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Biomedical subjects

R J Kryscio

Publications and source records attributed to R J Kryscio.

At least 19 recordsLinked to original sources
PubMed2006

Risk factors for transitions from normal to mild cognitive impairment and dementia.

OBJECTIVE: To identify risk factors associated with transitions from cognitively normal to various forms of mild cognitive impairment (MCI) and then from MCI into early dementia with death as a competing state. METHODS: Cognitive assessments from 554 subjects participating in a longitudinal study at the University of Kentucky AD Center were used to classify individuals into one of three transient states at any visit: cognitively normal, amnestic MCI, or mixed MCI. Between visits subjects could die or become demented. A series of polytomous logistic models were used to model transitions among these states over time and to determine how the log odds of these transitions vary with age, education, sex, family history of dementia, and APOE status. RESULTS: Age affects all transitions among transient states as well as those to dementia or death. Presence of at least one apolipoprotein 4 allele affects transitions from cognitively normal into amnestic MCI or into dementia. At most 12 years of education affects transitions into mixed MCI. Transitions do not vary with sex or family history. CONCLUSION: Aside from age, the usual risk factors associated with conversion from cognitively normal into dementia are likely risk factors for transitions into mild cognitive impairment.

Aged↗
PubMed2006

Posaconazole as salvage therapy for zygomycosis.

Zygomycosis, an infection that is associated with significant morbidity and mortality, is becoming common in immunocompromised patients. Posaconazole is a new extended-spectrum azole antifungal that has demonstrated in vitro and in vivo activity against zygomycetes. This report provides the results from the first 24 patients with active zygomycosis who were enrolled in two open-label, nonrandomized, multicentered compassionate trials that evaluated oral posaconazole as salvage therapy for invasive fungal infections. Posaconazole was usually given as an oral suspension of 200 mg four times a day or 400 mg twice a day. Eleven (46%) of the infections were rhinocerebral. Duration of posaconazole therapy ranged from 8 to 1,004 days (mean, 292 days; median, 182 days). Rates of successful treatment (complete cure and partial response) were 79% in 19 subjects with zygomycosis refractory to standard therapy and 80% in 5 subjects with intolerance to standard therapy. Overall, 19 of 24 subjects (79%) survived infection. Survival was also associated with surgical resection of affected tissue and stabilization or improvement of the subjects' underlying illnesses. Failures either had worsening of underlying illnesses or requested all therapy withdrawn; none of the failures received more than 31 days of posaconazole. Posaconazole oral solution was well tolerated and was discontinued in only one subject due to a drug rash. Posaconazole appears promising as an oral therapy for zygomycosis in patients who receive required surgery and control their underlying illness.

Administration, Oral↗
PubMed2005

Memories that last in old age: motor skill learning and memory preservation.

Using an automated test panel, age-associated declines in learning, remembering and performing a novel visuomotor task were assessed in 497 normal adults ranging from 18 to 95 years old. As predicted, task performance times slowed with increasing age in the cross-sectional portion of the study. However in the subsequent longitudinal study, while motor learning was significantly slower in adults over 62 years old, motor memory was pristinely preserved in normal adults from 18 to 95 years old. When tested 2 years after the first training session and without intervening rehearsal, mean performance times were retained and continued to improve by 10% in young adults and 13% in aged adults, reflecting long lasting preservation of motor memories. While the maximum lifetime of an unpracticed, novel motor memory in humans is not known, the present study suggests that new motor memories can be retained for at least 2 years without rehearsal in normal aged adults. This age-resistant component of motor memory stands in contrast to the well-known decrements in other motor and cognitive processes with human aging.

Adolescent↗
PubMed2005

Longitudinal functional alterations in asymptomatic women at risk for Alzheimer's disease.

PURPOSE: The authors sought to determine whether known alterations of brain function in normal individuals who are at high risk for Alzheimer's disease (AD) worsen or stay the same after a significant interval of time. METHODS: The authors used functional magnetic resonance imaging (fMRI) to observe cortical activation during confrontation naming in 14 women with high AD risk and 10 with low risk, based on family history and apolipoprotein-E4 allele status. They repeated the identical scan protocol in the same patients after 4 years. RESULTS: fMRI activation in high-AD-risk participants was found to be further diverged from that of their low-AD-risk counterparts over this period. CONCLUSION: fMRI may report on the presence and progression of neuropathology in the ventral temporal cortex or in functionally connected regions in presymptomatic AD.

Alzheimer Disease↗
PubMed2003

Risk of malignancy in unilocular ovarian cystic tumors less than 10 centimeters in diameter.

OBJECTIVE: To determine the natural history and to estimate the risk of malignancy of unilocular ovarian cystic tumors less than 10 cm in diameter followed conservatively by transvaginal ultrasound. METHODS: From 1987 to 2002, 15,106 asymptomatic women at least 50 years old entered the University of Kentucky's Ovarian Cancer Screening Program and underwent initial transvaginal ultrasonography. If the screen revealed nothing abnormal, women were asked to repeat transvaginal ultrasonography yearly. If the screen revealed abnormalities, transvaginal ultrasonography was repeated in 4 to 6 weeks, along with Doppler flow ultrasonography and CA 125 testing. RESULTS: Of the 15,106 women at least 50 years old, 2763 women (18%) were diagnosed with 3259 unilocular ovarian cysts. A total of 2261 (69.4%) of these cysts resolved spontaneously, 537 (16.5%) developed a septum, 189 (5.8%) developed a solid area, and 220 (6.8%) persisted as a unilocular lesion. During this time, 27 women received a diagnosis of ovarian cancer, and ten had been previously diagnosed with simple ovarian cysts. All ten of these women, however, developed another morphologic abnormality, experienced resolution of the cyst before developing cancer, or developed cancer in the contralateral ovary. No woman with an isolated unilocular cystic ovarian tumor has developed ovarian cancer in this population. CONCLUSION: The risk of malignancy in unilocular ovarian cystic tumors less than 10 cm in diameter in women 50 years old or older is extremely low. The majority will resolve spontaneously and can be followed conservatively with serial transvaginal ultrasonography.

