Comparative physical and immunological aspects of the chimpanzee and guinea-pig subcutaneous chamber models of Neisseria gonorrhoeae infection.

Physical and immunological characteristics of the chimpanzee and guinea-pig subcutaneous chamber models for Neisseria gonorrhoeae infection were compared to evaluate their usefulness for gonococcal research. Urethral infection in chimpanzees anatomically resembled the human infection; however, individual variation in response, limited availability, and the presence of interfering micro-organisms in the urethra were found to limit the usefulness of the chimpanzee in immunological research. Although the guinea-pig subcutaneous chamber model may not be suitable for studying the attachment of gonococci to host cells or for the local production of IgA, it does have the immunological advantages of being more sensitive to infection, less variable in response, free of interfering micro-organisms, and is readily available to investigators. Except for differences in sensitivity and variability, results with the guinea-pig model paralleled results obtained in experiments with chimpanzees. Unlike chimpanzees, guinea-pigs are a comparatively inexpensive, rapidly replenishable animal, which after subcutaneous implantation with small porous chambers provide a convenient model for studying most immunological aspects of gonococcal infections.     

Asystole and severe bradycardia in preterm infants

Transient episodes of apnea and bradycardia are common in preterm infants. Pronounced asystole or sinus arrest, however, is relatively rare and the clinical significance of such events is unknown. OBJECTIVE: The purpose of our study was to: (1) evaluate the prevalence of severe bradycardic and asystolic events in infants studied with polygraphic cardiorespiratory monitoring, (2) characterize these events, and (3) correlate the events with other clinical findings. METHODS: A total of 583 studies were performed in 454 preterm infants at a post-conceptional age 37.4 +/- 2.5 (range 34-42 weeks). Asystolic pauses were defined as no QRS complex for >or=3 s consistent with a heart rate <20 beats per minute (bpm). Severe bradycardia was defined as no QRS for >or=2 s consistent with a heart rate of 21-30 bpm. RESULTS: Eight infants (29.5 +/- 3.9 weeks' gestational age, birth weight 1,283 +/- 445 g) met the criteria of having had at least 1 asystolic event (heart rate 相似文献   

Localization of breast cancer resistance protein (BCRP) in microvessel endothelium of human control and epileptic brain

PURPOSE: Breast cancer resistance protein (BCRP) is a half adenosine triphosphate (ATP)-binding cassette (ABC) transporter expressed on cellular membranes and included in the group of multidrug resistant (MDR)-related proteins. Recently, upregulation of different MDR proteins has been shown in human epilepsy-associated conditions. This study investigated the expression and cellular distribution of BCRP in human control and epileptic brain, including a large number of both neoplastic and nonneoplastic specimens from patients with chronic pharmacoresistant epilepsy. METHODS: Several epileptogenic pathologies, such as hippocampal sclerosis (HS), focal cortical dysplasia (FCD), dysembryoplastic neuroepithelial tumor, oligodendroglioma astrocytoma, and glioblastoma multiforme were studied by using Western blot and immunocytochemistry. RESULTS: With Western blot, we could demonstrate the presence of BCRP in both normal and epileptic human brain tissue. In contrast to P-glycoprotein (P-gp) and multidrug resistance-associated protein (MRP) 2, BCRP expression levels did not change in tissue from patients with HS, compared with control hippocampus. No BCRP immunoreactivity was observed in glial or neuronal cells, including reactive astrocytes and dysplastic neurons in FCD. BCRP expression was, however, increased in tumor brain tissue. Immunocytochemistry demonstrated that BCRP was exclusively located in blood vessels and was highly expressed at the luminal cell surface and in newly formed tumor capillaries. This localization closely resembles that of P-gp. The higher expression observed in astrocytomas by Western blot analysis was related to the higher vascular density within the tumor tissue. CONCLUSIONS: These results indicate a constitutive expression of BCRP in human endothelial cells, representing an important barrier against drug access to the brain. In particular, the strong BCRP expression in the microvasculature of epileptogenic brain tumors could critically influence the bioavailability of drugs within the tumor and contribute to pharmacoresistance.     

