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Biomedical subjects

D P Ryan

Publications and source records attributed to D P Ryan.

At least 37 records · Page 2Linked to original sources
PubMed1999

Diltiazem reduces pulmonary arterial pressures in recurrent pulmonary hypertension associated with pulmonary hypoplasia.

BACKGROUND/PURPOSE: Recurrent pulmonary hypertension in the neonatal population is an unusual event with dire consequences. Pulmonary hypertension seen in association with pulmonary hypoplasia may be refractory to conventional medical management. The effect of the calcium channel antagonist diltiazem was studied in five patients with severe pulmonary hypertension. METHODS: A retrospective review of the hospital records was performed to determine the efficacy of diltiazem for refractory pulmonary hypertension. All five patients experienced and did not respond to maximal conventional therapy, which included inhaled nitric oxide, intravenous nitrates, and extracorporeal membrane oxygenation (ECMO). Right ventricular pressures were determined by transthoracic echocardiograms and were used to document improvement in the pressure gradients. Statistical analyses were performed using a paired Student's ttest. A P value of less than .05 was considered significant. RESULTS: Diltiazem significantly reduced the right ventricular systolic pressure (RVSP) from 82 +/- 8.4 mm Hg to 58.4 +/- 7 mm Hg (P = .008). Two patients died; one had a large ventricular septal defect, and the other suffered multisystem organ failure secondary to sepsis. The surviving patients were weaned off diltiazem and did not experience recurrent pulmonary hypertension. CONCLUSIONS: In cases of pulmonary hypoplasia with recurrent pulmonary hypertension, diltiazem may be considered as a therapy. A multicenter prospective trial is advocated.

Blood Pressure↗
PubMed1999

Reality testing in cancer treatment: the phase I trial of endostatin.

Shortly before his death in 1995, Kenneth B. Schwartz, a cancer patient at Massachusetts General Hospital (MGH), founded The Kenneth B. Schwartz Center at MGH. The Schwartz Center is a non-profit organization dedicated to supporting and advancing compassionate health care delivery which provides hope to the patient, support to caregivers, and encourages the healing process. The center sponsors the Schwartz Center Rounds, a monthly multidisciplinary forum where caregivers reflect on important psychosocial issues faced by patients, their families, and their caregivers, and gain insight and support from fellow staff members. The September 1999 Schwartz Center Rounds addressed the growing attention around the phase I trial of Endostatin. Endostatin represents a new treatment paradigm. It is an anti-angiogenic protein, an endogenous fragment of collagen XVIII. In an attempt to ensure a fair allocation of a very limited number of treatment slots in this classical phase I trial, a lottery was established. More than 1,400 patients enrolled within two days of the lottery, all vying for three places in the first cohort. Two contrasting cases are presented, each a potentially eligible patient. The discussion focuses on the dilemma presented by patients desperate for an unproven treatment and the responsibility of staff to explain and support without compounding the hype or suffocating the hope.

Adult↗
PubMed1998

Evaluation of an electronic hand-held spirometer in patients with asthma.

In this pilot study we assessed patient compliance and acceptability of data recorded in the home environment by asthmatics using a Vitalograph 2110 spirometer which measures peak expiratory flow rate (PEFR) and forced expiratory volume in 1 s (FEV1). This meter automatically time and date stamps all measurements and can also assess the technical acceptability of results. Data are uploaded to a personal computer for review and analysis. We recruited 30 patients (10 male and 20 female, age range 21-72 years) from the chest clinic at Guy's Hospital (n = 20) and from a GP clinic (n = 10). Patients were asked to record spirometry data using the meter at set times (8.00 a.m. and 8.00 p.m.) for 2 weeks. The spirometer incorporated an alarm to remind patients to take measurements. All patients completed the study. Mean (SD) compliance with spirometer use was 100.8% (49.9%). Nineteen patients had a compliance rate of between 80% and 120% of expected use. Timing of recordings was compared with the scheduled times of 8.00 a.m. and 8.00 p.m. Values recorded with +/- 2 h were judged as acceptable. For morning recordings 67.4% of all values and for evening recordings 71.7% of all values met this criterion. Technical acceptability of spirometry data was also assessed by using quality assurance criteria recorded by the spirometer. Valid tests were performed for 75.2% of all recordings. Twenty-two patients performed valid tests for 80-100% of the time. We suggest that the use of an electronic meter in the home environment is practical and is likely to generate more accurate and reliable data.

