Abnormal stimulus-response intensity functions in posttraumatic stress disorder: an electrophysiological investigation

OBJECTIVE: The purpose of this study was to explore the relationship between combat-related posttraumatic stress disorder (PTSD) and specific augmentation versus reduction patterns for the N100 and P200 components of auditory event-related potentials evoked by tones of increasing intensity. METHOD: Event-related potentials of subjects with PTSD (N=36), subjects with no psychopathology (N=20), subjects with major depression but no PTSD (N=10), and subjects with a history of chronic alcohol abuse but no PTSD (N=8) were recorded. Brain responses were evoked by a 2000-Hz tone presented in intensity blocks of 65, 72.5, 80, 87.5, and 95 dB (SPL). RESULTS: Evoked data from five PTSD subjects were of poor quality and excluded from further analyses. For all but one subject with no psychopathology and for all subjects with a history of alcohol abuse or major depression (but no PTSD), the Cz amplitude of the P200 response component showed augmentation as a nearly linear function of tone intensity. As a group, subjects with PTSD showed no such increase in P200 response magnitude. Examination of the data from individual subjects with PTSD showed that 42% exhibited augmentation patterns similar to those seen for subjects in the comparison groups. However, 58% showed evidence of P200 reduction, with the response to the loudest tone being smaller than responses to tones of intermediate intensity. CONCLUSIONS: The data suggest that there is a significant subgroup of patients with combat-related PTSD who enter into a state of protective inhibition at relatively low stimulus intensities. It is hypothesized that this is an appropriate adaptive mechanism for these subjects rather than an indication of a core neurobiological abnormality.     

Endotoxin potentiates hepatocyte apoptosis in cholestasis

BACKGROUND:

Cholestasis is a component of liver disease of almost any etiology, including septic liver injury. The cellular mechanisms of liver injury in cholestasis and sepsis remain unresolved. We evaluated apoptosis, a well-orchestrated and potentially reversible mechanism of cell death, in bile duct-ligated and endotoxin-injected rats.

STUDY DESIGN:

Male Sprague-Dawley rats were randomly assigned to six groups (n = 6–9): bile duct-ligated+endotoxin (B+E), sham+endotoxin (S+E), bile duct-ligated (B), sham (S), endotoxin (E), and normal (N). On day 1, the bile ducts of B+E and B rats were ligated and severed. S+E and S animals underwent biliary manipulation only. On day 3, B+E, S+E, and E groups received 3 mg/kg endotoxin IV. On day 4, livers from all rats were excised, fixed, and stained (hematoxylin and eosin and terminal deoxynucleotidyl transferase dUTP nick-end labeling [TUNEL]). Portions were frozen for DNA fragmentation analysis. Caspase 3 activity was determined using isolated hepatocytes.

RESULTS:

Livers from all groups (B+E, S+E, E, and B) except normal and sham displayed apoptosis by hematoxylin and eosin staining, TUNEL staining, and DNA fragmentation. Histologic evaluation revealed 10% to 20% necrosis in endotoxin-treated animals (B+E, S+E, and E). Caspase 3 activity was significantly higher in endotoxin-treated animals versus animals without endotoxin (treated 0.450 ± 0.08 versus nontreated 0.135 ± 0.05, p < 0.0001) (mean ± SD).

CONCLUSIONS:

Cholestatic livers had apoptosis without progression to necrosis. When exposed to the second insult of endotoxin, cholestatic livers received an acute on chronic apoptotic trigger, and proceeded to necrosis. Endotoxin was a potent hepatotoxic insult because all treated rat livers displayed both apoptosis and necrosis.     

