Dendritic cell elimination as an assay of cytotoxic T lymphocyte activity in vivo

We show in this paper that the survival of antigen-loaded dendritic cells in vivo may be used as a sensitive readout of CTL activity. We have previously shown that dendritic cells labeled with the fluorescent dye CFSE and injected sub-cutaneously into mice migrate spontaneously to the draining lymph node where they persist for several days. In the presence of effector CTL responses, dendritic cells loaded with specific antigen rapidly disappear from the draining lymph node. In this paper we extend the above observations and set up a simple and sensitive method to reveal CTL activity in individual mice in vivo. Dendritic cells were labeled with two different fluorochromes, loaded with antigen or left untreated, and mixed together before injection into mice. We show that only the dendritic cells loaded with specific antigen were cleared from the draining lymph node, while dendritic cells not loaded with antigen remained unaffected. Cytotoxic responses generated by immunization with peptide-loaded dendritic cells, or by infection with influenza virus, could be revealed using this method. Comparison of the differential survival of dendritic cells populations mixed together also allowed us to accurately evaluate the disappearance of dendritic cells, irrespective of variability in the injection site and other parameters. Given the ability of dendritic cells to efficiently take up and present complex antigens, nucleic acids and apoptotic bodies, this method may also allow the evaluation of cytotoxic activity against antigens that are not characterized in terms of peptide epitopes.     

A multiyear prospective study of the risk factors for and incidence of diarrheal illness in a cohort of Peace Corps volunteers in Guatemala

BACKGROUND: Diarrheal illness is the most common medical disorder among travelers from developed to developing countries and is common among expatriate residents in developing countries. OBJECTIVE: To assess the risk factors for and incidence of diarrheal illness among Americans living in a developing country. DESIGN: Prospective longitudinal study. SETTING: Rural Guatemala. PATIENTS: Cohort of 36 Peace Corps volunteers. MEASUREMENTS: Collection of daily dietary and symptom data for more than 2 years; identification by multivariate Poisson regression analyses of risk factors for clinically defined episodes of diarrheal illness. RESULTS: The 36 Peace Corps volunteers in this study had 307 diarrheal episodes (median, 7 per person), which lasted a median of 4 days (range, 1 to 112) and a total of 10.1% of the 23 689 person-days in the study. The incidence density (episodes per person-year) was 4.7 for the study as a whole, 6.1 for the first 6-month period, 5.2 for the second 6-month period, and 3.6 thereafter. Statistically significant risk factors for diarrheal illness included drinking water whose source (for example, the tap) and, therefore, quality, was unknown to the person; eating food prepared by a Guatemalan friend or family; eating food at a small, working-class restaurant; eating fruit peeled by someone other than a Peace Corps volunteer; drinking an iced beverage; and eating ice cream, ice milk, or flavored ices. The relative risks comparing the presence of these exposures during the first 6-month period overseas with their absence during the second year of residence ranged from 1.90 to 2.67, and the summary attributable risk percentage (that is, the percentage of diarrheal episodes that could be ascribed to the exposures) was 75.4%. Exposures generally were riskier if they occurred during travel elsewhere in Guatemala rather than in the person's usual work area. CONCLUSIONS: Diarrheal illness of mild-to-moderate severity continued to occur throughout Peace Corps service but decreased in incidence as length of stay increased. Various dietary behaviors increased the risk for diarrheal illness, which suggests that avoidance of potentially risky foods and beverages is beneficial.     

Otitis media in early childhood and later language.

The relationship between early otitis media with effusion (OME) experience and later language development was examined in a prospective cohort study of 30 children from middle-class families and 33 children from low-income families. Ear status was monitored using otoscopy and tympanometry during wellness and illness periods between birth and 3 years of age. Language was assessed using standardized tests and a language sample between 4 1/2 and 6 years. Findings suggested no reliable relationship between early OME experience and later language development.     

Perinatal cocaine effects on neonatal stress behavior and performance on the Brazelton Scale

Fifty-two newborns were assessed for the effects of maternal cocaine use on their performance on the Brazelton Neonatal Behavior Assessment Scale and on their stress behaviors during the Brazelton as tapped by the Neonatal Stress Scale. The cocaine-exposed newborns experienced more obstetric complications, had smaller head circumferences, showed more limited habituation abilities on the Brazelton Scale, and exhibited more stress behaviors than control newborns.     

