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Biomedical subjects

M J Marsh

Publications and source records attributed to M J Marsh.

At least 19 recordsLinked to original sources

Hemodynamic response to continuous infusion of dobutamine in Alagille's syndrome.

BACKGROUND: Alagille's syndrome is a rare condition that is characterized by paucity of interlobular bile ducts and peripheral pulmonary artery stenosis. Liver transplantation in the setting of peripheral pulmonary stenosis and right ventricular hypertension seems to be associated with a higher mortality, which raises the concern that these patients are unable to increase their cardiac output in the immediate posttransplantation period to meet the demands of reperfusion and early graft dysfunction and cope with further increases in pulmonary vascular resistance. METHOD: Cardiac catheterization was performed in 15 children with Alagille's syndrome and peripheral pulmonary artery stenosis to measure the cardiac output response to dobutamine infusion. The cardiac output was measured before and during each increment of infusion of dobutamine at 10 microg/kg/min and 20 microg/kg/min by using a thermodilution catheter placed in the pulmonary artery. RESULTS: There was a significant change in the baseline cardiac index (P<0.001) with an infusion of 20 microg/kg/min of dobutamine with an increase from 4.4(1.0) L/min/m2 to 6.4(1.5) L/min/m2. There was, however, a wide variation between individuals in the increase in cardiac index, ranging from 7.3-95%. There was no correlation between the baseline systolic right ventricular/aortic pressure ratios and the increase in cardiac index (r=0.1086). CONCLUSION: The increase in cardiac index, in response to dobutamine in patients with Alagille's syndrome, is independent of the more conventional measurement of the right ventricular pressure. This method of producing a hemodynamic response is closer to the response that results after liver transplantation, and thus, it may be a better way of predicting the outcome of liver transplantation in these patients.

Adolescent↗

Episcleritis and scleritis: clinical features and treatment results.

PURPOSE: To evaluate the clinical experience with episcleritis and scleritis at a tertiary care eye center. METHODS: Retrospective chart review. RESULTS: One hundred thirty-four patients with scleral inflammation were seen over a 12-year period. Thirty-seven patients had episcleritis, and 97 patients had scleritis. Ocular complications occurred in only 13.5% of patients with episcleritis but in 58.8% of patients with scleritis (P <.0001). No patient with episcleritis had a decrease in visual acuity, whereas 15.9% of patients with scleritis did. Only 16.7% of patients with episcleritis required more than topical corticosteroids for treatment, and these patients required oral nonsteroidal anti-inflammatory drugs. Conversely, 30.4% of patients with scleritis required nonsteroidal anti-inflammatory drugs, 31.9% oral prednisone, and 26.1% systemic immunosuppressive drugs (P <.0001). Necrotizing scleritis and posterior scleritis more often were associated with ocular complications, occurring in 91.7% and 85.7%, respectively, than were diffuse anterior scleritis and nodular anterior scleritis (P =.020). Patients with necrotizing scleritis and posterior scleritis were more likely to be treated with oral corticosteroids or immunosuppressive drugs (90% and 100%, respectively) than were patients with diffuse anterior scleritis and nodular anterior scleritis (56.4% and 21.4%, respectively, P =.002). CONCLUSIONS: Scleritis is a severe ocular inflammation, often associated with ocular complications, and nearly always treated with systemic medications. Nearly 60% of these patients will need oral corticosteroids or immunosuppressive drugs to control the disease.

Adolescent↗

Submacular surgery trials randomized pilot trial of laser photocoagulation versus surgery for recurrent choroidal neovascularization secondary to age-related macular degeneration: I. Ophthalmic outcomes submacular surgery trials pilot study report number 1.

