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Biomedical subjects

J Lutz

Publications and source records attributed to J Lutz.

At least 19 recordsLinked to original sources
PubMed2001

Is sentinel lymph node biopsy reliable and indicated after preoperative chemotherapy in patients with breast carcinoma?

BACKGROUND: Many studies support the concept and accuracy of sentinel lymph node biopsy (SNB) for staging patients with breast carcinoma, which can be performed with low morbidity in lymph node negative patients. Preoperative chemotherapy (PC) plays an important role in the treatment of patients with operable breast carcinoma and is another approach with which to reduce radical surgery in patients with more advanced disease. It is of interest whether the sentinel lymph node accurately represents the axillary status after PC and, thus, whether the sentinel node concept can be applied to both groups. METHODS: Thirty-three patients underwent SNB after chemotherapy and prior to axillary lymph node dissection. RESULTS: The average greatest tumor dimension before chemotherapy (33 mm +/- 2 mm) was significantly larger (P = 0.000) than after therapy (20 mm +/- 3 mm). Histopathologic complete remission was seen in only three patients. One or two sentinel lymph nodes (average, 1.7 lymph nodes) were identified with certainty in 29 of 33 procedures and accurately predicted axillary lymph node status in all of these patients. Breast-conserving surgery was possible in 21 patients (64%), and axillary lymph nodes were involved in 22 patients (67%). CONCLUSIONS: Even after patients undergo PC, SNB seems to be a reliable method for accurate staging of the axilla in those more advanced breast carcinoma. Thus, axillary dissection may be avoided in certain patients. Lymph node involvement seems to be likely in women with suspicious axillary findings before chemotherapy who have no visible sentinel lymph nodes on preoperative lymphosintigraphy and in patients without recurrent tumors. Further investigation of the SNB concept in this patient group should be evaluated in larger studies.

Adult↗
PubMed2001

Expression of TNFalpha by muscle fibers in biopsies from children with untreated juvenile dermatomyositis: association with the TNFalpha-308A allele.

Juvenile dermatomyositis (JDM) is the most common pediatric inflammatory myopathy. In patients with JDM, the A --> G polymorphism in the tumor necrosis factor alpha (TNFalpha)-308 promoter region (TNFalpha-308A) is associated with prolonged disease course and increased production of TNFalpha by peripheral blood mononuclear cells (Arthritis Rheum. 43, 2368-2377, 2000). Magnetic resonance imaging directed biopsies from 21 white children with untreated JDM were evaluated for TNFalpha expression. Using monoclonal antibody to TNFalpha, fresh frozen sections were processed by the standard immunohistochemical technique. We investigated the association among the expression of TNFalpha by muscle fibers, disease activity, duration of untreated disease, and the TNFalpha-308 polymorphism. Untreated children with JDM who had the TNFalpha-308A allele had an increased number of TNFalpha stained muscle fibers than children with the TNFalpha-308G allele (P = 0.001). There was no association with disease activity or duration of untreated disease. We speculate that muscle fiber production of TNFalpha provides a microenvironment in which TNFalpha acts synergistically with other mediators to prolong muscle fiber damage.

Alleles↗
PubMed2001

Juvenile dermatomyositis: the association of the TNF alpha-308A allele and disease chronicity.

Little is known concerning factors associated with the outcome of juvenile dermatomyositis (JDM), which can be variable and lethal. Previous work has documented that the association of DQA1*0501 with JDM is higher than in control groups and that the first symptoms (rash and weakness) of JDM appear to follow evidence of an infectious process--most frequently upper respiratory in nature. Preliminary data show that a long period of symptoms being left untreated before starting therapy and the TNF alpha-308A allele are associated with prolonged JDM symptoms requiring > or = 36 months of immunosuppressive therapy. A short duration of untreated disease is associated with a relative increase in CD8(+) T cells and CD56(+) natural killer (NK) cells in the untreated JDM muscle biopsy compared with a longer duration of untreated disease. The TNF alpha-308A allele is overrepresented in white children with JDM. In addition, it is associated with pathologic calcifications, increased production of TNF alpha by peripheral blood mononuclear cells in vitro and JDM muscle fibers in vivo, and occlusion of capillaries, which may be mediated in part by elevated circulating levels of thrombospondin-1, a potent anti-angiogenic factor. We speculate that DQA1*0501 is associated with JDM susceptibility to an infectious process, eliciting and activating NK cells early in the disease course. We conclude that the TNF alpha-308A allele indicates directly (or is a surrogate marker of) children with JDM who produce higher concentrations of TNF alpha in response to this undefined inflammatory stimulus, as well as increased concentrations of TSP-1 with resultant small vessel occlusion, contributing to subsequent disease chronicity.

