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Biomedical subjects

D A Harrison

Publications and source records attributed to D A Harrison.

At least 37 records · Page 2Linked to original sources
PubMed1998

Drosophila unpaired encodes a secreted protein that activates the JAK signaling pathway.

In vertebrates, many cytokines and growth factors have been identified as activators of the JAK/STAT signaling pathway. In Drosophila, JAK and STAT molecules have been isolated, but no ligands or receptors capable of activating the pathway have been described. We have characterized the unpaired (upd) gene, which displays the same distinctive embryonic mutant defects as mutations in the Drosophila JAK (hopscotch) and STAT (stat92E) genes. Upd is a secreted protein, associated with the extracellular matrix, that activates the JAK pathway. We propose that Upd is a ligand that relies on JAK signaling to stimulate transcription of pair-rule genes in a segmentally restricted manner in the early Drosophila embryo.

Amino Acid Sequence↗
PubMed1998

Management of ophthalmic complications of homocystinuria.

OBJECTIVE: To determine the safety and efficacy of surgical versus medical management in the treatment of ophthalmic complications of homocystinuria, and also to document ocular complications of homocystinuria other than lens dislocation. DESIGN: Retrospective case series. PARTICIPANTS: Forty-five patients with ophthalmic complications of homocystinuria participated. INTERVENTION: Eighty-four surgical procedures were performed on 40 patients. There were 82 procedures done with the patients under general anesthesia and 2 with the patients under local anesthesia. Medical therapy was attempted initially in all patients with lens dislocation and was the sole therapy used for five patients. MAIN OUTCOME MEASURES: Complications resulting from medical or surgical treatment and final visual acuity were studied. RESULTS: All patients had a history of lens subluxation or dislocation. Fourteen (31%) were receiving dietary treatment at the time of presentation and 29 (64%) were mentally retarded. Eighty-two procedures were performed with the patients under general anesthesia with 2 surgical complications and 1 postsurgical complication. Lens dislocation into the anterior chamber was the most frequent indication for surgery (50%) followed by pupillary block glaucoma (12%). Prophylactic peripheral iridectomy was not successful in preventing lens dislocation into the anterior chamber in five patients. Anesthetic precautions such as stockings to prevent deep venous thrombosis, preoperative hydration, or aspirin were given in 85% of cases. Other common ophthalmic complications found include optic atrophy (23%), iris atrophy (21%), anterior staphylomas (13%), lenticular opacities (9%), and corneal opacities (9%). CONCLUSION: Laser iridectomy was unsuccessful in preventing lens dislocation into the anterior chamber. With appropriate anesthetic precautions and modern microsurgical techniques, the risks associated with the surgical management of ocular complications of homocystinuria are reduced. Surgical treatment should be considered, especially for cases of repeated lens dislocation into the anterior chamber or pupillary block glaucoma. If a conservative, nonsurgical approach is undertaken, these patients must be observed carefully for repeat episodes of lens dislocation.

Adolescent↗
PubMed1998

Identifying loci required for follicular patterning using directed mosaics.

We have developed a 'directed mosaic' system in Drosophila by using the GAL4 system to control the expression of the yeast recombinase, FLP, in a spatial and temporal fashion. By directing FLP expression, we show that it is possible to efficiently and specifically target loss-of-function studies for vital loci to the developmental pathway of interest. A simple F1 adult phenotypic screen demonstrated that most adult tissues can be analyzed with this approach. Using GAL4 lines expressed during oogenesis, we have refined the system to examine the roles of vital loci in the development of the follicular epithelium. We have identified essential genes involved in egg chamber organization, cell migration and cell shape. Further, we have used this technique to gain insights into the role of the Drosophila EGF receptor pathway in establishing the egg axes. Finally, using different UAS-FLP, GAL4 and existing FRT lines, we have built stocks that permit the analysis of approximately 95% of the genome in follicular mosaics.

