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Biomedical subjects

J Cunningham

Publications and source records attributed to J Cunningham.

At least 37 records · Page 2Linked to original sources
PubMed2001

Nonresponse in a follow-up to a representative telephone survey of adult drinkers.

OBJECTIVE: Examined predictors of nonresponse among respondents who agreed to receive a follow-up questionnaire on alcohol use after participating in a representative telephone survey, and among respondents who did and did not return the follow-up questionnaire. METHOD: A total of 2,072 (52.2% female) respondents to a representative monthly telephone survey were assessed on sociodemographic variables and alcohol use. Respondents were asked whether they would be willing to fill out an additional mailed questionnaire on alcohol use and attitudes toward drinking. Almost half (n = 956; 46%) of respondents agreed to participate in the follow-up survey; 430 (45%) of those individuals completed and returned the questionnaire. RESULTS: Agreement to receive the follow-up questionnaire was unrelated to alcohol use. Regarding gender, men were 1.42 times more likely than women to exhibit nonresponse in returning the follow-up questionnaire (95% CI: 1.08-1.42). After adjusting for the impact of demographic factors, respondents who consumed alcohol at least once per week were 1.43 times more likely than respondents who drank less frequently to exhibit nonresponse in returning the questionnaire (95% CI: 1.05-1.93). Respondents who consumed five or more standard drinks at least once per week were 1.83 times more likely to exhibit nonresponse in returning the questionnaire, compared with respondents who engaged in heavy drinking less frequently (95% CI: 1.15-2.92). CONCLUSIONS: Mailout questionnaires following a representative telephone survey may bias samples toward obtaining fewer men, fewer weekly drinkers and fewer heavier drinkers. Although the magnitude of these biases were relatively small, epidemiological studies on alcohol use may wish to oversample men and heavier drinkers in follow-up studies recruiting from population surveys.

Adult↗
PubMed2001

Self-assessed health among indigenous Australians: how valid is a global question?

OBJECTIVES: This study assessed the validity of a global measure of self-assessed health among Indigenous Australians. METHODS: Logistic regression was used to identify factors associated with self-assessed health in a nationally representative sample. RESULTS: Among 8782 adult respondents, poorer self-assessed health was strongly associated with several factors, including age, number of health conditions, and recent health actions. The association with health conditions was attenuated when the respondent's primary language was not English. CONCLUSIONS: Self-assessed health may be a valid measure among indigenous Australians whose primary language is English. However, although the measure draws on common experiences of health and illness, it may obscure differences in how people incorporate these experiences into social actions.

Adolescent↗
PubMed2001

Ultrasonography incorrectly diagnoses gallbladder polyps.

To determine the accuracy of ultrasound-diagnosed polypoid lesions of the gallbladder in their institution, the authors reviewed the records of 41 patients with polypoid lesions of the gallbladder who underwent cholecystectomy, and collected data concerning age, sex, symptoms, and histopathologic diagnosis. Histopathologic evaluation confirmed polyps in only two patients (4.9%) categorized as having polypoid lesions of the gallbladder. Most specimens from patients with ultrasonography reports suggesting small polyps manifested cholesterolosis (17 of 41) or cholelithiasis (15 of 41). No specimen harbored malignancy. Mean patient age was 47.4 years, and the most common symptoms were pain (85%), nausea (44%), vomiting (29%), and abnormal liver function test results (14%). The accuracy of sonography for diagnosing polypoid lesions of the gallbladder was poor. Many of the small polyps seen on sonography most likely represented a stone embedded in the gallbladder wall or other abnormality. Because of the likelihood of cholelithiasis, the authors recommend that patients with biliary symptoms and ultrasonography findings suggesting polypoid lesions of the gallbladder undergo cholecystectomy.

Adult↗
PubMed2001

Hypercalcemia and human nature.