Adolescent↗
PubMed2001

Contribution of androgens to chronic allograft nephropathy is mediated by dihydrotestosterone.

BACKGROUND: Donor and recipient gender influence long-term allograft outcome after kidney transplantation. Sex hormones are likely to contribute to these gender-related differences. The present study investigated the role of androgens and their inhibition on the development of chronic allograft nephropathy. METHODS: Male or female Fisher (F344) kidneys were orthotopically transplanted into intact male Lewis recipients. Animals were treated either with testosterone, the antiandrogen flutamide, the 5alpha-reductase inhibitor finasteride, or vehicle. Twenty weeks after transplantation animals were harvested for histology, immunohistology, and molecular analysis. RESULTS: Testosterone treatment resulted in an increased proteinuria as well as profound glomerulosclerosis, tubulointerstitial fibrosis, and mononuclear cell infiltration that paralleled enhanced intragraft mRNA levels of transforming growth factor-beta (TGF-beta) and platelet-derived growth factor-A and -B chain (PDGF-A and -B). In contrast, flutamide and finasteride reduced glomerulosclerosis as well as the inflammatory cell infiltration associated with decreased TGF-beta, PDGF-A, and -B chain mRNA expression. No gender-related donor differences were noted between the groups. CONCLUSIONS: Our data suggest that dihydrotestosterone mediates the adverse effects of androgens on chronic allograft nephropathy. The inhibition of androgens improves long-term allograft outcome after kidney transplantation.

Androgen Antagonists↗
PubMed2000

Caffeine decreases the occurrence of cadmium-induced forelimb ectrodactyly in C57BL/6J mice.

BACKGROUND: Cadmium is a well-known animal teratogen. Caffeine is an alkaloid widely consumed by humans. Interactions between teratogens and nonteratogenic doses of other agents are becoming widely studied, as they may shed light on understanding mechanisms of teratogenicity or possible prevention of teratogenic effects. METHODS: C57BL/6JBK mice were injected intraperitoneally (ip) with cadmium sulfate (Cd) at 0, 1.00 (LDCd), 2.50 (MDCd), or 5.00 (HDCd) mg/kg, immediately followed by subcutaneous (sc) administration of 0 or 50 mg/kg caffeine (CAFF) on gestation day (GD) 9. Fetuses were examined on GD 18 for ectrodactyly and other gross morphological malformations. RESULTS: Amelioration of cadmium-induced forelimb ectrodactyly by CAFF was seen in both the high-dose cadmium (HDCd = 65.4%, HDCd+CAFF = 39.2%) and medium-dose cadmium (MDCd = 46.2%, MDCd+ CAFF = 20.8%) treatment groups (P < 0.025). Bilateral expression of ectrodactyly was also decreased in the presence of caffeine. A statistically significant reduction in Cd-induced abnormalities, including: eye, abdominal, and other skeletal defects, was not seen with caffeine addition, although they did trend downward in the caffeine-supplemented groups. Litter size, fetal weight, fetal mortality, and dam weight also were not affected by co-treatment with caffeine. CONCLUSIONS: This study provides evidence that a subteratogenic dose of caffeine can ameliorate cadmium-induced forelimb ectrodactyly in the Cd-sensitive C57BL/6J inbred mouse strain.

