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Biomedical subjects

V King

Publications and source records attributed to V King.

At least 19 recordsLinked to original sources
PubMed2004

Prevalence of polycystic ovaries in women with self-reported symptoms of oligomenorrhoea and/or hirsutism: Northern Finland Birth Cohort 1966 Study.

BACKGROUND: The aim of this study was to investigate the prevalence of polycystic ovaries (PCO) among women with self-reported oligomenorrhoea and/or hirsutism and to see whether women with symptoms and PCO have less favourable levels of biochemical markers than controls or women with symptoms and normal ovaries. METHODS: The ultrasonographic ovarian morphology and the hormonal and metabolic profile of female cases with self-reported symptoms typical of polycystic ovary syndrome (PCOS) (n = 196) and asymptomatic controls (n = 67) at the age of 31 years were examined in a general population-based Northern Finland Birth Cohort 1966. RESULTS: The prevalence of PCO (37.3 versus 18.2%; P = 0.004) was significantly higher in the cases (oligomenorrhoea and/or hirsutism) than in the controls. PCO morphology was detected in 18.4% of those who reported only hirsutism, in 47.9% of those reporting only oligomenorrhoea, and in 70.4% of those reporting both symptoms. In the cases with PCO compared to (i) the controls and (ii) the cases without PCO, body mass index (P = 0.026 and P = 0.011), ovarian volume [right P = 0.001, left P = 0.208 (non-significant) and right P < 0.001, left P = 0.022], mean follicle number (P < 0.001 and P < 0.001), testosterone (P = 0.063 and P = 0.029), free androgen index (P = 0.007 and P = 0.013) and insulin (P = 0.033 and P = 0.040) were higher, and sex hormone-binding globulin (P = 0.039 and P = 0.068) and glucose:insulin ratio (P = 0.060 and P = 0.054) lower. Cases with PCO also had higher waist:hip ratio (P = 0.011), infertility rate (P = 0.005) and glucose (P = 0.045) and lower insulin-like growth factor-binding protein-1 (P = 0.012) than controls. The clinical, hormonal and metabolic characteristics did not differ significantly between cases without PCO and controls with the exception of infertility rate, which was significantly higher in the cases without PCO (26.4 vs. 10.0%; P = 0.009). CONCLUSIONS: In a general population, women with symptoms of oligomenorrhoea and/or hirsutism more often have PCO than asymptomatic women. Levels of biochemical and clinical markers in symptomatic women with PCO differed from and were less favourable than those in symptomatic women without PCO or asymptomatic women, implying an increased risk for health.

Adult↗
PubMed2001

Nuclear magnetic resonance study of doxorubicin binding to cardiolipin containing magnetically oriented phospholipid bilayers.

Doxorubicin (DOX) is a potent anthracycline cancer drug whose interaction with anionic membrane phospholipids, such as cardiolipin (CL), is thought to contribute to its cytotoxicity as well as induce cardiotoxic side effects. We have studied the interaction of DOX with a CL containing model membrane system using high resolution, oriented sample (31)P and (2)H NMR. The model membrane system is composed of a bilayer forming phospholipid and a detergent that breaks the extended bilayers into disc-shaped micelles (bicelles) that can orient in a magnetic field. The effects of DOX on the phospholipid bilayer were monitored using samples containing dimyristoylphosphatidylcholine (DMPC), selectively deuterated in either headgroup or acyl chain positions, and measuring the changes in (2)H quadrupolar splittings as DOX was added. Changes in quadrupolar splittings upon DOX addition provide evidence for interaction with both surface and buried sites within the membrane bilayer.

Cardiolipins↗
PubMed2001

Influence of relative binding affinity on efficacy in a panel of anti-CD3 scFv immunotoxins.

