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Biomedical subjects

T Spencer

Publications and source records attributed to T Spencer.

At least 91 records · Page 5Linked to original sources
PubMed1993

Nortriptyline treatment of children with attention-deficit hyperactivity disorder and tic disorder or Tourette's syndrome.

Although as many as 50% of patients with Tourette's syndrome (TS) also meet diagnostic criteria for Attention-deficit Hyperactivity Disorder (ADHD), until recently little attention has been paid to ADHD symptoms in the assessment of therapeutic outcome of TS or patients with chronic motor tics (CMT). Because antipsychotics are of limited value in controlling the symptoms of ADHD and stimulants can exacerbate tics, alternative treatments for patients with chronic tic disorder (CTD) (TS or CMT) plus ADHD (CTD+ADHD) patients are direly needed. We examined the efficacy of the tricyclic antidepressant nortriptyline in the treatment of pediatric patients with CTD+ADHD ascertained from systematic chart reviews of all subjects with this diagnosis treated with nortriptyline. Of the 12 identified patients, 67% had significant improvement in CTD symptomatology and 92% significantly improved ADHD symptoms without major adverse effects over an average follow-up period of 19 months. Although the conclusions from this retrospective report can be only seen as preliminary until replicated in a controlled investigation, the magnitude and persistence of the response is encouraging and suggest a therapeutic role for nortriptyline in the treatment of CTD+ADHD patients.

Adolescent↗
PubMed1993

Bupropion exacerbates tics in children with attention-deficit hyperactivity disorder and Tourette's syndrome.

Concerns have been raised regarding the development of tics in some children with attention-deficit hyperactivity disorder (ADHD) receiving stimulants. Because in many patients with Tourette's syndrome (TS) the ADHD symptoms are the major source of disability, alternative nonstimulant treatments are needed. Initial reports on bupropion have suggested that it may be an effective alternative in children and adults with ADHD. The value of bupropion as an alternative treatment for patients with comorbid TS and ADHD is determined by the question of association with exacerbation of tics. The purpose of this study was to examine an apparent association with exacerbation of tics in patients with comorbid TS and ADHD. A careful retrospective analysis was conducted of clinic cases of patients who all had comorbid TS and ADHD treated with bupropion. We present four cases of children with ADHD and comorbid TS treated with bupropion in whom tics were exacerbated by this medicine. This series suggests that bupropion may not be an appropriate alternative to stimulants in the treatment of ADHD in TS.

Attention Deficit Disorder with Hyperactivity↗
PubMed1993

A retrospective study of serum levels and electrocardiographic effects of nortriptyline in children and adolescents.

OBJECTIVE: We retrospectively evaluated a large pediatric population treated with nortriptyline (NT) in an outpatient psychopharmacology clinic to assess pharmacokinetic and electrocardiographic (EKG) effects. METHODS: A systematic search revealed 82 children and adolescents treated naturalistically with NT. All patients with available EKGs and serum NT levels were included in the series with the exception of those receiving concomitant antipsychotic agents. Forty-three percent of subjects were receiving medications in addition to NT. RESULTS: Patients received an average (+/- SE) NT dose of 2.0 +/- 0.1 mg/kg yielding mean serum NT levels of 105.5 +/- 7.4 ng/mL. There was a linear relationship of NT dose (mg/kg) to serum NT levels (r = 0.50, p < 0.0001). NT treatment resulted in small increases in heart rate, and PR, QRS, and QTc intervals (all ps < 0.01), of similar magnitude in children and adolescents. Individuals with the highest baseline EKG indices had the least amount of change in those indices with NT treatment. There were only a few statistically significant associations between NT dose or serum NT levels and EKG parameters. NT treatment was significantly associated with the onset of asymptomatic sinus tachycardia (heart rate > 100 beats per minute), and prolongation of the EKG QRS (> 100 msec) and QTc (> 440 msec) intervals. CONCLUSIONS: These findings suggest: (1) NT has a predictable dose to level relationship, (2) the effect of NT on the EKG in this age group is mild and similar to that reported with other tricyclic antidepressants, and (3) there are few age-specific differences in NT-induced EKG changes.

