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Biomedical subjects

J Cullen

Publications and source records attributed to J Cullen.

At least 19 recordsLinked to original sources
PubMed1999

Informant-based staging of dementia using the clinical dementia rating.

The staging of dementia is ideally based on both an examination of the patient and a history taken from an informant. However, in some circumstances, only an informant history is possible. The aim of this study was to assess the validity of the Clinical Dementia Rating (CDR) when the rating is based solely on informant data. The CDR was used in a study of 360 persons aged 78 or older who were participants in a community survey, the Sydney Older Persons Study. The CDR was completed in two ways: (1) a social scientist made the ratings based on an informant interview; and (2) a physician made the ratings after an examination of the subject. All CDRs were scored in the conventional way, as well as by the revised method proposed by Gelb and St. Laurent (Alzheimer Dis Assoc Disord 1993;4:202-11). The informant CDR showed moderate agreement with the clinician CDR, showing that it would be a valid substitute in situations in which the subject could not be examined. The revised scoring method was slightly easier to implement than the conventional method.

Aged↗
PubMed1998

Lamivudine therapy of WHV-infected woodchucks.

Hepatitis B viruses establish a chronic, productive, and noncytopathic infection of hepatocytes. Viral products are produced by transcription from multiple copies (5-50) of covalently closed circular (ccc) viral DNA. This cccDNA does not replicate, but can be replaced by DNA precursors that are synthesized in the cytoplasm. The present study was carried out to determine if long-term treatment with an inhibitor of viral DNA synthesis would lead to loss of virus products, including cccDNA, from the liver of woodchucks chronically infected with woodchuck hepatitis virus. Viral DNA synthesis was inhibited with the nucleoside analog, lamivudine (2'-deoxy-3'-thiacytidine). Lamivudine treatment produced a slow but progressive decline in viral titers in serum, to about 0.3% or less of the initial level. However, even after maintenance of drug therapy for 3-12 months, > 95% of the hepatocytes in most animals were still infected. Significant declines in the percentage of infected hepatocytes and of intrahepatic cccDNA levels were observed in only three woodchucks, two in the group receiving lamivudine and one in the placebo control group. Moreover, virus titers eventually rose in woodchucks receiving lamivudine, suggesting that drug-resistant viruses began to spread through the liver starting at least as early as 9-12 months of treatment. Three types of mutation that may be associated with drug resistance were found at this time, in a region upstream of the YMDD motif in the active site of the viral reverse transcriptase. The YMDD motif itself remained unchanged. Not unexpectedly, the lamivudine therapy did not have a impact on development of liver cancer.

Amino Acid Sequence↗
PubMed1998

Manual asymmetries in goal-directed movement: examination of the motor output hypothesis.

Two experiments are reported which examined the viability of motor output hypothesis as an explanation for manual asymmetries in goal-directed movement. Experiment 1 isolated the variability due to force generation by directly assessing precision of force production during an isometric wrist flexion task. Experiment 2 examined the additional role of externally based and internally created timing patterns on the performance of a repetitive force production task. Virtually no effects involving hand were apparent in either experiment. These findings provide no support for a hypothesis based solely on motor output to adequately account for hand differences in the performance of rapid, goal-directed movement.

Adult↗
PubMed1998

Health habits and risk of cognitive impairment and dementia in old age: a prospective study on the effects of exercise, smoking and alcohol consumption.

Previous research has yielded inconsistent results on the effects of exercise, smoking and alcohol use on cognitive impairment and dementia in old age. We analysed data from the Sydney Older Persons Study to see if these health habits were associated with cognitive functioning, dementia or Alzheimer's disease. Health habits were assessed in Wave 1 of the study, when the subjects were aged 75 years or over. Three years later, the subjects were tested for cognitive functioning and clinically examined for dementia and Alzheimer's disease. The analysis was restricted to the 327 subjects examined in Wave 2 who were non-demented in Wave 1. There were few significant associations between health habits and cognitive performance and these were not found consistently across cognitive measures. No associations were found with dementia or Alzheimer's disease. While these health habits do not affect risk for dementia and cognitive impairment in the very elderly, who are at highest risk for these disorders, we cannot discount a role at younger ages.

Aged↗
PubMed1997

The role of platelet-activating factor in conscious, normotensive endotoxemia.

