Risk factors for low bone mineral density in individuals residing in a facility for the people with intellectual disability.

BACKGROUND: Individuals with intellectual disability (ID) are known to have a high prevalence of both low bone mineral density (BMD) and fractures with significant attendant morbidity. Effective strategies aimed at reducing fractures will be facilitated by the identification of predisposing risk factors. METHODS: Bone mineral density was measured by quantitative ultrasound of the calcaneus performed on 79 women and 132 men residing in a facility for adults with ID. Multiple variable logistic regression analysis was performed to determine the significance of risk factors for low BMD. RESULTS: Mobility impairment consistently appeared to be a significant risk factor for low BMD regardless of age or sex and especially for middle-aged men with profound ID. Further risk was identified for postmenopausal women taking enzyme inducing anticonvulsant medications and middle-aged men who were either smokers or tended to be short. Hispanic followed by Caucasian origin also put middle-aged males at a greater risk than their African-American counterparts. CONCLUSIONS: Specific risk factors for low BMD, some of which have potential for modification, were identified in the study population. Targeted strategies for risk factor reduction may result in a decrease in the high rate of fractures among these individuals.

Endometrial adenocarcinoma presenting in a premenopausal patient with tuberous sclerosis.

BACKGROUND: Endometrial adenocarcinoma is very uncommon in women under 40 years of age. CASE: A 39-year-old woman with tuberous sclerosis and severe intellectual disability presented with irregular bleeding unresponsive to oral contraceptive therapy. She was subsequently found to have a deeply invasive endometrial adenocarcinoma. CONCLUSION: Caregivers must pay particular attention to signs and symptoms in non-verbal patients. Persistent irregular bleeding on oral contraceptive therapy warrants additional evaluation.

Low prevalence of abnormal cervical cytology in an institutionalized population with intellectual disability.

BACKGROUND: The present study was designed to determine the prevalence of abnormal cervical cytology in an institutionalized population with intellectual disability. METHOD: A retrospective review of charts for 162 women at a large state-owned facility was performed. Slides from 310 cervical Papanicolau smears were re-screened by a cytotechnologist and then reviewed by a pathologist. RESULTS: The prevalence of abnormal cytology (three out of 162 participants) and biopsy confirmed that the prevalence cervical dysplasia (one out of 310 smears) was low. CONCLUSION: The present preliminary study suggests that further investigation of the optimal interval for cervical cancer screening is warranted in this population.

Ureteral segment replacement using a circumferential small-intestinal submucosa xenogenic graft.

We wished to determine whether small-intestinal submucosa (SIS) will epithelialize when used as a ureteral replacement material. An 11-mm segment of native ureter was excised from eight New Zealand White rabbits and replaced with an 11-mm porcine SIS graft, which was circumferentially wrapped around a ureteral stent. The SIS ureteral grafts were harvested at 11 days or 35 days postimplantation and examined grossly and by standard light microscopy techniques. Partial epithelialization with the ingrowth of urothelium, smooth muscle cells, and blood vessels was observed in the grafts harvested at 11 days postimplantation. The SIS ureteral grafts examined at 35 days postimplantation showed additional restructuring of the smooth muscle cell layer and more organized epithelialization in comparison to the SIS graft examined at 11 days. After 35 days of regenerative healing, elements of all three layers of the native ureter were observed within the collagen matrix of the SIS graft. No significant complications were observed, but all subjects (8/8) demonstrated mild intra-abdominal adhesions. Mild collecting system dilatations were observed in 4/4 (100%) of the animals harvested at 35 days and in 0/4 (0%) of the animals harvested at 11 days. We have this demonstrated in this preliminary study that SIS xenografts will epithelialize when used as a ureteral replacement material. The repair mechanism of these ureteral grafts occurred through a regenerative healing process rather than by scar formation. With further studies, this material may prove to be a useful treatment option in patients with ureteral injuries.

Effect of sirolimus on the metabolism of apoB100- containing lipoproteins in renal transplant patients.