The in vitro cell killing potency of an immunotoxin reflects the aggregate of several independent biochemical properties. These include antigen binding affinity; internalization rate, intracellular processing and intrinsic toxin domain potency. This study examines the influence of antigen binding affinity on potency in various immunotoxin fusion proteins where target antigen binding is mediated by single chain antibody variable region fragments (scFv). Firstly, the relationship between affinity and potency was examined in a panel of four scFv immunotoxins generated from different anti-CD3 monoclonal antibodies fused to the 38 kDa fragment of Pseudomonas aeruginosa exotoxin A (PE38). Of these four scFv-PE38 immunotoxins, the one derived from the anti-CD3 monoclonal antibody UCHT1 has highest cell killing potency. Analysis of these four scFv-PE38 immunotoxins indicated a correlation between antigen binding affinity and immunotoxin potency in the cell killing assay with the exception of the scFvPE38 immunotoxin derived from the antibody BC3. However this scFv appeared to suffer a greater drop in affinity ( approximately 100x), relative to the parent Mab than did the other three scFvs used in this study (2-10x). Secondly, the scFv(UCHT1)-PE38 immunotoxin was then compared with a further panel of scFv(UCHT1)-derived immunotoxins including a divalent PE38 version and both monovalent and divalent Corynebacterium diphtheriae toxin (DT389) fusion proteins. When the scFv-UCHT1 domain was amino-terminally positioned relative to the toxin, as in the scFv(UCHT1)-PE38, an approximately 10-fold higher antigen-binding affinity was observed than with the C-terminal fusion, used in the DT389-scFv(UCHT1) molecule. Despite this lower antigen-binding activity, the DT389-scFv immunotoxin had a 60-fold higher potency in the T-cell-killing assay. Thirdly, a divalent form of the DT389-scFv construct, containing tandem scFv domains, had a 10-fold higher binding activity, which was exactly reflected in a 10-fold increase in potency. Therefore, when comparing immunotoxins in which scFvs from different antibodies are fused to the same toxin domain (DT or PE) a broad correlation appears to exist between binding affinity and immunotoxin potency. However, no correlation between affinity and potency appears to exist when different toxin domains are combined with the same scFv antibody domain.

ADP Ribose Transferases↗
PubMed2001

Optimization of the anti-(human CD3) immunotoxin DT389-scFv(UCHT1) N-terminal sequence to yield a homogeneous protein.

The production and regulatory approval processes for biopharmaceuticals require detailed characterization of potential products. Therapeutic proteins should preferably be homogeneous, although limited, reproducible, heterogeneity may be tolerated. A diphtheria toxin-based anti-(human CD3) immunotoxin, DT389-scFv(UCHT1), was expressed in Escherichia coli and purified following refolding [DT389 corresponds to amino acids 1-389 of diphtheria toxin, scFv is single-chain variable-region antibody fragment and UCHT1is an anti-(human CD3) monoclonal antibody]. Biochemical characterization of this molecule by MS and N-terminal sequencing by Edman degradation revealed that the protein was heterogeneous at the N-terminus, containing species both with (60%) and without (40%) the initiator methionine residue. In an attempt to generate an N-terminally homogeneous molecule, a panel of seven N-terminal variants was designed, based on the published specificity of bacterial methionine aminopeptidase. Following bacterial expression, partial purification and separation on SDS/PAGE, these proteins were subjected to N-terminal sequencing by Edman degradation. Three of the mutants yielded a 100% homogeneous amino acid sequence. By contrast, the original DT389-scFv(UCHT1) protein and four variant proteins yielded two sequences with varying ratios corresponding to species with and without methionine. The N-terminal sequences of the three homogeneous clones were MLADD and MLDD, where the methionine was completely retained, and SADD, where the methionine was completely removed. One of the homogeneous mutants (SADD) was expressed, refolded and purified and found to be equipotent with the parent immunotoxin. Thus, using a rational mutagenesis approach, three N-terminally homogeneous variants of DT389-scFv(UCHT1) have been identified, at least one of which is functionally indistinguishable from the parent immunotoxin. This approach is generally applicable to biopharmaceutical production and immunotoxin development in particular.