Animals↗
PubMed1998

Penetrating keratoplasty with a valved glaucoma drainage implant for congenital glaucoma and corneal scarring secondary to hydrops.

The simultaneous management of glaucoma and corneal opacification is sometimes required in infants with severe congenital glaucoma if timely visual rehabilitation is to be achieved. A 1-month-old female infant presented with an enlarged, protuberant, opaque cornea in each eye and elevated intraocular pressure. An intrastromal, fluid-filled cleft was noted in both corneas. It resolved over 3 weeks as corneal scarring progressed. Peripheral corneal clearing allowed a view of an essentially normal anterior chamber. Penetrating keratoplasty and Ahmed (New World Medical Inc., Rancho Cucamonga, CA) valve implant surgery with mitomycin-C were performed simultaneously in the two eyes 1 months apart. At 15 months of age, the patient's grafts were clear and the intraocular pressure was well controlled in both eyes. One eye required multiple procedures for eventual glaucoma control. No postoperative overfiltration occurred. The authors conclude that the use of a valved implant should be considered in patients who require urgent simultaneous corneal and glaucoma surgery for severe congenital glaucoma. This combination may improve early postoperative control of aqueous outflow and positively affect long-term graft survival in these difficult cases.

Administration, Topical↗
PubMed1997

Risk and predictors for pregnancy-related complications in women with heart disease.

BACKGROUND: The physiological changes of pregnancy can result in cardiovascular complications in the mother, which in turn may have fetal implications. Prior studies have focused on specific cardiac lesions or identified univariate predictors. There is a need to refine the risk stratification of women with heart disease so they can receive appropriate obstetrical counseling and care. METHODS AND RESULTS: We examined the outcomes of 221 women with heart disease who underwent 276 pregnancies and received their obstetrical care at three Toronto hospitals from 1986 through 1994. Those who underwent therapeutic abortions were excluded. Among the study participants, there were 24 miscarriages and 252 completed pregnancies (pregnancies not ending in miscarriage). Maternal heart failure, arrhythmia, or stroke occurred in 45 completed pregnancies (18%). There were no maternal deaths. Poor maternal functional class or cyanosis, myocardial dysfunction, left heart obstruction, prior arrhythmia, and prior cardiac events were predictive of maternal cardiac complications. These predictors were incorporated into a point score that can be used to estimate the probability of a cardiac complication in the mother. The rate of cardiac complications for a patient with 0, 1, and >1 of the above factors was 3%, 30%, and 66%, respectively. Neonatal complications occurred in 42 completed pregnancies (17%). Neonatal events included death (2), respiratory distress syndrome (16), intraventricular hemorrhage (2), premature birth (35), and small-for-gestational-age birth weight (14). Poor maternal functional class or cyanosis was predictive of neonatal events. CONCLUSIONS: Despite low maternal and neonatal mortality, pregnancy in women with heart disease is associated with significant cardiac and neonatal morbidity. The probability of maternal cardiac or neonatal events can be predicted from baseline characteristics of the mother.

Adolescent↗
PubMed1997

Sustained ventricular tachycardia in adult patients late after repair of tetralogy of Fallot.

OBJECTIVES: We sought to determine the features associated with sustained monoform ventricular tachycardia (VT) in adult patients late after repair of tetralogy of Fallot (TOF) and to review their management. BACKGROUND: Patients with repair of TOF are at risk for sudden death. Risk factors for ventricular arrhythmia have been identified from patients with ventricular ectopic beats because of the low prevalence of sustained VT. METHODS: From a retrospective chart review of patients assessed between January 1990 and December 1994, 18 adult patients with VT were identified and compared with 192 with repaired TOF free of sustained arrhythmia. RESULTS: There was no significant difference in age at repair, age at follow-up or operative history. Patients with VT had frequent ventricular ectopic beats (6 of 9 vs. 21 of 101), low cardiac index ([mean +/- SD] 2.4 +/- 0.4 vs. 3.0 +/- 0.8) and more structural abnormalities of the right ventricle (outflow tract aneurysms and pulmonary or tricuspid regurgitation) than control patients. Electrophysiologic map-guided operation was performed in 10 of 14 patients who required reoperation. VT has reoccurred in three of these patients. Four patients did not undergo operation (three received amiodarone; one underwent defibrillator implantation). Two patients with VT also had severe heart failure and died. CONCLUSIONS: Most patients with VT late after repair of TOF have outflow tract aneurysms or pulmonary regurgitation, or both. These patients have a greater frequency of ventricular ectopic beats than arrhythmia-free patients after repair of TOF. A combined approach of correcting significant structural abnormalities (pulmonary valve replacement or right ventricular aneurysmectomy, or both) with intraoperative electrophysiologic-guided ablation may reduce the potential risk of deterioration in ventricular function and enable arrhythmia management to be optimized.