BACKGROUND: Sirolimus (Rapamune, rapamycin, RAPA) is a potent immunosuppressive drug that has reduced the rate of acute rejection episodes by more than 40% in phase III trials when added to an immunosuppression regimen of cyclosporine (CsA) and prednisone. However, RAPA treatment tends to increase lipid levels, particularly among patients with pre-existing hyperlipidemia. METHODS: To identify the metabolic pathway(s) leading to RAPA-mediated hyperlipidemia, five patients with renal transplants maintained on CsA+/-prednisone+/- azathioprine (AZA) were studied before and after 6 weeks of treatment with RAPA (off RAPA and on RAPA, respectively). Each study patient was infused with a single bolus of [2H4]-lysine to derive metabolic parameters for apoB100-containing lipoproteins by using kinetic analysis based upon quantitation of isotopic enrichment by gas chromatography-mass spectrometry. RESULTS: Serial lipid measurements revealed that four patients displayed increased plasma triglyceride levels after RAPA treatment, which coincided with significantly higher plasma VLDL-apoB100 concentrations (21.7+/-12.1 mg/dl off RAPA vs. 38.7+/-14.8 mg/dl on RAPA, mean+/-SD, P<0.05). Kinetic analysis showed that the RAPA-induced increase in VLDL-apoB100 concentrations was due to a significant reduction in the fractional catabolic rate (FCR) of very low-density lipoprotein (VLDL) apoB100 (0.83+/-0.65 off RAPA vs. 0.24+/-0.10 on RAPA, mean+/-SD, P<0.05), rather than an enhanced VLDL-apoB100 synthesis. In one patient, RAPA treatment induced hypercholesterolemia but not hypertriglyceridemia. This hypercholesterolemia was due to elevated low-density lipoprotein (LDL) cholesterol levels, which coincided with a decreased FCR of LDL-apoB100. Heparin-induced lipoprotein lipase activity was significantly lower in the immunosuppressed hyperlipidemic patients than in normolipidemic controls. However, RAPA treatment did not significantly alter basal lipoprotein lipase activity in renal transplant patients in this study. CONCLUSIONS: This study indicates that for renal transplant patients in whom RAPA treatment induces hyperlipidemia, this effect is the result of reduced catabolism of apoB100-containing lipoproteins.

Effects of irrigation fluid temperature on core body temperature during transurethral resection of the prostate.

OBJECTIVES: To determine the effect irrigation fluid temperature has on core body temperature changes in patients undergoing transurethral resection of the prostate (TURP). METHODS: Fifty-six male patients (mean age 71.2 +/- 8.2 years) scheduled for TURP were enrolled in the study. Patients were randomized to one of two groups. Group 1 consisted of 27 patients who received room temperature irrigation fluid (70 degrees F) throughout TURP; group 2 consisted of 29 patients whose procedure was performed with warmed irrigation fluid (91.5 degrees F). The irrigation fluid used for both groups was glycine. The baseline temperature, final temperature, total time in the operating room, and amount of irrigation fluid used during the procedure were recorded for each patient. RESULTS: No significant difference in the average time spent in the operating room or in the total irrigation fluid used between the two groups was observed. Of the 27 patients who received room temperature irrigation fluid, 15 (55.6%) had a decrease in body temperature. A decrease in temperature was observed in 21 (72.4%) of the 29 patients who received warm irrigation fluid. Groups 1 and 2 had 12 (44.4%) of 27 and 8 (27.6%) of 29 patients, respectively, who demonstrated an elevation in their core body temperature. CONCLUSIONS: The results of our study suggest that irrigation fluid temperature is not a factor responsible for altering the core body temperature in patients undergoing TURP.

A new diagnostic algorithm for the evaluation of microscopic hematuria.