Adolescent↗
PubMed1993

Nortriptyline in the treatment of ADHD: a chart review of 58 cases.

OBJECTIVE: The potential benefit of the tricyclic antidepressant medication, nortriptyline (NT), in the treatment of children and adolescents with attention deficit hyperactivity disorder (ADHD) was evaluated. METHOD: A systematic search was conducted from a computerized data base of all clinic patients in an outpatient pediatric psychopharmacology unit treated with NT for ADHD. The records of the 58 subjects identified (37 children and 21 adolescents) were reviewed for overall response, dose, serum levels, and adverse effects. RESULTS: Ninety-seven percent of the identified subjects had failed to respond to an average of four previous medication trials, 84% had at least one comorbid diagnosis with ADHD, and 47% were receiving at least one concurrent medication. NT doses ranged from 0.4 to 4.5 mg/kg (X +/- SD = 2.0 +/- 1.0 mg/kg) and subjects received NT from 0.4 to 57.9 months (11.9 +/- 14.0 months). Overall, 76% of subjects were considered to have a moderate to marked improvement by an independent rater, which was corroborated by their clinicians. There was no association between response and age, rate of comorbidity, number of previous medication trials, or concurrent pharmacotherapy (all p NS). Although there were no overall differences in serum NT levels between responders and nonresponders, significantly more patients within the suggested therapeutic range in adults of 50 to 150 ng/ml were classified as "markedly improved" than those outside this range (68% versus 35%, p < 0.03). Mild adverse effects were reported in 20 subjects (34%). CONCLUSIONS: These findings suggest that NT may be an effective well-tolerated agent for ADHD children and adolescents. Additional controlled investigations utilizing NT for ADHD should be undertaken.

Adolescent↗
PubMed1993

Comparison of clonidine response in the treatment of attention-deficit hyperactivity disorder with and without comorbid tic disorders.

OBJECTIVE: Clonidine has been suggested as an alternative pharmacotherapy for patients with attention-deficit hyperactivity disorder (ADHD) and comorbid tic disorders. To examine the efficacy of clonidine in this population of children, the use of clonidine in the treatment of children with ADHD with and without comorbid tic disorders was examined in a retrospective chart review of 54 children over a 4-year period. METHOD: Treatment was administered openly to these patients in a Pediatric Psychopharmacology Clinic, and response was assessed using clinical global improvement measures. RESULTS: Clonidine treatment resulted in improvement in both the ADHD (39/54; 72%) and tic symptoms (18/24; 75%) groups. The findings suggested that the children with ADHD with comorbid tic disorders (23/24; 96%) have a more frequent positive behavioral response to clonidine than children with ADHD without comorbid tic disorders (16/30; 53%). CONCLUSIONS: This report provides further support of a role for clonidine in the treatment of children with ADHD, particularly for those with comorbid tic disorders.

Adolescent↗
PubMed1993

Desipramine treatment of children with attention-deficit hyperactivity disorder and tic disorder or Tourette's syndrome.

OBJECTIVE: As many as 50% of patients with Tourette's syndrome (TS) also meet diagnostic criteria for attention-deficit hyperactivity disorder (ADHD). Since antipsychotics are of limited value in controlling the symptoms of ADHD and stimulants can exacerbate tics, alternative treatments are directly needed. The purpose of this study was the examination of the efficacy of desipramine (DMI) in the treatment of pediatric patients with chronic tic disorder (CTD; TS or chronic motor tics) + attention-deficit hyperactivity disorder (ADHD). METHOD: All pediatric patients with the diagnosis of CTD that were treated with DMI were ascertained from retrospective systematic chart reviews of a psychopharmacology clinic and a neurology service specialized in movement disorders. RESULTS: Of the 33 identified patients, 30 had comorbid CTD + ADHD and three had CTD alone. In all, 82% had significant improvement in CTD symptomatology and 80% significantly improved ADHD symptoms without major adverse effects over an average follow-up period of 16 months. CONCLUSIONS: Although the conclusions from this retrospective report can be seen as preliminary only until replicated in a controlled investigation, the magnitude and persistence of the response is encouraging and suggest a therapeutic role for DMI in the treatment of CTD + ADHD patients.

