after index nephrectomy. Although clinical presentation is variable, palliative resection should be reserved for those who develop complications, such as upper gastrointestinal bleeding, and, in other series, obstructive jaundice. Routine debulking resections do not appear to be indicated because current biological therapies effectively and reliably control disease over long periods.     

Development of molecularly targeted therapies in biliary tract cancers: reassessing the challenges and opportunities

Biliary tract cancers (BTCs), which encompass intra- and extrahepatic cholangiocarcinomas as well as gallbladder carcinomas, are a genetically diverse collection of cancers. Most patients with BTC will present with unresectable or metastatic disease. Although the standard systemic chemotherapy approaches are emerging, the prognosis remains poor. Development of molecularly targeted therapies in advanced BTC remains challenging. Recent early-stage clinical trials with targeted therapies appear promising, although the relationships between subsets of patients with positive responses to therapy and tumor genetics remain unexplored. Here we summarize the relevant molecular pathogenesis, recent and ongoing clinical trials with targeted agents, and the key issues in clinical trial design in BTC.     

Neurobehavioral dysfunction in patients with subcortical vascular mild cognitive impairment and subcortical vascular dementia

Amnestic mild cognitive impairment (MCI) is considered to be a prodromal stage of Alzheimer's disease. Likewise, subcortical vascular MCI (svMCI) is considered as a prodromal stage of subcortical vascular dementia (SVaD). The objective of this study was to investigate neuropsychiatric features in patients with svMCI compared to healthy controls and patients with SVaD. We evaluated 31 patients with svMCI, 42 with SVaD, and 28 healthy controls who underwent neuropsychiatric assessments using the Neuropsychiatric Inventory (NPI) and the Frontal Behavioral Inventory (FBI). On both the NPI and FBI, SVaD patients had the most severe neuropsychiatric symptoms, followed by svMCI patients and then healthy controls, suggesting that svMCI might be a prodromal stage of SVaD in terms of neuropsychiatric abnormalities. When we compared the differences of mean scores between negative and positive symptoms in FBI, negative symptoms tended to be more predominant than positive symptoms in both svMCI and SVaD patients, but the tendency was stronger in SVaD patients than in svMCI patients. These results suggest that vascular cognitive impairment with small vessel disease would start with both negative and positive neuropsychiatric symptoms and progress to present more severe negative symptoms. These behavioral ratings may be useful for early detection of vascular cognitive impairment associated with small vessel disease.