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Biomedical subjects

W J Hall

Publications and source records attributed to W J Hall.

At least 19 recordsLinked to original sources
PubMed2001

Survival benefit with an implanted defibrillator in relation to mortality risk in chronic coronary heart disease.

Although improved patient survival has been reported in several randomized trials with the implanted cardioverter-defibrillator, <15% of patients treated with defibrillators during trials receive life-saving benefit from this therapy. We evaluated the survival benefit from defibrillator therapy in relation to the severity of the mortality risk in patients with coronary heart disease. Using data from the Multicenter Automatic Defibrillator Implantation Trial, we partitioned the study population into high- and low-risk subsets for each of 3 physiologically meaningful risk factors (ejection fraction, QRS duration, and history of heart failure requiring therapy). Risk of death was evaluated by Cox proportional-hazards regression analyses in patients with single and multiple risk factors. The defibrillator was associated with a significant (p = 0.002) reduction in mortality only in high-risk subsets with ejection fraction <0.26, QRS duration > or =0.12 second, and history of heart failure requiring treatment. The Cox hazard ratio for the risk of death progressively increased >1.0 as a function of the number of risk factors present. Defibrillator therapy was associated with a progressive reduction in the hazard ratio <1.0 (improved survival) at each increased level of mortality risk. Patients at the highest mortality risk (all 3 risk factors; hazard ratio 4.33) achieved the largest mortality reduction (hazard ratio 0.20) from defibrillator therapy. In patients with chronic coronary heart disease, the magnitude of the survival benefit from the implanted defibrillator is directly related to the severity of cardiac dysfunction and its associated mortality risk.

Aged↗
PubMed2001

Clinical implications for affected parents and siblings of probands with long-QT syndrome.

BACKGROUND: Whenever a proband is identified with long-QT syndrome (LQTS), his or her parents and siblings should be evaluated regarding the possibility of carrying the disorder. In the majority of cases, one of the proband's parents and one or more siblings are affected. The aim of this study was (1) to determine whether the clinical severity of LQTS in the proband is useful in identifying first-degree family members at high risk for cardiac events, and (2) to evaluate the clinical course of affected parents and siblings of LQTS probands. METHODS AND RESULTS: The clinical and ECG characteristics of 211 LQTS probands and 791 first-degree relatives (422 parents and 369 siblings) were studied to determine if the clinical profile of the proband is useful in determining the clinical severity of LQTS in affected parents and siblings. Affected female parents of an LQTS proband had a greater cumulative risk for a first cardiac event than affected male parents. The probability of a parent or sibling having a first cardiac event was not significantly influenced by the severity of the proband's clinical symptoms. Female sex and QT(c) duration were risk factors for cardiac events among affected parents, and QT(c) was the only risk factor for cardiac events in affected siblings. CONCLUSIONS: The severity profile of LQTS in a proband was not found to be useful in identifying the clinical severity of LQTS in affected first-degree relatives of the proband.

Adolescent↗
PubMed2001

Response of C-reactive protein and serum amyloid A to influenza A infection in older adults.

Influenza epidemics are associated with significant morbidity and mortality in the elderly, with a substantial proportion of deaths due to cardiovascular events. Elevations of acute-phase proteins have been associated with an increased risk of atherosclerotic events. Therefore, serum amyloid A (SAA) and C-reactive protein (CRP) were measured during influenza illness and 4 weeks later in 7 young persons, 15 elderly outpatients, and 36 hospitalized adults. Striking elevations were seen in mean acute SAA and CRP levels in all groups, but hospitalized patients had the highest levels (SAA, 503 vs. 310 microg/mL [P=.006]; CRP, 120 vs. 34 microg/mL [P<.001]). The presence of dyspnea, wheezing, and fever was also associated with high CRP levels. Influenza infection is associated with significant elevations of SAA and CRP levels in elderly patients, especially those who require hospitalization. It is possible that direct effects of CRP may exacerbate preexisting atherosclerotic lesions and may help explain cardiovascular events associated with acute influenza.

