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Biomedical subjects

C M Bradley

Publications and source records attributed to C M Bradley.

At least 19 recordsLinked to original sources

MR nerve imaging in a prospective cohort of patients with suspected carpal tunnel syndrome.

OBJECTIVES: To evaluate the reliability and diagnostic accuracy of high-resolution MRI of the median nerve in a prospectively assembled cohort of subjects with clinically suspected carpal tunnel syndrome (CTS). METHODS: The authors prospectively identified 120 subjects with clinically suspected CTS from five Seattle-area clinics. All subjects completed a hand-pain diagram and underwent a standardized nerve conduction study (NCS). The reference standard for determining CTS status was a classic or probable hand pain diagram and NCS with a difference >0.3 ms between the 8-cm median and ulnar peak latencies. Readers graded multiple imaging parameters of the MRI on four-point scales. The authors also performed quantitative measurements of both the median nerve and carpal tunnel cross-sectional areas. NCS and MRI were interpreted without knowledge of the other study or the hand pain diagram. RESULTS: Intrareader reliability was substantial to near perfect (kappa = 0.76 to 0.88). Interreader agreement was lower but still substantial (kappa = 0.60 to 0.67). Sensitivity of MRI was greatest for the overall impression of the images (96%) followed by increased median nerve signal (91%); however, specificities were low (33 to 38%). The length of abnormal signal on T2-weighted images was significantly correlated with nerve conduction latency, and median nerve area was larger at the distal radioulnar joint (15.8 vs 11.8 mm(2)) in patients with CTS. A logistic regression model combining these two MR variables had a receiver operating characteristic area under the curve of 0.85. CONCLUSIONS: The reliability of MRI is high but the diagnostic accuracy is only moderate compared with a research-definition reference standard.

Adult↗

Lipoprotein(a) as a risk factor for maternal cardiovascular disease mortality in kindreds with familial combined hyperlipidemia or familial hypertriglyceridemia.

Most but not all epidemiologic studies have shown that lipoprotein(a) [Lp(a)] is a risk factor for cardiovascular disease (CVD). Lp(a) levels are also strongly genetically influenced. The purpose of this study was to evaluate the association between Lp(a) levels in adult offspring and parental CVD mortality in 61 kindreds with familial forms of hyperlipidemia. The study sample consisted of offspring-parent pairs in which offspring had fasting Lp(a) measurements and parents had 20-year vital status data and standardized cause-of-death classification if deceased. Linear regression analyses, using a robust variance estimator, were performed separately for 241 offspring with known maternal history (114 mothers) and 194 offspring with known paternal history (93 fathers). Maternal history of CVD mortality was significantly (p=0.004) associated with 2.4-fold higher median Lp(a) levels in offspring compared with those with no maternal history, independent of diabetes, lipid-lowering medications and hormone use. No association was observed between paternal CVD mortality and offspring Lp(a) levels (p=0.505). Adjusting for apolipoprotein(a) kringle 4 number did not alter these parent-specific associations. In conclusion, Lp(a) levels in offspring may be associated with maternal but not paternal history of CVD mortality. This parent-specific finding needs to be confirmed in other samples of high-risk families.

Adolescent↗

Cardiovascular disease mortality in familial forms of hypertriglyceridemia: A 20-year prospective study.

BACKGROUND: Familial combined hyperlipidemia (FCHL) and familial hypertriglyceridemia (FHTG) are 2 of the most common familial forms of hyperlipidemia. There is a paucity of prospective data concerning the risk of cardiovascular disease (CVD) in such families. The purposes of this study were to estimate 20-year total and CVD mortality risk among relatives in these families and to evaluate plasma triglyceride as a predictor of death. METHODS AND RESULTS: The study was based on lipid and medical history data from 101 families ascertained in 2 studies conducted in the early 1970s. Vital status and cause of death was determined during 1993 to 1997 for 685 family members, including first-degree relatives of the probands and spouse control subjects. Compared with spouse control subjects, 20-year CVD mortality risk was increased among siblings and offspring in FCHL (relative risk 1.7, P=0.02) after adjustment for baseline covariates. In FHTG families, the relative risk was also 1.7 but was not statistically significant (P=0.39). Baseline triglyceride was associated with increased CVD mortality risk independent of total cholesterol among relatives in FHTG families (relative risk 2.7, P=0.02) but not in FCHL families (relative risk 1.5, P=0.16) after adjustment for baseline covariates. CONCLUSIONS: This prospective study establishes that relatives in FCHL families are at increased risk for CVD mortality and illustrates the need for effective prevention strategies in this group. Baseline triglyceride level predicted subsequent CVD mortality among relatives in FHTG families, adding to the growing evidence for the importance of hypertriglyceridemia as a risk factor for CVD.

