Surgeon-performed ultrasound in the management of thyroid malignancy

Surgeon-controlled real-time ultrasound (US) is a new adjunct in the management of patients with thyroid malignancy. The introduction of US as a routine evaluation tool has increased the recognition of nonpalpable thyroid cancers and cervical lymph node metastases. We report our experience and the change in management of patients with thyroid cancer due to the use of US. We reviewed the records of all patients undergoing neck operations for thyroid cancer since 2002. US was performed by a surgeon preoperatively in all patients and intraoperatively when non-palpable cervical lymph nodes were present. Suspicious nonpalpable thyroid nodules underwent US-guided fine-needle aspiration (FNA) for cytology. Seventy-two patients underwent operations for thyroid cancer. US influenced the management in 57 per cent (41/72) of patients. US was useful in 1) identification and guidance for the FNA of nonpalpable cancers in 28 per cent (20/72), 2) identification of nonpalpable nodules in the contralateral lobe in 38 per cent (27/72), 3) preoperative diagnosis of nonpalpable metastatic lymph nodes in 24 per cent (17/72), and intraoperative guidance for their excision. Surgeon-performed US changed and enhanced the pre- and intraoperative management in more than half the patients with thyroid cancer.     

Arthroscopic capsulolabroplasty for posteroinferior multidirectional instability of the shoulder

BACKGROUND: Arthroscopic treatment of posteroinferior multidirectional instability of the shoulder is not well documented. PURPOSE: To evaluate pathologic lesions of posteroinferior multidirectional instability and the results of arthroscopic capsulolabroplasty. STUDY DESIGN: Prospective nonrandomized clinical trial. METHODS: Thirty-one patients with posteroinferior multidirectional instability were prospectively evaluated after arthroscopic capsulolabroplasty (mean follow-up, 51 months). Labral lesion and height were measured in the MRI arthrogram and arthroscopic examination. RESULTS: All patients had a labral lesion and variable capsular stretching in the posteroinferior aspect. There were 11 type I labral lesions (incomplete detachment), 12 type II (the Kim's lesion: incomplete and concealed avulsion), 6 type III (chondrolabral erosion), and 2 type IV (flap tear). All patients with type II and III lesions had chondrolabral retroversion, with lost labral height in the MRI arthrogram and arthroscopic examination. Twenty-one patients had an excellent Rowe score, nine had good scores, and one had a fair score. Thirty patients had stable shoulders, and one had recurrent instability. All patients had improved shoulder scores and function and pain scores. CONCLUSIONS: Symptomatic patients with posteroinferior multidirectional instability had posteroinferior labral lesions, including retroversion of the posteroinferior labrum, which were previously unrecognized. Restoration of the labral buttress and capsular tension by arthroscopic capsulolabroplasty successfully stabilized shoulders with posteroinferior multidirectional instability.     

Do we still believe in the dopamine hypothesis? New data bring new evidence

Schizophrenia is characterized by positive symptoms, negative symptoms and cognitive impairment. The dopamine hypothesis of schizophrenia postulates that an excess of dopamine subcortically is associated with the positive symptoms. At the same time, the negative and cognitive symptoms of schizophrenia are thought to arise from a deficit of dopamine in the cortex. Evidence for the co-existence of subcortical dopamine excess and cortical dopamine deficit in the schizophrenic brain is presented. Neuroreceptor-imaging techniques, such as SPECT and PET, have been used to provide that evidence. After amphetamine challenge (to stimulate dopamine release), dopamine transmission was substantially increased in the brains of schizophrenic subjects compared with healthy controls. In addition, amphetamine challenge was associated with an increase in positive symptoms of schizophrenia. Furthermore, acute dopamine depletion studies indicated that there was an increased occupancy of D2 receptors by dopamine at baseline in schizophrenia in comparison with healthy controls. This is consistent with the notion of hyperstimulation of D2 receptors in schizophrenia. In the cortex, dopamine type-1 (D1) receptors were found to be up-regulated in patients with schizophrenia compared to controls; in the dorsolateral prefrontal cortex, a brain region involved in working memory, this increase correlated with a poor performance on the n-back task. The up-regulation of D1 receptors may represent a compensatory effect of the dopamine deficit in the cortex. These findings provide evidence for a corticalsubcortical imbalance in the schizophrenic brain.     

