Citations

Cluster headache is the most severe of the primary headaches. Positron emission tomography and functional MRI studies have shown that the ipsilateral posterior hypothalamus is activated during cluster headache attacks and is structurally asymmetric in these patients. These changes are highly specific for the condition and suggest that the cluster headache generator may be located in that brain area; they further suggest that electrical stimulation of that region might produce clinical improvement in chronic cluster headache sufferers refractory to medical therapy. In five patients with severe intractable chronic cluster headache, hypothalamic electrical stimulation produced complete and long-term pain relief with no relevant side-effects. We therefore consider it essential to propose criteria for selecting chronic cluster headache patients for hypothalamic deep brain stimulation before this procedure is undertaken at other academic medical centres.

Background— The incidence, determinants, and outcome of postoperative atrial fibrillation (AF) after surgery for mitral regurgitation (MR) are poorly defined but may have important implications for timing of mitral valve surgery. Methods and Results— In 762 patients in sinus rhythm with no AF history undergoing MR surgical correction, we examined the rates and prognostic implications of postoperative AF for early AF (within 2 weeks postoperatively) and late AF (>2 weeks after surgery). During postoperative follow-up, 180 patients (24%) experienced new AF (early AF in 136 and late AF in 111). Isolated early AF without recurrence was observed in 69 patients characterized by high angina class and lower left ventricular ejection fraction but no significant left atrial (LA) enlargement. However, overall early AF predicted late AF: 62±5% of patients with early AF had late AF at 10 years compared with 9±1% of patients without early AF ( P <0.0001). Large LA size strongly and independently predicted early AF ( P =0.01) and late AF ( P =0.003). For late AF, the predictive value of an enlarged LA was cumulative to that of early AF. Postoperative AF was associated with an increased subsequently higher risk of stroke or congestive heart failure (adjusted risk ratio=1.46 [1.04 to 2.05], P =0.03). Conclusions— Postoperative AF is common after surgical correction of MR in patients with no prior history of AF and is associated with increased subsequent morbidity. LA enlargement is independently predictive of postoperative AF and as such, should be integrated into the clinical decision-making process in patients with MR.

AbstractAlthough useful palliation can often be achieved when external beam irradiation and chemotherapy are used to treat locally advanced gastrointestinal malignancies, local control and long‐term survival are infrequent in view of the limited tolerance of surrounding organs and tissues. In view of dose limitations of external beam irradiation, intraoperative irradiation (IORT) with electrons has been used as a supplement to external treatment in an attempt to improve the therapeutic ratio of local control versus complications. An IORT dose of 10 to 20 Gy has been combined with fractionated external beam doses of 45 to 55 Gy in 1.8 Gy fractions in studies performed in the United States, Japan, Europe, and Scandinavian countries. In this paper the indications for and the results of aggressive combined techniques that include IORT are discussed. Results obtained with external beam techniques alone or with chemotherapy and resection are presented by site to demonstrate the need for higher doses of irradiation. When results from IORT series are compared to standard treatment with regard to disease control and survival, local control appears better with locally advanced colorectal, gastric, and pancreatic cancer; and survival appears better with colorectal ± biliary cancers. With pancreatic cancer, improvements in local control do not translate into increased survival in view of the high incidence of subsequent liver and peritoneal failures. Implications for future strategies in all sites are discussed.

AbstractOur aim was to examine the long‐term success of cholecystoenterostomy performed for the relief of benign extrahepatic biliary obstruction. Concern about the ability of cholecystoenterostomy to provide reliable long‐term biliary decompression has led many to abandon its use for benign biliary obstruction. Thirty‐four patients who underwent cholecystoenterostomy for benign biliary obstruction over a 17‐year period were reviewed. Patients were followed until cholecystoenterostomy failure, death, or to date. Failure was defined as recurrent biliary obstruction or cholangitis requiring therapeutic intervention. Mean follow‐up was 8.0 years. Early postoperative morbidity occurred in 11 patients (32%), but only one early complication (cholangitis) was related directly to the cholecystoenteric anastomosis. Five patients (15%) experienced late biliary tract complications related directly to the cholecystoenterostomy including recurrent biliary stones with biliary obstruction in four and anastomotic stricture in one. All required reoperation and conversion to choledochoenterostomy at a mean of 112 months. Cholecystoenterostomy can provide reasonably effective long‐term biliary decompression in selected patients with benign biliary obstruction.