Acute Disease↗
PubMed2001

Prothrombotic changes in hemostatic parameters and C-reactive protein in the elderly with winter acute respiratory tract infections.

Mortality rates attributable to cerebrovascular and ischemic heart disease increase among older adults during the winter. Prothrombotic changes in the hemostatic system related to seasonal factors, such as ambient temperature changes, and winter acute respiratory tract infections, may contribute to this excess seasonal mortality. A prospective nested case-control study was conducted to assess the impact of winter acute respiratory tract infections on fibrinogen, factor VII, factor VIIa, D-dimer, prothrombin fragment 1.2, PAI-1, soluble P-selectin and C-reactive protein (CRP) in older adults. The change in laboratory parameters from baseline (fall) to the time of infection in both middle-aged and elderly individuals was compared with matched non-infected controls. In older adult participants with winter acute respiratory tract infections, significant increases occurred in fibrinogen and C-reactive protein, but not in any other markers. The mean fibrinogen increased 1.52 g/L (38%) and the mean CRP increased 37 mg/L (370%) over baseline (both p <0.001). In a multivariate analysis, both infection and season were associated with the increase in fibrinogen, but only infection was associated with the CRP increase. Old age magnified the increase in CRP but not in fibrinogen. Winter acute respiratory tract infections induce an exaggerated inflammatory response in older adults. The associated increase in fibrinogen, an independent risk factor for ischemic heart disease, may be partly responsible for the excess winter vascular mortality.

Acute Disease↗
PubMed2000

Clinical and genetic variables associated with acute arousal and nonarousal-related cardiac events among subjects with long QT syndrome.

In patients with the long QT syndrome (LQTS), the occurrence of cardiac events (syncope or cardiac arrest) is frequently associated with acute arousal caused by exercise, swimming, emotion, or noise. However, cardiac events may also occur during sleep or with ordinary daily activities. The purpose of this study was to determine whether there are differential clinical, electrocardiographic, and genetic features among LQTS patients who experienced cardiac events with and without acute arousal. We identified 1,325 patients with cardiac events from the International LQTS Registry. Based on the precipitating conditions of the first event, 427 patients were classified as arousal, 345 as nonarousal, and the remaining 553 were unknown (not classifiable). Gene linkage was known in 78 of the 772 patients with classifiable first events. The age at first cardiac event was significantly younger in the arousal than the nonarousal group (11.7 vs. 15.5 years, respectively; p<0.001). The arousal-type patients had a higher rate of subsequent cardiac events during follow-up after the index event than the nonarousal-type patients (p = 0.02). Arousal-related cardiac events occurred in 85% of LQT1, 67% of LQT2, and 33% of LQT3 patients (p = 0.008). This study provides evidence that the genotype is an important determinant of the LQTS phenotype in terms of arousal and nonarousal-related cardiac events.

Acute Disease↗
PubMed2000

Effectiveness and limitations of beta-blocker therapy in congenital long-QT syndrome.

BACKGROUND: beta-blockers are routinely prescribed in congenital long-QT syndrome (LQTS), but the effectiveness and limitations of beta-blockers in this disorder have not been evaluated. METHODS AND RESULTS: The study population comprised 869 LQTS patients treated with beta-blockers. Effectiveness of beta-blockers was analyzed during matched periods before and after starting beta-blocker therapy, and by survivorship methods to determine factors associated with cardiac events while on prescribed beta-blockers. After initiation of beta-blockers, there was a significant (P<0.001) reduction in the rate of cardiac events in probands (0.97+/-1.42 to 0.31+/-0.86 events per year) and in affected family members (0. 26+/-0.84 to 0.15+/-0.69 events per year) during 5-year matched periods. On-therapy survivorship analyses revealed that patients with cardiac symptoms before beta-blockers (n=598) had a hazard ratio of 5.8 (95% CI, 3.7 to 9.1) for recurrent cardiac events (syncope, aborted cardiac arrest, or death) during beta-blocker therapy compared with asymptomatic patients; 32% of these symptomatic patients will have another cardiac event within 5 years while on prescribed beta-blockers. Patients with a history of aborted cardiac arrest before starting beta-blockers (n=113) had a hazard ratio of 12.9 (95% CI, 4.7 to 35.5) for aborted cardiac arrest or death while on prescribed beta-blockers compared with asymptomatic patients; 14% of these patients will have another arrest (aborted or fatal) within 5 years on beta-blockers. CONCLUSIONS: beta-blockers are associated with a significant reduction in cardiac events in LQTS patients. However, syncope, aborted cardiac arrest, and LQTS-related death continue to occur while patients are on prescribed beta-blockers, particularly in those who were symptomatic before starting this therapy.