Dental Services for Migrant and Seasonal Farmworkers in US Community/Migrant Health Centers

CONTEXT: Migrant and seasonal farmworkers are recognized as a medically underserved population, yet little information on need, access, and services is available-particularly with regard to oral health care. PURPOSE: This study describes the facilities, services, staffing, and patient characteristics of US dental clinics serving migrant and seasonal farmworkers, and identifies trends and issues that may impede or improve dental care access and service. METHODS: National databases were used to identify community and migrant health centers providing oral health care to migrant and seasonal farmworkers. Mailed surveys collected information on clinic history, operational details, services provided, patient demographics, employment and resource needs, and perceived barriers to care. FINDINGS: Among the 81 respondents (response rate 41%), hours of operation varied from 1 evening a week to more than 40 hours a week; 52% had no evening hours. Almost all the clinics offered preventive, diagnostic, and basic restorative dental services, and roughly two thirds also offered complex restorative services. Patients most frequently sought emergency dental care (44%) followed by basic restorative services (32%) and preventive services (26%). The dentist position was the most difficult to fill, and new funding sources were cited as the most important resource need. Respondents perceived cost of services, lack of transportation, and limited clinic hours as primary barriers to care. CONCLUSIONS: While some barriers to care have been almost universally addressed (eg, language), there is evidence that some impediments remain and may present significant obstacles to a broad improvement in oral health care for migrant and seasonal farmworkers.     

Combined effects of the orally active cisplatin analog, JM216, and radiation in antitumor therapy

Purpose: We evaluated the orally administered platinum agent, JM216, in combination with ionizing radiation both in vivo and in vitro against human tumor cells. Methods: H460 human lung carcinoma cells were used as a subcutaneous xenograft in nude mice. JM216 (30 mg/kg) was administered orally, and radiation treatments (2 Gy) were given 1 h after JM216 delivery for five consecutive days. For in vitro analysis, attached H460 cells were treated with JM216 (15 μM) for 1 h and then irradiated. Cells were rinsed 20 min later, and survival was determined by clonogenic assay. Results: Tumor growth delay measurements showed that the combination of JM216 and radiation was additive in vivo, with an enhancement ratio of 1.24. In vitro clonogenic survival experiments demonstrated a dose enhancement ratio of 1.23. Isobologram analysis showed that this interaction was also additive. Conclusions: These data demonstrate that the combination of JM216 and fractionated radiotherapy is more effective against human lung cancer xenografts than either agent alone, and the in vivo results were supported by those observed using an in vitro system with the same tumor cell line. Received: 20 December 1999 / Accepted: 24 May 2000     

The vulva is relatively insensitive to menses-induced irritation

Skin patch testing of menses and venous blood on the vulva (labia majora) and the upper arm was performed to assess the potential contribution of these biological fluids to vulvar irritation during menstruation. After 24 and 48 hours of occlusive exposure, the skin of the labia majora was relatively unaffected by these fluids compared to the skin of the upper arm: no significant irritation was observed on the labia at either exposure time, but discernible irritation was elicited on the upper arm after 48 hours of exposure. Pre-treatment of the upper arm with a petrolatum-based emollient attenuated the upper arm response. Semi-occlusive conditions also reduced the degree of upper-arm irritation elicited test materials and an irritant control, sodium lauryl sulfate. The relative insensitivity of the vulva to irritation by menses or blood was not predictable a priori because some irritants elicit heightened responses on the vulva relative to the arm (3). These results suggest that the vulva (labia majora) may be adapted to be less sensitive to menses-induced skin irritation than other anatomical sites.     

Epidermal growth factor receptor signaling regulates goblet cell production after small bowel resection

Background/Purpose

Intestinal adaptation is a compensatory response to massive small bowel loss in which there are increased numbers of absorptive enterocytes. However, the generation of secretory epithelial cell subtypes in this process has not been investigated. The purpose of this study was to examine the adaptive changes of several small intestinal cell lineage changes in response to massive small bowel resection (SBR).

Methods

A 75% SBR or sham operation was performed on male Sprague-Dawley rats. On postoperative day 7, the remnant ileum was harvested and immunohistochemical staining for goblet, Paneth, and enteroendocrine cells was performed. Cell subtypes were evaluated as cells per micrometer of villus/crypt length and compared among operations.

Results

A significant increase in goblet cell density occurred after SBR. Intestinal resection did not alter the number of Paneth and enteroendocrine cells. In additional experiments, inhibition of epidermal growth factor receptor signaling was associated with a diminished goblet cell density.