PURPOSE: To report complications and changes in vision during 2 years of follow-up of patients with age-related macular degeneration assigned randomly to surgical removal or to laser photocoagulation of subfoveal recurrent neovascular lesions in a pilot trial designed to test methods, to refine estimates of outcome rates, and to project patient accrual rates for a larger multicenter randomized trial to evaluate submacular surgery. PATIENTS AND METHODS: Eligible patients with previous laser photocoagulation of extrafoveal or juxtafoveal choroidal neovascularization secondary to age-related macular degeneration were enrolled at 15 collaborating clinical centers. Assignments to treatment arm were made by personnel at a central coordinating center. Adherence to eligibility criteria and treatment assignment was assessed centrally at a photograph reading center. Patients were examined at 3, 6, 12, and 24 months after treatment for data collection purposes. Outcome measures reported include treatment complications, adverse events, requirements for additional treatment, and 2-year changes in visual acuity from baseline. RESULTS: Of 70 patients enrolled, 36 were assigned to laser photocoagulation and 34 to submacular surgery; all were treated as assigned. One patient in each group died before the 2-year examination. Visual acuity was measured at the 2-year examination for 31 of the surviving patients (89%) in the laser arm and for 28 of the surviving patients (85%) in the surgery arm. The 2-year measurements for 36 of the 59 patients (61%) were made by an examiner masked to treatment assignment and to the identity of the study eye. Improvements and losses of visual acuity were observed in both treatment arms; 20 of 31 study eyes (65%) in the laser arm and 14 of 28 study eyes (50%) in the surgery arm had visual acuity 2 years after enrollment that was better than or no more than 1 line worse than the baseline level. Changes in visual acuity and the size of the central macular lesions from baseline to the 2-year examination were similar in the treatment arms. Few serious complications were observed in either arm at the time of initial treatment; serious adverse events were rare. During follow-up, 11 laser-treated eyes and 18 surgically treated eyes had additional intraocular procedures. CONCLUSIONS: The data from this pilot trial suggest no reason to prefer submacular surgery over laser photocoagulation for treatment of patients with age-related macular degeneration who have lesions similar to those studied in this pilot trial. Any clinical trial designed to compare submacular surgery with laser photocoagulation in eyes with age-related macular degeneration and subfoveal recurrent neovascular lesions must enroll several hundred patients in order to reach a statistically valid conclusion regarding differences between these two methods of treatment with respect to either changes in visual acuity or complication rates.

Aged↗

Pars planitis: clinical features and class II HLA associations.

OBJECTIVE: To describe a cohort of patients with pars planitis followed at a single tertiary care institution, determine the frequency of multiple sclerosis and/or optic neuritis in patients with this disorder, and calculate gene frequencies of human leukocyte antigen (HLA) class II alleles in these patients. DESIGN: Fifty-three patients with the diagnosis of pars planitis underwent clinical record review or telephone interview for follow-up or both; 32 of these underwent phlebotomy for analysis of HLA class II alleles. MAIN OUTCOME MEASURES: Outcomes included visual acuity, occurrence of multiple sclerosis and/or optic neuritis, and HLA class II gene frequencies. RESULTS: With a mean follow-up of 2 years, approximately 90% of patients maintained a visual acuity better than 20/40 in at least one eye. The most frequently encountered ophthalmic complications included cystoid macular edema, cataract, and epiretinal membrane formation. Of 37 patients with pars planitis who had medical or neurologic follow-up evaluations, 6 (16.2%) developed multiple sclerosis. The HLA-DR15 allele, coding for one of the two HLA-DR2 subtypes, was associated with pars planitis (odds ratio = 2.86, 95% confidence interval = 1.42-5.78, P = 0.004). CONCLUSIONS: A common immunogenetic predisposition to multiple sclerosis and pars planitis may be associated with the HLA-DR15 allele. This association may represent genetic linkage to the HLA-DR locus or a role for the HLA-DR15 gene product in the pathogenesis of both of these diseases.

Adolescent↗

Randomised controlled trial of budesonide for the prevention of post-bronchiolitis wheezing.

BACKGROUND: Previous studies suggest that recurrent episodes of coughing and wheezing occur in up to 75% of infants after acute viral bronchiolitis. AIM: To assess the efficacy of budesonide given by means of a metered dose inhaler, spacer, and face mask in reducing the incidence of coughing and wheezing episodes up to 12 months after acute viral bronchiolitis. METHODS: Children under the age of 12 months admitted to hospital with acute viral bronchiolitis were randomised to receive either budesonide or placebo (200 microg or one puff twice daily) for the next eight weeks. Parents kept a diary card record of all episodes of coughing and wheezing over the next 12 months. RESULTS: Full follow up data were collected for 49 infants. There were no significant differences between the two study groups for the number of infants with symptom episodes up to six months after hospital discharge. At 12 months, 21 infants in the budesonide group had symptom episodes compared with 12 of 24 in the placebo group. The median number of symptom episodes was 2 (range, 0-13) in those who received budesonide and 1 (range, 0-11) in those who received placebo. Because there is no pharmacological explanation for these results, they are likely to be caused by a type 1 error, possibly exacerbated by there being more boys in the treatment group. CONCLUSION: Routine administration of budesonide by means of a metered dose inhaler, spacer, and face mask system immediately after acute viral bronchiolitis cannot be recommended.

Acute Disease↗

Effects of smoking in pregnancy on neonatal lung function.

