PubMed Health⌕ Search

Biomedical subjects

K M Fitzgerald

Publications and source records attributed to K M Fitzgerald.

At least 19 recordsLinked to original sources
PubMed2001

Autosomal dominant inheritance of a negative electroretinogram phenotype in three generations.

PURPOSE: We report an abnormal electroretinogram with a negative configuration in a child who presented with moderate myopia, nystagmus, and visual developmental delay. We investigated the electroretinogram and explored the possibility of a metabotropic glutamate receptor subtype 6 mutation in six family members spanning four generations. METHODS: Case report and family study: Complete eye examinations and Ganzfeld electroretinograms were recorded from the maternal great-grandmother, maternal grandmother, mother, uncle, and sibling of the 7-month-old female proband. The electroretinogram was repeated in the proband at 17 months of age. Dark adaptometry was performed in all adult subjects. Fundus photographs and visual field examinations were administered to the grandmother and mother. The metabotropic glutamate receptor subtype 6 gene was amplified and sequenced in all affected subjects. RESULTS: The proband had a negative electroretinogram and a normal fundus. The maternal grandmother, uncle, and mother had an abnormal electroretinogram identical to the proband yet had no visual complaints. The ophthalmology examinations in the adult subjects were normal, and subsequent examination of the proband at 17 months, 5 years, and 6.5 years of age showed no changes in the fundus or refractive error. Her nystagmus resolved by 5 years of age. Rod threshold and visual fields were normal in the affected adult subjects. No mutation in the metabotropic glutamate receptor subtype 6 gene was found. CONCLUSIONS: In this family, a negative electroretinogram was not associated with decreased rod threshold, visual acuity loss, visual field loss, muscle disease, or metabotropic glutamate receptor subtype 6 mutation. Additional study will be required to understand the nature of the negative electroretinogram phenotype in this family.

Adult↗
PubMed2001

Growth and development in term infants fed long-chain polyunsaturated fatty acids: a double-masked, randomized, parallel, prospective, multivariate study.

OBJECTIVE: To evaluate the effects of dietary intake of the long-chain polyunsaturated fatty acids, arachidonic acid (AA), and docosahexaenoic acid (DHA) on multiple indices of infant growth and development. DESIGN: A double-masked, randomized, parallel trial was conducted with term infants fed formulas with or without AA+DHA for 1 year (N = 239). Reference groups of breastfed infants (N = 165) weaned to formulas with and without AA+DHA were also studied. Infants in the formula groups were randomized at </=9 days of age to a control formula with no AA or DHA (n = 77) or 1 of 2 otherwise identical formulas containing AA+DHA (AA, 0.46% and DHA, 0.14% of total fatty acids) from either egg-derived triglyceride (egg-DTG [n=80]) or fish oil and fungal oil (fish/fungal [n = 82]) at levels similar to the average in breast milk samples as measured in the reference group. All formulas contained 50% of energy from fat with the essential dietary fatty acids, linoleic acid (20% fatty acids) and alpha-linolenic acid (2% fatty acids). The main study outcomes were AA and DHA levels in plasma and red blood cells, and multiple measures of infant development at multiple ages from birth to 14 months: growth, visual acuity, information processing, general development, language, and temperament. RESULTS: AA and DHA levels in plasma and red cells were higher in AA+DHA-supplemented groups than in the control formula group and comparable to those in reference groups. No developmental test results distinguished these groups. Expected differences in family demographics associated with breastfeeding were found, but no advantages to breastfeeding on any of the developmental outcome demonstrated. CONCLUSIONS: These findings do not support adding AA+DHA to formulas containing 10% energy as linoleic acid and 1% energy as alpha-linolenic acid to enhance growth, visual acuity, information processing, general development, language, or temperament in healthy, term infants during the first 14 months after birth.infant development, breast feeding, infant formula, long-chain polyunsaturated fatty acids, docosahexaenoic acid.

Arachidonic Acid↗
PubMed2001

The negative ERG is not synonymous with nightblindness.