OBJECTIVES: To evaluate a new diagnostic algorithm for microscopic hematuria in which intravenous urography (IVU) is performed as a secondary radiographic study when microhematuria has persisted for 3 months after the initial workup with renal ultrasound (US) and cystoscopy was negative. METHODS: We evaluated 372 consecutive patients who presented with microhematuria and negative urine cultures and cytologic findings at our institution. All patients underwent renal US scanning and cystoscopy as their initial evaluation. All patients underwent re-evaluation 3 months after the initial workup. Patients with persistent microhematuria with no apparent etiology were then evaluated with IVU. RESULTS: The initial evaluation was negative in 212 of 372 patients. Eighty-one of these patients had persistence of their microhematuria at the 3-month follow-up without a definitive diagnosis. Seventy-five of these patients underwent IVU. Abnormalities were found in 11 of the 75 patients. Six patients had renal stones, two had ureteral stones, two had ureteral tumors, and one had a tumor of the renal pelvis. Forty of the 131 patients with resolution of their microhematuria underwent IVU at their request. All those studies were normal. CONCLUSIONS: The combination of cystoscopy and renal US along with urinalysis, urine culture, and cytology is a good initial evaluation in patients with microhematuria. Those patients with persistent microhematuria after 3 months without definite etiology of the bleeding may still benefit from IVU.

Prevalence of low bone density in women with developmental disabilities.

This study was designed to assess the prevalence and severity of low bone mineral density in an institutionalized population of postmenopausal women (n = 79) with developmental disabilities, using quantitative ultrasound of the calcaneus. The results demonstrate that this population has a significantly lower quantitative ultrasound index (QUI) of the calcaneus compared with a referent population of age-matched control subjects without mental disabilities. We used the QUI T-score threshold of <-2.0 standard deviations (SDs) to define individuals at high risk for osteoporosis, and 82% of the study participants met this criterion. Furthermore, approx 43% of the population had a heel QUI that was more than 2 SDs below that of age-matched control subjects, consistent with a severe degree of demineralization.

Hydrogen peroxide release from human eosinophils on fibronectin: scopoletin enhances eosinophil activation.

We have examined the release of H(2)O(2) from PAF or TNFalpha-stimulated human eosinophils on fibronectin (FN)-coated polystyrene plates. H(2)O(2) release was measured by the standard scopoletin-horseradish peroxidase (SCOP-HRP) method and compared with that measured by a new microplate fluorescent assay for H(2)O(2) using a novel HRP substrate A6550. We observed that the SCOP-HRP method gave a 25-fold higher estimate of H(2)O(2) release from eosinophils than did the A6550-HRP method. Microscopic examination of PAF or TNFalpha-stimulated eosinophils in buffer alone or A6550-HRP reaction mixture showed that the cells remained generally round, while eosinophils in SCOP-HRP reaction mixture were spread on the fibronectin-coated surface. Measurement of the cellular ATP content after PAF-stimulation showed that only eosinophils activated in SCOP-HRP had a 50% fall in ATP content. This supported our conclusion that measurement of H(2)O(2) release from eosinophils in SCOP-HRP reaction mixture is problematic since the SCOP-HRP system activates eosinophils. However, we also found that A6550-HRP, when present throughout the incubation, resulted in a lower estimate of H(2)O(2) release than expected. The method used to detect eosinophil H(2)O(2) release greatly influences the absolute amount of H(2)O(2) detected.

Use of a prostate model to assist in training for digital rectal examination.