Expression of multidrug transporters MRP1, MRP2, and BCRP shortly after status epilepticus, during the latent period, and in chronic epileptic rats

PURPOSE: Overexpression of multidrug transporters may play a role in the development of pharmacoresistance by decreasing extracellular drug levels in the brain. However, it is not known whether overexpression is due to an initial insult or evolves more gradually because of recurrent spontaneous seizures. In the present study, we investigated the expression of different multidrug transporters during epileptogenesis in the rat. In addition, we determined whether these transporters affected phenytoin (PHT) distribution in the brain. METHODS: Expression of multidrug resistance-associated proteins MRP1 and MRP2 and breast cancer-resistance protein (BCRP) was examined after electrically induced status epilepticus (SE) by immunocytochemistry and Western blot analysis. Brain/blood PHT levels were determined by high-performance liquid chromatography (HPLC) analysis in the presence and absence of the MRP inhibitor probenecid. RESULTS: Shortly after SE, MRP1, MRP2, and BCRP were upregulated in astrocytes within several limbic structures, including hippocampus. In chronic epileptic rats, these proteins were overexpressed in the parahippocampal cortex, specifically in blood vessels and astrocytes surrounding these vessels. Overexpression was related to the occurrence of SE and was present mainly in rats with a high seizure frequency. Brain PHT levels were significantly lower in epileptic rats compared with control rats, but pharmacologic inhibition of MRPs increased the PHT levels. CONCLUSIONS: Overexpression of MRP and BCRP was induced by SE as well as recurrent seizures. Moreover, overexpression was associated with lower PHT levels in the brain, which was reversed through inhibition of MRPs. These data suggest that administration of antiepileptic drugs in combination with specific inhibitors for multidrug transporters may be a promising therapeutic strategy in pharmacoresistant patients.     

Relationship of the ventilatory response to hypoxia with neonatal apnea in preterm infants

OBJECTIVE: Correlate the ventilatory response of preterm infants to hypoxic exposure with incidence of neonatal apnea.Study design Seventeen stable convalescing premature infants underwent bedside cardiorespiratory monitoring of respiration using respiratory inductance plethysmography, heart rate, and oxygen saturation (SaO(2)) for a 12-hour period. These studies were scored for number of apneas > or =15 and > or =20 seconds. Infants then underwent a 3-minute hypoxic exposure. Minute ventilation (V(E)) was calculated for 30-second epochs from the time inspired oxygen reached 15%. Linear regression analysis was used to correlate the change in V(E) normalized for decrease in SaO(2) (DeltaV(E)/DeltaSaO(2)) during the first and third minutes of hypoxic exposure with the number of apneic episodes during the 12-hour study. RESULTS: The majority of infants exhibited an anticipated biphasic ventilatory response to hypoxia. There was a significant positive correlation between DeltaV(E)/DeltaSaO(2) during the first and third minutes of hypoxic exposure and number of apneic episodes > or =15 and > or =20 seconds during the preceding 12 hours. CONCLUSIONS: Preterm infants with a greater number of apneic episodes exhibit an increased ventilatory response to hypoxic exposure, suggesting that apnea of prematurity may be associated with enhanced peripheral chemoreceptor activity.     