Adolescent↗
PubMed1993

Patterns of psychiatric comorbidity, cognition, and psychosocial functioning in adults with attention deficit hyperactivity disorder.

OBJECTIVE: Although attention deficit hyperactivity disorder is a common disorder of childhood, its status as a disorder in adults is not clear. The authors reasoned that if the adult diagnosis of the disorder is a valid clinical entity, it should be similar to the childhood disorder with regard to patterns of psychiatric and cognitive findings. METHODS: Eighty-four adults with a clinical diagnosis of childhood-onset attention deficit hyperactivity disorder confirmed by structured interview who were referred for treatment were studied. Findings were compared with those from a preexisting study group of referred children with attention deficit hyperactivity disorder, nonreferred adult relatives of those children who also had attention deficit hyperactivity disorder, and adults without the disorder who were relatives of normal children. Subjects were evaluated with a comprehensive battery of psychiatric, cognitive, and psychosocial assessments. RESULTS: The referred and nonreferred adults with attention deficit hyperactivity disorder were similar to one another but more disturbed and impaired than the comparison subjects without the disorder. The pattern of psychopathology, cognition, and functioning among the adults with attention deficit hyperactivity disorder approximated the findings for children with the disorder. CONCLUSIONS: These results show that referred and nonreferred adults with attention deficit hyperactivity disorder have a pattern of demographic, psychosocial, psychiatric, and cognitive features that mirrors well-documented findings among children with the disorder. These findings further support the validity of the diagnosis for adults.

Adult↗
PubMed1993

Role of transforming growth factor alpha (TGF-alpha) in the transformation of ras-transfected rat intestinal epithelial cells.

Most intestinal tumors express transforming growth factor alpha (TGF-alpha) while normal immature crypt cells, the targets for tumor initiation, do not. We have used a rat intestinal cell line derived from immature epithelial crypt cells (IEC-18) to investigate the role of this growth factor in intestinal tumorigenesis. ras transformation of IEC-18 cells induces expression and secretion of TGF-alpha. By studying several independently derived IEC-ras clones, we have established that the amount of TGF-alpha secreted is proportional to the level of activated ras expressed by each clone. The growth of all ras-transformed IEC clones is significantly inhibited by neutralizing antibodies against TGF-alpha and by an antisense TGF-alpha expression vector, indicating a mitogenic role for this growth factor through an autocrine loop. To determine whether TGF-alpha itself can transform intestinal cells, IEC-18 clones transfected with TGF-alpha expression vectors were isolated and characterized. None of the TGF-alpha-expressing clones show any signs of tumorigenic transformation even when they secrete as much TGF-alpha as the IEC-ras clones. It seems, therefore, that TGF-alpha per se does not have the capacity to transform rat epithelial intestinal cells and that its role is mostly related to autocrine growth stimulation.

Animals↗
PubMed1992

Automated detection and quantification of microaneurysms in fluorescein angiograms.

Fluorescein angiograms from diabetics were digitised for analysis using digital image-processing techniques. Computer algorithms were written to detect and count microaneurysms present in the images. The accuracy, speed and reproducibility of the technique were assessed and compared with those of manual counts made by clinicians from both digitised and analogue images. Free-response ROC (receiver operating characteristic) curves were used to assess the performance of both the clinicians and the computer by comparing the results with "gold standards" compiled from prints of the original fluorescein angiograms. The computer performed as well as the clinicians when the latter were analysing the digitised images (512 x 512 pixel resolution), but only when one image was acquired at 4 times this resolution did the computer's performance match that of the clinicians analysing the analogue image. The automated technique was more reproducible than the manual method.

