Differentiation of benign and malignant cervical lymph nodes with color Doppler sonography

OBJECTIVE: This study proposed to evaluate the efficacy of color Doppler sonography in detecting possible differences in blood flow patterns between malignant and benign cervical lymph nodes. SUBJECTS AND METHODS: During a period of 12 months, the palpable cervical lymph nodes of 48 untreated patients were prospectively evaluated with color Doppler sonography and Doppler flow wave analysis. Histopathologic diagnoses were obtained by sonographically guided fine-needle aspiration biopsy and/or excisional biopsy. RESULTS: We found 16 benign lymph nodes (four were tuberculous lymphadenitis, four were reactive hyperplasia, and eight were unspecified) and 32 malignant lymph nodes (13 were squamous cell carcinomas, nine were adenocarcinomas, four were small-cell carcinomas, three were lymphomas, and three were miscellaneous). Color Doppler flow patterns were seen in six (38%) of the 16 benign lymph nodes and in 29 (91%) of the 32 malignant lymph nodes. Twenty-six (81%) of the 32 malignant lymph nodes had abnormal flow patterns, with resistance indexes less than 0.6. However, three (19%) of the 16 benign lymph nodes also had abnormal flow patterns, and only seven (54%) of 13 squamous cell carcinomas had abnormal flow patterns. CONCLUSION: Color Doppler sonography has limited clinical value in differentiating malignant from benign cervical lymph nodes and in obviating biopsy.     

Changes in levels of soluble T-cell activation markers, sIL-2R, sCD4 and sCD8, in relation to disease exacerbations in patients with systemic lupus erythematosus: a prospective study

OBJECTIVES: To assess serial activation of T-cell subsets in relation to auto-antibody production and the occurrence of disease exacerbations in patients with systemic lupus erythematosus (SLE). METHODS: To study the possible role of T-cells in the pathophysiology of the disease, 16 consecutive exacerbations were prospectively studied in a cohort of patients with SLE, and serial plasma levels of sIL-2R, sCD4, and sCD8 preceding and during these exacerbations were determined. Levels of these molecules were related to total IgM and IgG, and anti-dsDNA. RESULTS: During major disease exacerbations (n = 6), levels of sIL-2R increased significantly (p < 0.001). Levels of sCD4 were predominantly in the normal range, whereas levels of sCD8 were frequently increased. No change in levels of both molecules could be detected in the period before the exacerbation. During minor exacerbations (n = 10), levels of sIL-2R remained stable. Levels of sCD4, however, tended to drop, whereas levels of sCD8 tended to rise. No correlations were found between sIL-2R, sCD4 or sCD8 on the one hand, and total IgM, IgG, or anti-dsDNA on the other. CONCLUSIONS: Levels of sIL-2R are increased, and rise before major exacerbations of SLE. Levels of sCD4 and sCD8, however, are not related to levels of sIL-2R, and do not reflect B-cell activation, nor disease activity during exacerbations of SLE. Thus for the clinical follow up of SLE measurement of levels of sCD4 or sCD8 is of limited value.     

Evidence-guided prescribing of combined oral contraceptives: consensus statement. An International Workshop at Mottram Hall, Wilmslow, U.K., March, 1996

Fatigue is a very common symptom in the general population. Fatigue most commonly results from social circumstances or psychological difficulties. This article discusses how to approach the fatigued patient and what investigations are necessary.     

Prospective, randomized trial of hypertonic glucose water and sodium tetradecyl sulfate for gastric variceal bleeding in patients with advanced liver cirrhosis