Antibodies, Monoclonal↗
PubMed2000

Investigation of the comparative toxicity of 5-FU bolus versus 5-FU continuous infusion circadian chemotherapy with concurrent radiation therapy in locally advanced rectal cancer.

PURPOSE: To compare the relative toxicities of bolus versus infusional 5-FU chemotherapy administrated concurrently during external beam irradiation in patients with locally advanced rectal cancer following surgical extirpation. METHODS: A total of 26 eligible patients were retrospectively identified as having been treated for rectal adenocarcinoma at the Stratton VAMC between 1989 and 1997. A comparative analysis of treatment dose intensities, treatment delays and toxicities in these patients was performed. RESULTS: Significantly less WBC toxicity was observed in the patients receiving infusional 5-FU chemotherapy. The other toxicities, with the exception of skin toxicity, were generally less frequent in the 5-FU infusional group. When the toxicities were corrected for 5-FU dose intensity, to yield toxicity per mg of 5-FU, statistically significant differences were found for hematological toxicity (WBC and platelets), and for gastrointestinal toxicity (frequency and severity of diarrhea and weight loss). The majority of patients receiving infusional 5-FU therapy were treated using a circadian pattern of treatment peaking around the time of the radiation therapy. Patients receiving infusional 5-FU were able to tolerate over twice the dose intensity as those receiving bolus administration. Local recurrence rate in all patients was 3.8% comparing favorably to other reported studies. Distant recurrence frequency was also acceptable at 34.6% for the group. CONCLUSION: Infusional 5-FU chemotherapy compared with bolus therapy during pelvic radiation minimizes toxicity to the patient while maximizing the dose of 5-FU that can be delivered. As infusional 5-FU therapy during radiation has previously been shown to increase disease free duration and survival, infusional 5-FU should be considered as an acceptable standard of care to prevent local recurrence of rectal adenocarcinoma following its resection. Shaping this infusional 5-FU chemotherapy within the day so that most of the daily dose is delivered around the time of the radiation therapy may further modify the toxic therapeutic ratio of combined modality therapy.

Adult↗
PubMed2000

Pegylation of magnetically oriented lipid bilayers.

We report NMR data for magnetically oriented phospholipid bilayers which have been doped with a lipid derivatized with a polyethylene glycol polymer headgroup to stabilize samples against aggregation. (13)C, (31)P, and (2)H NMR data indicate that the incorporation of PEG2000-PE (1% molar to DMPC) does not interfere with the orientation properties of bicelles prepared at 25% w/v with or without the presence of lanthanide. Bicelles prepared at 10% w/v are also shown to orient when PEG2000-PE is added. The addition of PEG2000-PE to cholesterol-containing, lanthanide-flipped bicelles is shown to inhibit sample phase separation and improve spectral quality. Furthermore, the addition of PEG2000-PE to high w/v bicelles (40% w/v) is demonstrated to lead to an increase in overall sample order.

Cholesterol↗
PubMed1999

Aging-specific expression of Drosophila hsp22.

hsp22 is among the least abundantly expressed Drosophila heat shock (hs) genes during both development and heat stress. In contrast, hsp22 was found to be the most abundantly expressed hs gene during Drosophila aging. During aging, hsp22 RNA was induced 60-fold in the head, with somewhat lower level induction in abdomen and thorax. Induction of the other hs gene RNAs was </=3-fold, except for hsp23, which was induced approximately 5-fold in thorax. hsp22 protein was detected using rat anti-hsp22 polyclonal antisera and was induced >150-fold, with particularly abundant expression in eye tissue. Aging-specific induction of hsp22 was reproduced by hsp22:lacZ fusion reporter constructs in transgenic flies. Analysis of specific promoter mutations in transgenic flies indicated that functional heat shock response elements are required for hsp22 induction during aging. Finally, comparison of hsp22 RNA and protein expression patterns suggests that aging-specific expression of hsp22 is regulated at both the transcriptional and the posttranscriptional levels. Aging-specific induction of hsp22 is discussed with regard to current evolutionary theories of aging.