The effects of endotoxin have been postulated to be mediated in large part by release of endogenous platelet-activating factor (PAF) due to the similarity of their hemodynamic and gastric effects in anesthetized animals, and to the ability of PAF inhibitors to ameliorate endotoxin's effects. We chose to examine the relationship with doses that would not produce circulatory shock, in unrestrained conscious animals, in order to mimic clinical situations. Adult male rats were prepared with vascular access, hemodynamic and temperature monitors, and gastric strain gauge transducers. After an overnight fast, rats received a 4-hr infusion of saline (0.5 ml/hr), endotoxin (12.5 mg/kg/hr), PAF (36 micrograms/kg/hr, or 600 ng/kg/min), or endotoxin plus the PAF inhibitor CV 3988 (1 mg/kg/hr, after an initial pretreatment of 1 mg/kg). Rats were killed, stomachs were harvested, and contents were analyzed at the end of the infusions. Blood pressure was not affected by any treatment, but all treated groups developed diarrhea and vasodilatation. Endotoxin and PAF infusions decreased heart rate and body temperature to a similar extent, although the PAF effect on temperature was delayed. The PAF inhibitor did not prevent the body temperature effect, but did reverse it. Gastric secretions were affected by PAF to a lesser extent than by endotoxin, and the PAF inhibitor did not decrease endotoxin's gastric secretory effects. PAF has similar systemic and gastric effects to endotoxin in conscious, unrestrained, normotensive animals. The systemic effects of endotoxin at 12.5 mg/kg/hr were prevented or reversed by the PAF inhibitor CV-3988 at 1 mg/kg/hr, but not the gastric secretory effects.

Animals↗
PubMed1997

Sensitivity and specificity of the neonatal brain-stem auditory evoked potential for hearing and language deficits in survivors of extracorporeal membrane oxygenation.

OBJECTIVE: We determined the sensitivity and specificity of neonatal brain-stem auditory evoked potentials (BAEP) as markers for subsequent hearing impairment and for developmental problems found later in infancy and childhood. METHODS: BAEP studies were performed before discharge in infants treated with extracorporeal membrane oxygenation (ECMO), and two specific abnormalities were analyzed: elevated threshold and delayed central auditory conduction. Behavioral audiometry was repeated during periodic follow-up until reliable responses were obtained for all frequencies, and standardized developmental testing was also conducted. The sensitivity and specificity of an elevated threshold on the neonatal BAEP for detecting subsequent hearing loss, and the relationship of any neonatal BAEP abnormality to language or developmental disorders in infancy, were calculated. RESULTS: Test results for 46 ECMO-treated infants (57.5%) were normal, and those for 34 infants (42.5%) were abnormal, with either elevated wave V threshold, prolonged wave I-V interval, or both on neonatal BAEP recordings. Most significantly, 7 (58%) of the 12 children with subsequent sensorineural hearing loss had left the hospital after showing normal results on threshold tests. There was no significant difference in the frequency of hearing loss between subjects with abnormal (5/21, or 24%) and those with normal BAEP thresholds (7/59, or 12%; Fisher Exact Test, p = 0.28). Therefore the sensitivity of neonatal BAEP testing for predicting subsequent hearing loss was only 42%. Neonatal BAEP specificity for excluding subsequent hearing loss was 76%. In contrast, on language development testing, 19 children demonstrated receptive language delay. Of these children, 12 (63%) had abnormal neonatal BAEP recordings and 7 (37%) had a normal BAEP threshold, normal central auditory conduction test results, or both (p = 0.04). CONCLUSIONS: Neonatal BAEP threshold recordings were of limited value for predicting subsequent hearing loss common in ECMO-treated survivors. However, an abnormal neonatal BAEP significantly increased the probability of finding a receptive language delay during early childhood, even in those with subsequently normal audiometry findings. Because neonatal ECMO is associated with a high risk of hearing and receptive language disorders, parents should be counseled that audiologic and developmental follow-up evaluations in surviving children are essential regardless of the results of neonatal BAEP testing.

Acoustic Impedance Tests↗
PubMed1997

Therapeutic vaccination of woodchucks against chronic woodchuck hepatitis virus infection.