An evidence-based staging system for cutaneous melanoma

A completely revised staging system for cutaneous melanoma was implemented in 2003. The changes were validated with a prognostic factors analysis involving 17,600 melanoma patients from prospective databases. This major collaborative study of predicting melanoma outcome was conducted specifically for this project, and the results were used to finalize the criteria for this evidence-based staging system. In fact, this was the largest prognostic factors analysis of prospectively followed melanoma patients ever conducted. Important results that shaped the staging criteria involved both the tumor-node-metastasis (TNM) criteria and stage grouping for all four stages of melanoma. Major changes in the staging include: (1) melanoma thickness and ulceration are the dominant predictors of survival in patients with localized melanoma (Stages I and II); deeper level of invasion (ie, IV and V) was independently associated with reduced survival only in patients with thin or T1 melanomas. (2) The number of metastatic lymph nodes and the tumor burden were the most dominant predictors of survival in patients with Stage III melanoma; patients with metastatic nodes detected by palpation had a shorter survival compared with patients whose nodal metastases were first detected by sentinel node excision of clinically occult or "microscopic" metastases. (3) The site of distant metastases (nonvisceral versus lung versus all other visceral metastatic sites) and the presence of elevated serum lactate dehydrogenase (LDH) were the dominant predictors of outcome in patients with Stage IV or distant metastases. (4) An upstaging was implemented for all patients with Stage I, II, and III disease when a primary melanoma is ulcerated by histopathological criteria. (5) Satellite metastases around a primary melanoma and in-transit metastases were merged into a single staging entity that is grouped into Stage III disease. (6) A new convention was implemented for defining clinical and pathological staging so as to take into account the new staging information gained from lymphatic mapping and sentinel node biopsy.     

Carcinoid tumors and fibrosis: an association with no explanation

Carcinoid tumors are slow-growing neuroendocrine neoplasms most commonly associated with the gut and broncho-pulmonary system. In many instances, they are identified at surgery for unexplained bowel obstruction or during exploration of the small bowel in search of a primary tumor once distant metastases have been detected. Carcinoid tumors of the small bowel often present with pronounced fibrosis in the peri-tumoral tissues, distant in the heart or lungs, and locally in the peritoneal cavity. Despite medical and therapeutic advances that have alleviated symptoms and prolonged life, a substantial subset of patients develops mesenteric and small bowel carcinoid fibrosis and/or carcinoid heart disease. Fibrosis, and increasingly cardiac heart disease, are important components of intestinal carcinoid disease and are of considerable clinical concern, as both of these conditions reflect a connective tissue disorder whose etiology, biology, and therapy are unknown. In the past, individuals with carcinoid disease died of metastasis and uncontrollable symptomatology. Currently, there exists no clinical method to determine the development of fibrosis and little is understood about the biological basis of fibrosis. The elucidation of the biology and management of fibrosis is thus an issue of paramount clinical and scientific importance in determining appropriate diagnostic and therapeutic strategy. Therefore, the unraveling of the molecular events indicative of fibrosis in these cells and the identification of appropriate therapeutic targets is of considerable patient-care relevance. We have surveyed the world literature over the past 40 yr to evaluate both the incidence of carcinoid processes and track the evolving understanding of this process. In addition, we have provided more current mechanistic information in regard to the biological basis of fibrosis associated with small bowel carcinoid tumors.     

High-level expression of functional chemokine receptor CXCR4 on human neural precursor cells

Neural precursor cells (NPCs) are self-renewing, multipotent progenitors that give rise to neurons, astrocytes and oligodendrocytes in the central nervous system (CNS). Fetal NPCs have attracted attention for their potential use in studying normal CNS development. Several studies of rodent neural progenitors have suggested that chemokines and their receptors are involved in directing NPC migration during CNS development. In this study, we established a consistent system to culture human NPCs and examined the expression of chemokine receptors on these cells. NPCs were found to express the markers nestin and CD133 and to differentiate into neurons, astrocytes and oligodendrocytes at the clonal level. Flow cytometry and RNase protection assay (RPA) indicated that NPCs express high levels of CXCR4 and low levels of several other chemokine receptors. When examined using a chemotaxis assay, NPCs were able to respond to CXCL12/SDF-1alpha, a ligand of CXCR4. Treatment with anti-CXCR4 antibody or HIV-1 gp120 abolished the migratory response of NPCs towards CXCL12/SDF-1alpha. These findings suggest that CXCR4 may play a significant role in directing NPC migration during CNS development.     