PURPOSE: To provide electroretinographic differentiation between 4 genetically distinct conditions associated with a negative. Schubert Bornschein type electroretinogram (ERG): Complete congenital stationary night blindness (cCSNB), incomplete CSNB (incCSNB), Duchenne muscular dystrophy, and a family with an autosomal dominantly inherited negative ERG. METHODS: ERGs were recorded in all subjects according to the ISCEV standards. Additionally, a long-duration flash was used under photopic testing conditions to separate depolarizing (ON) and hyperpolarizing (OFF) bipolar cell contributions. Dark adaptometry was obtained in cooperative adult subjects. RESULTS: We were unable to differentiate between these 4 genetically distinct conditions using the scotopic ERG response to the bright white flash only. The photopic, cone-derived ERG to both short- and long-duration flashes was more informative in making distinctions between these 4 disorders and understanding the possible mechanisms behind the abnormal ERG. CONCLUSION: None of these disorders are progressive or a result of abnormal photoreceptor phototransduction. We suggest that they each represent a signal transmission error at the photoreceptor to depolarizing bipolar cell synapse that affects both rod and cone output. We propose that vision is spared in the latter 2 conditions because of timing errors in transmission as opposed to a complete signaling block, as seen in cCSNB.

Electroretinography↗
PubMed2000

Clinical and electroretinographic findings in fetal alcohol syndrome.

PURPOSE: Fetal exposure to alcohol is a serious public health problem and is associated with anomalies of the eye ground, as well as neurodevelopmental delay, growth delay, and characteristic facial features. Our purpose is to report the incidence of abnormal electroretinogram (ERG) results in children with fetal alcohol syndrome and raise awareness of the diagnosis of fetal alcohol syndrome in ophthalmology. METHODS: A retrospective review was performed on the records of 11 children with the diagnosis of fetal alcohol syndrome. The results of the ophthalmologic examination, magnetic resonance imaging, visual acuity test, and ERG are reported. RESULTS: The magnetic resonance imaging results were abnormal in all subjects tested. The ophthalmology examination showed optic nerve hypoplasia in 91% of the subjects. Visual acuity was reduced in all but one subject. The ERG results were abnormal, showing reduced b-wave amplitude, increased a- and b-wave implicit time, reduced Rmax, and increased log (k). The scotopic ERG was more severely affected than the photopic ERG. CONCLUSIONS: Prenatal alcohol exposure can lead to changes in retinal function as evidenced by an abnormal ERG response. The ERG can therefore be a tool with which to identify suspected alcohol embryopathy.

Abnormalities, Multiple↗
PubMed1999

ERG phenotype of a dystrophin mutation in heterozygous female carriers of Duchenne muscular dystrophy.

PURPOSE: Mutations in the dystrophin gene result in Duchenne muscular dystrophy (DMD). DMD is associated with an abnormal electroretinogram (ERG) if the mutation disrupts the translation of retinal dystrophin (Dp260). Our aim was to determine if incomplete ERG abnormalities would be associated with heterozygous carriers of dystrophin gene mutations. METHODS: Ganzfeld ERGs were obtained under scotopic and photopic testing conditions from a family which includes the heterozygous maternal grandmother, the heterozygous mother, and her children, two affected boys and dizygotic twin sibs, an unaffected male and heterozygous female. Southern blot analyses were done to characterise the dystrophin mutation. RESULTS: The dystrophin gene was found to contain a deletion encompassing exon 50. The ERGs in the two affected boys were abnormal, consistent with the DMD ERG phenotype. Serial ERGs of the heterozygous females were abnormal; however, they were less severely affected than the DMD boys. The ERG of the female sib showed a greater abnormality than her mother and maternal grandmother. The unaffected twin had a normal ERG. CONCLUSIONS: The ERG shows abnormalities associated with carrier status in this family with a single exon deletion. A large study of confirmed obligate carriers is planned to clarify further the value of the ERG in detecting female heterozygous carriers of dystrophin gene mutations.

Adult↗
PubMed1997

Visual acuity, erythrocyte fatty acid composition, and growth in term infants fed formulas with long chain polyunsaturated fatty acids for one year. Ross Pediatric Lipid Study.

The CNS and the retina are enriched in long chain polyunsaturated (LCP) fatty acids, specifically docosahexaenoic acid (DHA, 22:6n-3) and arachidonic acid (AA, 20:4n-6), which are present in human milk but not in most infant formulas. In the present study of 134 formula-fed and 63 breast-fed infants, we prospectively evaluated whether providing a source of DHA and AA or DHA alone in formula would increase red blood cell (RBC) phospholipid levels of these fatty acids, enhance visual function, or affect growth during the first year. Healthy term infants < 7 d old were randomized to be fed formulas containing linoleic acid (approximately 10% kcal) and alpha-linolenic acid (approximately 1% kcal) plus (1) no added LCP fatty acids (control formula), (2) DHA (0.12 wt% fatty acids) and AA (0.43 wt%) from egg yolk phospholipid (AA + DHA formula), or (3) DHA (0.2 wt%) from fish oil (DHA formula). A breast-fed group was studied concurrently and permitted formula supplementation after 3 mo. Visual acuity was measured using both the acuity card procedure and a visual evoked potential method at 2, 4, 6, 9, and 12 mo. Infants fed the control formula had 10-40% lower RBC levels of DHA and AA than infants in the breast-fed group. Infants fed the AA + DHA formula had levels of both LCP within approximately 10% of the values for infants in the breast-fed group, and infants fed the DHA formula had 25-55% higher DHA levels and 15-40% lower AA levels. There were no differences in growth or in visual function during this 12-mo feeding study.