Adult↗

Parental occupations as risk factors for craniosynostosis in offspring.

In a population-based case-control study, we examined relations between maternal and paternal occupations and the risk of infant craniosynostosis. Cases were 212 children born to Colorado residents and diagnosed during 1986-1989 with radiographically confirmed synostosis of unknown etiology. Controls were 291 children randomly selected from state birth records and frequency matched to cases on month and year of birth. Trained staff conducted telephone interviews of mothers of case and control children. Information was obtained about each job held by either parent during the pregnancy, and any job that the father held during the 3 months before the last menstrual period before conception. Jobs were coded using 1980 Census occupation and industry codes. We found no strong associations for maternal occupations. Of paternal occupations, two groups were associated with moderately increased odds ratios after adjustment for maternal smoking and altitude: agriculture and forestry (odds ratio = 2.3; 95% confidence interval = 1.0-5.2), and mechanics and repairmen (odds ratio = 2.7; 95% confidence interval = 1.2-6.1). For both, the odds ratios were higher for males.

Adolescent↗

Increased risk of craniosynostosis with maternal cigarette smoking during pregnancy.

We analyzed data from a population-based case control study to determine whether maternal prenatal smoking or alcohol drinking might increase the risk of craniosynostosis. Between 1986 and 1989, the Colorado Craniosynostosis Registry ascertained 233 children whose diagnoses were confirmed by an independent radiologist. Of the 212 (91%) cases who participated 86 had lambdoid, 69 had sagittal, 25 had coronal, 18 had metopic, and 14 had multiple suture synostosis. Random sampling of birth certificate records yielded 367 eligible controls, of whom 291 (79%) participated. Study staff interviewed case and control mothers between 1989 and 1991 for prenatal smoking and alcohol drinking. We used Mantel-Haenszel and polychotomous logistic regression techniques to estimate the relative odds of craniosynostosis for smoking and drinking in all cases and in relevant case subgroups. Smoking was associated with a relative odds of craniosynostosis of 1.7 (95% confidence interval, 1.2-2.6). For smoking of more than one pack per day, the relative odds were 3.5 (1.5-8.4) for all types of synostosis combined, and 5.6 (2.1-15.3) for coronal synostosis. No strong or significant association was noted for drinking. Maternal prenatal smoking may increase the risk of craniosynostosis in this population.

Adult↗

Outcome after fractures of the femur in Paget's disease.

We reviewed ninety-three patients who had one hundred and seven complete fractures of the femur between them and were treated over a twenty-five year period in Western Australia and South Australia. Operative surgical management of complete fractures in the middle and distal thirds was usually successful. In contrast, fractures proximal to the middle third were regularly associated with non-union, implant failure and requirement for revision surgery. In view of this significant difference in outcome after fracture of the pagetic femur in different sites, a comprehensive surgical management strategy is recommended in order to avoid complications.

Aged↗

Arthroscopic removal of acrylic cement from unreduced hip prosthesis.

A case is reported in which entrapped polymethylmethacrylate following traumatic dislocation of a total hip replacement prevented complete reduction. A combined arthroscopic and fluoroscopic technique was used to remove the entrapped polymethylmethacrylate. Manipulation of the total hip prosthesis was done after removal of polymethylmethacrylate to minimize mechanical abrasion. This technique allows direct visual assessment of the articulating surfaces as well as the mechanical stability of the prosthesis. The morbidity related to the procedure is minimal and a short rehabilitation period is the major advantage.

Aged↗

Pigmentary abnormalities and mosaicism for chromosomal aberration: association with clinical features similar to hypomelanosis of Ito.