Mass closure of the abdominal wound with delayed absorbable suture in surgery for gynecologic cancer

There has been a resurgence of interest recently in the optimal method of closure of the midline abdominal wound. The focus has been on the high-risk patient in particular. The controversy centers on interrupted versus continuous fascial closure and the choice of suture material. For three years on a gynecologic cancer service, running mass closure with delayed absorbable suture (Polyglactin) was used. Two hundred fifty-six patients were evaluable for analysis. The minimum follow-up time was two years. There was no wound dehiscence. Fourteen patients (5.5%) developed incisional hernias. The mass closure technique using delayed absorbable suture was effective in very-high-risk patients.     

Pathophysiology of preeclampsia.

Preeclampsia is a complex clinical syndrome, with hypertension representing but one manifestation. Pathogenetically important events in the development of preeclampsia include incomplete trophoblastic invasion of the maternal spiral arteries, poor trophoblastic perfusion, elaboration of a putative endothelial cell toxin, and endothelial cell injury with resulting activation of coagulation, impairment of vasodepressor function, and altered endothelial permeability. These changes lead to the clinical signs and symptoms, which occur relatively late in the course of preeclampsia. The primary immunologic, genetic, and biochemical basis of preeclampsia remains speculative.     

Experience with the Groshong long-term central venous catheter

A study of the Groshong catheter in a gynecologic oncology population is presented, describing the catheter's ease of insertion, and patient acceptance and compliance in catheter care. From December 1985 through November 1987, 72 Groshong catheters were inserted in 67 patients. The Groshong differs from conventional Hickman-type catheters in design and maintenance. Thirty-two of 72 catheters (44%) were inserted under local anesthesia. The remaining catheters were inserted under general anesthesia at the time of major gynecologic procedures. None of the cases required fluoroscopy. The insertion technique is less traumatic than conventional approaches because of a stainless steel tunneling device. The median duration of use was 191 days. There were no cases of pneumothorax or catheter occlusion. Catheter removal was required in four cases with skin infection unresponsive to local therapy and in two cases with bacteremia. One patient developed thrombosis of the right subclavian vein but was treated without catheter removal. One patient with a skin infection at the exit site accidentally dislodged her catheter. The overall complication rate was 11% (8 of 72 cases).     

Preeclampsia: an endothelial cell disorder

Despite intense study preeclampsia remains enigmatic and a major cause of maternal and fetal morbidity and mortality. Most investigative efforts have focused on the hypertensive component of this disorder with reduced attention given to other equally important characteristics. Increased sensitivity to pressor agents and activation of the coagulation cascade occur early in the course of preeclampsia, often antedating clinically recognizable disease. Inasmuch as endothelial cell injury reduces the synthesis of vasorelaxing agents, increases the production of vasoconstrictors, impairs synthesis of endogenous anticoagulants, and increases procoagulant production, these cells are likely to be implicated in the pathophysiology of preeclampsia. Indeed, evidence of endothelial cell injury is provided by the most characteristic morphologic lesion of preeclampsia, glomerular endotheliosis. Additional support for this hypothesis is derived from reports that indicate increased levels of circulating fibronectin (which can be released from injured endothelial cells) and increased factor VIII antigen present in the blood of preeclamptic women. More recently, direct evidence of activities that injure endothelial cells in vitro and increase the contractile sensitivity of isolated vessels has been presented. We propose that poorly perfused placental tissue releases a factor(s) into the systemic circulation that injuries endothelial cells. The changes initiated by endothelial cell injury set in motion a dysfunctional cascade of coagulation, vasoconstriction, and intravascular fluid redistribution that results in the clinical syndrome of preeclampsia.     

The management of diaphragmatic lesions in ovarian carcinoma

Cytoreduction is currently an essential feature of the treatment of carcinoma of the ovary. Occasionally, optimal reduction is achieved except for localized diaphragmatic lesions. Two patients who were treated with primary cytoreduction for epithelial ovarian carcinoma had localized full-thickness diaphragmatic metastasis. Often resection is avoided because of concern about pneumothorax. A safe and easy method is described for removing peritoneal and diaphragmatic muscular metastasis without the need for a thoracostomy tube. These patients were cytoreduced without morbidity. The first patient is currently free of disease at 17 months after surgery. The second patient had a 13-month disease-free interval before her abdominal recurrence.