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Biomedical subjects

M O'Keefe

Publications and source records attributed to M O'Keefe.

At least 91 records · Page 5Linked to original sources

Cyclocreatine (1-carboxymethyl-2-iminoimidazolidine) inhibits growth of a broad spectrum of cancer cells derived from solid tumors.

In an effort to investigate the role of creatine kinase and its substrates in malignancy we have tested the effect of cyclocreatine [1-carboxymethyl-2-iminoimidazolidine (CCr)] on the growth of tumor cells in vitro and in vivo. CCr is phosphorylated by creatine kinase to yield a synthetic phosphagen [(N-phosphorylcyclocreatine (CCr approximately P)] with thermodynamic and kinetic properties distinct from those of creatine phosphate. We show that CCr accumulates as CCr approximately P in tumor cells expressing a high level of creatine kinase, and that the accumulation of this phosphagen is detrimental to tumor cell growth. Tumor cell lines expressing a low level of creatine kinase accumulate much less CCr approximately P, and consequently are growth inhibited only at higher concentrations of CCr. When these resistant cells are transfected with a creatine kinase B expression vector, they express creatine kinase, accumulate CCr approximately P, and are growth inhibited. In vivo, in nude mouse xenografts, the rate of growth of a high creatine kinase expressing tumor cell line is inhibited in animals fed 1% CCr. Our results indicate that CCr inhibits the growth of tumor cells in vitro and in vivo.

Animals↗

Results of Crawford tube intubation in children.

Between 1987-1991 we inserted Crawford tubes in the nasolacrimal system in 24 children with recurrent epiphora following unsuccessful probing. Twenty-two are free of epiphora and discharge from 6 months to 4 years after the removal of tubes and 2 children show no improvement. Apart from mild epistaxis at the time of the tube insertion and tube displacement within 2 weeks of insertion in 3 children, we report no other complications.

Child↗

Two cases of coloboma associated with unbalanced translocations.

Two cases of coloboma are recorded, both secondary to previously unreported unbalanced translocations. These cases underline the association of chromosomal abnormalities and coloboma, particularly when accompanied by systemic abnormalities. They also highlight the importance of a full systemic assessment of coloboma patients and adequate genetic counselling for both patients and their families.

Chromosome Aberrations↗

Follow-up study on premature infants with and without retinopathy of prematurity.

The ocular complications in population of 131 premature infants, with and without retinopathy of prematurity (ROP) are reported. An increased incidence of strabismus (20% with ROP and 25% without ROP) and myopia (27.5% with ROP and 8.8% without ROP) was shown. Significant visual loss occurred in 10.7% overall, increasing to 35% with stage 3 disease and 100% with stage 4. With the increased survival rate of premature infants, the relevance to future management of this expanding group of young people is considered.

Birth Weight↗

Ophthalmic findings in classical galactosaemia--prospective study.

Thirty three children with classical galactosaemia diagnosed through newborn screening are considered. It is concluded that cataract formation has a direct relationship with poor dietary control. Erythrocyte galactose-1-phosphate (Gal-1-P) levels do not correspond to cataract formation unless many times higher than normal. The value of crystalline lens biomicroscopy is confirmed as a useful method for monitoring the dietary and biochemical control in classical galactosaemia.

Cataract↗

Diode laser for retinopathy of prematurity--early outcome.

Diode laser treatment for retinopathy of prematurity was successful in 81% of 21 eyes with 'threshold' (zone 2, stage 3+) disease. This compares favourably with cryotherapy and argon laser photocoagulation. The retinal outcome and technique are discussed.

Female↗

Congenital aplasia of the iris sphincter and dilator muscles.

Congenital aplasia of the iris sphincter and dilator muscles is rare. We describe a 3-month-old boy with a patent ductus arteriosus who had this anomaly, with no other ocular or systemic abnormalities. The child, whom we followed for over 7 years, had reduced accommodative amplitudes. This anomaly, although it bears some similarity to Gillespie's syndrome, circumpupillary aplasia and aniridia, is an isolated, nonprogressive condition that general physicians need to differentiate from the neurologically dilated pupil so that misdirected, unnecessary investigations can be avoided.

Accommodation, Ocular↗

Spirometric and endoscopic evaluation of airway collapse in infants with bronchopulmonary dysplasia.

We evaluated eight infants with bronchopulmonary dysplasia (BPD) at ages from 2 to 13 months who had repeated episodes of clinical respiratory deterioration associated with agitation. These episodes limited further weaning from ventilation or necessitated recurrent intubation and reinstitution of ventilation. All infants underwent spirometric evaluation and six also had endoscopic examination during simulated agitation episodes (elicited by toe pinching). All babies were found to have a very prolonged near zero expiratory airflow pattern, accompanied by vigorous diaphragmatic and abdominal muscle activity and rapid development of hypoxia. Six patients had endoscopically documented tracheal collapse under the same simulated circumstances. The episodes ceased with calming or sedation of the infants.

Airway Obstruction↗

Cryotherapy for retinopathy of prematurity--a prospective study.