Patients on hemodialysis may develop severe and symptomatic hypercalcemia if skeletal buffering is ineffective. We report a case of persistent hypercalcemia with apparent extrarenal vitamin D synthesis. Associated aluminium intoxication was suggested on desferrioxamine challenge and adynamic uremic osteodystrophy confirmed on bone biopsy. Plasma calcitriol did not suppress with corticosteroids but did with ketoconazole. No other evidence for underlying granulomatous disease was found. We discuss our approach to less usual causes of hypercalcemia, and emphasise the pitfalls associated with factitious disorders.

Adult↗
PubMed2001

Long-term habituation of the speech-elicited mismatch negativity.

A significant issue in the use of the mismatch negativity evoked potential (MMN) concerns its low signal-to-noise ratio (SNR). One can improve the noise level by increasing the number of samples included in the averaged response. However, improvement achieved in this way assumes that the signal, the MMN, remains stable for extended test times, an assumption which has not been tested. If the MMN is not stable, or exhibits habituation over the test session, then SNR would be adversely affected. MMN response magnitude was measured in 5-min intervals over the course of a test session in response to various speech syllable contrasts. Significant long-term habituation of MMN was observed for all three subject populations tested: young adults, school-age children, and guinea pigs. The time course of the habituation and the stimulus conditions under which it occurs have important implications for research and clinical applications of the MMN. Recording procedures that minimize habituation effects may be used to advantage to improve the signal-to-noise ratio of the MMN.

Adolescent↗
PubMed2000

Convection-enhanced delivery of AAV vector in parkinsonian monkeys; in vivo detection of gene expression and restoration of dopaminergic function using pro-drug approach.

Using an approach that combines gene therapy with aromatic l-amino acid decarboxylase (AADC) gene and a pro-drug (l-dopa), dopamine, the neurotransmitter involved in Parkinson's disease, can be synthesized and regulated. Striatal neurons infected with the AADC gene by an adeno-associated viral vector can convert peripheral l-dopa to dopamine and may therefore provide a buffer for unmetabolized l-dopa. This approach to treating Parkinson's disease may reduce the need for l-dopa/carbidopa, thus providing a better clinical response with fewer side effects. In addition, the imbalance in dopamine production between the nigrostriatal and mesolimbic dopaminergic systems can be corrected by using AADC gene delivery to the striatum. We have also demonstrated that a fundamental obstacle in the gene therapy approach to the central nervous system, i.e., the ability to deliver viral vectors in sufficient quantities to the whole brain, can be overcome by using convection-enhanced delivery. Finally, this study demonstrates that positron emission tomography and the AADC tracer, 6-[(18)F]fluoro-l-m-tyrosine, can be used to monitor gene therapy in vivo. Our therapeutic approach has the potential to restore dopamine production, even late in the disease process, at levels that can be maintained during continued nigrostriatal degeneration.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed2000

Consequences of neural asynchrony: a case of auditory neuropathy.

The neural representation of sensory events depends upon neural synchrony. Auditory neuropathy, a disorder of stimulus-timing-related neural synchrony, provides a model for studying the role of synchrony in auditory perception. This article presents electrophysiological and behavioral data from a rare case of auditory neuropathy in a woman with normal hearing thresholds, making it possible to separate audibility from neuropathy. The experimental results, which encompass a wide range of auditory perceptual abilities and neurophysiologic responses to sound, provide new information linking neural synchrony with auditory perception. Findings illustrate that optimal eighth nerve and auditory brainstem synchrony do not appear to be essential for understanding speech in quiet listening situations. However, synchrony is critical for understanding speech in the presence of noise.

Auditory Cortex↗
PubMed2000

Pamidronate therapy as prevention of bone loss following renal transplantation.