Background— Swimming is a relatively genotype-specific arrhythmogenic trigger for type 1 long-QT syndrome (LQT1). We hypothesize that mimickers of concealed LQT1, namely catecholaminergic polymorphic ventricular tachycardia (CPVT), may also underlie swimming-triggered cardiac events. Methods and Results— Between August 1997 and May 2003, 388 consecutive, unrelated patients were referred specifically for LQTS genetic testing. The presence of a personal and/or family history of a near-drowning or drowning was determined by review of the medical records and/or phone interviews and was blinded to genetic test results. Comprehensive mutational analysis of the 5 LQTS-causing channel genes, KCNQ1 (LQT1), KCNH2 (LQT2), SCN5A (LQT3), KCNE1 (LQT5), and KCNE2 (LQT6), along with KCNJ2 (Andersen-Tawil syndrome) and targeted analysis of 18 CPVT1-associated exons in RyR2 , was performed with the use of denaturing high-performance liquid chromatography and direct DNA sequencing. Approximately 11% (43 of 388) of the index cases had a positive swimming phenotype. Thirty-three of these 43 index cases had a “Schwartz” score (≥4) suggesting high clinical probability of LQTS. Among this subset, 28 patients (85%) were LQT1, 2 patients (6%) were LQT2, and 3 were genotype negative. Among the 10 cases with low clinical probability for LQTS, 9 had novel, putative CPVT1-causing RyR2 mutations. Conclusions— In contrast to previous studies that suggested universal LQT1 specificity, genetic heterogeneity underlies channelopathies that are suspected chiefly because of a near-drowning or drowning. CPVT1 and strategic genotyping of RyR2 should be considered when LQT1 is excluded in the pathogenesis of a swimming-triggered arrhythmia syndrome.

Transcutaneous partial pressure of oxygen (TcPO2) predicts wound healing in critical ischemia. However, no studies have controlled for the effect of wounds on TcPO2. In this study, in 24 hip or knee arthroplasty cases without vascular disease, TcPO2 was measured preoperatively at the incision site, contralaterally, and at a reference site on the chest wall. The measurements were repeated at 2 days and 2 months postoperatively and compared. TcPO2, normal preoperatively, decreased at all sites on the second postoperative day (p < 0.001), with a trend toward a greater decrease at the wound (p 1/4 0.09). All wounds healed, and TcPO2 returned to baseline at all sites 2 months postoperatively. In conclusion, acute surgical wounds are associated with a significant and widespread decrease in cutaneous TcPO2 in the setting of normal arterial perfusion. This decrease is likely multifactorial and deserves further investigation.

The mechanisms underlying CD4+ T cell depletion in human immunodeficiency virus (HIV) infection are not well understood. Comparative studies of lymphoid tissues, where the vast majority of T cells reside, and peripheral blood can potentially illuminate the pathogenesis of HIV-associated disease. Here, we studied the effect of HIV infection on the activation and depletion of defined subsets of CD4+ and CD8+ T cells in the blood, gastrointestinal (GI) tract, and lymph node (LN). We also measured HIV-specific T cell frequencies in LNs and blood, and LN collagen deposition to define architectural changes associated with chronic inflammation. The major findings to emerge are the following: the GI tract has the most substantial CD4+ T cell depletion at all stages of HIV disease; this depletion occurs preferentially within CCR5+ CD4+ T cells; HIV-associated immune activation results in abnormal accumulation of effector-type T cells within LNs; HIV-specific T cells in LNs do not account for all effector T cells; and T cell activation in LNs is associated with abnormal collagen deposition. Taken together, these findings define the nature and extent of CD4+ T cell depletion in lymphoid tissue and point to mechanisms of profound depletion of specific T cell subsets related to elimination of CCR5+ CD4+ T cell targets and disruption of T cell homeostasis that accompanies chronic immune activation.

Abstract Quantitative measurements of environmental factors greatly improve the quality of epidemiologic studies but can pose challenges because of the presence of upper or lower detection limits or interfering compounds, which do not allow for precise measured values. We consider the regression of an environmental measurement (dependent variable) on several covariates (independent variables). Various strategies are commonly employed to impute values for interval-measured data, including assignment of one-half the detection limit to nondetected values or of “fill-in” values randomly selected from an appropriate distribution. On the basis of a limited simulation study, we found that the former approach can be biased unless the percentage of measurements below detection limits is small (5–10%). The fill-in approach generally produces unbiased parameter estimates but may produce biased variance estimates and thereby distort inference when 30% or more of the data are below detection limits. Truncated data methods (e.g., Tobit regression) and multiple imputation offer two unbiased approaches for analyzing measurement data with detection limits. If interest resides solely on regression parameters, then Tobit regression can be used. If individualized values for measurements below detection limits are needed for additional analysis, such as relative risk regression or graphical display, then multiple imputation produces unbiased estimates and nominal confidence intervals unless the proportion of missing data is extreme. We illustrate various approaches using measurements of pesticide residues in carpet dust in control subjects from a case–control study of non-Hodgkin lymphoma.