Adolescent↗
PubMed2000

The doctors of time.

Throughout human history, we have sought to understand the changes we observe in ourselves and in others with the passage of time. Does this so-called aging process have some purpose, and to what extent can we control what are otherwise inexorable consequences? Although various philosophical traditions have offered different interpretations of the relation between age and time, a more unified concept of human aging may be developing. Ancient philosophical concepts are converging with insights from developmental genetics, molecular biology, and clinical research. This new approach suggests that aging is a continuum of human growth and development, full of potential and highly modifiable by a combination of personal responsibility and appropriate medical care. In providing this care to older adults, skillful physicians use time as a key diagnostic and therapeutic tool to interpret symptoms properly and to place treatment choices in the context of human values that may change with age. We who care for older adults are the doctors of time. Sadly, in our contemporary system of medical care, time is one of the least understood and most poorly used tools. A medical care system that is increasingly oriented toward minimizing the time spent caring for older adults cannot possibly increase the quality of life for the rapidly growing elderly population. With the potential for substantial life extension within our grasp, we must develop attitudes and skills that are more compatible with the value systems of our older patients.

Aging↗
PubMed2000

Multiple interacting gene products may influence susceptibility to malignant hyperthermia.

Malignant hyperthermia (MH) is a potentially lethal disorder triggered in susceptible individuals on exposure to common anaesthetic agents. Crises reflect the consequences of disturbed skeletal muscle calcium homeostasis. MH is an autosomal dominant, genetically heterogeneous trait. Defects in a single major gene have been assumed to determine susceptibility status in individual families. However, in some pedigrees phenotypic and genotypic data are discordant. One explanation, in contrast to the current genetic model, is that susceptibility is dependent upon the effects of more than one gene. Using the transmission disequilibrium test we assessed the involvement of 8 MH candidate loci (RYR1, CACNA1S, CACNA2D1, MHS4 at 3q13.1, MHS6 at 5p, LIPE, DM1, dystrophin) by analysis of data from 130 MH nuclear families. Results suggested that variations in more than one gene may influence MH susceptibility in single families.

Anesthetics, Inhalation↗
PubMed2000

Setting targets for sedation with a target-controlled propofol infusion.

We studied 30 unpremedicated patients undergoing muscle biopsy under femoral nerve block to determine sedation levels reached with a Diprifusor target-controlled propofol infusion, in order to establish the equivalent of the ED50 for different levels of depth of sedation. Infusion was started at 0.8 microg x ml(-1) and altered by increments of 0.1 microg x ml(-1) after equilibrium between target and calculated concentrations, until the desired level of sedation was reached. The ED50 target propofol concentrations for sedation at sedation levels 2 (drowsy), 3 (drowsy, responds to verbal stimulation) and 4 (responsive to physical stimulation only) were 1.0 microg x ml(-1), 1.6 microg x ml(-1) and 2.1 microg x ml(-1), respectively. At sedation level 3, several patients exhibited spontaneous movement, hindering surgery. Oxygen supplementation is recommended for sedation at level 4.

Adult↗
PubMed1999

Comparison of respiratory syncytial virus humoral immunity and response to infection in young and elderly adults.