OBJECTIVES: To assess the accuracy of prostate size estimation on digital rectal examination (DRE) before and after training with a three-dimensional prostate model relative to prostate volume by transrectal ultrasound (TRUS). METHODS: A total of 100 subjects underwent DRE by one of four family physicians (FP1, n = 34; FP2, n = 26; FP3, n = 22; and FP4, n = 18). One half were examined before any training on DRE prostate size examination and one half after the physicians were trained. Training involved teaching with a three-dimensional prostate model having posterior surface areas corresponding to the average dimensions of six different prostate volumes. The FPs were instructed to estimate the prostate size on the DRE to the nearest 5 g. A single urologist unaware of the DRE results performed TRUS on all patients to measure the prostate volume. RESULTS: Before training, the DRE size estimates ranged from 10 to 100 g (mean +/- SD 32.8 +/- 21.6), with a TRUS volume of 11 to 122 g (mean +/- SD 38.9 +/- 23.1). The correlation between the DRE and TRUS estimates was 0.25, suggesting low agreement (intraclass correlation coefficient [ICC] 0.35, 95% confidence interval 0.31, 0. 38). After training, 50 different patients had DRE size estimates of 10 to 100 g (mean +/- SD 39.4 +/- 19.7) and TRUS volume of 10 to 119 g (mean +/- SD 41.5 +/- 24.1). The correlation between the techniques was higher in patients examined after training (r = 0. 765), suggesting much better agreement between the techniques (ICC 0. 87; 95% confidence interval 0.86, 0.88). Among the physicians, agreement between DRE and TRUS was higher after training (ICC 0.64 to 0.96) than before training (ICC 0.02 to 0.49). CONCLUSIONS: Although the subjects examined before and after training differed, the agreement between TRUS and DRE prostate size estimates by the FPs appeared to be stronger after training with a three-dimensional prostate model. This model may be a useful tool to assist in training FPs and medical students to measure prostate size on DRE.

Sirolimus in pediatric gastrointestinal transplantation: the use of sirolimus for pediatric transplant patients with tacrolimus-related cardiomyopathy.

Hypertrophic obstructive cardiomyopathy (HOCM) associated with the use of tacrolimus is a rare complication of liver and intestinal transplantation seen almost exclusively among pediatric patients. Reduction of tacrolimus dosage or conversion to cyclosporin A (CsA) has been used as an effective treatment in reviewed cases. We present three pediatric transplant recipients who developed hypertrophic obstructive cardiomyopathy while under tacrolimus immunosuppression and were treated with conversion to sirolimus (Rapamycin). The patients (ages 6 yr, 12 yr and 11 months) were transplant recipients (liver, n = 2; liver and intestine, n = 1) who developed significant cardiomyopathy 15 and 96 months post-transplant. One patient died of post-transplant lymphoproliferative disorder 21 days after starting sirolimus. One patient had received two liver transplants and had been on CsA for 12 yr before conversion to tacrolimus at 60 months post-transplant for acute and chronic rejection. The surviving patients were receiving mycophenolate mofetil, tacrolimus and steroids at the time of diagnosis. Dose reduction of tacrolimus and treatment with beta blockers failed to alleviate the hemodynamic changes. The patients were converted to sirolimus 1.6, 37 and 148 months post-transplant and maintained a whole-blood trough level of 15-20 ng/mL 21 days after starting sirolimus. Repeat echocardiograms in the surviving patients showed improvement in cardiomyopathy. One patient had one rejection episode (intestinal biopsy, mild acute cellular rejection) after starting sirolimus that responded to a transient increase in steroids. The early demise of the third patient after sirolimus conversion prevented an adequate assessment of cardiomyopathy. Conversion to sirolimus was associated with a reduction in the cardiomyopathy of the two surviving patients while still providing effective immunosuppression. To our knowledge this observation has not been previously reported.

An alternative to synthetic aortic grafts using jejunum.

Synthetic materials currently used for arterial grafts can provoke serious complications such as infection, rejection, and incomplete reendothelialization. Porcine small intestinal submucosa (SIS) allografts (homografts) may not share these disadvantages yet still may provide an effective graft alternative. This study was designed to provide additional information concerning the performance of this material when used as an allo-patch graft. A porcine model was selected to enable hemodynamic comparisons to the adult human physiology. Slaughterhouse small intestine was used to prepare the SIS graft material. A well-vascularized section ofjejunum was resected, rinsed, and maintained in 0.9% NaCl solution containing 10% gentamicin. The graft was prepared by removing the serosal layer, inverting the material, and discarding the mucosal surface in a similar manner. The remaining submucosa and stratum compactum constituted the graft material and was subdivided into sizes from 1.5 to 3.0 cm2 tacked to foil for manageability, and was returned to the gentamicin solution. The surgery was initiated with a femoral arterial line in the anesthetized swine, followed by isolation and preparation of the infrarenal aorta for grafting. Cross-clamps were applied and a 1.0 x 1.5-cm section of aortic wall was resected. Two sides of allograft were freed from the foil and sewn into the aorta. Then the remaining sides were removed from the foil and final graft placement was completed. The graft was harvested at postoperative day 28 and presented for microscopic examination. Results confirmed that reendothelialization with neovascularization had occurred during this interval.