Thirteen patients with hypopigmentation of the skin characteristic of hypomelanosis of Ito, and with developmental disabilities or structural malformations, or both, were examined at our center. Eight were found to have abnormal karyotypes in lymphocytes, fibroblasts, or both. No single clinical feature was predictive of chromosome imbalance in this group of patients. Cytogenetic findings included a balanced de novo X-autosome translocation; ring 10; 45,X/46,X,+ring; mosaic del 13q11 (fibroblasts); mosaic triploidy (fibroblasts); mosaic tetrasomy 12p (fibroblasts); mosaic apparently balanced 15;22 translocation (peripheral blood); and mosaic trisomy 18 (peripheral blood). Hypomelanosis of Ito is characterized by swirly hypopigmentation or depigmentation of the skin with or without other malformations. Autosomal dominant, autosomal recessive, and X-linked dominant inheritance have been suggested but not confirmed. Chromosomal aneuploidy has also been reported. We believe that hypomelanosis of Ito is an etiologically heterogeneous physical finding, and recommend karyotyping of multiple tissues of all patients with abnormal cutaneous pigmentation associated with developmental delay or structural malformations.

Adolescent↗

Characterization of an unusual and complex chromosome 21 rearrangement using somatic cell genetics and cloned DNA probes.

In a previous case of a newborn infant with typical Down syndrome, chromosome analysis indicated the presence of an unusual and complex translocation of chromosome 21. The patient's cells contained one normal chromosome 21 and a rearranged, F group-sized submetacentric chromosome. This abnormal chromosome appeared to involve duplication of the distal portion of 21q with translocation to the short arm, and a deletion of C-band-positive centromeric heterochromatin. Using linearly ordered cloned DNA probes, we report the detailed molecular examination of this abnormal chromosome, which has been isolated on a hamster background in a hybrid cell line. Both short arm and pericentromeric sequences are present on this chromosome, as well as distal 21q sequences. However, a substantial portion of proximal 21q is deleted. The distal boundary of this deleted section can be pinpointed within the region between two loci (D21S8 and D21S54), a distance of about 5,000 kb. This study illustrates the power of using precisely mapped, linearly ordered DNA probes to characterize this type of rearrangement. In addition, this hybrid cell line can also be used as a member of a mapping panel to map DNA sequences regionally on chromosome 21.

Animals↗

Nonfluorescent dicentric Y in males with hypospadias.

We report three boys with severe hypospadias and bilaterally palpable testes with abnormalities of the Y chromosome detected by Q-banding. Severe hypospadias with palpable testes is an unusual presentation for Y chromosome abnormalities. Based on our experience, we recommend that boys with this phenotype undergo complete cytogenetic evaluation, because Y chromosome abnormalities prompt additional management concerns.

Humans↗

Mosaicism for ring 19: a case report.

A male with mosaicism for ring 19 presented with a complex cardiac malformation, microcephaly and minor dysmorphic features. Intellectual development has been within normal limits. This chromosome aberration has been reported only twice before and no clear phenotype-karyotype correlations are recognized.

Abnormalities, Multiple↗

Trisomy Xq in a male: the isochromosome X Klinefelter syndrome.

We report on a male with trisomy Xq resulting from an isochromosome Xq which is preferentially inactivated: 47,XY,+i(Xq). Six previous cases have been reported. These patients are similar to patients with classical Klinefelter syndrome (47,XXY) in that they have infertility, decreased masculinization, gynecomastia, and elevated luteinizing hormone (LH) and follide stimulating hormone (FSH) levels. They may differ in having average intelligence and normal to short stature. These findings indicate that extra copies of the long arm of X have phenotypic expression, even though activated only in early development.

Adolescent↗

Studies on performance with aspirin and paracetamol and with the centrally acting analgesics meptazinol and pentazocine.

Effects of aspirin (325 and 650 mg) and paracetamol (500 and 1000 mg), and of the centrally acting analgesics meptazinol (100 and 200 mg) and pentazocine (25 and 50 mg) on visuo-motor coordination and dynamic visual acuity, together with critical flicker fusion, digit symbol substitution, complex reaction time and subjective assessments of mood, were studied from 0.75-2.0 h after ingestion by seven healthy female adults. The study was double-blind and placebo controlled, and triprolidine (10 mg) was used as the active control. No effects of meptazinol and paracetamol on performance were observed. Pentazocine (25 mg) impaired performance on digit symbol substitution (p less than 0.05) and aspirin (650 mg) appeared to have shortened complex reaction time (p less than 0.05). Meptazinol (100 mg) increased the component of mood assessments related to wakefulness (p less than 0.05). Impaired performance with pentazocine may involve opioid receptor activity, while the apparent alerting effect of meptazinol may relate to its cholinergic activity. The possible effect of aspirin on reaction time needs to be confirmed.