Little information about immunity to respiratory syncytial virus (RSV) and disease pathogenesis in elderly persons exists. Humoral immunity to RSV was assessed in 41 young, 56 healthy elderly, and 49 frail elderly adults by measuring baseline RSV specific IgG by enzyme immunoassay (EIA) and microneutralization assay (MNA) in serum. A comparison of the immune response of 11 young and 28 elderly persons with natural RSV infection was also performed. Despite significant differences in age and functional status, no decreases in RSV antibody levels by either EIA or MNA were noted in the elderly compared with the young. Mean baseline MNA titers expressed as log2 were 10.5 +/- 1.1 for the young, 10.5 +/- 1.5 for the healthy elderly, and 10.9 +/- 1.6 for the frail elderly. The frail elderly who attend a daycare had the highest RSV titers to F by EIA at 16.6 +/- 2.0, compared with 15.4 +/- 1.4 and 15.1 +/- 1.4 in the healthy elderly and young, respectively. This finding may reflect recent infection due to their communal setting or increased production of non-neutralizing antibody. The immune response of older persons to RSV infection was as vigorous as the younger subjects, with 79% having a >/=fourfold rise in MNA titers compared to 64% in the young. These data suggest that the severe clinical manifestations of RSV in the elderly are not due to a significant defect in humoral immunity.

Adult↗
PubMed1999

Evaluation of a handwashing intervention to reduce respiratory illness rates in senior day-care centers.

To decrease respiratory infections in senior day care, staff were educated on viral transmission and the value of hand washing. Fanny packs with alcohol foam supplemented hand washing and were alternated monthly between centers. Infection rates were unchanged with alcohol foam use. The intervention year's infection rate was significantly lower than the previous 3 years, suggesting a benefit of education.

Adult↗
PubMed1999

Segregation of malignant hyperthermia, central core disease and chromosome 19 markers.

Malignant hyperthermia (MH) is an autosomal dominant disorder presenting under general anaesthesia. It is occasionally associated with a myopathy, central core disease (CCD), named after its predominant histochemical characteristic. The penetration of CCD is variable, but typically affected individuals show delayed motor milestones in infancy and remain physically compromised. It was thought until recently that individuals with CCD were always susceptible to MH. Individuals from eight CCD families were screened for the presence of 13 mutations in the skeletal muscle ryanodine receptor gene, reported previously to be associated with MH and/or CCD: none was detected. In seven of these families, where CCD and MH co-existed, we examined the segregation of CCD, MH susceptibility and chromosome 19q markers. In four families, there was complete co-segregation between MH, CCD and the chromosome 19 markers, but in one large pedigree there was a clear lack of segregation of CCD with either MH or chromosome 19 markers and there was no segregation between MH and these markers. This is unequivocal evidence that CCD, in common with MH, is genetically heterogeneous. In the two other families, CCD segregated with chromosome 19 markers but not all individuals with CCD were susceptible to MH. We recommend determination of MH susceptibility in all patients with CCD, irrespective of the MH status of their relatives with CCD.

Adult↗
PubMed1999

Ovarian cancer: comparison of observer performance for four methods of interpreting CT scans.

PURPOSE: To assess the effects of four interpretative methods on observers' mean sensitivity and specificity by using computed tomography (CT) of ovarian carcinoma as a model. MATERIALS AND METHODS: CT scans in 98 patients with ovarian carcinoma and 49 women who were disease free were retrospectively reviewed by four experienced blinded radiologists to compare single-observer reading, single-observer reading with an anatomic checklist, paired-observer reading (simultaneous double reading), and replicated reading (combination of two independent readings). Confidence level scoring was used to identify three possible disease forms in each patient: extranodal tumor, lymphadenopathy, and ascites. Patient conditions were then categorized as abnormal or normal. RESULTS: There were no significant improvements in sensitivity or specificity for classification of patient conditions as abnormal or normal when comparing single-observer interpretation with single-observer interpretation with a checklist or paired-observer interpretation. Although there was no significant improvement in the mean sensitivity (93% vs 94%) by using the replicated reading method, there was a statistically significant improvement in mean specificity (85% vs 79%) for the replicated readings compared with single-observer interpretations (P < .05). CONCLUSION: Diagnostic aids such as checklists and paired simultaneous readings did not lead to an improved mean observer performance for experienced readers. However, an increase in the mean specificity occurred with replicated readings.