AIMS: To assess the effects of smoking during pregnancy on lung mechanics and lung volumes in the immediate neonatal period, before infants are exposed to passive smoking. METHODS: Lung function tests were carried out within 72 hours of delivery in infants born to 100 non-smoking and 189 smoking mothers. Lung growth was assessed by plethysmography and lung mechanics using the single breath occlusion technique and oesophageal balloon/pneumotachography. Antenatal maternal serum cotinine values were obtained from 133 mothers. RESULTS: Smoking was associated with a significant reduction in birthweight (mean 256 g, 95% CI 0.164 to 0.392), and length (mean 1.26 cm, 95% CI 0.48 to 2.00). Lung volume was not reduced when related to weight. Smoking was associated with a highly significant reduction in static compliance (Crs). This effect remained significant after relating Crs to weight and lung volume. Regression analyses showed that the Crs association was limited to the boys. Smoking was associated with a small but significant reduction in respiratory system conductance (Grs) (single breath occlusion technique) and total pulmonary conductance (Gp). These associations were limited to girls. CONCLUSIONS: Smoking in pregnancy reduces static compliance in boys and conductance in girls. There was no evidence that maternal smoking adversely affected fetal lung growth.

Adult↗

Scanning laser ophthalmoscope fundus perimetry after surgery for choroidal neovascularization.

PURPOSE: Submacular surgery is under investigation for the treatment of subfoveal choroidal neovascularization secondary to age-related macular degeneration, ocular histoplasmosis syndrome, and other causes. The aims of this study were to determine whether the macular area from which choroidal neovascularization was removed surgically remained functional and whether there was any qualitative difference between eyes with different disease conditions or between eyes of younger and older patients. METHODS: Our study included 19 patients (19 eyes) with choroidal neovascularization, seven cases caused by age-related macular degeneration and 12 caused by ocular histoplasmosis syndrome, pathologic myopia, or idiopathic causes. All tests were performed at least 6 months after surgical removal of choroidal neovascularization. All patients underwent fundus perimetry with the scanning laser ophthalmoscope for evaluation of dense and relative scotomas and fixation site. RESULTS: After submacular surgery in 19 patients, 10 patients (one with age-related macular degeneration and nine with pathologic myopia, ocular histoplasmosis syndrome, or an idiopathic cause of choroidal neovascularization) fixated within an area that ophthalmoscopically and angiographically was an area of retinal pigment epithelial disturbance occupied by choroidal neovascularization preoperatively. Of 12 patients without age-related macular degeneration, seven of eight patients younger than 50 years of age compared with two of four patients 50 years or older fixated within the area of retinal pigment epithelial disturbance. CONCLUSIONS: Our data suggest that in patients without age-related macular degeneration who undergo submacular surgery, the surgically disturbed area previously occupied by choroidal neovascularization can remain functional postoperatively. Furthermore, occasionally a patient with age-related macular degeneration undergoing submacular surgery still can fixate in the area from which the choroidal neovascularization was removed.

Adolescent↗

Early detection of necrotizing enterocolitis by gastrointestinal tonometry.

The diagnosis of necrotizing enterocolitis (NEC) in neonates has traditionally depended on a combination of clinical signs, biochemical parameters and radiological changes. The measurement of intramucosal pH by gastrointestinal tonometry provides a simple means of long-term monitoring which may detect the development of NEC before conventional techniques. We present our experience of tonometry in two 'at risk' term neonates with Hypoplastic Left Heart Syndrome.

Enterocolitis, Pseudomembranous↗

Extracorporeal support for intractable cardiorespiratory failure due to meningococcal disease.

BACKGROUND: Meningococcal disease is still associated with considerable mortality, despite the use of early antibiotics and management in specialised intensive care units, due principally to early refractory myocardial depression and hypotension as well as severe acute respiratory distress syndrome. Extracorporeal membrane oxygenation (ECMO) is a complex technology that uses a modified "heart-lung" machine to provide temporary cardiac and respiratory support. We reviewed the UK and Australian experience of the use of ECMO in patients with refractory cardiorespiratory failure due to meningococcal disease. METHODS: The records from all 12 known patients supported with ECMO for meningococcal disease in the UK and Australia since 1989 were reviewed. FINDINGS: 12 patients (aged 4 months to 18 years, median 26 months) with meningococcal disease received ECMO over 8 years. In seven patients, ECMO was required early for cardiac support for intractable shock within 36 h of admission to intensive care. In the other five patients, ECMO was indicated for respiratory failure due to severe adult respiratory distress syndrome, which tended to occur later in the disease. The paediatric risk of mortality score ranged from 13 to 40 (median 29, median predicted risk of mortality 72%). Six of the 12 patients required cardiopulmonary resuscitation before ECMO and the other six were deteriorating despite maximal conventional therapy. Overall, eight of the 12 patients survived, with six leading functionally normal lives at a median of 1 year (range 4 months to 4 years) of follow-up. INTERPRETATION: ECMO might be considered to support patients with intractable cardiorespiratory failure due to meningococcal disease who are not responding to conventional treatment.