BACKGROUND: Very rapid bone loss, osteopenia and skeletal morbidity after renal transplantation have been well documented and found to occur in a sex dependent fashion. Glucocorticoids, cyclosporine and pre-existing uremic osteodystrophy have been implicated in the pathogenesis of the skeletal lesions. Glucocorticoid induced osteopenia is also a serious clinical problem in patients with various nonrenal diseases and can be prevented, or at least attenuated, by pamidronate and other bisphosphonates. METHOD: We prospectively studied 26 male patients undergoing renal transplantation, and randomized them to receive either placebo or intravenous pamidronate (0.5 mg/kg) at the time of transplantation and again one month later. All patients received immunosuppression comprising prednisolone, cyclosporine and azathioprine. The bone mineral density (BMD) of the second, third and fourth lumbar vertebrae and of the femoral neck was measured at the time of transplantation and at three months and 12 months after transplantation using dual energy X-ray absorptiometry (DXA). RESULTS: Twelve months after transplantation, the mean (+/- SEM) BMD of the lumbar vertebrae in patients who received placebo had decreased 6.4% (P < 0.05). In contrast, patients who received pamidronate experienced no significant reduction of BMD at the lumbar vertebrae. At the femoral neck, placebo-treated patients showed a reduction of BMD of 9% (P < 0.005), whereas there was no significant change in the pamidronate treated group. The two study groups had similar patient profiles, serum parathyroid hormone (PTH) and aluminium concentrations. After transplantation, comparable falls in the serum creatinine and PTH concentration were found in the two groups. Apart from transient hypocalcemia in two patients, no significant adverse effects of pamidronate were noted. CONCLUSION: This study has shown that the early rapid bone loss that occurs in men during the first 12 months after renal transplantation can be prevented by two intravenous doses of pamidronate given at transplantation and one month later. The regimen was simple to administer, well tolerated and potentially applicable to other clinical groups of glucocorticoid treatment patients.

Absorptiometry, Photon↗
PubMed2000

Optimising the performance of intermittent pneumatic compression devices.

OBJECTIVES: this study was designed to determine whether an intermittent pneumatic compression device (IPC) with an increased maximal inflation pressure, a decreased time to maximal pressure and a longer duration of compression would improve venous return compared to a standard IPC device. METHODS: thirty limbs in 15 volunteers without evidence of venous disease were studied using duplex scanning at rest and during the application of two different IPC devices with different compression parameters. The first device IPC-1 (SCD 5325, Kendall) has a six-chambered cuff applying 45 mmHg after 12 s, sequentially from ankle to thigh followed by 60 s of non-compression. The second device IPC-2 (Vena-Assist(R), ACI Medical) has a foot, ankle and calf cuff, applies a pressure of 80 mmHg, has a pressure rise time of 0.3 s, maintains inflation for 5.5 s, and has a cycling time of 1 min. Peak venous velocity and acceleration time were measured at rest and during the IPC application. Measurements were obtained in supine position from the common femoral vein 1 cm above the saphenofemoral junction to include the entire venous outflow from the limb. RESULTS: peak venous velocity at rest was significantly higher in the right limb than in the left limb (26+/-7.2 vs. 22+/-5.7 cm/s, p<0.01). Peak venous velocity was significantly increased by both IPC devices (p <0.0001). IPC-2 achieved significantly higher peak venous velocity than IPC-1 (55.1+/-17.8 vs. 37.4+/-6.9 cm/s, p<0.0001). Acceleration time was also found to be significantly shorter (370+/-93.4 vs. 560+/-83.5 ms, p<0.0001) in IPC-2 than in IPC-1, respectively. CONCLUSIONS: we have demonstrated that progressive inflation at the foot, ankle and calf, increasing maximal inflation pressure and decreasing time to maximal pressure result in increased venous return. These changes may improve the efficacy of IPC devices in the prevention of deep-venous thrombosis (DVT) formation.

Adult↗
PubMed2000

Potent suppression of the parathyroid glands by hydroxylated metabolites of dihydrotachysterol(2).

