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Biomedical subjects

J Lutz

Publications and source records attributed to J Lutz.

At least 19 recordsLinked to original sources
PubMed2006

Angiotensin type 1 and type 2 receptor blockade in chronic allograft nephropathy.

Angiotensin-II (Ang-II) type 1 (AT(1)) receptor blockers may delay the progression of chronic allograft nephropathy (CAN). However, neither the optimal time for initiating AT(1) receptor blockade in order to delay CAN potentially nor the role of Ang-II type 2 (AT(2)) receptors under AT(1) receptor blockade is known. Both AT receptors can regulate p53 expression and apoptosis. We investigated what time of initiation with AT(1) blockers most effectively delayed CAN as well as the role of the AT(2) receptor, and how angiotensin receptor blockade affected apoptosis and its regulating factors in this context in a rat model. Kidneys of Fisher (F344) rats were transplanted into Lewis rats. Animals were treated with AT(1) (candesartan) and/or AT(2) (PD123319) receptor antagonists, a calcium channel blocker, or vehicle (treatment periods: day -7 before to week 24 after transplantation (long term), week 12 to week 24 (late), day -7 to day +5 (early)) and observed the animals for 24 weeks. Reduction of proteinuria, grade of CAN, and number of apoptotic cells was most pronounced in animals receiving long-term AT(1) receptor blockade. A combined AT(1)/AT(2) blocker treatment reduced CAN similarly to AT(1) blocker treatment alone. The number of apoptotic cells and the level of p53 mRNA were significantly lower in long-term AT(1) blocker-treated animals. In summary, AT(1) receptor blockade delayed the progression of CAN, particularly in animals treated long term. Reduction of apoptosis could be related to these beneficial effects. The AT(2) receptor does not appear to play an important role in CAN.

Angiotensin Receptor Antagonists↗
PubMed2006

[Inflammatory lesions of the brainstem and the cerebellopontine angle].

Inflammatory lesions of the brainstem and the cerebellopontine angle are often critical for the patient, because crucial neuronal and vascular structures are found in this region. The patient's prognosis mainly depends on rapid identification of the inflammation site and the radiological evaluation of the inflammation pathogenesis to develop therapeutic strategies. Therefore, cross-sectional imaging is complementary to laboratory and CSF analysis as well as biopsies. This article gives a survey of inflammatory lesions of the brainstem and the cerebellopontine angle.

Brain Stem↗
PubMed2005

Comparison of the original Amsler grid with the modified Amsler grid: result for patients with age-related macular degeneration.

PURPOSE: To compare the sensitivity of the original Amsler grid presenting white lines on a black background with that of the modified standard version of the grid presenting black lines on a white background in the detection of visual disturbances. PATIENTS AND METHODS: One hundred eighty-two patients (182 eyes) with dry and exudative age-related macular degeneration and a history of metamorphopsia were instructed to use an Amsler grid. None of the patients were familiar with an Amsler grid or had used it previously. If the disease was present in both eyes, one eye was chosen as the study eye by randomization. Both grid types were presented and used for documentation of central visual field changes. The sequence of presentation of the respective grid was also chosen by randomization. Original Amsler grid questions were used for grading ("metamorphomas" and "scotomas"). Visual acuity of patients ranged from 0.1 to 0.7. Subgroup analysis was performed based on the visual acuity levels. RESULTS: For the overall study population, the original Amsler grid provided significantly better results than the modified version. Evaluation of data for the different subgroups showed no significant difference between patients with visual acuity ranging from 0.1 to 0.3. For patients with visual acuity of 0.5 or better, the original Amsler grid was significantly more informative and reliable than the modified version. CONCLUSION: For patients with macular diseases, use of the original Amsler grid (white lines on a black background) should be recommended. This is particularly important for patients with visual acuity of 0.5 or better.

Aged↗
PubMed2005

Improving medical emergency team (MET) performance using a novel curriculum and a computerized human patient simulator.