Aging↗
PubMed1999

Are religious grandparents more involved grandparents?

OBJECTIVES: This study explores how various aspects of a grandparent's religiousness are related to involvement with their grandchildren. METHODS: The study ascertains whether religious grandparents are significantly more involved with their grandchildren than less religious grandparents by testing a series of bivariate and multivariate regression models. Multiple measures both of religiousness and of grandparent involvement are used. The study also examines factors that potentially confound, link, or explain the connection between religious involvement and grandparenting (e.g., demographic factors, health, community involvement, traditional values, ties to others). The sample of 585 grandparents comes from two related studies of rural families, the Iowa Youth and Families Project and the Iowa Single Parent Project. RESULTS: Overall, the results indicate that religious grandparents are more involved grandparents, and this involvement is explained in part by their generally greater involvement in all types of family and social ties--religious grandparents are more likely to be enmeshed in social ties to others. DISCUSSION: The implications of these findings are discussed in light of prior research that finds little influence of religion. We also consider the implications of our results for the future of grandparent involvement.

Adolescent↗
PubMed1999

A study of infectious intestinal disease in England: microbiological findings in cases and controls.

A study was undertaken to identify the microorganisms and toxins in stool specimens associated with infectious intestinal disease (IID) among cases in the community and presenting to general practitioners (GPs) and in asymptomatic controls. Population based cohorts were recruited from practice lists in 70 practices and followed for 26 weeks (cohort component). Seven hundred and sixty-one cases of IID identified from the cohorts, 2893 cases who presented to GPs in 34 of the practices (GP component), and age/sex matched control subjects (555 and 2264, respectively) submitted stool specimens by post for comprehensive microbiological examination. Campylobacter spp (12.2% of stools tested), rotavirus group A (7.7%), and small round structured virus (SRSV) (6.5%) were the organisms most commonly detected in the GP component. SRSV was identified in 7.0% of cases in the community cohort. No target microorganisms or toxins were identified in 45.1% and 63.1% of cases in the two components. Aeromonas spp, Yersinia spp, and some enterovirulent groups of Escherichia coli were detected as frequently in controls as in cases. The higher frequency of detection of campylobacter, salmonella, and rotavirus among cases who presented to GPs than among those in the community suggests that those pathogens cause more severe illness. No enteropathogens were detected from a large proportion of cases although comprehensive standard methods were used to seek them.

Case-Control Studies↗
PubMed1998

Perceived self-efficacy and grandparenting.

OBJECTIVES: This study identifies grandparents who feel efficacious in their role and the consequences of such beliefs for actual involvement with an adolescent grandchild. METHODS: The sample of 883 grandparents comes from two related studies of rural families, the Iowa Youth and Families Project and the Iowa Single Parent Project. Our research questions are answered by testing a series of bivariate and multivariate regression models. RESULTS: Results show much variability in perceptions of being able to influence one's grandchild. Church attendance, knowledge of one's own grandparents, a farm history, a strong grandparent-parent bond, proximity, and having fewer grandchildren emerged as significant predictors of grandparents' perceptions of efficacy. Grandparents with strong self-efficacious beliefs play an active role in the lives of their grandchildren. DISCUSSION: With an increasing number of grandparents taking responsibilities for their grandchildren, a greater understanding of the experiences and resources that enhance their sense of personal efficacy in this role warrants priority in generational studies.

Adolescent↗
PubMed1998

Nursing clients of Greek ethnicity at home.

The home healthcare nurse who cares for persons with Greek ancestry should be aware of their unique cultural heritage. The nurse should also be aware that Greek people throughout the world are proud and independent, valuing their religious faith and practices, good health, education, and success. Care should be designed to include appreciation of traditions and customs that these clients may have. The nurse should make a special effort to develop trust with the Greek client and family members in order to effectively implement culturally competent healthcare.