BACKGROUND: Dihydrotachysterol(2), a licensed pharmaceutical, is hydroxylated to 25-hydroxydihydrotachysterol(2) (25(OH)DHT(2)) and 1 alpha,25-dihydroxydihydrotachysterol(2) (1 alpha,25(OH)(2)DHT(2)) in man. We have compared the biological activity of these metabolites with calcitriol and the 'non-calcaemic' analogue, 22-oxacalcitriol (OCT) in bovine parathyroid cell cultures and in rats. METHODS: The effect of each sterol on parathyroid hormone (PTH) secreted by primary bovine parathyroid cells was measured. High-performance liquid chromotography and gas chromotography-mass spectrometry were used to investigate in vitro 25(OH)DHT(2) metabolism. Rats were given a single intraperitoneal injection or five daily injections of each sterol, and changes in ionized calcium and PTH were measured. RESULTS: In vitro, all sterols suppressed PTH significantly. Calcitriol and OCT were of similar potency, but 1 alpha, 25(OH)(2)DHT(2) and 25(OH)DHT(2) required higher concentrations to suppress PTH equally. We were unable to detect metabolism of 25(OH)DHT(2) to 1 alpha,25(OH)(2)DHT(2) in vitro. In rats, a single dose of 0.5 microg/rat of calcitriol increased ionized calcium at 30 and 40 h (statistically significant at 48 h). 50 microg of OCT and 1 alpha,25(OH)(2)DHT(2) did not cause significant hypercalcaemia at 48 h, although 1 alpha,25(OH)(2)DHT(2) caused hypercalcaemia at 30 h. In contrast, 50 microg of 25(OH)DHT(2) caused hypercalcaemia at 48 h but not at 30 h. Five daily doses of 0.001 microg/rat of calcitriol caused a significant rise in calcium and a 50% fall in PTH. OCT and 1 alpha,25(OH)(2)DHT(2) at 0.025 and 0.5 microg/rat respectively caused similar suppression of PTH but without hypercalcaemia. CONCLUSION: 1 alpha,25(OH)(2)DHT(2) and 25(OH)DHT(2) are potent suppressors of PTH in vitro and in vivo. 25(OH)DHT(2) may be active by virtue of its pseudo-1 alpha-hydroxyl group. Hypercalcaemia caused by a single dose of 1 alpha,25(OH)(2)DHT(2) appeared to be more transient than calcitriol. Five daily doses of 1 alpha, 25(OH)(2)DHT(2) and OCT could achieve 50% suppression of PTH without significant increments in ionized calcium. In contrast, suppression of PTH by calcitriol was associated with significant increments in ionized calcium. These data suggest that like OCT, 1 alpha, 25(OH)(2)DHT(2) can dissociate calcaemic actions from parathyroid-suppressing actions in a manner that may be therapeutically useful.

Animals↗
PubMed2000

Speech-evoked neurophysiologic responses in children with learning problems: development and behavioral correlates of perception.

OBJECTIVES: To evaluate the maturational progression of speech-evoked P1/N1/N2 cortical responses over the life span, determine whether responses are distinctive in clinical populations experiencing learning problems and elucidate the functional significance of these responses. DESIGN: The P1/N1/N2 complex was measured in 150 normal subjects (5 to 78 yr) and 86 subjects with learning problems (LP) (8 to 15 yr) to a synthetic CV syllable. Analyses included description and comparison of the developmental time course in both groups and evaluation of the relationship between P1/N1/N2 and children's performance on speech discrimination tasks and standardized learning measures. RESULTS: Findings revealed significant changes in waveform morphology, latency and amplitude as a function of age. Maturational patterns in the group of children with learning problems did not differ from the normal group. P1/N1/N2 parameters were significantly correlated with standardized tests of Spelling, Auditory Processing and Listening Comprehension in the LP group. Moreover, there was a predictive relationship between Auditory Processing and N2 latency. CONCLUSIONS: The P1/N1/N2 complex changes throughout life from school-age to old age. The developmental sequence throughout the school-age years is similar in normal and LP children. Thus, differences in the rate of P1/Nl/N2 latency and amplitude development do not appear to be distinctive in these two populations. The relationship between P1/N1/N2 parameters and standardized measures of learning (particularly between Auditory Processing and N2 latency) provides new information about the role of these responses in hearing and highlights the potential value in characterizing auditory processing deficits.

Adolescent↗
PubMed1999

Coexpression of factor VIII heavy and light chain adeno-associated viral vectors produces biologically active protein.