Adult↗
PubMed1997

Prenatal glucocorticoids improve pulmonary morphometrics in fetal sheep with congenital diaphragmatic hernia.

PURPOSE: Prenatal glucocorticoids reverse pulmonary immaturity in rodents with pharmacologically induced congenital diaphragmatic hernia (CDH). The authors applied quantitative stereologic morphometric techniques to test whether these effects could be reproduced in large animals (sheep) with surgically created CDH. METHODS: Diaphragmatic hernias were created surgically in fetal lambs at gestational day 80. The fetuses were treated with intravenous cortisol (n = 6) or normal saline control (n = 5) from days 133 to 135. Lungs distended at 15 cm pressure from each group were harvested at day 136, processed histologically, and studied by brightfield microscopy at 400 x using a 42-point equidistant counting grid. Ten morphometric parameters (Mean +/- SEM) were measured by point-counting 60 fields/lung, and analysis of variance was performed. RESULTS: The CDH-cortisol-treated lungs showed striking significant maturational improvements when compared with lungs of CDH-normal saline controls by seven of ten morphometric parameters. CONCLUSIONS: (1) Prenatal glucocorticoids accelerate lung maturity in fetal lambs with CDH by seven quantitative morphometric parameters. (2) The observation that prenatal glucocorticoid therapy improves measures of maturity for both CDH rodent and sheep models encourages proceeding with a Phase I human clinical trial in ultrasound-confirmed CDH.

Animals↗
PubMed1996

Refinements in pediatric microtia reconstruction.

Auricular construction for a child born with microtia is a rewarding endeavor that can provide the patient with a realistic pinna. However, not all reconstructive problems have been solved. For example, the donor sites for the rib harvest and for subsequent skin grafting are not without morbidity and scar formation. Furthermore, in some children, an unexpected shortage of rib can be encountered. Surgical techniques that address these problems are described.

Child↗
PubMed1996

Surgical evaluation and management of refractory constipation in older children.

Chronic constipation is a common childhood problem that accounts for 3% to 5% of pediatric visits and 10% to 25% of referrals to pediatric gastroenterologists. The etiology of constipation can be elusive, and extensive investigation often fails to identify a specific cause. The authors conducted a 5-year retrospective review of the patients referred for deep transanal rectal biopsy to determine the usefulness of this procedure in the evaluation and subsequent surgical management of refractory constipation. Specimens obtained by transanal rectal biopsy established a diagnosis for 30 of the 70 patients, and 17 of these 30 had subsequent procedures in the treatment of their constipation. The authors conclude that transanal rectal biopsy identifies a significant number of patients with previously unidentified neuroenteric disorders who may benefit from additional surgery in the treatment of constipation refractory to medical management.

Biopsy↗
PubMed1996

Type IV laryngotracheoesophageal clefts: surgical management for long-term survival.

Complete laryngotracheoesophageal clefts (types III and IV) are rare congenital anomalies that occur when the primitive foregut fails to separate into the tracheobronchial tree and the esophagus. This article summarizes a 10-year institutional experience with six infants who had type IV clefts, presents a modification of the authors' surgical approach, and identifies pitfalls in the management of these infants. Three of the six children are long-term survivors. The recognition of specific complicating issues leads to a standardized approach, which can result in successful repair and long-term survival.

Abnormalities, Multiple↗
PubMed1996

Prenatal glucocorticoid therapy reverses pulmonary immaturity in congenital diaphragmatic hernia in fetal sheep.