Anthropometry↗
PubMed1996

Results of 1000 consecutive elective abdominal aortic aneurysm repairs.

In order to identify major risks for death and complications from elective repair of abdominal aortic aneurysm, the authors analyzed their experience with the last 1000 such repairs over a 15-year period. Of the patients, 772 were men and 228 were women; average age was 70 (range 37-92) years. Some 20% of the patients had severe chronic obstructive pulmonary disease and 33% had baseline creatinine level > 115 mumol/l. Fifteen patients were dialysis-dependent and 24% (242/1000) had significant cardiac disease. Operation used a retroperitoneal approach in 834 patients and a transperitoneal approach in 166. The perioperative mortality rate was 2.4%, but this did not change either chronologically or with technique: some 50% of the deaths were due to cardiac causes. Renal and pulmonary impairment did not affect mortality or complication; 64% of non-fatal complications were distributed in the renal (17%), pulmonary (19%) and cardiac groups (28%). The authors' experience showed that patients with cardiac disease remain at significant risk for post-abdominal aortic aneurysm repair complications in spite of selective preoperative cardiac evaluation. Renal and pulmonary risk factors did not cause additional mortality or morbidity. They suggest that elective abdominal aortic aneurysm repair can be performed with low mortality and morbidity, even in increasing numbers of high-risk patients.

Adult↗
PubMed1995

Preclinical evaluation of LU 79553: a novel bis-naphthalimide with potent antitumor activity.

LU 79553 is a novel bis-naphthalimide which is highly cytotoxic in vitro with EC50 (concentration required for 50% inhibition of growth) ranging from 2 x 10(-7) to 5 x 10(-10) M. A number of studies were conducted to examine its antitumor activity in human xenograft models. In addition, we wanted to explore the possible schedule dependency of LU 79553 cytotoxicity in these xenograft models. Complete regression of MX-1 (mammary carcinoma) xenografts was observed when LU 79553 was administered i.v. daily for 5 doses at 20 mg/kg (2 cycles starting on Days 6 and 20) or every 3 days for 2 doses at 55 mg/kg (2 cycles starting on Days 6 and 13) or every 7 days for 4 doses. Complete regression was also seen in the MX-1 model when tumors were staged at 1-2 g prior to the initiation of treatment. Regressions (complete or partial) were observed in the LX-1 (lung), CX-1 (colon), DLD (colon), and LOX (melanoma) xenograft models. A significant increase in the median survival time of OVCAR-3- (ovarian carcinoma) bearing mice was noted in LU 79553-treated animals (treated/control = 195%). The excellent activity of this compound in such a wide variety of tumor types suggests LU 79553 merits further investigation in clinical trials.

Amides↗
PubMed1995

Abnormal electroretinogram associated with developmental brain anomalies.

PURPOSE: We have encountered abnormal ERGs associated with optic nerve hypoplasia, macular, optic nerve and chorioretinal colobomata and developmental brain anomalies. Brain anomalies include cortical dysgenesis, lissencephaly, porencephaly, cerebellar and corpus callosum hypoplasia. We describe six exemplar cases. METHODS: Scotopic and photopic ERGs adherent to international standards were performed as well as photopic ERGs to long-duration stimuli. CT or MRI studies were also done. The ERGs were compared to age-matched normal control subjects. RESULTS: ERG changes include reduced amplitude b-waves to blue and red stimuli under scotopic testing conditions. Implicit times were often delayed. The photopic responses also showed reduced amplitude a- and b-waves with implicit time delays. The long-duration photopic ERG done in one case shows attenuation of both ON- and OFF-responses. CONCLUSIONS: Common underlying developmental genetic or environmental unifying casualties are speculated to be at fault in causing these cases of associated retinal and brain abnormalities. No single etiology is expected. Multiple potential causes acting early in embryogenesis effecting neuronal induction, migration and differentiation are theorized. These occur at a time when brain and retinal cells are sufficiently undifferentiated to be similarly effected. We call these cases examples of Brain Retina Neuroembryodysgenesis (BRNED). Homeobox and PAX genes with global neuronal developmental influences are gene candidates to unify the observed disruption of brain and retinal cell development. The ERG can provide a valuable clinical addition in understanding and ultimately classifying these disorders.