Acetaminophen↗

Studies on the central effects of the H1-antagonist, loratadine.

Effects of loratadine (10, 20 and 40 mg) on visuo-motor coordination, dynamic visual acuity, short-term memory, digit symbol substitution, and on subjective assessments of mood were tested before, and 0.5, 1.5, 3.5 and 5.5 h after ingestion by 6 healthy female adults. There were no effects of 10 or 20 mg loratadine. With 40 mg loratadine the number of substitutions on the digit symbol test was reduced 5.5 h after ingestion, and on dynamic visual acuity response time was increased at 3.5 h and the number of responses missed was increased at 5.5 h. Triprolidine (10 mg) which was used as active control impaired performance on all the tasks and impaired performance was observed at all times after ingestion. Loratadine is a promising antihistamine for individuals involved in skilled activity. The anticipated single daily dose of 10 mg is unlikely to impair performance.

Adult↗

Behavioural responses to diazepam of drug-naive and experienced monkeys (Macaca mulatta).

Effects of 5 mg/kg diazepam given once a week for several weeks to drug-naive and drug-experienced monkeys were studied on a spatial delayed-alternation task. In both groups response latency was increased and the number of correct responses was reduced. The effects were consistent over weeks in the experienced monkeys, but in the naive monkeys there were greater initial effects on response latency and on repeat errors, and these lessened over 2-3 weeks. Thereafter, effects resembled those observed in the experienced group. Results are discussed in terms of the possible factors involved in the development and persistence of tolerance to benzodiazepines.

Animals↗

Effects of a mu-opioid receptor agonist (codeine phosphate) on visuo-motor coordination and dynamic visual acuity in man.

Effects of codeine (30, 60 and 90 mg) on visuo-motor coordination and dynamic visual acuity, together with critical flicker fusion, digit symbol substitution, complex reaction time and subjective assessments of mood, were studied from 0.75-2.0 h after ingestion by six healthy female adults. The study was double-blind and placebo controlled, and triprolidine (10 mg) was used as the active control. The effect on visuo-motor coordination was limited and was dose related and linear, and performance was altered on visuo-motor coordination with 60 and 90 mg codeine, and on dynamic visual acuity with 90 mg codeine (P less than 0.05). No other effect of codeine was detected. Modulated neuromuscular function is likely to be the common denominator of the changes in performance with codeine, though nausea, but not sedation, may be a contributory factor. It is possible that altered performance with codeine may involve interactions with different receptors than those which lead to sedation.

Adult↗

Isolation and analysis of the 21q+ chromosome in the acute myelogenous leukemia 8;21 translocation: evidence that c-mos is not translocated.

Acute myelogenous leukemia (AML), subgroup M2, is associated with a nonrandom chromosomal translocation, t(8;21)(q22,q22). The oncogene c-mos also has been localized to the q22 band on chromosome 8. There is also evidence that genes on chromosome 21 may be important in the development of leukemia. To determine whether the c-mos oncogene has been translocated in AML-M2 with this translocation and to isolate DNA sequences and genes from these two chromosomes that may be important in malignancy, we constructed somatic cell hybrids between a Chinese hamster ovary cell (CHO) mutant defective in glycine metabolism and myeloblasts with an 8;21 translocation from a patient with AML. We isolated the 21q+ chromosome of this translocation in a somatic cell hybrid and showed that the c-mos oncogene had not been translocated to chromosome 21, ruling out the possibility that translocation of c-mos to chromosome 21 is necessary for development of AML-M2. In addition, there was no detectable rearrangement of the c-mos locus within a 12.4-kilobase region surrounding the gene, indicating that rearrangement of the coding region of the gene itself or alteration of proximal 5' or 3' flanking sequences is not involved. We used this hybrid to determine whether specific DNA sequences and biochemical markers from chromosomes 8 and 21 had been translocated in this case.

Animals↗