The Low-Grade Lymphomas

The lymphomas comprise a spectrum of diseases with vast variation in histologic appearance, presentation and natural history, and response to therapy. At one end of the spectrum are the low-grade lymphomas (LGLs), indolent malignancies characterized by paradox. Despite an exceedingly low growth fraction, the LGLs are usually extensive at presentation, and yet they rarely involve privileged sites, such as cortical bone or central nervous system, and rarely destroy adjacent tissue. They are exquisitely responsive to many different therapeutic interventions, but responses to most agents are transient and similar. Finally, although survival of most LGL patients is measured in years, the course of the disease is punctuated by both transient and long-term responses to treatment, and also by spontaneous regression and transformation to more aggressive lymphomas in the absence of therapy, rendering the evaluation of the true impact of treatment quite difficult. The focus of this review is on the management of the LGLs, in particular the role of radiotherapy.     

Comparison of ambulatory and inpatient experiences in five specialties

This study compared medical student evaluations of ambulatory and inpatient components of third-year clerkships in internal medicine, obstetrics/gynaecology, paediatrics, psychiatry, and surgery. Seventy-two students completed evaluation questionnaires at the conclusion of each of five clerkships over 12 months. Although ambulatory and inpatient evaluations were comparable across all five specialties in several areas, ambulatory education was rated more favorably in scheduling, clear definition of student roles and responsibilities, appropriate supervision, timely and constructive feedback, being welcomed, and working in a non-threatening environment.Student feedback thus implied that ambulatory experiences were comparable to, or better than, inpatient experiences and suggests areas for improving clinical education in inpatient settings.     

Drinking water source and chlorination byproducts in Iowa. III. Risk of brain cancer.

The authors conducted a population-based case-control study in Iowa of 375 brain cancer patients and 2,434 controls. A postal questionnaire was used to gather information on lifetime residential history, sources of drinking water, beverage intake, and other potential risk factors. Exposure to chlorination byproducts in drinking water was estimated by combining questionnaire data with historical information from water utilities and trihalomethane levels in recent samples. The analysis included 291 cases (77.6%) and 1,983 controls (81.5%), for whom water quality information was available for at least 70% of lifetime years. Proxies represented 74.4% of cases. The mean number and mean duration of places of residence were comparable between direct and proxy respondents, suggesting little contribution to bias. After multivariate adjustment, odds ratios for brain cancer were 1.0, 1.1, 1.6, and 1.3 for exposure to chlorinated surface water of 0, 1-19, 20-39, and > or =40 years (p trend = 0.1). Among men, odds ratios were 1.0, 1.3, 1.7, and 2.5 (p trend = 0.04), and among women, 1.0, 1.0, 1.6, and 0.7 (p trend = 0.7)). Similar findings were found with estimates of average lifetime level of trihalomethanes. The association was stronger among men with above-median tap water consumption. These observations deserve further attention, especially in view of increasing glioma rates.     

The social class determinants of income inequality and social cohesion.

The authors argue that Wilkinson's model omits important variables (social class) that make it vulnerable to biases due to model mis-specification. Furthermore, the culture of inequality hypothesis unnecessarily "psychopathologizes" the relatively deprived while omitting social determinants of disease related to production (environmental and occupational hazards) and the capacity of the relatively deprived for collective action. In addition, the hypothesis that being "disrespected" is a fundamental determinant of violence has already been refuted. Shying away from social mechanisms such as exploitation, workplace domination, or classist ideology might avoid conflict but reduce the income inequality model to a set of useful, but simple and wanting associations. Using a nonrecursive structural equation model that tests for reciprocal effects, the authors show that working-class position is negatively associated with social cohesion but positively associated with union membership. Thus, current indicators of social cohesion use middle-class standards for collective action that working-class communities are unlikely to meet. An erroneous characterization of working-class communities as noncohesive could be used to justify paternalistic or punitive social policies. These criticisms should not detract from an acknowledgment of Wilkinson's investigations as a leading empirical contribution to reviving social epidemiology at the end of the century.     

Repeated use of computerized case simulations in a test format does not present a security risk

BACKGROUND: Computer-based examination formats permit evaluation of patient care strategies in a realistic context. Because such examinations are complex and difficult to develop, the same case simulations must often be used on multiple occasions. METHODS: To determine if repeated, serial administration of computerized case simulations influences performance, 8 simulations were administered over 2 consecutive years to 252 third-year medical students at the conclusion of 16 surgical clerkship rotations (8 per year). One-way analyses of variance were used to compare scores across rotations during the year and to compare scores between 2 consecutive academic years. Scheffe pairwise comparisons were used to identify trends within each academic year. RESULTS: The data demonstrate an increase in scores across rotations during the year. There is, however, no difference between scores in successive years. CONCLUSIONS: The data are consistent with an increase in knowledge during the course of the year, without evidence that test information transfer influences the performance of successive classes.     