Brain↗
PubMed1995

Long-term results of in situ saphenous vein bypass. Analysis of 2058 cases.

OBJECTIVE: The authors evaluated the long-term patency and outcome of patients undergoing infrainguinal reconstruction using the in situ saphenous vein. SUMMARY BACKGROUND DATA: The in situ saphenous vein bypass has demonstrated excellent patency and limb salvage rates in numerous studies. The authors previously reported their early results with these bypass procedures, and this article represents their long-term experience with 2058 in situ saphenous vein bypasses during a 20-year period. This comprises the largest series with long-term follow-up of in situ saphenous vein bypasses in the literature. METHODS: From 1975 to 1995, 3148 autogenous vein bypasses were performed at the authors' institution, of which 2058 used the saphenous vein in situ. The indication for operation was limb-threatening ischemia in 1875 of 2058 patients (91%). In 88% of patients with an intact ipsilateral saphenous vein, an in situ bypass was completed successfully. One thousand twenty-three bypasses (69%) were terminated at the infrapopliteal level. Of these bypasses, 1562 of 2058 (76%) were completed using the closed in situ technique. RESULTS: The 30-day patency rate was 96%, and the cumulative secondary patency was 91%, 81%, and 70% at 1, 5, and 10 years, respectively. Limb salvage rates using the in situ bypass were 97%, 95%, and 90% at 1, 5, and 10 years, respectively. CONCLUSION: The infrainguinal inflow source, length of bypass, specific outflow vessel, or vein diameter did not have a significant effect on immediate or long-term bypass performance. These data suggest that the in situ saphenous vein is an excellent conduit for femoropopliteal and femoral to infrageniculate bypasses for limb salvage.

Adolescent↗
PubMed1994

Optic nerve hypoplasia in association with brain anomalies and an abnormal electroretinogram.

Abnormal electroretinograms (decreased amplitude and prolonged implicit time > 2 standard deviations) in several patients with optic nerve hypoplasia (ONH) and developmental brain anomalies led us to study the electroretinogram (ERG) in 34 consecutive cases of ONH presenting to our practice. Ages of the subjects were between 7 months and 13 years (mean, 4 years). ERGs were recorded from each eye by means of a contact lens electrode and ganzfeld stimuli. Rod-dominated dark-adapted responses were recorded as well as cone-dominated light-adapted responses. When clinically indicated, brain imaging by either computed tomography (CT) or magnetic resonance imaging (MRI) was performed. The ERG was abnormal in 12 (35%) of the children, including five (42%) with unilateral ONH. Imaging studies of the brain in 12 children with ONH and an abnormal ERG disclosed brain malformations in nine (75%) of them compared to five (23%) in the group with ONH and a normal ERG. An abnormal ERG associated with ONH and brain malformations may represent retinal or transsynaptic degeneration beyond the ganglion cell layer and implies a shared causative mechanism.

Adolescent↗
PubMed1994

Retinal signal transmission in Duchenne muscular dystrophy: evidence for dysfunction in the photoreceptor/depolarizing bipolar cell pathway.

There have been reports of abnormal retinal neurotransmission determined by electroretinography in boys with Duchenne and Becker muscular dystrophy. Dystrophin may play a role in transmitting signals between photoreceptors and the excitatory synapse of the ON-bipolar cell. These electroretinographic changes appeared to be limited to the rod ON-pathway but we felt there was also similar abnormality in the cone ON-pathway. We used long-duration stimuli to separate ON-(depolarizing bipolar cell) and OFF (hyperpolarizing bipolar cell) contributions to the cone-dominated ERG to better understand how the retina functions in boys with Duchenne muscular dystrophy. We recorded the electroretinograms of 11 boys with Duchenne muscular dystrophy and found abnormal signal transmission at the level of the photoreceptor and ON-bipolar cell in both the rod and cone generated responses. The OFF-bipolar cell that responds to the offset of the stimulus continues to function normally. The results support our hypothesis that retinal dystrophin plays a role in receptor function or controlling ion channels at the level of the photoreceptor and depolarizing bipolar cell.