Algorithms↗
PubMed1992

Growth deficits in children treated with desipramine: a controlled study.

Using multiple assessment methods, growth deficits in weight and height were examined in a clinical sample of children and adolescents with attention deficit hyperactivity disorder treated chronically (mean 14 months) with desipramine (DMI) and two comparison samples of children treated chronically with methylphenidate (MPH) and a not-treated group. Although there were statistically significant weight deficits in children treated with both DMI and MPH compared with normal controls, only those treated with MPH sustained height deficits that attained statistical significance. It appears that DMI may be an appropriate alternative for patients with stimulant-associated severe suppression of growth in height.

Adolescent↗
PubMed1991

Quantification of diabetic maculopathy by digital imaging of the fundus.

Measurement of the extent of diabetic retinopathy is an essential part of assessing the efficacy of local or systemic treatment regimens. Current clinical studies use empirical grading of retinopathy which is performed by a trained observer using standard photographs. This method is relatively arbitrary, as well as time consuming and vulnerable to observer error. We have developed a digital fundus imaging system and image processing programs which provide objective, quantitative measures of macular oedema, retinal exudates, and microaneurysms in diabetic retinopathy. Using fluorescein angiograms, the degree of macular oedema is quantified both in terms of area of fundus involved and severity of oedema by analysis of the temporal changes in intensity of fluorescence. Fluorescein angiograms are also used for the detection and counting of microaneurysms, by a combination of shade correction, matched filtering, and shape algorithms. For detection and measurement of retinal exudates, a colour transparency projected through a red free filter is analysed using a combination of shade correction and thresholding techniques. The system described is in clinical use, and has potential for a wide variety of applications. With further development, digital analysis of fundus images should supercede the currently used manual semi-quantitative methods, providing faster, more accurate, objective quantitative results.

Aneurysm↗
PubMed1991

An outbreak of Streptococcus pyogenes infection associated with calcium oxalate urolithiasis in guinea pigs (Cavia porcellus).

An outbreak of Streptococcus pyogenes infection occurred in a colony of 800 Dunkin-Hartley guinea pigs resulting in 364 (46%) deaths involving breeders, sucklings, weaners, but mainly adults used as a source of blood meals for haematophagus flies (Glossina palpalis). Clinical signs included bleeding from the nose, mouth and vagina before death. Necropsy revealed pneumonia with consolidation of one or both lungs, haemopericardium and haemothorax. There were yellowish-grey deposits in the urinary bladder of more than 50% of both affected breeders and adults used for feeding haematophagus flies. Beta-haemolytic Streptococcus pyogenes was isolated in pure culture from many tissues including the urinary bladder. The survivors were treated with oxytetracycline (Terramycin-LA; Pfizer) using the intra-muscular route and the response was good.

Animals↗
PubMed1990

Role of the human transferrin receptor cytoplasmic domain in endocytosis: localization of a specific signal sequence for internalization.

Wild-type and mutant human transferrin receptors have been expressed in chicken embryo fibroblasts using a helper-independent retroviral vector. The internalization of mutant human transferrin receptors, in which all but four of the 61 amino acids of the cytoplasmic domain had been deleted, was greatly impaired. However, when expressed at high levels, such "tailless" mutant receptors could provide chicken embryo fibroblasts with sufficient iron from diferric human transferrin to support a normal rate of growth. As the rate of recycling of the mutant receptors was not significantly different from wild-type receptors, an estimate of relative internalization rates could be obtained from the distribution of receptors inside the cell and on the cell surface under steady-state conditions. This analysis and the results of iron uptake studies both indicate that the efficiency of internalization of tailless mutant receptors is approximately 10% that of wild-type receptors. Further studies of a series of mutant receptors with different regions of the cytoplasmic domain deleted suggested that residues within a 10-amino acid region (amino acids 19-28) of the human transferrin receptor cytoplasmic domain are required for efficient endocytosis. Insertion of this region into the cytoplasmic domain of the tailless mutant receptors restored high efficiency endocytosis. The only tyrosine residue (Tyr 20) in the cytoplasmic domain of the human transferrin receptor is found within this 10-amino acid region. A mutant receptor containing glycine instead of tyrosine at position 20 was estimated to be approximately 20% as active as the wild-type receptor. We conclude that the cytoplasmic domain of the transferrin receptor contains a specific signal sequence located within amino acid residues 19-28 that determines high efficiency endocytosis. Further, Tyr 20 is an important element of that sequence.