Adult↗
PubMed1997

Pulmonary valve replacement late after repair of tetralogy of Fallot.

BACKGROUND: Pulmonary valve incompetence is usually well tolerated after tetralogy of Fallot repair but may result in late progressive right heart failure as manifested by increasing fatigue, dyspnea, and frequently arrhythmias. METHODS: All patients who underwent pulmonary valve replacement in our center late after repair of tetralogy of Fallot were reviewed. RESULTS: Eighty-five patients had elective pulmonary valve replacement late (median, 9.3 years) after repair. Operative risk was low (1.1%). Ninety percent of survivors are in New York Heart Association class I. Survival 10 years after pulmonary valve replacement is 95%, with 86% of the patients free of reoperation for valve failure. CONCLUSIONS: Pulmonary valve replacement is infrequently required after repair of tetralogy of Fallot. Pulmonary valve replacement may be performed electively with little risk; it improves symptoms of right heart failure and provides satisfactory long-term survival with low risk of early valve failure. As the population of patients who have had repair of tetralogy of Fallot ages, pulmonary valve replacement will become a more frequent consideration.

Adolescent↗
PubMed1997

A comparison of thiopentone-isoflurane anaesthesia vs propofol infusion in children having repeat minor haematological procedures.

We have performed a randomized, cross over study in 22 children suffering from acute leukaemia, who underwent repeated anaesthesia for bone marrow aspiration and lumbar puncture. For their first anaesthetic, the children (aged 3-10 years old) received, either a thiopentone/isoflurane anaesthetic or intravenous propofol, both supplemented with nitrous oxide. On a second occasion they received the alternative technique. Of those children receiving thiopentone/isoflurane, 32% had significant coughing during anaesthesia, two progressing to laryngospasm requiring 100% oxygen. None of the patients receiving propofol had a respiratory disturbance (P = 0.016). 68% of the children preferred the propofol anaesthetic. Only one child in the thiopentone/isoflurane group preferred this technique. Twenty-seven per cent had no preference. There was no significant difference in length of anaesthetic time (P = 0.07) or the time taken for recovery (P = 0.17) between the two groups. There was a large individual variation in propofol requirements and movement was common during stimulation of patients in this group, though this did not adversely affect the surgical procedure.

Acute Disease↗
PubMed1996

Percutaneous catheter closure of the persistently patent ductus arteriosus in the adult.

The USCI patent ductus occluder has been shown to be an effective nonsurgical technique for closure of the persistently patent ductus in a primarily pediatric population. Its clinical impact in the adult has been reported only within small subgroups of larger pediatric studies or for a small population. This study was conducted to determine the feasibility, success rate, and complications of device closure for the persistently patent ductus arteriosus (PDA) in the adult. The population consisted of 55 patients (4 men and 51 women; mean age 38.8 +/- 15.0 years) with follow-up of 2.2 +/- 2.1 years. All patients underwent echocardiography obtained as part of their follow-up assessment. The device was successfully placed in 54 patients, with 75% clinical and echocardiographic closure at the first follow-up assessment 2.4 +/- 2.6 months). One patient with initial clinical and echocardiographic evidence of closure was subsequently found to have an open ductus. Spontaneous closure (2 patients) or second implant (6 patients) resulted in 86% closure at the most recent assessment. Thus, the percutaneous PDA double-umbrella occluder device is a feasible and effective technique for closing persistent PDA in the adult and will result in occlusion of the shunt in most patients without the need for thoracotomy.