We are interested in using recombinant adeno-associated viral vectors in the treatment of hemophilia A. Because of the size constraints of recombinant adeno-associated viral vectors, we delivered the heavy and light chains of the human factor 8 (hFVIII) cDNA independently by using two separate vectors. Recombinant AAV vectors were constructed that utilized the human elongation factor 1alpha promoter, a human growth factor polyadenylation signal, and the cDNA sequences encoding either the heavy or light chain of hFVIII. Portal vein injections of each vector alone, a combination of both vectors, or a hFIX control vector were performed in C57BL/6 mice. An ELISA specific for the light chain of hFVIII demonstrated very high levels (2-10 microgram/ml) of protein expression in animals injected with the light chain vector alone or with both vectors. We utilized a chromogenic assay in combination with an antibody specific to hFVIII to determine the amount of biologically active hFVIII in mouse plasma. In animals injected with both the heavy and light chain vectors, greater than physiological levels (200-400 ng/ml) of biologically active hFVIII were produced. This suggests that coexpression of the heavy and light chains of hFVIII may be a feasible approach for treatment of hemophilia A.

Animals↗
PubMed1999

Disturbance of cerebral function in people exposed to drinking water contaminated with aluminium sulphate: retrospective study of the Camelford water incident.

OBJECTIVE: To establish whether people exposed to drinking water contaminated with 20 tonnes of aluminium sulphate in the Camelford area of Cornwall in the south west of England in July 1988 had suffered organic brain damage as opposed to psychological trauma only. DESIGN: Retrospective study of affected people. PARTICIPANTS: 55 affected people and 15 siblings nearest in age to one of the group but who had not been exposed to the contaminated water were studied. MAIN OUTCOME MEASURES: Various clinical and psychological tests to determine medical condition and anxiety levels in affected people. Assessment of premorbid IQ (pFSIQ) with the national adult reading test, a computerised battery of psychomotor testing, and measurement of the difference in latencies between the flash and pattern visual evoked potentials in all participants. RESULTS: The mean (SE) pFSIQ was above average at 114.4 (1.1). The most sensitive of the psychomotor tests for organic brain disease was the symbol digit coding (SDC) test (normal score 100, abnormal <85). PARTICIPANTS performed less well on this test (54.5 (6.0)) than expected from their pFSIQ (P<0.0001) and a little less poorly on the averaged less discriminating tests within the battery (86.1 (2.5), P<0.0001). In a comparison with the 15 sibling pairs (affected people's age 41.0 (3.3) years v sibling age of 42.7 (3.1) years (P=0.36) the exposed people had similar pFSIQ (114.7 (2.1)) to their siblings (116.3 (2.1), (P=0.59) but performed badly on the symbol digit coding test (51.8 (16.6)) v (87.5 (4.9) for siblings, P=0.03). The flash-pattern differences in exposed people were greater than in 42 unrelated control subjects of similar age (27.33 (1.64) ms v 18. 57 (1.47) ms, P=0.0002). The 15 unexposed siblings had significantly better flash-pattern differences than their affected siblings (13.4 (2.4) ms v 29.6 (2.9) ms, P=0.0002). No effect of anxiety could be shown on these measurements from the analysis of the anxiety scores of exposed people. CONCLUSION: People who were exposed to the contaminated water at Camelford suffered considerable damage to cerebral function, which was not related to anxiety. Follow up studies would be required to determine the longer term prognosis for affected individuals.

Adolescent↗
PubMed1999

Teaching and assessing ethics and law in the dental curriculum.

The General Dental Council's recommendations on dental education places a new emphasis on the importance of ethics and law in the dental curriculum, stating that students should have an awareness of moral and ethical responsibilities involved in the provision of care to individual patients and to populations. The duties of care to protect a patient's life and health at all times, to respect their autonomy to make informed choices about what happens to them, and to do this fairly and without prejudice, are widely accepted as the fundamental ethical principles governing all health care. The specifics of these duties of care are detailed in Maintaining Standards: guidance to dentists on professional and personal conduct, published by the GDC.

Adult↗