Adolescent↗

Preservation of the inner retina in retinitis pigmentosa. A morphometric analysis.

OBJECTIVE: To determine the extent of preservation in the inner retina in retinitis pigmentosa (RP). METHODS: We analyzed sectioned maculae of 21 postmortem eyes with RP and 19 age-matched, normal, postmortem eyes. Eyes were divided into 2 groups: severe and moderate RP. Cell nuclei were counted in the outer nuclear, inner nuclear, and ganglion cell layers within thirty 100-microns intervals from the foveola to 1500-microns eccentricity. RESULTS: Statistically significant (P < or = .05) loss of both the outer nuclear and ganglion cell layers was present in the groups with moderate and severe RP when compared with the control groups. However, even in the group with severe RP, 30% of the ganglion cells were histologically intact. Similarly, 78% and 88% of the inner nuclear layer cells were preserved in the groups with severe and moderate RP, respectively. Different inheritance modes showed no statistically significant differences in any of the retinal layers. CONCLUSIONS: Despite a statistically significant (P < or = .05) loss of cells found in all retinal layers, a large percentage of the inner retinal neurons remained histologically intact. Current experimental therapies, such as photoreceptor transplantation and implantation of a visual prosthesis, are based on the premise that some inner retinal neurons are preserved after death of photoreceptors in RP. Our observations support this assumption.

Aged↗

Clinical validation of cardiac output measurements using femoral artery thermodilution with direct Fick in ventilated children and infants.

OBJECTIVE: To validate clinically cardiac output (CO) measurements using femoral artery thermodilution in ventilated children and infants by comparison with CO estimated from the Fick equation via a metabolic monitor. DESIGN: Prospective, comparison study. SETTING: Paediatric intensive care unit of a university hospital. PATIENTS: 24 ventilated infants and children, aged 0.3 to 175 months (median age 19 months). INTERVENTIONS: Oxygen consumption measurements were made and averaged over a 5-min period, at the end of which arterial and mixed venous blood samples were taken and oxygen saturations measured by co-oximetry, with CO being calculated using the Fick equation. Over this 5-min period, five sets of femoral arterial thermodilution (FATD) measurements were made and averaged. One comparison of CO values was made per patient. RESULTS: Mean Fick CO was 2.55 l/min (range 0.24 to 8.71 l/min) and mean FATD CO was 2.51 l/min (range 0.28-7.96 l/min). The mean bias was 0.03 l/min (95% confidence interval -0.07 to 0.14 l/min), with limits of agreement of -0.45 to 0.52 l/min. When indexed to body surface area, the mean Fick cardiac index became 3.51 l/min per m2 (1.52-6.98 l/min per m2) and mean FATD 3.49 l/min per m2 (1.74-6.84 l/min per m2). The mean bias was 0.02 l/min per m2 (95% confidence interval -0.11 to 0.15 l/min per m2) with limits of agreement of-0.57 to 0.61 l/min per m2. The mean FATD coefficient of variation was 5.8% (SEM 0.5%). CONCLUSIONS: FATD compares favourably with Fick derived CO estimates in infants and children and may represent an advance in haemodynamic monitoring of critically ill children.

Adolescent↗

Visual function abnormalities and prognosis in eyes with age-related geographic atrophy of the macula and good visual acuity.