Conclusions

The adaptive response of the intestine to massive bowel loss results in an expansion of the goblet cell population in addition to greater numbers of absorptive enterocytes. Although the mechanism and purpose for selective expansion of these stem cell-derived lineages are not presently known, epidermal growth factor receptor signaling appears to be a common pathway.     

Disposition of cocaine and its metabolites in human sweat after controlled cocaine administration

BACKGROUND: Sweat testing is a noninvasive technique for monitoring drug exposure in treatment, criminal justice, and employment settings. METHODS: We evaluated cocaine excretion in 9 participants' sweat after they received 3 low doses (75 mg/70 kg) of cocaine HCl subcutaneously within 1 week and, 3 weeks later, 3 high doses (150 mg/70 kg). Six additional participants completed portions of the study. PharmChek sweat patches (n = 1390) were collected throughout a 3-week washout period, reflecting previously self-administered drugs, and during and after controlled dosing. RESULTS: Cocaine was the primary analyte detected with 24% of patches positive at the gas chromatography-mass spectrometry limit of quantification of 2.5 ng/patch and 7% of patches at the proposed Substance Abuse and Mental Health Services Administration cutoff of 25 ng/patch. Ecgonine methyl ester (EME) was detected more often and at generally higher concentrations than benzoylecgonine. In patches containing both metabolites, there was no statistically significant difference in the benzoylecgonine/EME ratio based on length of patch wear. During washout, 2 participants' weekly patches tested positive (> or =25 ng/patch) during the first week; one remained positive during week 2; and none were positive during week 3. Cocaine and EME were detectable within 2 h; benzoylecgonine was not detected until 4-8 h after low doses and slightly sooner after high doses. The majority of drug was excreted within 24 h. Over 70% of weekly patches worn during low doses were positive for cocaine (> or =25 ng/patch), increasing to 100% during high doses. CONCLUSION: Sweat testing is an effective and reliable method of monitoring cocaine exposure.     

Benefits of a school-based asthma treatment program in the absence of secondhand smoke exposure: results of a randomized clinical trial

BACKGROUND: Daily maintenance medications are recommended for all children with mild persistent to severe persistent asthma; however, poor adherence to these medications is common. OBJECTIVE: To evaluate the impact of school-based provision of inhaled corticosteroids on asthma severity among urban children with mild persistent to severe persistent asthma. DESIGN: Children aged 3 to 7 years with mild persistent to severe persistent asthma were identified at the start of the 2000-2001 and 2001-2002 school years in Rochester. Children were assigned randomly to a school-based care group (daily inhaled corticosteroids provided through the school) or a usual-care group (inhaled corticosteroids not given through school). MAIN OUTCOME MEASURE: Improvement in parent-reported symptom-free days. RESULTS: Of 242 eligible children, 184 were enrolled from 54 urban schools. Data for 180 children were available. Parents of children in the school-based care group had a greater improvement in quality of life compared with parents of children in the usual-care group (change score, 0.63 vs 0.24; P =.047); also, children in the school-based care group vs the usual-care group missed less school because of asthma (mean total days missed, 6.8 vs 8.8; P =.047) and experienced more symptom-free days during the early winter months (mean days per 2-week period, 9.2 vs 7.3; P =.02). A post hoc analysis revealed that all significant findings were produced by differences among children who were not exposed to secondhand smoke. Furthermore, among children not exposed to smoke, those in the school-based care group vs the usual-care group had more symptom-free days overall (11.5 vs 10.5; P =.046), had fewer days needing rescue medications (1.6 vs 2.3; P =.03), and were less likely to have had 3 or more acute visits for asthma (6 [13%] of 47 children vs 17 [31%] of 54 children; P =.03). CONCLUSIONS: School-based provision of inhaled corticosteroids significantly improved symptoms, quality of life, and absenteeism among urban children with mild persistent to severe persistent asthma. This effect was seen only among children not exposed to secondhand smoke.