Adolescent↗
PubMed1996

Interventional cardiology for the adult patient with congenital heart disease: the Toronto Hospital experience.

Interventional cardiac procedures for patients with congenital heart disease, developed for the pediatric patient, have been adapted for the adult patient. In this review these unique procedures are reviewed with emphasis on the experience at The Toronto Congenital Cardiac Centre for Adults. Procedures directed to closing shunts include: occlusion of patent ductus arteriosus, coil embolization of aorto-systemic collaterals, coronary fistulas, and Blalock-Taussig shunts, and early attempts at nonsurgical occlusion of atrial septal defects. Balloon dilation procedures include management of pulmonary valve stenosis, peripheral pulmonary artery stenosis, and more recently the application of stents in dilation of coarctation of the aorta. Development of interventional techniques for adult congenital heart disease involves a diverse number of procedures which provide successful nonsurgical options for many patients with congenital heart disease.

Adult↗
PubMed1996

Sudden cardiac death in the adult with congenital heart disease.

Preliminary results of a review of sudden cardiac death in the adult with congenital heart disease were presented at the Canadian Adult Congenital Heart (CACH) Network meeting during the Canadian Cardiovascular Society's annual meeting in October 1994. Of 125 patients who were known to have died, sufficient details were available for 92 to determine the circumstance of death. Sudden death occurred in 23 patients (estimated incidence 5.3 per 1000 patients followed per year) at an average age of 33.5 +/- 11.9 years. Surgical procedures included intracardiac repair in 12, palliative procedures in only six and no cardiac surgery in six. Nine patients with sudden death had Eisenmenger syndrome. Right or left ventricular abnormalities were present in 15 of 21 patients with premorbid echocardiographic evaluation. A prior history of ventricular arrhythmia was available in only three patients. Sudden death is a significant cause of mortality in adults with congenital heart disease. Determination of risk factors will be an important aspect of the patient database under development by the CACH Network.

Adult↗
PubMed1995

Predictors of response to amine-specific antidepressants.

Discriminant function analysis of data from a double-blind comparative trial of lofepramine (a noradrenaline-specific reuptake inhibitor) and fluoxetine (a serotonin-specific reuptake inhibitor), involving 183 patients was used to identify predictors of response. Psychic anxiety significantly predicted a positive response to antidepressant medication, whereas psychomotor retardation, observed sadness, subjective lassitude and somatic complaints were significant predictors of nonresponse. Age, gender, endogenicity, duration of illness and number of previous episodes were not predictive of response. Significant differences were found between predictors of response to fluoxetine and lofepramine (P < 0.001 all groups). Predictors of response to lofepramine were similar to overall predictors, i.e., psychic anxiety predicted responders whilst observed sadness, psychomotor retardation, lassitude, inability to feel and somatic complaints predicted nonresponders. In contrast, baseline weight loss predicted response to fluoxetine, whereas anxiety, reduced insight and a tendency to blame others significantly predicted nonresponse. Such findings have practical implications for the management of depressive illness.

Adult↗
PubMed1995

Activation of a Drosophila Janus kinase (JAK) causes hematopoietic neoplasia and developmental defects.