Abnormalities, Drug-Induced↗
PubMed2000

Lipopolysaccharide pretreatment protects from renal ischemia/reperfusion injury : possible connection to an interleukin-6-dependent pathway.

In vivo administration of low doses of lipopolysaccharide (LPS) to rodents can protect these animals from subsequently administrated, usually lethal doses of endotoxin or LPS. In this study we tested the effects of LPS pretreatment on ischemia/reperfusion injury in the kidney. Male C57/B1 mice were pretreated with different doses of LPS or phosphate-buffered saline on days -4 and -3. The right kidney was removed, and the vessels of the left kidney were clamped for 30 or 45 minutes on day 0. Creatinine levels and survival of animals were monitored. To test the involvement of cytokines, additional animals were harvested before ("time 0") and 15 minutes, 1, 2, 8, and 16 hours after reperfusion for histology, immunohistochemistry, terminal deoxynucleotidyltransferase-mediated UTP end-labeling assay, and reverse transcriptase-polymerase chain reaction analysis (including tumor necrosis factor (TNF)-alpha, interleukin (IL)-1, IL-6, inducible nitric oxide synthase (iNOS), and interferon (IFN)-gamma messenger RNA (mRNA)). In controls, renal ischemia of 30 minutes was nonlethal, whereas 73% of the animals died within 48 +/- 18 hours, after 45 minutes of ischemia. All different doses of LPS protected the animals from lethal renal ischemia/reperfusion injury. Starting at similar levels, serum creatinine increased significantly in controls but not in LPS-pretreated animals over time. As early as 2 hours after reperfusion, tubular cell damage was significantly more pronounced in controls than in LPS-treated mice. In controls, tubules deteriorated progressively until 8 hours of reperfusion. At this time, more than 50% of tubular cells were destroyed. This destruction was accompanied by a pronounced leukocytic infiltration, predominantly by macrophages. In contrast, LPS pretreatment prevented the destruction of kidney tissue and infiltration by leukocytes. The terminal deoxynucleotidyltransferase-mediated UTP end-labeling assay revealed significantly more apoptotic cells in controls compared with LPS-pretreated animals. IL-1, IFN-gamma, and iNOS mRNA expression did not differ between the groups throughout the time points examined. However, the expression of TNF-alpha mRNA was significantly increased at 2 hours and IL-6 mRNA was significantly down-regulated before ischemia and shortly after reperfusion in the LPS-pretreated kidneys. Therefore, we found that sublethal doses of LPS induced cross-tolerance to renal ischemia/reperfusion injury. Our data suggest that increased TNF-alpha and reduced IL-6 mRNA expression might be responsible. However, more studies are needed to decipher the exact mechanism.

Animals↗
PubMed2000

Effect of angiotensin-converting enzyme inhibition on growth factor mRNA in chronic renal allograft rejection in the rat.

BACKGROUND: Despite considerable progress in immunosuppression, the incidence of chronic renal allograft rejection has not decreased. Recent studies have revealed that angiotensin-converting enzyme (ACE) inhibition ameliorates graft arteriosclerosis, glomerulosclerosis, and tubular atrophy. Moreover, it decreases systemic and glomerular capillary hydrostatic pressure in a rat kidney allograft model. We evaluated the effects of the ACE inhibitor enalapril on cytokine and growth factor expression in chronically rejecting rat kidney allografts. METHODS: Kidneys of Fisher (F344) rats were orthotopically transplanted into Lewis (Lew) rats. To prevent acute rejection, cyclosporine A (1.5 mg/kg/day) was given to all recipients during the first 10 days after transplantation. Enalapril (60 mg/L) or vehicle was added to the drinking water 10 days after transplantation. Animals were harvested 20 weeks after transplantation for histologic and immunohistologic studies, as well as for evaluation of cytokine and growth factor mRNA by semiquantitative polymerase chain reaction. RESULTS: Controls developed severe signs of chronic rejection, such as glomerular and vascular lesions, associated with a large number of infiltrating leukocytes. Enalapril-treated animals developed less proteinuria and other signs of chronic rejection. The mRNA levels of transforming growth factor-beta 1 (TGF-beta 1), platelet-derived growth factor A and B chain (PDGF A and B), insulin-like growth factor-I (IGF-I), interleukin-1 (IL-1), and monocyte chemoattractant protein-1 (MCP-1) were significantly reduced in the enalapril group and were most pronounced for IL-1 and PDGF A. In addition, we found an increased level of renal angiotensinogen mRNA after treatment with enalapril. CONCLUSIONS: Treatment with enalapril attenuated the development of proteinuria, ameliorated morphological damage, decreased leukocyte infiltration, and prevented a rise in renal mRNA levels of growth factors and cytokines in kidney grafts in a rat model of chronic renal allograft rejection.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed2000