BACKGROUND/AIMS: Therapeutic vaccination is a new approach to treat patients with chronic hepatitis B virus infection. We have used the woodchuck model to examine the efficacy and safety of this approach. METHODS: Seven woodchucks chronically infected with woodchuck hepatitis virus were immunized with surface antigen from this virus, purified from plasma, in conjunction with a peptide named FIS (encompassing amino acids 106-118: FISEAIIHVLHSR from sperm whale myoglobin), which is recognized by T helper lymphocytes. As controls, two woodchucks chronically infected with woodchuck hepatitis virus were immunized: one with FIS only and the other with surface antigen only. RESULTS: Co-immunization with surface antigen and FIS, but not with FIS or surface antigen alone, induced anti-surface antibodies in 7/7 immunized woodchucks. In the two woodchucks in which the highest titer of anti-surface antibody was elicited, severe liver damage was observed: one died of fulminant hepatitis and the other became seriously ill with hepatic injury and had to be sacrificed. CONCLUSIONS: Co-immunization of chronically infected woodchucks with surface antigen and a peptide recognized by T helper cells produces a good anti-surface antibody response. However, this strategy needs to be optimized before its implementation in humans. Although our experiments are not strictly comparable to vaccination of chronically hepatitis B virus-infected patients with recombinant or plasma-derived vaccines, we believe that precautions should be taken to avoid the risk of severe liver injury when immunizing hepatitis B virus carriers.

Amino Acid Sequence↗
PubMed1996

Apolipoprotein E polymorphism does not predict risk of restenosis after coronary angioplasty.

A recent report has suggested that the E4 allele of apolipoprotein (apo) E increases the risk of restenosis after percutaneous transluminal coronary angioplasty (PTCA) and also that it interacts synergistically with the deletion (D) allele of the angiotensin-converting enzyme (ACE) to increase the risk sixteen-fold. To investigate this further, we genotyped 231 subjects with successful PTCA who underwent planned repeat angiography at 4 months to assess the degree of restenosis. Subjects carrying the apo E4 allele (n = 71) were well matched with non-carriers (n = 160) for clinical and pre- and post-PTCA angiographic features. We found no increase in either apo E4 allele frequency (18.4% versus 15.6%, P = 0.42) or apo E4 homozygosity (2/106 versus 5/125, P = 0.30) in those with restenosis compared with those without. The relative risk of restenosis for apo E4 carriers was 1.11 (95% CI = 0.87-1.42). In apo E4 carriers, restenosis frequency was similar in those also carrying the ACE D allele and those without (28/55 (50.9%) versus 9/16 (56.2%), P = 0.71) and there was no significant increase in restenosis risk in carriers of both the apo E4 and ACE D alleles compared to the rest (odds ratio 1.30, 95% CI 0.68-2.50, P = 0.39). We conclude that in our cohort, the apo E4 allele does not either independently or acting synergistically with the ACE D allele increase the risk of restenosis after PTCA, and that apo E genotyping will not be a useful predictor of risk before the procedure.

Alleles↗
PubMed1996

High-frequency jet ventilation in the early management of respiratory distress syndrome is associated with a greater risk for adverse outcomes.

OBJECTIVE: The objective of this investigation was to determine if high-frequency jet ventilation (HFJV) used early in the treatment of premature infants with respiratory distress syndrome was effective in reducing pulmonary morbidity without increasing the occurrence of adverse neurologic outcomes. STUDY DESIGN: A total of 73 premature infants who met the inclusion criteria (gestational age of less than 33 weeks, birth weight of more than 500 g, age of less than 24 hours, need for assisted ventilation with peak inspiratory pressure of more than 16 and FIO2 more than 0.30, and roentgenographic evidence of respiratory distress syndrome) were randomized to either conventional (n = 36) or to high-frequency jet (n = 37) ventilation. Our goals were to maintain the infants on the assigned ventilator for at least 7 days unless they could either be extubated or meet crossover criteria. Univariate analyses were initially used to compare the two groups. Stepwise logistic regression was subsequently used to assess whether various factors independently influenced adverse outcomes. RESULTS: The two groups of infants were similar in all obstetrical, perinatal, and neonatal demographic characteristics. The mean birth weight and gestational age in the conventional group were 930 g and 26.6 weeks and in the HFJV group, 961 g and 26.9 weeks. The infants were randomized at similar ages (7.1 and 7.3 hours of life, respectively). Their prerandomization ventilator settings and arterial blood gases were nearly identical. There were no differences in pulmonary outcomes (occurrence of air leaks, need for oxygen or ventilation at 36 weeks postconception), and there were no differences in the mean number of days oxygen was required, number of days ventilated, or length of hospital stay. Infants ventilated with HFJV were significantly more likely to develop cystic periventricular leukomalacia (10 vs 2, P = .022) or to have a poor outcome (grade IV hemorrhage, cystic periventricular leukomalacia, or death) (17 vs 7, P = .016). Logistic regression analysis revealed HFJV to be a significant independent predictor of both cystic periventricular leukomalacia and a poor outcome. The presence of hypocarbia was not an independently significant predictor of adverse outcomes. CONCLUSIONS: With the HFJV treatment strategy that we used, use of the high-frequency jet ventilator in the early management of premature infants with respiratory distress syndrome resulted in significantly more adverse outcomes than in those treated with conventional mechanical ventilation.