In mammals, many cytokines and growth factors stimulate members of the Janus kinase (JAK) family to transduce signals for the proliferation and differentiation of various cell types, particularly in hematopoietic lineages. Mutations in the Drosophila hopscotch (hop) gene, which encodes a JAK, also cause proliferative defects. Loss-of-function alleles result in lethality and underproliferation of diploid tissues of the larva. A dominant gain-of-function allele, Tumorous-lethal (hopTum-l), leads to formation of melanotic tumors and hypertrophy of the larval lymph glands, the hematopoietic organs. We show that a single amino acid change in Hop is associated with the hopTum-l mutation. Overexpression of either wild-type hop or hopTum-l in the larval lymph glands causes melanotic tumors and lymph gland hypertrophy indistinguishable from the original hopTum-l mutation. In addition, overexpression of Hop in other tissues of the larva leads to pattern defects in the adult or to lethality. Finally, overexpression of either hop or hopTum-l in Drosophila cell culture results in tyrosine phosphorylation of Hop protein. However, overexpression of hopTum-l results in greater phosphorylation than overexpression of the wild-type. We conclude that hopTum-l encodes a hyperactive Hop kinase and that overactivity of Hop in lymph glands causes malignant neoplasia of Drosophila blood cells.

Animals↗
PubMed1995

Outcome of corneal grafting with donor tissue from eyes with primary choroidal melanomas. A retrospective cohort comparison.

OBJECTIVES: To determine if melanomas have occurred in the recipients of corneas from donor eyes with primary choroidal melanomas and to determine the success of corneal grafting with tissue taken from eyes with primary choroidal melanomas. DESIGN: Retrospective cohort comparison and follow-up patient questionnaire. SETTING: A tertiary medical center in Rochester, Minn. PATIENTS: In patients who received corneal transplants, we reviewed 47 consecutive corneas transplanted from donor eyes enucleated for choroidal melanomas and compared them with 47 corneal grafts from donor eyes without melanomas matched for recipient age (+/- 10 years), date of operation (+/- 12 months), corneal storage time (+/- 24 hours), and operation type. RESULTS: No melanomas occurred in either group over a mean follow-up of 5.4 years (range, 0.4 to 15 years). There was no significant difference between the two groups in corneal thickness and endothelial cell loss at 2 months and 1 year after transplantation and in the probability of a rejection episode. CONCLUSIONS: There is no evidence of tumor transmission by transplantation of corneas from donor eyes with primary choroidal melanomas. Corneas transplanted from donor eyes with primary choroidal melanomas have similar outcomes to corneas transplanted from donor eyes without melanomas.

Adult↗
PubMed1995

Cardiopulmonary function in adult patients late after Fontan repair.

OBJECTIVES: The clinical status and exercise assessment of adult patients late after the Fontan operation were reviewed to determine cardiovascular function. BACKGROUND: The Fontan operation is the final operation for many patients with tricuspid atresia or a single ventricle. Follow-up reports describe most patients to be in Canadian Cardiovascular Society functional class I or II. Objective measures of cardiac performance in the pediatric age group have shown significant dysfunction. METHODS: Forty-seven adult patients were seen late after the Fontan operation at the Toronto Congenital Cardiac Centre for Adults. Thirty of these underwent cycle ergometry to determine maximal exercise capacity. Maximal ventilation, maximal oxygen uptake and anaerobic threshold were determined from a ramp exercise protocol. Ejection fraction at rest and during exercise was measured with gated radionuclide angiography. Results were compared with those of eight normal volunteers. Results are given as mean +/- SD. RESULTS: Thirty patients underwent cardiopulmonary exercise testing 6.7 +/- 3.9 years after a first Fontan operation. Clinically 93% were in functional class I or II. The Fontan group patients had a significantly lower maximal work load (548 +/- 171 vs. 1,094 +/- 190 kilopond-meters, p < 0.00001), anaerobic threshold (11.2 +/- 2.9 vs. 23.6 +/- 4.6 ml/kg per min) and maximal oxygen consumption (14.8 +/- 4.5 vs. 42.1 +/- 10.0 ml/kg per min). Systemic ventricular ejection fraction was lower at rest (38 +/- 12% vs. 58 +/- 7%) and during exercise (40 +/- 15% vs. 70 +/- 8%). CONCLUSIONS: Despite a clinical impression of good function, by objective measures adult patients continue to have significant cardiovascular limitation late after the Fontan operation.

Adult↗