Adolescent↗
PubMed1993

The effects of dystrophin gene mutations on the ERG in mice and humans.

PURPOSE: The authors' earlier findings of a negative electroretinogram (ERG) in a boy with Duchenne muscular dystrophy (DMD) led them to investigate dystrophin gene deletions and ERGs in five boys with DMD. The authors wanted to determined whether there were similar ERG findings in an animal model for DMD, the mdx mouse. METHODS: Ganzfeld ERGs were recorded in five boys with DMD after a complete ophthalmic examination. The dystrophin gene was analyzed by Southern blot hybridization. ERGs were recorded in anesthetized mdx and control mice with a modified Grass photostimulator (Grass Instrument Company, Quincy, MA). RESULTS: Ophthalmic examinations in all five boys had normal findings, yet an abnormal negative ERG was recorded for each subject. The subjects' gene deletions were variable, ranging from large deletions to no detectable deletions. The ERGs of the mdx mice were normal and did not differ significantly from those of the control mice. CONCLUSIONS: The authors believe the unique ERG recorded for the human subjects is a manifestation of DMD associated with defects at the dystrophin gene locus and represents a new clinical entity. The ERG of the mdx mouse may be spared for several reasons, including milder effects of the mouse gene defect, differences in muscle and retinal gene product, or species differences in the biochemical role of dystrophin. The ERG shows promise of becoming a noninvasive diagnostic tool for DMD and its milder allelic forms.

Animals↗
PubMed1992

Is long vein bypass from groin to ankle a durable procedure? An analysis of a ten-year experience.

Long vein bypass from the femoral artery to the level of the ankle may be performed with good initial success despite extreme bypass length and limited outflow tracts. However, the long-term performance of these bypasses remains to be defined. During the last 10 years we have performed single greater saphenous vein in situ bypass to the ankle level in 270 patients. There were 187 male and 83 female patients, and 61% of the patients were diabetic. The operative mortality rate was 3.7%. Cumulative bypass patency was 79% at 3 years and 73% at 5 years. In a similar manner, limb salvage was 93% at 3 years and 89% at 5 years. The patency rate was similar for various inflow arteries (common femoral, 88 cases; proximal superficial femoral, 135 cases; and deep femoral, 41 cases) and outflow tracts (dorsal pedal, 72 cases; anterior tibial, 59 cases; posterior tibial, 72 cases, and peroneal, 67 cases). Short bypasses, composite bypasses, free-vein grafts, and bypasses proximal to 10 cm above the ankle were excluded from this analysis. These data show that a long bypass to the ankle level for limb salvage is a durable procedure. The basic concept of bypassing all occlusive disease to the distal open artery in patients undergoing limb salvage should be an acceptable dictum. Excellent long-term patency and limb salvage rates are achievable by following this principle.

Adult↗
PubMed1991

Experimental autoallergic sialadenitis in the LEW rat. I. Parameters of disease induction.

Experimental autoallergic sialadenitis (EAS) is an autoimmune mononuclear cell infiltration of the submandibular salivary gland that results in tissue destruction and glandular dysfunction. A previous report has described an animal model of induced EAS in LEW rats following sensitization with allogeneic WF submandibular gland (SMG). The present study extends this observation to an EAS disease model induced following sensitization of LEW rats with syngeneic LEW SMG. Furthermore, we describe the characterization of the mononuclear cells in the glandular infiltrates, evaluate the production of autoantibodies, and establish the parameters important for reproducible induction of EAS. Our results demonstrate that EAS can be induced in a completely syngeneic system and the histopathology of disease induction in the syngeneic and allogeneic model systems is similar. Helper/inducer (CD4+) and suppressor/cytotoxic (CD8+) T-cell subsets are the dominant cell types in the salivary mononuclear cell infiltrate. An anti-duct autoantibody was found in the serum of virtually all LEW rats with EAS. Although closely associated with disease development, the presence of this antibody was not a prerequisite for development of histopathologic disease. Induction of disease in both the syngeneic and allogeneic models of EAS is dependent upon administration of Bordetella pertussis at the time of sensitization. Finally, the histopathology of the cellular infiltrates in both the allogeneic and syngeneic models of EAS resemble those observed in the salivary tissues of Sjögren's patients. While there are several differences between EAS in the LEW rat and the full expression of Sjögren's syndrome, EAS may serve as a model to study the salivary gland component of this complex human disease.

Animals↗