Auto-positive end-expiratory pressure during tracheal gas insufflation: testing a hypothetical model.

OBJECTIVE: The major benefit of tracheal gas insufflation (TGI) is an increase in CO2 elimination efficiency by removal of CO2 from the anatomical deadspace. In conjunction with mechanical ventilation, TGI may also alter variables that affect CO2 elimination, such as minute ventilation and peak airway pressure (peak Paw) and cause the development of auto-positive end-expiratory pressure (auto-PEEP). We tested the hypothesis that TGI-induced auto-PEEP alters ventilatory variables. We predicted that TGI-induced auto-PEEP offsets the beneficial effects of TGI on CO2 elimination and that keeping total PEEP (ventilator PEEP + auto-PEEP) constant enhances the CO2 elimination efficiency afforded by TGI. DESIGN: Prospective study of two series of patients with acute respiratory distress syndrome receiving mechanical ventilation. SETTING: Intensive care units at a university medical center. PATIENTS: Each series consisted of eight sequential hypercapnic patients. INTERVENTIONS: In series 1, we examined the effect of continuous TGI at 0 and 10 L/min on PaCO2, without compensating for the development of auto-PEEP. In series 2, we examined this same effect of continuous TGI while reducing ventilator PEEP to keep total PEEP constant. TGI-induced auto-PEEP was calculated based on dynamic compliance measurements during zero TGI flow conditions (deltaV/deltaP) after averaging the two baseline values for peak Paw and tidal volume and assuming compliance did not change between the zero TGI and TGI flow conditions (deltaVTGI/deltaPTGI). MEASUREMENTS AND MAIN RESULTS: In series 1, total PEEP increased from 13.2 +/- 3.2 cm H2O to 17.8 +/- 3.5 cm H2O without compensation for auto-PEEP (p = .01). PaCO2 decreased (p = .03) from 56.2 +/- 10.6 mm Hg (zero TGI) to 52.9 +/- 9.3 mm Hg (TGI at 10 L/min), a 6% decrement. In series 2, total PEEP was unchanged (p = NS). PaCO2 decreased (p = .03) from 59.5 +/- 10.4 mm Hg (zero TGI) to 52.2 +/- 8.3 mm Hg (TGI at 10 L/min), a 12% decrement. There was no significant change in PaO2; there were no untoward hemodynamic effects in either series. CONCLUSIONS: These data are consistent with the hypothesis that mechanical ventilation + TGI causes an increase in auto-PEEP that can blunt CO2 elimination. In addition to the ventilator modifications necessary to keep ventilatory variables constant when TGI is used, it is also necessary to reduce ventilator PEEP to keep total PEEP constant and further enhance CO2 elimination efficiency.

Aged↗
PubMed2000

Nonviral and viral gene transfer to the kidney in the context of transplantation.