Community Health Nursing↗
PubMed1998

Cold exposure regulates the renin-angiotensin system.

The effect of cold exposure on the systemic renin-angiotensin system and on regulation of the angiotensin II (Ang II) receptor was examined in target organs for Ang II with cardiovascular relevance (left ventricle, kidney, lung) and metabolic relevance [interscapular brown adipose tissue (ISBAT), liver] to the functional consequences of cold exposure. In time course studies, the effects were examined of 4 hr or 1, 3 and 7 days of exposure to cold (4 degrees C) on plasma Ang II concentration and Ang II receptor binding characteristics in rat liver. Plasma Ang II concentration increased 10-fold after 4 hr of cold exposure, returned to control levels at days 1 and 3 of cold exposure, and was again increased (2-fold) at 7 days of cold exposure. The affinity of [125I]Sar1, Ile8-Ang II binding in membranes prepared from rat liver was not altered in cold-exposed rats. The density (Bmax) of binding sites in liver from cold-exposed rats was increased by day 1 and remained elevated over time-matched controls. Alterations in Ang II receptor density did not parallel plasma Ang II concentration in their time course, suggesting that cold-induced regulation of the Ang II receptor was not substrate mediated. In rats from the 7-day time point of cold exposure, Ang II receptor binding characteristics were examined in ISBAT and lung. Increases in Ang II receptor density were evident in ISBAT but not lung. To determine whether cold-induced increases in food intake contributed to elevations in plasma Ang II concentration and/or Ang II receptor density, a group of cold-exposed rats (7 days) were pair-fed to food intake levels of control rats. Pair-feeding of cold-exposed rats eliminated increases in plasma Ang II and norepinephrine concentration but did not prevent increases in Ang II receptor density in liver, ISBAT, kidney and left ventricle. Moreover, increases in Ang II receptor density were augmented in kidney and left ventricle from cold-exposed rats that were pair-fed. Results from these studies demonstrate that cold exposure resulted in an increase in plasma Ang II concentration through mechanisms related to increased food intake. Elevations in food intake in cold-exposed rats contributed to tissue-specific increases in Ang II receptor density. Moreover, cold-induced increases in Ang II receptor density were not related to plasma Ang II concentration.

Adipose Tissue↗
PubMed1998

Drug abuse treatment success among needle exchange participants.

OBJECTIVE: Although lowering incidence rates of human immunodeficiency virus (HIV) transmission is the primary goal of needle exchange programs (NEPs), other desirable outcomes are possible. Referring exchange participants to more comprehensive drug abuse treatment programs has the potential to reduce or eliminate the use of drugs. This possibility was evaluated by comparing the treatment responses of new admissions with an outpatient opioid agonist treatment program in Baltimore, Maryland. METHODS: New admissions (1994 - 1997) to an opioid agonist treatment program were first grouped by referral source (needle exchange, n = 82 vs. standard referrals, n = 243) and then compared on admission demographic and clinical variables and response to treatment during the first three months. Outcome measures included retention rates, self-reported drug use and injecting frequencies, self-reported illegal activities for profit, and results from weekly urinalysis testing for opioids and cocaine. RESULTS: Patients from the NEP were significantly older and more likely to be male, African American, and unemployed than standard referral patients. Needle exchange patients also had a greater baseline severity of drug use than patients in the standard referral group. Despite these baseline differences, both groups achieved comparably good short-term treatment outcomes (including reduced drug use and criminal activity for profit); treatment retention was also good, although slightly better in the standard referral group (88% vs. 76%). CONCLUSION: These data demonstrate the feasibility and merits of creating strong linkages between NEPs and more comprehensive drug abuse treatment clinics.

Adult↗
PubMed1997

Cardiac function, perfusion, and morbidity in irradiated long-term survivors of Hodgkin's disease.