Psoriatic arthritis: performance of rheumatologists in daily practice

OBJECTIVES: To assess, using standardised patients (SPs), how rheumatologists diagnose psoriatic arthritis, whether the diagnostic efficiency is influenced by specific characteristics of the rheumatologists, and to study the relationship with costs. METHODS: Twenty three rheumatologists were each visited by one of two SPs (one male, one female) presenting as a patient with psoriatic arthritis. SPs remained incognito for all meetings for the duration of the study. Immediately after the encounter, SPs completed case-specific checklists on the medical content of the encounter. Information on ordered laboratory and imaging tests was obtained from each hospital. RESULTS: Fourteen rheumatologists diagnosed psoriatic arthritis correctly. They inspected the skin for psoriatic lesions more often than those rheumatologists who established other diagnoses. Rheumatologists diagnosing psoriatic arthritis spent more on additional laboratory and imaging investigations. These were carried out after the diagnosis to confirm it and to record the extent and severity of the disease. No differences in type of practice, number of outpatients seen each week, working experience, or sex were found between rheumatologists who made the correct diagnosis and those who made other diagnoses. The correct diagnosis was more often missed by rheumatologists who saw the male SP, who presented with clear distal interphalangeal DIP joint arthritis only, causing confusion with osteoarthritis of the DIP joints. CONCLUSION: There is a considerable amount of variation in the delivery of care among rheumatologists who see an SP with psoriatic arthritis. Rheumatologists focusing too much on the most prominent features (DIP joint arthritis) sometimes seem to forget "the hidden (skin) symptoms".     

Cytokine profile of cervical cancer cells

OBJECTIVE: In patients with cervical carcinoma, the presence of cytokines produced by T(H)2 cells, and the presence of an eosinophilic inflammatory infiltrate, has been associated with a less effective immune response and tumor progression. In the present study, we have investigated the cytokine profile of cervical carcinoma cells. In addition, we have measured whether differences in cytokine profiles between normal and malignant cervical epithelial cells are present. METHODS: For this purpose we have determined the mRNA expression patterns of 20 relevant cytokines by RT-PCR and Southern blotting in 3 normal primary cervical epithelial cell cultures (NPE) and 10 cervical cancer cell lines (CCCL). RESULTS: TGF-beta(1), IL-4, IL-12p35, and IL-15 were produced by all CCCL and NPE. TNF-alpha, IL-10, IL-5, and RANTES were present in most NPE, but not in any of the CCCL. MCP-1 was expressed in all CCCL but in only one NPE. The presence of the anti-inflammatory cytokine TGF-beta(1) in cervical carcinomas was confirmed by RNA in situ hybridization on tissue sections of carcinomas from which the CCCL originated. CONCLUSIONS: Our results suggest that cervical carcinoma cells produce immunomodulatory cytokines and that cytokine expression patterns change after malignant transformation. The implications of locally produced cytokines by cervical cancer cells are further discussed.     

Acceptability and effects of an educational leaflet on infections in type 2 diabetes patients: a randomized controlled trial in primary care

AIM: To determine the acceptability of an educational leaflet regarding the prevention and treatment of infections of the lower respiratory tract (LRTIs) and urinary tract (UTIs) and to determine the effects of the leaflet on knowledge and attitude of DM2 patients in primary care. METHOD: In a randomized controlled intervention trial 200 DM2 patients enlisted in two practices, one urban and one rural, from the Utrecht general practitioners Research Network (HNU) were selected. Per practice, 50 patients were randomly assigned to the intervention group and 50 to the control group. The intervention was a leaflet on diabetes and LRTIs and UTIs based on the results of focus group interviews. The leaflet was sent to the patients homes. The outcome measures were acceptability of the leaflet and differences in knowledge and attitude, measured by a questionnaire. RESULTS: The mean age was 68 years and 55% was male. There were no substantial differences in characteristics between the two groups. Among the intervention group, the leaflet was appreciated as understandable (100%) and inviting (79%). Compared to the control group, specific knowledge and attitude did not substantially differ. Patients in the intervention group had a slightly more positive attitude about 'being attentive to signs indicating pneumonia' (median difference, 1 point; p=.003) and they also answered 'UTI is mostly caused by a bacteria' more often correctly (risk difference, 18%; 95% CI, 4-33%, p=.016). CONCLUSION: A leaflet on prevention and treatment of LRTIs and UTIs is considered acceptable among DM2 patients, but a multi-faceted educational approach may be needed to improve health behavioral determinants.