OBJECTIVE: To assess the feasibility of conducting clinical trials of prenatal steroid therapy for congenital diaphragmatic hernia (CDH) in humans, the authors tested whether prenatal glucocorticoid, currently the standard treatment to minimize respiratory distress syndrome in premature infants, might improve the pulmonary immaturity in severe CDH in a large animal model. SUMMARY BACKGROUND DATA: The authors have used the nitrofen-induced rat model of CDH, which demonstrates immature lungs by biochemical, morphometric, and molecular biologic criteria. They also have shown that the lethally immature lungs of the full-term CDH rats can be improved by biochemical, morphometric, physiologic, and molecular criteria by treating the mothers with parenteral steroids at doses extrapolated from the current therapy used to accelerate lung development of premature human babies. METHODS: During a 3-year period in 88 fetal sheep, 1) left-sided diaphragmatic hernias were created surgically at varying gestational ages (day 78-90; term = 142-145 days) and size to maximize severity (n = 45), 2) placement and design of indwelling fetal intravenous catheters were optimized (n = 13), and 3) timing and dosage of cortisol administration were determined (n = 17). As a result, diaphragmatic hernias were created on day 80, intravenous catheters were placed on day 120, and twice-daily intravenous cortisol injections (n = 8) or saline as the control (n = 5) were administered (days 133-135). Lambs were delivered on day 136 via cesarean section to avoid steroid-induced abortion; vascular access was obtained, and the fetuses were ventilated at standard settings. Physiologic data were collected, and lungs were harvested for biochemical and histologic analysis. RESULTS: Significant improvements were measured in postductal arterial oxygen pressure ([PaO2] 38 +/- 6 mmHg after cortisol therapy compared with 20 +/- 3 mmHg for saline controls; p = 0.002) and in dynamic compliance (0.42 +/- 0.05 mL/cm H2O vs. 0.29 +/- 0.01 mL/cm H2O; p = 0.01). Lung glycogen levels in the right lung of the cortisol group were significantly better than controls (4.6 +/- 0.3 mg/g lung vs. 6.8 +/- 0.4 mg/g; p = 0.002), as were protein/DNA levels (8.3 +/- 0.9 mg/mg vs. 14.5 +/- mg/mg; p < 0.05). Striking morphologic maturation of airway architecture was observed in the treated lungs. CONCLUSIONS: Prenatal glucocorticoids correct the pulmonary immaturity of fetal sheep with CDH by physiologic, biochemical, and histologic criteria. These data, combined with previous small animal studies, have prompted the authors to initiate a prospective phase I/II clinical trial to examine the efficacy of prenatal glucocorticoids to improve the maturation of hypoplastic lungs associated with CDH.

Animals↗
PubMed1995

Left ventricular failure complicating severe pediatric burn injuries.

PURPOSE: Despite improvements in the overall survival rates for critically burned children, failed resuscitation may account for 54% of deaths following burn injuries. Clinical and experimental studies have implicated failure of the right side of the heart in adults, biventricular failure in elderly patients, and inadequate resuscitation as causes of refractory burn shock. This retrospective study of resuscitation at a tertiary pediatric burn center showed that myocardial depression is a complicating factor in the treatment of the pediatric burn victim. METHODS: From 1989 to 1992, 28 critically burned children (> or = 60% total burn surface area) were resuscitated primarily at our center (admission within 24 hours of injury). Twenty-seven children had central lines, nine of whom underwent pulmonary artery catheterization for intensive hemodynamic monitoring because standard resuscitative therapy had failed. The average amount of fluid received at 8 and 24 hours after injury was within 10% of the calculated volume based on the Parkland formula. RESULTS: Indexes of a failing rescue attempt included respiratory distress (PaO2/FlO2 < or = 200), central venous pressure of greater than 10 mm Hg, and urine output of less than 1 mL/kg/h. Filling pressures were found to be normal or elevated in all children, indicating adequate volume replacement. Evaluation of cardiac function was performed using a thermodilution technique and showed that 100% of the study group had depressed left ventricular function, with an average left ventricular stroke work index (LVSWI) of 19.9 g.m/m2 (normal, 44 to 68 g.m/m2), whereas only 38% had concomitant right ventricular failure. This left-sided dysfunction persisted throughout the acute resuscitation period but was improved after appropriate modification of fluid resuscitation and initiation of vasopressors (average final LVSWI, 38.0 g.m/m2). There were no complications from placement of the Swan-Ganz catheters in this group. CONCLUSION: Cardiogenic failure is a major determinant of a failing pediatric burn resuscitation, and, contrary to the adult burn patient, the myocardial depression is predominantly left-sided. Information from pulmonary artery catheters can help direct therapy by providing indications for vasopressors and modifying fluid resuscitation.