PURPOSE: The incidence of cardiotoxicity and clinical cardiac events following mantle irradiation (RT) in patients with Hodgkin's disease using modern techniques is controversial. The use of quantitative, prognostically validated noninvasive tests to assess systolic and diastolic cardiac function and regional myocardial blood flow may reveal preclinical abnormalities associated with subsequent clinical events of myocardial infarction, cardiac death, or angina. The goals of this study are to determine, through noninvasive measures, the presence and time course of alterations in cardiac systolic and diastolic function and of relative myocardial blood flow in long-term survivors of Hodgkin's disease, and assess their correlation with subsequent clinical cardiac end points. METHODS AND MATERIALS: Equilibrium radionuclide angiocardiography (ERNA) was used to assess left ventricular (LV) systolic and diastolic function by measuring LV ejection fraction (LVEF) and peak filling rate (PFR), respectively, in patients without known ischemic heart disease who received RT. Electrocardiography was performed to assess electrical cardiac function under conditions of rest and either exercise or dipyridamole vasodilator stress. Quantitative rest/stress myocardial perfusion imaging with thallium-201 and/or Tc-99m sestamibi was used to assess myocardial perfusion. Patients at least 1.0 year after RT were eligible if they were <50 years old at RT, had no known cardiac disease, and remained free of clinical recurrence of Hodgkin's disease. Fifty patients, ages 10.2-46.1 years (mean 26.0 +/- 8.6) at RT, were tested 1.1 to 29.1 years (mean 9.1 +/- 7.5) after RT. Seventeen of these patients were tested two times separated by 1.1 to 8.1 years. The mean central cardiac RT dose was 35.1 +/- 7.8 Gy (range 18.5-47.5) in daily 15-2.0 Gy fractions. Twelve patients were concomitantly irradiated to the left ventricle, usually through partial transmission left lung shields (mean 17.0 +/- 2.2 Gy, range 14.3-21.3). RESULTS: No patients had signs or symptoms of cardiac disease at the time of evaluation. The mean LVEF at the time of initial testing was 59.6 +/- 6.2% (n = 50; range 42-73%; normal > or =50%), and the mean peak filling rate (PFR) was 3.46 +/- 0.88 end diastolic volumes per second (EDV/s) (range 1.5-5.4 EDV/s; normal > or =2.54 EDV/s). The 12 patients also treated to the left ventricle had a normal mean ejection fraction that was lower (56.6 +/- 5.0%) than that of the other 38 patients (LVEF = 60.6 +/- 6.3%, p = 0.051) when initially evaluated. Average PFR was similar in the two groups. For the 15 patients who had repeat tests, changes in LVEF were generally modest in individual patients, and there was no change in the group mean. For all patients, no significant association was found between cardiac function indices and age at RT, dose, or interval from RT to testing. Myocardial perfusion scintigraphy demonstrated mild ischemia in one or more segments in two patients, and borderline normal perfusion in three patients. Rest and stress ECG testing demonstrated mild repolarization abnormalities in three, and one patient was abnormal at rest and had nondiagnostic changes with stress. CONCLUSIONS: Patients irradiated to the heart incidental to the treatment of Hodgkin's disease using modern techniques have generally normal measures of left ventricular function and myocardial perfusion. Modest differences in the normal left ventricular ejection fraction observed may be attributable to the cardiac volume irradiated. Some patients may manifest improved cardiac function as time from RT elapses, while a significant deterioration of ejection fraction was not observed and reduction in diastolic peak filling rate is uncommon. The previously reported increased risk of cardiac death may relate to use of older techniques of RT employing higher doses and lack of cardiac shielding, and uncontrolled patient selection with additional behaviors and cardiac risk factors.

Adolescent↗
PubMed1997

Evaluation of the effects of nursery depopulation on the persistence of porcine reproductive and respiratory syndrome virus and the productivity of 34 farms.