Blood Pressure↗
PubMed1995

Insertion/deletion polymorphism in the angiotensin-converting enzyme gene and risk of restenosis after coronary angioplasty.

Early restenosis in over 30% of cases limits the benefits of percutaneous transluminal coronary angioplasty (PTCA). The mechanisms that underlie restenosis are uncertain, although experimental evidence suggests that the renin-angiotensin system is involved in the vascular response to angioplasty. An insertion(I)/deletion(D) polymorphism in the angiotensin-converting enzyme (ACE) gene, which influences plasma ACE level, has been associated with an increased risk of myocardial infarction in those with the DD genotype. To investigate whether this polymorphism influences the risk of restenosis after PTCA, 233 patients who underwent single-vessel angioplasty in the Subcutaneous Heparin and Angioplasty Restenosis Prevention (SHARP) study were genotyped for the I/D polymorphism and pre-PTCA, post-PTCA, and 4-month clinical and quantitative angiographic data were compared in the three genotype groups. The groups, (II 53, ID 117, and DD 63) were well matched for baseline clinical and both pre- and post-PTCA angiographic features. At 4-month follow-up there was no significant difference between the genotype groups with respect to any of the quantitative angiographic criteria of restenosis: minimal luminal diameter at the site of the angioplasty (DD 1.35 [SE 0.10] mm, ID/II 1.43 [0.05] mm, difference -0.08 [95% CI -0.30 to 0.14]), numbers of subjects with more than 50% diameter stenosis (DD 49%, ID/II 46%, relative risk 1.06 [0.79 to 1.43]), or the number of subjects with more than 50% loss of the acute diameter gain after PTCA (DD 54%, ID/II 43%, 1.26 [0.94 to 1.67]). Likewise, there was no difference in the number of subjects with angina or a positive exercise stress test. We conclude that, in patients undergoing elective PTCA, the I/D polymorphism in the ACE gene does not influence the extent of restenosis, and typing for the polymorphism will not be a useful predictor of risk before the procedure.

Adult↗
PubMed1995

Time course of resolution of persistent air leak in spontaneous pneumothorax.

Persistent air leak (PAL) following tube drainage for spontaneous pneumothorax (SP) is a potentially troublesome complication. The optimum time to intervene surgically is not known. We therefore investigated the rate of resolution of PAL (defined as continued air leak at 2 days after tube insertion) in patients treated medically. We retrospectively reviewed the records of 214 patients presenting with SP over 5 yr. One hundred and forty-two (67%) had tube drainage and in 73 (51%) of these a PAL developed. Overall median time to resolution in the 43 patients with PAL treated medically was 8 days from tube insertion, but PAL resolution was longer in those with underlying lung disease (n = 19) than those without such disease (11 days vs. 7 days, P = 0.05). In patients with normal lungs 20/24 had resolved by 9 days but subsequently the rate of resolution was much slower. In those with abnormal lungs only 8/19 had resolved by 9 days (P < 0.05 compared with those with normal lungs) but the rate of resolution in such patients appeared to change little subsequently. The size of the initial SP did not influence the rate of resolution of PAL. For patients with PAL and normal lungs, surgery at 7-9 days from tube insertion would provide a reasonable opportunity for the PAL to resolve with medical treatment. For those with underlying lung disease there is no clear optimal time and decisions need to be taken on an individual basis.

Adolescent↗
PubMed1994

Histologic and microbiologic features of biopsy samples from patients with normal and inflamed pouches.