Adolescent↗
PubMed1995

Permissive hypercapnia as a ventilatory strategy in burned children: effect on barotrauma, pneumonia, and mortality.

OBJECTIVE: To document the incidence of barotrauma, pneumonia, and respiratory death associated with a mechanical ventilation protocol based on permissive hypercapnia in pediatric burn patients. DESIGN: Retrospective review. MATERIALS AND METHODS: Patients were managed using a mechanical ventilation protocol based on permissive hypercapnia, tolerating moderate (pH > 7.20) respiratory acidosis to keep inflating pressures below 40 cm H2O. MAIN RESULTS: Over a 2.5-year interval, 54 burned children (11% of 495 acute admissions) with an average age of 6.5 years (range 5 weeks to 17 years), average burn size of 44% (range 0 to 98%), and median burn size of 46% required mechanical ventilatory support for an average of 12.5 days (range 1 to 56 days). Inhalation injury was diagnosed in 34 (63%) of the children and 72% percent were admitted within 24 hours of injury. Overt barotrauma occurred in 5.6% of the patients, pneumonia in 32%, and respiratory death in 0%. CONCLUSIONS: A conventional ventilation protocol based on permissive hypercapnia is associated with acceptable rates of barotrauma and pneumonia. The low incidence of respiratory death associated with this strategy suggests that it also minimizes ventilator-induced lung injury.

Acidosis, Respiratory↗
PubMed1995

An evaluation of estrus synchronization programs in reproductive management of dairy herds.

The objectives of this experiment were to evaluate the effect of various estrus synchronization programs on estrus detection rate (EDR) and pregnancy rate (PR) in lactating cows. Spring-calving, lactating dairy cows (n = 3,096) were allocated to one of six treatments: 1) PG (n = 514), estrus detection for 10 d before the onset of the breeding season (BS), cows detected in estrus received PGF2 alpha (PGF) 8 d after estrus, and all cows to be bred by d 11 of BS; 2) PG+EBZ (n = 510), as in PG plus cows treated with PGF received 1 mg of estradiol benzoate 48 h later; 3) C (n = 522), progestogen (controlled intravaginal drug release; CIDR) inserted per vaginum 10 d before BS for 8 d, PGF treatment on the day before CIDR removal, and AI within 6 d after CIDR withdrawal; 4) C+EBZ (n = 520), as in C, plus 10 mg of estradiol benzoate 10 d before BS; 5) C+BUS (n = 517), as in C plus 10 micrograms of buserelin on the day of CIDR insertion; or 6) CON (n = 513), no treatment, and a 32-d period of AI. Relative to other CIDR-treated groups, estradiol benzoate at the time of CIDR insertion reduced (P < .05) the EDR (C, 85.0%;C+EBZ, 75.9%; C+BUS, 88.5%). The PR to first AI was reduced (P < .05) by C compared with other treatments (PG, 60.9%; PG+EBZ, 57.2%; C, 46.6%; C+EBZ, 60.5%; C+BUS, 57.9%; CON, 60.1%). The interval from the onset of BS to AI and pregnancy was reduced (P < .05) by up to 9 d by estrus synchronization relative to controls (PG, 5.5 +/- .2 d; PG+EBZ, 5.2 +/- .2 d; C 1.7 +/- .1 d; C+EBZ, 2.3 +/- .1 d; C+BUS, 106 +/- .04d, CON, 10.4 +/- .3 d). In conclusion an 8-d progestogen-buserelin-PGF treatment resulted in the best overall estrus detection and pregnancy rates, which would be beneficial to a compact calving program.

Administration, Intravaginal↗
PubMed1995

Metabolic and luteal sequelae to heightened dietary fat intake in undernourished, anestrous beef cows induced to ovulate.