Amino Acid Sequence↗
PubMed1989

Isolation and characterization of the cDNA for pulmonary surfactant-associated protein-B (SP-B) in the rabbit.

Pulmonary surfactant contains phospholipids including dipalmitoyl-phosphatidylcholine and three surfactant-associated proteins designated SP-A, SP-B and SP-C. A cDNA for rabbit SP-B has been isolated from a fetal (30 days gestation) rabbit lung cDNA library constructed in lambda gt11. The cDNA and deduced amino acid sequences show strong homology with the cDNAs and predicted 40 kDa proproteins for human and canine SP-B. Strong homology is also observed with the amino acid sequences directly determined for the mature 8 kDa bovine and porcine SP-B isolated from lung lavage. SP-B is remarkable for its high cysteine and proline content and for the hydrophobic nature of the organic solvent-soluble, mature protein. In vitro translation of sense but not antisense RNA transcribed from the cDNA led to the production of 40 kDa and 32 kDa proteins. These proteins were immunoprecipitated by an antibody raised against bovine SP-B. Northern blot analysis revealed the mRNA for rabbit SP-B appears in fetal rabbit lung late in gestation and falls slightly in the neonate.

Amino Acid Sequence↗
PubMed1988

The trisomy (5)(q31-qter) syndrome: study of a family with a t(5:14) translocation.

We report a child with multiple malformations caused by trisomy for the distal part of the long arm of chromosome No 5. A neonatal diagnosis of Down's syndrome had previously been made on the basis of clinical examination and the detection of an additional chromosome not unlike No 21. A subsequent clinical re-evaluation, with the cooperation of the parents who permitted further studies, led to the confirmation of the true diagnosis. The mother was the carrier of a balanced translocation between chromosome No 5 and No 14. The child had severe growth and psychomotor retardation and characteristic features: microcephaly, antimongoloid slant, epicanthus, low set ears, down-turned mouth, and long upper lip. She was hypertonic and a congenital heart disease (atrial septal defect) was present. We have compared this case with others known to be trisomic for segment 5q31-qter.

Abnormalities, Multiple↗
PubMed1987

A new interstitial deletion of chromosome No. 4 del(4) (q22::q25).

A female child is described with multiple anomalies including epicanthus, frontal bossing, short sternum, polydactyly, cleft of the larynx, renal cysts, and unusual dermatoglyphics. She died aged 3 months and was found to have a unique de novo deletion of chromosome No. 4 (q22-q25). This case is compared with other long arm deletions of 4q and reference made to assignment of genetic markers to chromosome No. 4.

Abnormalities, Multiple↗
PubMed1987

MR imaging of pituitary adenoma: CT, clinical, and surgical correlation.

Twenty-five patients with suspected pituitary adenoma were evaluated prospectively with CT and MR. Nine patients underwent transsphenoidal surgery, and three of these showed a documented decrease in size of mass on bromocriptine therapy. CT was more sensitive than MR for detecting focal lesions (seven vs three) and sellar-floor erosion (12 vs six). MR was superior to CT in identifying infundibular abnormalities (seven vs six), focal abnormalities of the diaphragma sellae (10 vs seven), cavernous sinus invasion (four vs two), and optic chiasm compression (six vs zero). Thus, MR may be the procedure of choice for optimal identification and localization of macroadenoma. For patients with suspected microadenoma, however, this preliminary series indicates that CT remains the radiographic procedure of choice.

Adenoma↗