BACKGROUND AND STUDY AIMS: Information about the appropriate endoscopic treatment of gastric variceal bleeding is sparse. We therefore designed a prospective and randomized study to evaluate and compare efficacy and complication rates of two agents, hypertonic glucose water (50% GW) and sodium tetradecyl sulfate (STS), in treating acute gastric variceal bleeding after esophageal varix eradication. PATIENTS AND METHODS: Of 51 patients with advanced cirrhosis of the liver (Child's C), with acute gastric variceal bleeding initially evaluated, 25 patients were randomized to receive 1.5% STS and 26 to receive 50% glucose water. Treatment was aimed at achieving initial and permanent hemostasis by variceal eradication. RESULTS: Control of acute gastric variceal bleeding was achieved in 80% of the STS group and 92% of the GW group. The rebleeding rate in the STS group was 70%, while in the GW group it was 30% (P < 0.05). Overall, obliteration was achieved in only 32% of the STS group and 81% of the GW group during admission (P < 0.05). There was a trend toward a higher gastric ulcer rate in the STS group compared with the GW group (92% vs. 30%; P < 0.05). The rebleeding control rate and permanent hemostasis rate in the GW group (70%, 54%) were also significantly higher than in the STS group (21%, 12%; P < 0.05; P < 0.05). The hospital mortality for the STS group was 50%, and for the GW group 30%. CONCLUSION: Treatment with hypertonic glucose water in gastric vericeal bleeding was superior to treatment with STS in controlling bleeding and in achieving vericeal obliteration, less rebleeding, and a lower complication rate. The results of this study suggest that hypertonic glucose water is a clinically effective, easily available, and safe sclerosing agent.     

Referral selection bias in the Medicare hospital mortality prediction model: are centers of referral for Medicare beneficiaries necessarily centers of excellence?

OBJECTIVE: Although the Health Care Financing Administration (HCFA) uses Medicare hospital mortality data as a measure of hospital quality of care, concerns have been raised regarding the validity of this concept. A problem that has not been fully evaluated in these data is the potential confounding effect of illness severity factors associated with referral selection and hospital mortality on comparisons of risk-adjusted hospital mortality. We address this issue. DATA SOURCES AND STUDY SETTING: We analyzed the 1988 Medicare hospitalization data file (MEDPAR). We selected data on patients treated at the two Mayo Clinic-associated hospitals in Rochester, Minnesota, and a group of seven other hospitals that treat many patients from large geographic areas. These hospitals have had observed mortality rates substantially lower than those predicted by the HCFA model for the period 1987-1990. STUDY DESIGN: Using the multiple logistic regression model applied by HCFA to the 1988 data, we evaluated the relationship between distance from patient residence to the admitting hospital and risk-adjusted hospital mortality. PRINCIPAL FINDINGS: Among patients admitted to Mayo Rochester-affiliated hospitals, residence outside Olmsted County, Minnesota was independently associated with a 33 percent lower 30-day mortality rate (p < .001) than that associated with residence in Olmsted County. When patients at Mayo hospitals were stratified by residence (Olmsted County versus non-Olmsted County), the observed mortality was similar to that predicted for community patients (9.6 percent versus 10.2 percent, p = .26), whereas hospital mortality for referral patients was substantially lower than predicted (5.0 percent versus 7.5 percent, p = < .001). After incorporation of the HCFA risk adjustment methods, distance from patient residence to the hospitals was also independently associated with mortality among the Mayo Rochester-affiliated hospitals and seven other referral center hospitals. CONCLUSIONS: The HCFA Medicare hospital mortality model should be used with extreme caution to evaluate hospital quality of care for national referral centers because of residual confounding due to severity of illness factors associated with geographic referral that are inadequately captured in the extant prediction model.     

The effect of immunization route on rat serum and tear antibody responses to Chlamydia trachomatis

Using reliable displacement radiobinding assay (RBA) and ELISA, the existence of anti-human growth hormone autoantibodies (hGHAA) was confirmed in idiopathic hypopituitary patients with growth impairment. Six of 35 hypopituitary patients (17.1%) and 1/85 (1.2%) control children proved positive for hGHAA by RBA (>control mean + 3 SD). IgG isotype-hGHAA by ELISAIgG (> control mean + 3 SD) were positive for 6/34 (17.7%) and 3/85 (3.5% hypopituitary and control children, respectively. Due to an asymmetry to the right of the ELISAIgG distribution, an alternative cutoff based on a nonparametric method was obtained, and positive results for hypopituitary children increased to 10/34 (29.4%). Three of 34 hypopituitary patients but no control children were positive for hGHAA of IgM isotype. The hGHAA were detected in children with or without perinatal problems. These autoantibodies may represent markers of a major autoimmune process involving a portion of the anterior pituitary and may contribute to the development of hypopituitarism in over 15% of hypopituitary children.     