BACKGROUND/AIMS: Local modulation of the immune response through genetic manipulation of the graft is an attractive novel approach to overcome the toxicity of immunosuppressive therapy to prevent acute graft rejection. We have previously reported that the cationic polymer polyethylenimine 25k (PEI 25k) transduced reporter genes when injected into the renal artery, but with a low transfection efficiency. Here we compare the risk/benefit profiles of such a nonviral versus a viral technique of gene transfer to the kidney in the context of renal transplantation. METHODS: Donor kidneys from Lewis rats were perfused in a closed circuit with an artificial cell-free medium containing PEI 25k complexed to an expression vector coding for the beta-galactosidase (beta-gal) gene and subsequently transplanted in a syngeneic animal. In a second set of experiments, donor kidneys were injected or perfused with a replication-deficient adenovirus encoding the beta-gal gene (AdCMV. beta-gal; 1 x 10(9) plaque-forming units) before transplantation. RESULTS: Perfusion of the kidney with PEI 25k/DNA complexes resulted in large areas of hypoperfusion characterized by injured glomeruli and tubuli, capillary thrombosis and accumulation of C3 in glomerular capillaries. Reperfusion of the kidney was achieved by lowering the PEI 25k/DNA ratio, but no detectable transfection was observed. In animals receiving adenovirus, the beta-gal activity increased with time and was localized mainly in proximal and distal tubular cells, as documented by beta-gal histochemistry and in situ hybridization. A significantly increased expression of beta-gal was achieved by perfusion of the kidney with AdCMV.beta-gal before transplantation, beta-gal staining mainly localizing in proximal and distal tubular cells. CONCLUSIONS: Unlike nonviral methods of gene delivery, adenovirus-mediated gene transfer to the kidney offers exciting perspectives for the development of molecular medicine in the field of organ transplantation.

Adenoviridae↗
PubMed2000

Tracheal gas insufflation. Limits of efficacy in adults with acute respiratory distress syndrome.

In mechanically ventilated adults with acute respiratory distress syndrome (ARDS), peak airway pressures (Paw(peak)) above 35 cm H(2)O may increase the risk of barotrauma or volutrauma. Tracheal gas insufflation (TGI), an adjunctive ventilatory technique, may facilitate a reduction in set inspiratory pressure in these patients, and thereby in the tidal volume (VT) and Paw(peak) used in their ventilation, without a consequent increase in arterial carbon dioxide tension (PaCO(2)). The purpose of this study was to: (1) assess the limits of efficacy of continuous TGI at two levels of decreased mechanical ventilatory support; and (2) determine an appropriate time interval after initiation of TGI at which to evaluate response. We prospectively studied eight adults with ARDS and increased airway pressures (40.2 +/- 2.7 cm H(2)O) who were managed with pressure-control ventilation (PCV). After obtaining baseline ventilatory and hemodynamic measures, we initiated TGI at 10 L/min, adjusting ventilator positive-end expiratory pressure (PEEP) to maintain baseline VT, and decreased the set inspiratory pressure by 5 cm H(2)O. Data were obtained after 30 and 60 min. Set inspiratory pressure was then decreased by an additional 5 cm H(2)O (total: 10 cm H(2)O), and data were again obtained after 30 min. Baseline (zero TGI) measures were then again recorded. Thirty minutes after decreasing the set inspiratory pressure by 5 cm H(2)O with TGI at 10 L/min, there was a 15% decrease in Paw(peak) and a 16% decrease in VT as compared with their baseline values. However, Pa(CO(2)) remained constant (59 +/- 10 mm Hg versus 57 +/- 6 mm Hg) (p = NS). There was no change in Pa(O(2)) or in hemodynamic variables, and no differences between variables, at 30 min versus 60 min in seven subjects. The remaining subject did not tolerate the reduction in set inspiratory pressure for 60 min. Thirty minutes after the set inspiratory pressure was decreased by 10 cm H(2)O with TGI at 10 L/min, there was a 26% decrease in Paw(peak) and a 26% decrease in VT. However, Pa(CO(2)) increased by 19% and Pa(O(2)) decreased by 13%. Six subjects completed this phase of the protocol for 30 min, and one subject completed it for 60 min. TGI can be used to rapidly facilitate a 5 cm H(2)O reduction in set inspiratory pressure without an increase in Pa(CO(2)). The ability to achieve a 5 cm H(2)O reduction in set inspiratory pressure without adverse physiologic effects was evident within 30 min. Attempts to further reduce set inspiratory pressure were not successful.