PURPOSE: Geographic atrophy (GA) may cause significant compromise of visual function, even when there still is good visual acuity (VA), because of parafoveal scotomas and foveal function abnormalities antedating visible atrophy. This study evaluates the visual function abnormalities at baseline and the 2-year worsening of VA and reading rate for eyes with GA compared with a group of eyes with drusen only. METHODS: Seventy-four eyes with GA and VA greater than or equal to 20/50 from a prospective natural history study of GA were included, as were 13 eyes with only drusen. Baseline visual function testing and 2-year VA and maximum reading rate are reported. RESULTS: The worsening of VA in decreased luminance and foveal dark-adapted sensitivity showed severe abnormalities for the GA group. Contrast sensitivity was significantly reduced for the eyes with GA. Half the eyes with GA, but none of the drusen eyes, had maximum reading rates below 100 words per minute. A scanning laser ophthalmoscope (SLO) measure of the scotoma near fixation combined with a measure of residual foveal function accounted for 54% of the variability in maximum reading rate in the eyes with GA. Of 40 eyes with GA observed for 2 years, half lost greater than or equal to 3 lines of VA and one quarter lost greater than or equal to 6 lines. The nine eyes with drusen with follow-up had no significant change in VA. Low foveal dark-adapted sensitivity, SLO measures of the scotoma within 1 degree of fixation, and low maximum reading rate were statistically significant risk factors for doubling of the visual angle. Significant reduction in maximum reading rates at 2 years was present for the eyes with GA. CONCLUSIONS: The eyes with GA with good VA have profound decreases in visual function, particularly in dim lighting and in reading. Half the eyes with GA had doubling in visual angle at 2 years after the baseline examination, whereas the drusen eyes remained essentially unchanged. Impaired visual function at baseline was predictive of an adverse outcome for the eyes with GA.

Aged↗

Serum lactate as a predictor of mortality after paediatric cardiac surgery.

OBJECTIVE: To assess the value of sequential lactate measurement in predicting postoperative mortality after surgery for complex congenital heart disease in children. DESIGN: Prospective observational study. SETTING: Sixteen bedded paediatric intensive care unit (PICU). SUBJECTS: Ninety nine children (90 survivors, nine non-survivors). MEASUREMENTS: Serum lactate and base deficit were measured on admission and every six hours thereafter. Data were analysed by Mann-Whitney and Fisher's exact tests. RESULTS: There was considerable overlap in initial lactate values between the survivor and non-survivor groups. Initial lactate was significantly raised in non-survivors (median 8.7, range 1.9-17.6 mmol/l) compared with survivors (median 2.4, range 0.6-13.6 mmol/l) (p = 0.0002). Twenty one patients (21.1%) with initial lactate concentrations greater than 4.5 mmol/l survived to PICU discharge. Using receiver operating characteristic analysis an initial lactate of 6 mmol/l had the optimum predictive value for mortality. Initial postoperative serum lactate > 6 mmol/l predicted mortality with sensitivity 78%, specificity 83%, and positive predictive value of only 32%. CONCLUSION: Initial lactate concentrations have poor positive predictive value for mortality. The routine measurement of lactate for this purpose cannot be justified in clinical practice.

Biomarkers↗

Clinicians' abilities to estimate cardiac index in ventilated children and infants.

OBJECTIVES: To evaluate the ability of clinicians involved in the provision of paediatric intensive care to estimate cardiac index in ventilated children, based on physical examination and clinical and bedside laboratory data. METHODS: Clinicians were exposed to all available haemodynamic and laboratory data for each patient, allowed to make a physical examination, and asked to first categorize cardiac index as high, high to normal, low to normal, or low, and then to quantify this further with a numerical estimate. Cardiac index was measured simultaneously by femoral artery thermodilution (coefficient of variation 5.37%). One hundred and twelve estimates were made by 27 clinicians on 36 patients (median age 34.5 months). RESULTS: Measured cardiac index ranged from 1.39 to 6.84 1/min/m2. Overall, there was poor correlation categorically (kappa statistic 0.09, weighted kappa 0.169) and numerically (r = 0.24, 95% confidence interval 0.06 to 0.41), although some variation was seen among the various levels of seniority. CONCLUSION: Assuming that objective measurement, and hence manipulation, of haemodynamic variables may improve outcome, these findings support the need for a safe, accurate, and repeatable technique for measurement of cardiac index in children who are critically ill.

Body Surface Area↗

The role of cultures in the management of ulcerative keratitis.

PURPOSE: To ascertain the importance of routine cultures and gram stains in the management of ulcerative keratitis. METHODS: We retrospectively reviewed 119 consecutive corneal ulcers seen at Sinai Hospital of Baltimore. Cultures were obtained of the corneal ulcer and of the lids and conjunctivae of both eyes. Gram stains were performed by the hospital microbiology department on corneal scrapings from each ulcer. RESULTS: Positive corneal cultures were obtained from 56 eyes (47.1%). Initial antibiotic therapy was changed based on culture results in 14.3% of culture-positive eyes that demonstrated a worsening clinical course. Gram stains were negative in all cases. The sensitivity and specificity of the lid and conjunctival cultures were determined. CONCLUSIONS: Corneal cultures are important in the management of ulcerative keratitis. Lid and conjunctival cultures have low sensitivity and specificity.

Anti-Bacterial Agents↗