Female↗
PubMed1998

Influence of the genotype on the clinical course of the long-QT syndrome. International Long-QT Syndrome Registry Research Group.

BACKGROUND: The congenital long-QT syndrome, caused by mutations in cardiac potassium-channel genes (KVLQT1 at the LQT1 locus and HERG at the LQT2 locus) and the sodium-channel gene (SCN5A at the LQT3 locus), has distinct repolarization patterns on electrocardiography, but it is not known whether the genotype influences the clinical course of the disease. METHODS: We determined the genotypes of 541 of 1378 members of 38 families enrolled in the International Long-QT Syndrome Registry: 112 had mutations at the LQT1 locus, 72 had mutations at the LQT2 locus, and 62 had mutations at the LQT3 locus. We determined the cumulative probability and lethality of cardiac events (syncope, aborted cardiac arrest, or sudden death) occurring from birth through the age of 40 years according to genotype in the 246 gene carriers and in all 1378 members of the families studied. RESULTS: The frequency of cardiac events was higher among subjects with mutations at the LQT1 locus (63 percent) or the LQT2 locus (46 percent) than among subjects with mutations at the LQT3 locus (18 percent) (P<0.001 for the comparison of all three groups). In a multivariate Cox analysis, the genotype and the QT interval corrected for heart rate were significant independent predictors of a first cardiac event. The cumulative mortality through the age of 40 among members of the three groups of families studied was similar; however, the likelihood of dying during a cardiac event was significantly higher (P<0.001) among families with mutations at the LQT3 locus (20 percent) than among those with mutations at the LQT1 locus (4 percent) or the LQT2 locus (4 percent). CONCLUSIONS: The genotype of the long-QT syndrome influences the clinical course. The risk of cardiac events is significantly higher among subjects with mutations at the LQT1 or LQT2 locus than among those with mutations at the LQT3 locus. Although cumulative mortality is similar regardless of the genotype, the percentage of cardiac events that are lethal is significantly higher in families with mutations at the LQT3 locus.

Adolescent↗
PubMed1998

Age- and sex-related differences in clinical manifestations in patients with congenital long-QT syndrome: findings from the International LQTS Registry.

BACKGROUND: Unexplained female predominance is observed in long-QT syndrome (LQTS), a congenital autosomal disorder with prolonged repolarization and syncope or sudden death due to ventricular tachyarrhythmias. Our objectives were to evaluate age- and sex-related differences in events among LQTS patients referred to the LQTS International Registry. METHODS AND RESULTS: Age- and sex-related occurrence of events was analyzed in 479 probands (70% females) and 1041 affected family members (QTc >440 ms, 58% females). LQTS-gene mutations were identified in 162 patients: 69 LQT1 carriers (KVLQT1 on 11p15.5), 62 LQT2 carriers (HERG on 7q35-36), and 31 LQT3 carriers (SCN5A on 3p21-24). Females predominated among 366 probands (71% females) and 230 symptomatic family members (62% females). Male probands were younger than females at first event (8+/-7 versus 14+/-10 years, P<0.0001) and had higher event rates by age 15 years than females (74% versus 51%, P<0.0001). Affected family members had similar findings. By Cox analysis adjusting for QTc duration, the hazard ratio for female probands of experiencing events by age 15 years was 0.48 (P<0.001), and it was 1.87 (P=0.09) by age 15 to 40 years. In female family members, the hazard ratio was 0.58 (P<0.001) by age 15 years, and it was 3.25 (P<0.001) by age 15 to 40 years. The event rate was higher in male than female LQT1 carriers (69% versus 32%, P=0.001). No age-sex difference in event rate was detected in LQT2 and LQT3 carriers. CONCLUSIONS: Among LQTS patients, the risk of cardiac events was higher in males until puberty and higher in females during adulthood. The same pattern was evident among LQT1 gene carriers. Unknown sex factors modulate QT duration and arrhythmic events, with preliminary evidence of gene-specific differences in age-sex modulation.

Adult↗