Brain-derived neurotrophic factor rapidly enhances phosphorylation of the postsynaptic N-methyl-D-aspartate receptor subunit 1

Although neurotrophins have traditionally been regarded as neuronal survival factors, recent work has suggested a role for these factors in synaptic plasticity. In particular, brain-derived neurotrophic factor (BDNF) rapidly enhances synaptic transmission in hippocampal neurons through trkB receptor stimulation and postsynaptic phosphorylation mechanisms. Activation of trkB also modulates hippocampal long-term potentiation, in which postsynaptic N-methyl-D-aspartate glutamate receptors play a key role. However, the final common pathway through which BDNF increases postsynaptic responsiveness is unknown. We now report that BDNF, within 5 min of exposure, elicits a dose-dependent increase in phosphorylation of the N-methyl-D-aspartate receptor subunit 1. This acute effect occurred in hippocampal synaptoneurosomes, which contain pre- and postsynaptic elements, and in isolated hippocampal postsynaptic densities. Nerve growth factor, in contrast, caused no enhancement of phosphorylation. These results suggest a potential mechanism for trophin-induced potentiation of synaptic transmission.     

Protective effect of calcitonin gene-related peptide against caerulein-induced pancreatitis in rats

The stimulation of sensory nerves by capsaicin exhibits the protective effect against caerulein-induced pancreatitis whereas deactivation of these nerves aggravates pancreatic damage evoked by overdose of caerulein. Calcitonin-gene related peptide (CGRP) has been identified as the prominent mediator of sensory nerves. The aim of the present study was to examine the influence of CGRP on the course of caerulein-induced pancreatitis (CIP). CIP led to a significant decrease in DNA synthesis and pancreatic blood flow (PBF) by 48% and 50% respectively, as well as a significant increase of pancreatic weight, plasma amylase concentration and development of the histological signs of pancreatic damage expressed as edema, leukocyte infiltration and vacuolization. Treatment with CGRP (2 x 10 micrograms/kg s.c.) attenuated the pancreatic tissue damage in caerulein-induced pancreatitis and completely reversed the deleterious effect of the ablation of sensory nerves on caerulein-induced pancreatitis. We conclude that CGRP exerts protective effect against caerulein-induced pancreatitis and is able to reverse the damage caused by deactivation of sensory nerves. Vasodilatation and preservation of pancreatic blood flow are involved in this effect.     

Robust, but transient expression of adeno-associated virus-transduced genes during human T lymphopoiesis

Recombinant adeno-associated viruses (rAAV) have been proposed to be gene transfer vehicles for hematopoietic stem cells with advantages over other virus-based systems due to their high titers and relative lack of dependence on cell cycle for target cell integration. We evaluated rAAV vector containing a LacZ reporter gene under the control of a cytomegalovirus (CMV) promoter in the context of primary human CD34+CD2- progenitor cells induced to undergo T-cell differentiation using an in vitro T-lymphopoiesis system. Target cells from either adult bone marrow or umbilical cord blood were efficiently transduced, and 71% to 79% CD2+ cells expressed a LacZ marker gene mRNA and produced LacZ-encoded protein after exposure to rAAV-CMV-LacZ. The impact of transgene expression on the differentiation of T cells was assessed by sequential quantitation of immunophenotypic subsets of virus-exposed cells and no alteration was noted compared with control. The durability of transgene expression was assessed and found to decay by day 35 with kinetics dependent on the multiplicity of infection. In addition, vector DNA was absent from CD4 or CD8 subselected CD3+ cells by DNA-polymerase chain reaction. These data suggest that rAAV vectors may result in robust transgene expression in primitive cells undergoing T-cell lineage commitment without toxicity or alteration in the pattern of T-cell differentiation. However, expression is transient and integration of the transgene unlikely. Recombinant AAV vectors are potentially valuable gene transfer tools for the genetic manipulation of events during T-cell ontogony but their potential in gene therapy strategies for diseases such as acquired immunodeficiency syndrome is limited.