Acute Disease↗
PubMed2000

Postexposure effectiveness of varicella vaccine.

OBJECTIVE: 1) To describe the postexposure effectiveness of varicella vaccine in a homeless shelter; and 2) to demonstrate an effective public health intervention and its implications. DESIGN: A prospective observational study. SETTING: A women and children's shelter in Philadelphia with 2 cases of varicella before intervention. OUTCOME MEASURES: Varicella in vaccinated and unvaccinated shelter residents; vaccine effectiveness for prevention of varicella when administered after exposure among children <13 years of age. RESULTS: Sixty-seven shelter residents received varicella vaccine after exposure, including 42 children <13 years of age. One child who was unvaccinated developed varicella, but no vaccinated child developed typical disease. Vaccine effectiveness was 95.2% (95% CI, 81.6%-98.8%) for prevention of any disease and 100% for prevention of moderate or severe disease among the children <13 years of age. CONCLUSION: When used within 36 hours after exposure to varicella in a setting where close contact occurred, varicella vaccine was highly effective in preventing further disease. This study provides support for the recent recommendation by the Advisory Committee on Immunization Practices to administer varicella vaccine after exposure: this practice should minimize the number of moderate or severe cases of disease and prevent prolonged outbreaks.

Chickenpox↗
PubMed2000

Non-invasive evaluation of the location, the functional integrity and the oxygen supply of implants: 19F nuclear magnetic resonance imaging of perfluorocarbon-loaded Ba2+-alginate beads.

19F nuclear magnetic resonance imaging (MRI) can be used as a non-invasive tool to simultaneously determine the location, the integrity and the oxygen supply of Ba2+-alginate implants. This requires that the beads (implants) are pre-loaded with the perfluorocarbon compound F-44E. Implantation of solid 19F-labelled beads into the peritoneum, below the kidney capsule or into the muscle of Wistar WU rats demonstrated that these beads could be detected by 19F-MRI for up to 18 months after implantation. This indicated that F-44E is not considerably released from the beads during implantation. The signal to noise ratio of liquid-core beads was higher by a factor of 4 than the signal to noise ratio of solid beads, but liquid-core beads were more fragile and also too large for implantation under the kidney capsule and into the intramuscular tissue. Quantitative 2-dimensional 19F-T1 maps (resolution 0.5 x 0.5 mm) could be deduced from 19F-MRI measurements. These T1-maps correlated to the local pO2-values. The partial oxygen pressure estimated in F-44E-loaded Ba2+-alginate beads showed that the oxygen supply inside the beads was very poor when they were implanted below the kidney capsule or into the peritoneal cavity. These low pO2-values obtained for the renal subcapsular site and the peritoneum may explain the failure of previous immunoisolated islet transplantation studies using these locations.

Alginates↗
PubMed2000

Angiographic and clinical follow-up of percutaneous revascularization for transplant coronary artery disease.

BACKGROUND: There are limited data on the use of percutaneous revascularization techniques for transplant coronary artery disease (CAD). METHODS: Medical records and angiographic results for cardiac transplant patients undergoing percutaneous revascularization at Emory University Hospital were reviewed. Procedural results, results of angiography 4Eth 6 months after intervention, and clinical follow-up were recorded. RESULTS: Nineteen patients underwent 51 interventions. Thirty-eight lesions (75%) were de novo and 13 (25%) were restenotic. All patients had hypertension, 37% had diabetes, 79% had elevated lipid levels, and 53% had at least one episode of moderate to severe allograft rejection (grade 3A or greater). The primary procedural success rate was 100% with no major complications. Six-month restenosis rate (defined as > 50%) was 49%. At 23+/-17 months follow-up, 6 patients were dead or retransplanted (31%). Thirteen patients were alive without retransplantation (9 New York Heart Association class I, 3 class II, 1 class III). CONCLUSION: Percutaneous revascularization is safe and has a high initial procedural success rate in patients with transplant CAD. However, the restenosis rate in this population remains higher than reported for atherosclerotic coronary disease and the long-term prognosis remains poor.