Cryotherapy has been shown to reduce the unfavourable outcome in retinopathy of prematurity with stage 3 threshold disease by 50%. In a prospective study cryotherapy had a favourable outcome in 13 of 24 eyes with stage 3 threshold disease. The visual outcome, refraction, and complications of cryotherapy are discussed.

Child, Preschool↗

Optic nerve hypoplasia, encephalopathy, and neurodevelopmental handicap.

Abnormalities of the central nervous system are frequently described in optic nerve hypoplasia. In a longitudinal study of 46 consecutive children (32 term, 14 preterm) with bilateral optic nerve hypoplasia 32 (69.5%) had associated neurodevelopmental handicap. Of these, 90% had structural central nervous system abnormalities on computed tomographic brain scans. Neurodevelopmental handicap occurred in 62.5% of the term and 86% of the preterm infants respectively. Term infants had a greater incidence of ventral developmental midline defects and proportionately fewer maternal and/or neonatal complications throughout pregnancy, while encephaloclastic lesions were commoner among the premature infants. An association of optic nerve hypoplasia with the twin transfusion syndrome and prenatal vascular encephalopathies is described.

Abnormalities, Multiple↗

Childhood blindness in the Republic of Ireland: a national survey.

We completed a national study of blindness in children under 16. Approximately 80% of the blind children (that is, with vision of 3/60 or less) in the Republic of Ireland (172 children) were seen, 93 males and 79 females. The survey was carried out between July 1989 and June 1990. It is the first such study to be carried out. Ninety seven (56%) children had lesions due to factors acting before the perinatal period. Of these, 28 (16% of the total number surveyed) had lesions due to genetic causes; 69 (40%) had lesions due to factors operating in the prenatal period other than genetic factors. Forty six (27%) had lesions due to factors acting in the perinatal period. Twenty two (13%) had lesions due to factors acting in childhood. (4% could not be categorised in this way). The commonest single primary diagnoses were birth asphyxia in 19 (11%) cases and retinopathy of prematurity in 19 (11%) cases.

Adolescent↗

Ocular manifestations in fetal alcohol syndrome.

Eight children with the fetal alcohol syndrome are described with ocular anomalies. They all had a strong history of maternal alcohol abuse throughout pregnancy, especially in the first trimester. All the children had eye abnormalities. These included external eye lesions, Peters' anomaly, lens opacification, ocular motility disorders, and optic nerve hypoplasia.

Child↗

Ophthalmic findings in maple syrup urine disease.

Maple Syrup Urine Disease is an autosomal recessive disorder of branched chain amino acid metabolism with an incidence in Ireland of one in 140,154 births. Ocular complications in untreated or late diagnosed patients includes optic atrophy, grey optic papilla, nystagmus, ophthalmoplegia, strabismus and cortical blindness. Seven patients with maple syrup urine disease were studied. All were diagnosed with the aid of newborn screening and commenced on early dietary treatment (mean age at diet introduction = 5 days). All remain physically well, with average intellectual performance, three having minor neurological defects and one strabismus. Early diagnosis, proper therapy and subsequent vigilant management may reduce substantially the risks of ophthalmic complications in this rare disease.

Child↗

Bacteraemia--a New York perception.

Positive blood cultures (in total 7541) obtained from patients of varied social background in a New York medical centre between 1984 and 1989 are reviewed. Streptococcus pneumoniae predominated in community-acquired infections, and coagulase-negative staphylococci and Staphylococcus aureus in nosocomial infections, the latter often arising from intravenous lines. The reported trend towards Gram-positive isolates is confirmed in this series.

Cross Infection↗

Childhood blindness.

Eighty five visually handicapped children who attended the eye department were assessed. The children had a mean age of 3.6 years--range 0.3-14.7 years. The aetiological factors for severe visual handicap (visual acuity less than 3/60) were evaluated into prenatal factors; factors operating at birth and the immediate perinatal period; or factors operating in childhood. Genetic counselling and improvements in the management of pre-term infants is recommended in the reduction of childhood blindness. A national computerised childhood blind register should be established.

Adolescent↗

Ocular complications in homocystinuria--early and late treated.

Homocystinuria due to cystathionine-beta-synthetase deficiency is an autosomal recessive disorder of methionine metabolism with an incidence in Ireland of 1 in 52,544 births. Ocular complications in untreated patients include ectopia lentis, secondary glaucoma, optic atrophy, and retinal detachment. There are no characteristic signs or symptoms in infancy, and early detection relies on screening of newborn babies. Nineteen patients with homocystinuria were studied; 14 received dietary treatment and vitamin supplementation starting in the newborn period. Of these, none developed ectopia lentis after a mean follow-up of 8.2 years, compared with a 70% dislocation rate in untreated patients with a similar follow-up period. Ectopia lentis developed and progressed in five patients diagnosed later in life, despite tight biochemical control. The risk of ocular complications in homocystinuria can be substantially reduced in patients started on treatment within six weeks of birth.

Adolescent↗