Adaptive ultrasonic measurement of blood vessel diameter and wall thickness: theory and experimental results.

An adaptive ultrasonic technique for measuring blood vessel diameter and wall thickness is presented. This technique allows one to use a target-specific transmitted waveform/receiver filter to obtain a larger signal-to-noise ratio (SNR) in the received signal than conventional techniques. Generally, SNR of a received wave increases as the intensity of the transmit wave increases; however, because of the FDA limitations placed on the amount of transmit energy, it is important to be able to make the most efficient use of the energy that is available to obtain the best possible SNR in the received signal. Adaptive ultrasonic measurement makes the most efficient use of the energy that is available by placing the maximum amount of energy in the largest target scattering mode. This results in more energy backscatter from a given target, which leads to a higher SNR in the received waveform. Computer simulations of adaptive ultrasonic measurement of blood vessel diameter show that for a SNR of 0 dB in the transmitted waveform, the standard deviation of the diameter measurements for a custom-designed transmitted waveform is about two orders of magnitude less than the standard deviation of the diameter measurements using more conventional waveforms. Diameter and wall thickness measurement experiments were performed on a latex tube and a bovine blood vessel using both custom-made and conventionally used transmitted waveforms. Results show that the adaptively designed waveform gives a smaller uncertainty in the measurements. The adaptive ultrasonic blood vessel diameter and wall thickness measuring technique has potential applications in examining vessels which are either too deep inside the body or too small for conventional techniques to be used, because of the low SNR in the received signal.

Cytokine mRNA expression in human platelets and a megakaryocytic cell line and cytokine modulation of platelet function.

Platelet formation and function are regulated, in vivo, to varying degrees by cytokines in the micro-environment. While white blood cells are the major source of cytokines within the cardiovascular system, the question addressed in this study was whether platelets and the platelet precursor, the megakaryocyte, may also serve as a source of cytokines. Cytokines produced by or carried within platelets could be released at sites of vascular injury and participate in wound healing. Platelets and a human megakaryocyte-like cell line, HU3, were found to express message for interleukin 7 (IL-7), stem cell factor (SCF), transforming growth factor beta (TGF-beta), cMpl, the IgE receptor subunits Fc epsilon RI alpha gamma and the transcription factor, NF-E2. Other cytokines expressed in HU3 cells but not in platelets included IL-1 beta, IL-6, IL-10, IL-13, TNF-alpha and the FC epsilon RI beta subunit. The HU3 cell line seemed to be further along the maturation/differentiation pathway to platelet formation than a second blood derived bipotential cell line, MB02. The MB02 cell line did not express IL-6, IL-10, SCF, TNF-omega nor cMpl. Furthermore, culturing the HU3 cells in TPO appeared to repress expression of Fc epsilon RI beta directing the cell closer to the platelet phenotype. In light of the presence of cytokine expression in platelets/megakaryocytes, agonist-induced platelet aggregation was measured in the presence of added cytokines as a means to evaluate potential cytokine modulation of platelet function. Collagen-induced aggregations were significantly enhanced by IL-6, SCF and TPO. Other cytokines tested significantly stimulated the thrombin receptor activating peptide, SFLLRNP-, U46619- and ADP-induced platelet aggregations with TPO being the most consistent activator. It is possible that cytokines released from platelets act in concert with cytokines released from other cellular sources to modulate haemostasis and thrombosis differentially depending upon the site of injury.