PROBLEM: Advance cardiac life support (ACLS) training does not address coordination of team resources to improve the ability of teams to deliver needed treatments reliably and rapidly. Our objective was to use a human simulation training educational environment to develop multidisciplinary team skills and improve medical emergency team (MET) performance. We report findings of a crisis team training course that is focused on organization. SETTING: Large center for human simulation training at a university affiliated tertiary care hospital. PARTICIPANTS: Ten courses were delivered and 138 clinically experienced individuals were trained (69 critical care nurses, 48 physicians, and 21 respiratory therapists). All participants were ACLS trained and experienced in responding to cardiac arrest situations. COURSE DESIGN: Each course had four components: (1) a web based presentation and pretest before the course; (2) a brief reinforcing didactic session on the day of the course; (3) three of five different simulated scenarios; each followed by (4) debriefing and analysis with the team. Three of five simulator scenarios were used; scenario selection and order was random. Trainees did not repeat any scenario or role during the training. Participants were video recorded to assist debriefing. Debriefing focused on reinforcing organizational aspects of team performance: assuming designated roles independently, completing goals (tasks) assigned to each role, and directed communication. MEASURES FOR IMPROVEMENT: Participants graded their performance of specific organizational and treatment tasks within specified time intervals by consensus. Simulator "survival" depended on supporting oxygenation, ventilation, circulation within 60 seconds, and delivering the definitive treatment within 3 minutes. EFFECTS OF CHANGE: Simulated survival (following predetermined criteria for death) increased from 0% to 89%. The initial team task completion rate was 10-45% and rose to 80-95% during the third session. LESSONS LEARNT: Training multidisciplinary teams to organize using simulation technology is feasible. This preliminary report warrants more detailed inquiry.

Computer Simulation↗
PubMed2003

[Kidney transplantation in Germany - 2002].

In Germany the number of kidney transplantations has increased rather slowly during recent years. While living donations increased, the number of postmortal donations decreased during the same time. In order to lower the number of patients on the waiting lists in Germany, the rate of postmortal or living donations as well as the number of marginal donors must be increased. Furthermore, risk factors related to the development of coronary heart disease or chronic allograft nephropathy, have to be strictly controlled in order to improve graft survival and, thus, reduce the waiting lists. In addition to the well established risk factors for graft survival such as HLA-missmatch, ischemia, coronary artery disease, metabolic diseases, or recipient/donor age others such as recipient/donor gender, social status, and patient education also influence graft survival. Screening for malignant tumors is crucial as donor and recipient age is increasing. Whether newer immunosuppressive substances such as mycophenolat mofetil (MMF), sirolimus, Il-2 receptor antagonists, or FTY720 prolong long term graft survival, has to be investigated in future clinical trials.

Adolescent↗
PubMed2003

Immunological effects of allopurinol in the treatment of experimental autoimmune uveitis (EAU) after onset of the disease.

PURPOSE: Allopurinol reduces oxidative tissue damage and exerts immunomodulating effects in the treatment of experimental autoimmune uveitis (EAU). However, the mechanism of the immunologic pathway remains unclear. In previous studies, treatment was started at the time of immunization. Therefore, whether allopurinol prevents the onset of the disease (i.e., acts in a protective manner) is not known. METHODS: Sixteen male Lewis rats were used: 6 EAU without therapy [control]; 4 EAU with allopurinol treatment starting 7 days after immunization [AL7]; and 6 EAU with allopurinol treatment starting 11 days after immunization [AL11]. Their sera were tested against Western blots of sodium dodecyl sulfate-polyacrylamide gel electrophoresis of retinal proteins. Based on digital image analysis, analysis of discriminance was done. RESULTS: There were significant immunomodulating effects in both therapy groups (Wilks' lambda 0.001, P < 0.008) compared to controls. However, the effects were more pronounced in the AL7 group, where peak intensities and the number of peaks were markedly more reduced. CONCLUSIONS: Immunomodulating effects of allopurinol can be detected even if the therapy starts after the onset of the disease. Thus allopurinol strongly influences the immunologic mechanism in this model of autoimmune disease. In view of its minimal side effects, the drug could be a promising alternative for the therapy and prophylaxis of uveitis and other autoimmune diseases.

Adjuvants, Immunologic↗
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↗