Nitric oxide synthetase and Helicobacter pylori in patients undergoing appendicectomy

BACKGROUND: This study was designed to determine whether Helicobacter pylori forms part of the normal microenvironment of the appendix, whether it plays a role in the pathogenesis of acute appendicitis, and whether it is associated with increased expression of inducible nitric oxide synthetase (iNOS) in appendicular macrophages. METHODS: Serology for H. pylori was performed on 51 consecutive patients undergoing emergency appendicectomy. Appendix samples were tested for urease activity, cultured and stained for H. pylori, graded according to the degree of inflammatory infiltrate, and probed immunohistochemically for iNOS expression. RESULTS: The mean age of the patients was 21 (range 7-51) years. Seventeen patients (33 per cent) were seropositive for H. pylori but no evidence of H. pylori was found in any appendix specimen. However, an enhanced inflammatory cell infiltration was observed in seropositive patients (P < 0.04) and the expression of macrophage iNOS in the mucosa of normal and inflamed appendix specimens was increased (P < 0.01). CONCLUSION: H. pylori does not colonize the appendix and is unlikely to be a pathogenic stimulus for appendicitis. Priming effects on mucosal immunology downstream from the foregut may occur after infection with H. pylori.     

Clinicopathologic findings of recurrent primary sclerosing cholangitis after orthotopic liver transplantation

Whether primary sclerosing cholangitis (PSC) occurs after orthotopic liver transplantation is controversial, largely because the pre-transplant diagnosis of PSC is based on nonspecific radiological and histological findings. We reviewed clinical, radiological, and histological records of 53 patients who underwent liver transplantation for PSC between 1985 and 1998. Three patients with patent hepatic arteries and no evidence of chronic rejection had radiological and histological findings that may have been due to recurrent PSC. Bile duct stricturing in these patients proved permanent and progressive and affected both the quality of life and graft survival. The first patient, who is 110 months after transplantation, has had repeated episodes of cholangitis for the last year. The second patient underwent excision of a strictured hepatic duct 45 months after transplantation and was ultimately retransplanted 95 months after initial transplantation. The third patient underwent left hemihepatectomy of an atrophied lobe 50 months after transplantation. Although the patient population assessed in this study is limited, putative recurrent PSC in the allografts has led either to graft loss or to clinically significant hepatobiliary complications of the graft. Received for publication on March 8, 1999; accepted on April 30, 1999     

Survival and outcome after endotracheal intubation for acute stroke

OBJECTIVE: To assess survival and functional outcome in patients endotracheally intubated after ischemic stroke (IS) or spontaneous intracerebral hemorrhage (ICH). BACKGROUND: Endotracheal intubation is both a necessary life support intervention and a measure of severity in IS or ICH. Knowledge of associated clinical variables may improve the estimation of early prognosis and guide management in these patients. METHODS: We reviewed 131 charts of patients with IS or ICH who were admitted to the Neurosciences Intensive Care Unit at Duke University Medical Center between July 1994 and June 1997 and required endotracheal intubation. Stroke risk factors, stroke type (IS or ICH) and location (hemispheric, brainstem, or cerebellum), circumstances surrounding intubation, neurologic assessment (Glasgow Coma Score [GCS] and brainstem reflexes), comorbidities, and disposition at discharge were documented. Survivors were interviewed for Barthel Index (BI) scores. RESULTS: Survival was 51% at 30 days and 39% overall. Variables that significantly correlated with 30-day survival in multivariate analysis included GCS at intubation (p = 0.03) and absent pupillary light response (p = 0.008). Increase in the GCS also correlated with improved functional outcome measured by the BI (p = 0.0003). In patients with IS, age and GCS at intubation predicted survival, and in patients with ICH, absent pupillary light response predicted survival. CONCLUSIONS: Predictors for mortality differ between patients with IS and ICH; however, decreased level of consciousness is the most important determinant of increased mortality and poor functional outcome. Absent pupillary light responses also correspond with a poor prognosis for survival, but further validation of this finding is needed.     

Activation of tyrosine receptor kinase plays a role in expression of long-term potentiation in the rat dentate gyrus

Long-term potentiation (LTP) in perforant path-granule cell synapses has been shown to be accompanied by an increase in glutamate release. The objective of this study was to examine the possibility that nerve growth factor (NGF), by activating tyrosine kinase, modulates glutamate release and, therefore, contributes to expression of LTP in dentate gyrus. The data indicate that NGF, in the presence of trans-1-aminocyclopentyl-1,3-dicarboxylate (ACPD), enhanced KCI-stimulated release and KCI-stimulated calcium influx in vitro and that these effects were blocked by the tyrosine receptor kinase (trk) inhibitor tyrphostin AG879. The data also indicate that NGF increased phosphorylation of trkA and the mitogen-activated protein kinase extracellular signal-regulated kinase (ERK) in dentate gyrus in vitro. In addition to its effects in vitro, tyrphostin AG879 inhibited the expression of LTP in perforant path-granule cell synapses and the accompanying increase in transmitter release. Analysis of phosphorylation of the two tyrosine kinase substrates trkA and ERK in synaptosomes prepared from untetanized and tetanized dentate gyrus revealed that LTP was associated with increased phosphorylation of both proteins; no evidence of such a change was observed in either tetanized or untetanized tissue prepared from tyrphostin-pretreated rats. These findings are consistent with the hypothesis that NGF, by interacting with trkA, triggers a sequence of tyrosine kinase-dependent phosphorylation steps that modulate glutamate release and calcium influx and impact on expression of LTP in dentate gyrus.