A highly sensitive fluorescent micro-assay of H2O2 release from activated human leukocytes using a dihydroxyphenoxazine derivative.

This study describes a simple, reliable, highly sensitive and quantitative fluorescence microplate-assay of H2O2 from activated leukocytes using a novel horse radish peroxidase (HRP) substrate N-acetyl-3,7-dihydroxyphenoxazine (A6550). Unlike the widely used fluorescent HRP substrate scopoletin, A6550 is non-fluorescent and becomes highly fluorescent upon HRP-catalyzed H2O2 oxidation. Using 50 microM A6550, the change in fluorescence due to H2O2 generated from phorbol 12-myristate 13-acetate-activated human eosinophils and neutrophils is found to have a linear cell dose response up to 1.5 x 10(4) and 5 x 10(4) cells, respectively. The increase in fluorescence from A6550 is specifically due to H2O2 generation since it is inhibitable by catalase. Oxidized A6550 is found to be highly stable and the H2O2 dose response is linear as long as the ratio of A6550:H2O2 in the reaction mixture is higher than five. Unlike scopoletin, A6550 has a very low background, which changes little with time. In addition, the high fluorescent yield of oxidized A6550 results in an increased sensitivity for the detection of H2O2. When the concentrations of A6550 and HRP were 10 microM and 0.2 U/ml, respectively, as low as 2 pmol of H2O2 could be reliably measured. The sensitivity of A6550/H2O2 assay is found to be at least 10-fold higher than with scopoletin as the HRP substrate. The protocol described in this study using A6550 to measure H2O2 release from activated granulocytes can be easily adapted to other cell types which generate H2O2.

Human lung mast cell activation leads to IL-13 mRNA expression and protein release.

Using reverse transcriptase-polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA), we studied the generation of the recently described Th2 cytokine interleukin-13 (IL-13) by anti-IgE-activated lung fragments (LF), lung mast cells (LMC), and the mast cell line HMC-1. We found that IL-13 messenger ribonucleic acid (mRNA) was constitutively expressed in LF and rapidly increased after anti-IgE challenge, persisting throughout a 16-h period. Quantitative-competitive PCR (QCPCR) demonstrated an increase from 1.2 fg to 120 fg of IL-13 mRNA/micrograms LF total cellular RNA. Time-course experiments showed that IL-13 protein was not increased in supernatants at 2 h after activation, but was upregulated by 8 h. Anti-IgE-activated LF supernatants contained 592.1 +/- 314.8 pg IL-13/g wet weight of tissue at 24 h (mean +/- SE; n = 11). LMC demonstrated upregulation of IL-13 mRNA expression following treatment with A23187 (n = 4), with maximal upregulation by 3 h; anti-IgE or phorbol myristate acetate (PMA) also led to increased IL-13 mRNA expression. QCPCR analysis of LMC IL-13 mRNA expression at 4 h after activation showed a 7-, 13.8-, and 13.2-fold increase after A23187, anti-IgE, and PMA, respectively. Quantities of IL-13 released from optimally activated LMC and peripheral blood T cells were comparable. HMC-1 also showed enhanced IL-13 mRNA beginning 30 min after A23187 activation, with peak expression from 1 to 10 h, followed by waning over the subsequent 24 h. A23187 stimulation of HMC-1 led to 100-fold upregulation of IL-13 mRNA within 4 h and detectable IL-13 in 24-h supernatants. These results demonstrate that activation of LF and LMC through multiple signal-transduction pathways results in increased IL-13 mRNA and protein expression temporally consistent with a potential role in chronic allergic inflammation.

Human lung mast cell IL-5 gene and protein expression: temporal analysis of upregulation following IgE-mediated activation.