Nursery depopulation has been described as an effective strategy for improving the performance of weaned pigs. In order to assess whether the strategy was effective under a wide range of conditions, a study was carried out on 34 farms in the USA. Four groups with different depopulation protocols were designed on the basis of the location of the depopulated facility (on site vs off site) and the period for which the nursery remained empty (seven days vs 14 days). The changes in average daily liveweight gain, percentage mortality, feed efficiency and treatment cost per pig produced were assessed 12 months before and after nursery depopulation. The ability to eliminate porcine reproductive and respiratory syndrome (PRRS) virus was examined by indirect fluorescent antibody testing of the nursery pigs. Significant improvements (P < 0.0001) were detected in both average daily gain and percentage mortality after depopulation when the differences within an individual group were analysed, but no significant differences (P > 0.14) were observed between the study groups. Serological testing indicated that antibodies to PRRS virus were still present in 14 of the 34 farms after depopulation.

Animals↗
PubMed1996

Symptomatic coronary artery disease after mantle irradiation for Hodgkin's disease.

PURPOSE: a) To assess the age-related incidence of morbid cardiac events including cardiac death (CD), nonfatal myocardial infarction (MI), and angina pectoris (AP) in all patients treated for Hodgkin's disease at a single institution; b) to examine the prevalence of cardiac risk factors and presence of coronary artery disease (CAD) in affected patients. METHODS AND MATERIALS: 475 patients were treated for Hodgkin's disease in our institution between 1954 and 1989. The status of 97% of the cohort was established either by patient visit and examination in 1992-1993, personal telephone contact, or documentation of death. The 326 of these patients who had mantle irradiation (RT) and survived 3 years formed the study population. Patients who experienced AP, MI, or CD secondary to CAD were assessed for the presence of specific cardiac risk factors. Cardiac catheterization and necropsy data were reviewed to determine the presence and degree of coronary artery stenosis. RESULTS: Eighteen of 326 patients (5.5%) have had a morbid cardiac event directly related to CAD. Seven patients had CD. Seven patients experienced nonfatal MI, and four patients had AP. The mean interval from RT to morbid cardiac event was 13.1 years (range: 4.4-27.0), and the mean age at the time of the event was 39.4 years (range: 24-65). Four of these patients had morbid cardiac events between ages 24-29 years. Based on US statistics of CD secondary to MI, the relative risk of CD for the treated group was 2.8 (3.1 for males and 1.8 for females). Remarkably, no difference was found in the risk of experiencing a morbid cardiac endpoint in patients stratified by either decile of age at which RT was given, or by duration of follow-up. Only one patient experiencing an event (AP) had received an anthracycline. The mean RT dose to the central cardiac volume for the affected patients was 44.3 Gy (range: 35-60.4). Autopsy or catheterization data were available on 15 patients and revealed 90-100% stenosis of at least one major vessel in 11 patients (73%), and no single artery was more commonly stenosed. Specifically, the left anterior descending and right coronary arteries were each greater than or equal to 60% stenosed in 10 out of 15 patients (67%), and either the left main or circumflex arteries were greater than or equal to 50% stenosed in 5 out of 15 patients (33%); triple vessel disease was present in seven patients. Risk factor data were available on all patients experiencing morbid cardiac events: 72% smoked, 72% were male, 78% had hypercholesterolemia, 61% were obese, 28% had a positive family history, 33% had hypertension, and 6% (one) had diabetes. The average number of risk factors per patient was 2.9; seven patients had at least four risk factors, and all patients had at least one risk factor. This frequency of risk factors is elevated when compared to the US population. CONCLUSIONS: In our institution, 5.5% of patients treated for Hodgkin's disease experienced a morbid cardiac event following RT to the central cardiac volume. The doses given were greater than commonly used today. Some patients experienced events at a young age, and the likelihood of experiencing CD was increased compared to the general population. This observation is consistent with RT as an additional risk factor in the induction of morbid cardiac events. Appropriate cardiac shielding and radiation doses, careful follow-up, which includes monitoring of cardiac function, and a preventative program of sensible dietary habits, exercise, and nonsmoking may be beneficial in reducing cardiac morbidity in long-term survivors of Hodgkin's disease.

Adolescent↗