Two experiments were conducted to evaluate the effects of dietary fat supplementation and a synthetic progestogen on metabolic hormone patterns and(or) in vitro and in vivo characteristics of induced corpora lutea (CL) in undernourished, post-partum beef cows. Metabolizable energy intake was restricted in all cows in both experiments before calving to achieve a body condition (BC) score of 4 (thin), with cows fed to maintain BW and condition after calving. In Exp. 1, 16 cows were fed isocaloric and isonitrogenous diets after calving with either no added fat (NL, n = 8) or added fat (HL, n = 8; .374 kg of fat/500 kg BW). In Exp. 2, 32 pluriparous cows that had reached targeted body condition were divided randomly at calving into a 2 x 2 factorial treatment arrangement: 1) HL-no implant; HL-CON, 2) HL-norgestomet implant d 14 to 21; HL-NORG, 3) NL-CON and, 4) NL-NORG. Forty-eight-hour calf removal on d 21 and GnRH on d 23 were used to induce CL. The HL diet increased (P < .03) serum growth hormone (GH) concentrations, changed the puerperal pattern of serum insulin from cubic (P < .05) to linear (P < .05), and increased (P < .01) the in vitro production of IGF-I by luteal tissue (Exp. 1). In Exp. 2, both HL diets and NORG treatments (HL-NORG, HL-CON, NL NORG) tended to promote an increased (P < .09) frequency of luteal activity after GnRH, but only HL-CON and NL-NORG enhanced (P < .04) luteal lifespan.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Neuronal intestinal dysplasia.

Neuronal intestinal dysplasia (NID) is one of the disorders of gastrointestinal motility with defined pathological changes. Although first described more than 20 years ago, the disease remains controversial. The histological findings do not correlate with the degree of symptoms. The etiology of NID is obscure, but an immunologic process has been suggested. The diagnosis can be made on biopsy specimens performed to identify Hirschsprung's disease, but treatment must be individualized. The clinical course is variable, with spontaneous improvement in some, relentless constipation or severe dysmotility, unresponsiveness to all therapy, in others. Duhamel or Soave pull-through procedures can be effective in selected cases.

Child↗
PubMed1995

A general practitioner's audit of paediatric secondary care of asthma.

Asthma is the most common chronic disease of childhood and one of the most common causes for acute admission to hospital. There appears to be an increase in prevalence over the last decade, and certainly asthma is a feature of day-to-day general practice. For some time we have felt in our practice that the standard of care received by children referred, either acutely or to outpatients, was substandard, with inappropriate interventions or lack of appropriate interventions being performed. In order to examine the validity of these sentiments, an audit of the primary/secondary care interface was performed on children the ages of 1-6 years inclusive, registered with the practice on 1 October 1993.

Acute Disease↗
PubMed1994

Follicular development during early pregnancy and the estrous cycle of the sow.

The objective of this study was to monitor and compare follicle populations and follicular development in pregnant and nonpregnant sows from Day 3 to Day 20 after breeding. Twenty-four sows were paired within parity on the day of artificial insemination and were randomly allocated within pair for insemination with either killed (n=12) or live spermatozoa (n=12). All the sows were artificially inseminated with the pooled ejaculate of the same boar. From Day 3 through Day 20 post estrus, ovarian follicles were scanned daily by ultrasonography. Ultrasound images were recorded on videotape and were retrospectively analyzed. Follicles were mapped to identify the existence of follicular waves. The follicles were then classified as small (< 3 mm), medium (3-5 mm), or large (> or =5 mm). Pregnancy diagnosis was performed on Day 21 by ultrasonography. Pregnant sows maintained a constant proportion of the follicle population in the small, medium and large follicle categories. However, in the nonpregnant sows, the proportion of follicles in the various size categories remained constant until Day 15. Thereafter, the proportion of small follicles decreased (P < 0.05) from Day 15 to 20, and the proportions of medium and large follicles increased (P < 0.05). The predictability of pregnancy status on Day 20 based on follicle populations in any of the 3 follicle categories was low. Moreover, there was no evidence of follicular waves during the estrous cycle or early pregnancy. In conclusion, the proportion of small follicles decreased while medium and large follicle increased from Day 15 through Day 20 of the estrous cycle, but not during a similar stage of pregnancy. This latter finding concurs with follicle recruitment from the pool of small follicles for ovulation following PGF2alpha secretion to induce luteolysis, which reduces progesterone concentrations and thereby allows for the stimulation of the pool of small follicles by gonadotropins.

Journal Article↗