The late-phase of allergic asthma is characterized by infiltration of the airway with eosinophils within 6 h of mast cell activation. Pro-eosinophilic/pro-allergic (TH2) cytokines, originally described as T-lymphocyte products, have recently been ascribed to mast cells as well. To date, however, it is unknown if TH2 cytokine gene expression by the human mast cells is subject to receptor-mediated regulation analogous to that of T-cells, and if messenger RNA (mRNA) expression results in protein secretion occurring in a temporal context consistent with the late-phase response. We examined interleukin-4 (IL-4), IL-5, and IL-6 mRNA expression induced by anti-IgE activation of human lung explants as assessed using reverse transcription/polymerase chain reaction (RT-PCR). Anti-IgE stimulation resulted in rapid and sustained upregulation of IL-5 message, but did not have analogous effects on IL-4 or IL-6. Using quantitative-competitive PCR, we demonstrated that 100 ng of total cellular RNA from human lung contained 1 fg of IL-5 mRNA; this increased to 100 fg 4 h after anti-IgE activation. The source of the anti-IgE-enhanced IL-5 mRNA is likely the mast cell itself, as anti-CD3 activation of lung led to a dissimilar array of cytokine expression. In addition, human lung mast cells purified to near homogeneity expressed IL-5 mRNA after activation, as shown by both RT-PCR and in situ hybridization. In both lung fragments and purified human lung mast cells, the modulation of IL-5 mRNA expression preceded the secretion of IL-5 protein, detected as early as 4 h after activation. Neither isolated purified mast cells nor purified peripheral blood T cells could be induced to secrete detectable amounts of IL-5 protein when activated only with antibodies against IgE or CD3-T cell receptor complex, respectively. However, mast cells (n = 4) and T cells (n = 6) cultured at comparable concentrations (4 x 10(6)/ml) activated through their respective antigen receptors in the presence of phorbol ester yielded comparable IL-5 production (253 +/- 126 pg/ml versus 183 +/- 75 pg/ml, mean +/- SE). We conclude that mast cells are analogous to T cells in the requirement of co-stimuli for the production of IL-5 protein. Moreover, the rapid kinetics of IgE-mediated IL-5 transcription and protein elaboration are consistent with a primary role for mast cell activation directly leading to late-phase airway eosinophilia.

IgE-dependent expression of interleukin-5 mRNA and protein in human lung: modulation by dexamethasone.

mRNA and protein expression of the Th2 cytokines IL-4 and IL-5 from human lung were examined during the first 4 hr following IgE-mediated triggering, a time representative of the evolving late-phase reaction (LPR). Lung explants were incubated for 16 hr at 37 degrees C in culture media alone or with added dexamethasone (10(-6) M), washed, and then challenged with buffer or anti-IgE (3 micrograms/ml). Using RNase protection assays, in 16/16 individual lungs IL-5 mRNA expression was observed at 4 hr following anti-IgE and at no points following buffer challenge. Fragments released 1129 +/- 499 ng of IL-5/g wet wt over a 24-hr period (mean +/- SEM, n = 5). Neither IL-4 transcripts nor protein were detected in any anti-IgE challenges. Both the IgE-mediated IL-5 mRNA and protein responses were below the limits of detection following dexamethasone preincubation, suggesting a mechanism for the potent inhibitory effects of these agents observed in the LPR.

Monte Carlo modeling of underwater-image formation: validity of the linear and small-angle approximations.

A Monte Carlo model has been used to compute a set of point-spread functions (PSF's) and modulation transfer functions (MTF's) that determine underwater-image quality in a range of different environments. The results have been used to analyze the range of application under which a linear-approximation theory holds. Conclusions of the study are that the linear-approximation theory Seems to hold quite well over a broad range of applications. The ramifications of the Wells small-angle-scattering theory that predicts the PSF from a knowledge of the volume-scattering function (VSF) are also considered.

Discrepancies are noted between a predicted and a computationally obtained MTF; these discrepancies increase with range. Therefore, the results of the simulations indicate that the small-angle-scattering theory is more valid at a limited number of attenuation lengths. The results of the simulations indicate that the theory is valid to approximately three attenuation lengths.