Adult↗
PubMed1999

19F-MRI in vivo determination of the partial oxygen pressure in perfluorocarbon-loaded alginate capsules implanted into the peritoneal cavity and different tissues.

Semipermeable hydrogels formed with a biocompatible alginate solution and Ba(2+) ions protect encapsulated cells and tissues from a foreign immune system. For the viability and metabolic activity of the encapsulated materials, a sufficient oxygen supply inside the capsules is necessary. Quantitative (19)F-MRI was performed on perfluorocarbon-loaded alginate capsules implanted into the peritoneal cavity, the musculus quadriceps femoris, and beneath the kidney capsule of rats, in order to determine in vivo the partial oxygen pressure (pO(2)) inside the capsules at these implantation sites. The temporal behavior of the pO(2) values was observed for at least 3 months. The most stable values over time were observed in the kidney, where inter-rat pO(2) differences were considerable. In the muscle, the values were very high directly after implantation and decreased to nearly zero after 2 weeks. In the peritoneal cavity, values changed randomly over a wide range between different rats and over time. Magn Reson Med 42:1039-1047, 1999.

Alginates↗
PubMed1999

Effects of systemically applied allopurinol and prednisolone on experimental autoimmune uveitis.

PURPOSE: To compare the effects of allopurinol to those of prednisolone on the oxidative tissue damage and inflammatory response in experimental autoimmune uveitis (EAU). METHODS: Experiments were performed using 27 male Lewis rats. EAU was induced by means of crude retina extract, Freund's adjuvant and pertussis toxin. One group of animals served as controls and two groups were treated systemically, one with allopurinol and one with prednisolone. At the end of the experiments lipid peroxides (LPO), myeloperoxidase activity (MPO), and histological changes were determined in the retinal tissue. LPO were measured by two different methods [thiobarbituric acid reactive substances (TBARS) and malondialdehyde-like substances]. RESULTS: Allopurinol led to a significant reduction in LPO and MPO levels. The steroid treatment also resulted in a significant reduction in MPO activity but LPO were significantly reduced only when measured as TBARS. Histological changes were significantly reduced by allopurinol only. DISCUSSION: Allopurinol is more effective than prednisolone in treating EAU. Its efficacy can be explained by the antioxidative/antiinflammatory and probably immunological action. The antiinflammatory effects of prednisolone are not sufficient to reduce the tissue damage. Allopurinol promises to be a useful alternative to steroids in the treatment of uveitis.

Allopurinol↗
PubMed1999

Developmental changes in response to subatmospheric pressure loading of the upper airway.

Children snore less than adults and have fewer obstructive apneas, suggesting a less collapsible upper airway. We therefore hypothesized that the compensatory upper airway responses to subatmospheric pressure loading decrease with age because of changes in upper airway structure and ventilatory drive. We measured upper airway upstream pressure-flow relationships during sleep in 20 nonsnoring, nonobese children and adults. Measurements were made by correlating maximal inspiratory airflow with the level of nasal pressure applied via a mask. The slope of the upstream pressure-flow curve (S(PF)) was used to characterize upper airway function. We found that S(PF) was flatter in children than in adults (8 +/- 5 vs. 30 +/- 18 ml x s(-1). cmH(2)O(-1), P < 0.002) and that S(PF) correlated with age (r = 0.62, P < 0.01) and body mass index (r = 0. 63, P < 0.01). The occlusion pressure in 100 ms during sleep was measured in six children and two adults; it correlated inversely with S(PF) (r = -0.80, P < 0.02). We conclude that the upper airway compensatory responses to subatmospheric pressure loading decrease with age. This is associated with increased body mass index, even in nonsnoring, nonobese subjects. Ventilatory drive during sleep plays a role in modulating upper airway responses.

Adolescent↗