In vivo vulnerability to competition by endogenous dopamine: comparison of the D2 receptor agonist radiotracer (-)-N-[11C]propyl-norapomorphine ([11C]NPA) with the D2 receptor antagonist radiotracer [11C]-raclopride

(-)-N-Propyl-norapomorphine (NPA) is a full dopamine (DA) D2 receptor agonist and [11C]NPA is a suitable radiotracer to image D2 receptors configured in a state of high affinity for agonists with positron emission tomography (PET). In this study the vulnerability of the in vivo binding of [11C]NPA to acute fluctuation in synaptic DA was assessed with PET in baboons and compared to that of the reference D2 receptor antagonist radiotracer [11C]raclopride. Three male baboons were studied with [11C]raclopride and [11C]NPA under baseline conditions and following administration of the potent DA releaser amphetamine (0.3, 0.5, and 1.0 mg kg(-1) i.v.). Kinetic modeling with an arterial input function was used to derive the striatal specific-to-nonspecific equilibrium partition coefficient (V3"). [11C]Raclopride V3" was reduced by 24 +/- 10%, 32 +/- 6%, and 44 +/- 9% following amphetamine doses of 0.3, 0.5, and 1.0 mg kg(-1), respectively. [11C]NPA V3" was reduced by 32 +/- 2%, 45 +/- 3%, and 53 +/- 9% following amphetamine doses of 0.3, 0.5, and 1.0 mg kg(-1), respectively. Thus, endogenous DA was more effective at competing with [11C]NPA binding compared to [11C]raclopride binding, a finding consistent with the pharmacology of these tracers (agonist vs. antagonist). These results also suggest that 71% of D2 receptors are configured in a state of high affinity for agonists in vivo. In conclusion, [11C]NPA might provide a superior radiotracer to probe presynaptic DA function with PET in health and disease.     

The association of grandmaternal and maternal factors with maternal adult stature

BACKGROUND: Stature is an important determinant of several reproductive and non-reproductive health problems. Documentation of secular trends in stature has been based primarily on cross-sectional studies of special populations, primarily of men. The objective of this study is to determine how growth and socio-economic status (SES) factors relate to stature changes among lineal female relatives, maternal grandmothers to mothers. METHODS: The study base was derived from a population-based intergenerational cohort which linked several statewide databases to data from the mothers' own birth certificates: the Washington State Intergenerational Cohort. Mothers in these ethnic groups were separately studied: non-Hispanic Whites, African Americans, Native Americans, Hispanics. We generated simple, partial, and multiple correlation coefficients to investigate the association between stature and other growth and SES factors. RESULTS: A mother's stature is determined partly by her own mother's stature and partly by her birthweight. These two measures are individually stronger predictors of stature than are several available SES factors considered in combination-grandmother's age, parity, marital status, and mother's age. The maximal multiple correlation models yielded R2 values from 18% to 28%. CONCLUSIONS: Growth measures are stronger predictors of intergenerational changes in stature than are the several available socio-economic factors. However, socio-economic factors are partly responsible for the level of achieved prenatal and postnatal growth. Since grandmother's stature is a determinant of mother's birthweight, which in turn is a determinant of infant birthweight, some environmentally influenced determinants of some birth outcomes are already established before a prospective mother is conceived or born.     

Using electronic health records to help coordinate care

The use of electronic health records that can securely transmit patient data among physicians will help coordinate the care of 60 million Americans with multiple chronic conditions. This article summarizes the different organizations in the United States that are developing this technology. It discusses some of the problems encountered and the current initiatives to resolve them. The article concludes with three recommendations for enhancing care coordination: (1) a common health record, such as the Continuity of Care Record, to facilitate the exchange of clinical information among health providers; (2) regional governance structures to encourage the exchange of clinical data; and (3) payment by purchasers of care, both public and private, to physicians for using electronic health records.