PURPOSE: This study was undertaken to assess the electron microscopic and microbiologic findings in tissue biopsy samples from patients with pouchitis and to compare them with findings in patients with normal pouches, conventional ileostomies, and normal ileum. METHODS: Tissue samples were obtained from 78 patients: 23 patients with normal pouches endoscopically and histologically (Group 1), 12 patients with endoscopic and histologic evidence of inflammation (pouchitis) (Group 2), 14 patients who had either endoscopic or histologic evidence of inflammation but not both (Group 3), 20 patients with conventional ileostomies (Group 4), and 9 patients without ileostomies from whom biopsy samples of normal ileum were obtained (Group 5). RESULTS: The mean total aerobic facultative counts in the biopsy samples from the pouchitis patients were significantly higher when compared with biopsy samples from Groups 4 and 5 (P < 0.05). There were no significant differences in the mean anaerobic counts among the five groups. Positive cultures were obtained in 90 percent of patients with pouches compared with 69 percent of patients with conventional ileostomies or normal ileum (P < 0.05). Intramural bacteria were observed on electron microscopy in biopsy specimens of 47 percent patients with pouches compared with 14 percent of patients with conventional ileostomies or normal ileum (P < 0.05). However, the proportion of patients with positive cultures or intramural bacteria was not increased in the pouchitis group compared with the normal pouch group. CONCLUSION: These data suggest that intramural aerobic facultative bacterial counts are elevated in patients with pouchitis and may play a role in the pathogenesis of pouchitis.

Adult↗
PubMed1994

Predictive value of neonatal electroencephalograms before and during extracorporeal membrane oxygenation.

We studied the prognostic significance of electroencephalograms recorded serially at 2- to 4-day intervals during the acute neonatal course of 119 near-term infants with severe respiratory failure treated by venoarterial extracorporeal membrane oxygenation (ECMO). A poor prognosis was defined as early death (n = 27), an abnormally low developmental assessment score (n = 14), or cerebral palsy (n = 14) at 12 to 45 months of age. The only electroencephalographic abnormalities that were significantly related to a poor prognosis were burst suppression (B-S) and electrographic seizure (ES). The 30 infants with two or more recordings of B-S or ES, when compared with the 58 neonates without such electroencephalographic abnormalities, had an odds ratio for a poor prognosis of 6.6 (95% confidence limits, 2.2 to 20.2). The 31 infants with a single ES or B-S recording did not have a significantly increased risk for a poor prognosis. Cardiopulmonary resuscitation immediately before ECMO (n = 8) and the lowest systolic blood pressure before or during ECMO were significantly related to the occurrence of ES or B-S recordings. There was no significant predilection of ES for either cerebral hemisphere. We conclude that in near-term neonates with respiratory failure, serial electroencephalographic recordings are of predictive value, and may facilitate clinical care including the decision to initiate or to continue ECMO.

Acute Disease↗
PubMed1994

Woodchuck hepatitis virus infections: very rapid recovery after a prolonged viremia and infection of virtually every hepatocyte.

Earlier studies have suggested that transient hepadnavirus infections in mammals are associated with virus replication in a large fraction of hepatocytes. Although the viremia that occurred during transient infections in some individuals would presumably lead to virus replication in all hepatocytes, these studies did not reveal if this was the case. The question of the extent of hepatocyte infection was therefore reinvestigated because of the implications of the results for the mechanisms of virus clearance. Woodchucks were inoculated with woodchuck hepatitis virus, and the course of hepatic infection was determined. These studies indicated that essentially 100% of the hepatocytes became infected in the majority of woodchucks. In 7 of 10 woodchucks, the viral infection was then rapidly cleared from the liver, generally in less than 4 weeks. In another three woodchucks, though productive infection was just as rapidly cleared, viral covalently closed circular DNA remained for weeks to months after other indicators of virus infection had disappeared from the liver. Bromodeoxyuridine labeling and anti-proliferating cell nuclear antigen staining to detect hepatocytes passing through S phase indicated an increase in hepatocyte proliferation during the recovery phase of infection. The rate of cell division appeared to be sufficient to replace no more than 2 to 3% of the hepatocytes per day, at the times at which the biopsies were performed. Histopathologic evaluation of the biopsy samples did not provide evidence for a massive amount of liver regeneration. Models to explain virus clearance, with or without massive immune system-mediated destruction of infected hepatocytes, are reviewed.

Animals↗
PubMed1994

Cytomegalovirus cholangitis after renal transplantation.

Clinically significant cytomegalovirus cholangitis is well recognized in patients with AIDS but is less common in other groups of immunocompromised patients. The authors describe a 59-year-old man who had undergone renal transplantation in whom this condition developed, and they emphasize that this diagnosis should be considered in renal transplant patients presenting with biliary obstruction. Careful examination of biopsy material for cytomegalovirus inclusion bodies is necessary.

Cholangitis↗