Age Distribution↗
PubMed2003

Preoperative differentiation of malignant from benign ovarian tumors: the efficacy of morphology indexing and Doppler flow sonography.

OBJECTIVE: The goal of this study was to determine the efficacy of morphology indexing and Doppler flow sonography as methods to predict risk of malignancy in sonographically confirmed ovarian tumors. METHODS: Risk of malignancy was assessed preoperatively in 442 ovarian tumors using a new morphology index (MI) based on tumor volume and wall structure. Each tumor was assigned a score of 0 to 10 based on increasing volume and morphologic complexity. Doppler flow studies were performed on 371 of these tumors. Following morphologic evaluation, all ovarian tumors were removed surgically. RESULTS: Of 315 tumors with a MI < 5 there was only 1 malignancy (a stage IA granulosa cell tumor <2 cm in diameter) whereas there were 52 malignancies in 127 tumors with a MI > or = 5. Stage of disease was as follows: stage I, 33; stage II, 6; stage III, 14. Risk of malignancy was related directly to MI score, varying from 0.3% in tumors with a MI < 5 to 84% in tumors with a MI > or = 8. A MI value of > or = 5 as indicative of malignancy was associated with the following statistical parameters: sensitivity 0.981, specificity 0.808, PPV 0.409, NPV 0.997. A pulsatility index (PI) < 1.0 as indicative of malignancy was associated with: sensitivity 0.528, specificity 0.776, PPV 0.288, NPV 0.906. A resistive index (RI) < 0.4 as indicative of malignancy was associated with: sensitivity 0.222, specificity 0.867, PPV 0.222, and NPV 0.867. The addition of Doppler flow indices to MI did not improve the accuracy of predicting malignancy. Likewise, the absence or presence of ovarian tumor blood flow was not reliable as a means to differentiate benign from malignant ovarian tumors. CONCLUSIONS: Morphology indexing is an accurate and inexpensive method of differentiating benign from malignant ovarian tumors, and can be a valuable adjunct in treatment planning. The addition of Doppler flow studies did not improve diagnostic accuracy of MI.

Adolescent↗
PubMed2002

Women at risk for AD show increased parietal activation during a fluency task.

BACKGROUND: Imaging studies have shown disparities in resting metabolism and in functional activation between cognitively normal individuals at high and low risk for AD. A recent study has shown increased parietal activation in high-risk subjects during a paired associates recall task, which the authors postulated might overlap activation typically observed in verbal fluency. OBJECTIVE: To determine whether parietal activation is altered in a letter fluency task in cognitively normal individuals at high risk for AD. METHODS: fMRI was used to compare cortical activation between two groups of cognitively normal women differing in their risk for developing AD. A letter fluency task was used, which activates left frontal and parietal regions. The risk groups differed in family history of AD and APOE allele status but were matched in age, education, and measures of cognitive performance. Average age of the study participants was 53 years. RESULTS: The regional patterns of brain activation were similar between groups and similar to patterns observed by other investigators. However, the high-risk group showed significantly increased activation in the left parietal region despite identical letter fluency performance between risk groups. CONCLUSIONS: Cognitively normal individuals at high risk for AD show increased brain activation in the left parietal region with letter fluency, a region adjacent to that observed by others using a recall task. This convergence of results indicates disruption of functional circuits involving the left parietal lobe in asymptomatic individuals at increased risk for AD.

Alzheimer Disease↗
PubMed2001

Neural substrates of facial emotion processing using fMRI.

We identified human brain regions involved in the perception of sad, frightened, happy, angry, and neutral facial expressions using functional magnetic resonance imaging (fMRI). Twenty-one healthy right-handed adult volunteers (11 men, 10 women; aged 18-45; mean age 21.6 years) participated in four separate runs, one for each of the four emotions. Participants viewed blocks of emotionally expressive faces alternating with blocks of neutral faces and scrambled images. In comparison with scrambled images, neutral faces activated the fusiform gyri, the right lateral occipital gyrus, the right superior temporal sulcus, the inferior frontal gyri, and the amygdala/entorhinal cortex. In comparisons of emotional and neutral faces, we found that (1) emotional faces elicit increased activation in a subset of cortical regions involved in neutral face processing and in areas not activated by neutral faces; (2) differences in activation as a function of emotion category were most evident in the frontal lobes; (3) men showed a differential neural response depending upon the emotion expressed but women did not.

Adult↗
PubMed2001

Differences in functional magnetic resonance imaging activation by category in a visual confrontation naming task.

OBJECTIVE: Cortical processing involved in seemingly similar tasks may differ in important ways. The authors mapped cortical regions engaged in a commonly performed picture naming task, seeking differences by semantic category. Functional magnetic resonance imaging was used during presentation of standardized line drawings in 18 healthy right-handed female participants, comparing living versus nonliving entities. During visual naming, across categories there was strong activation of left frontal (BA45/47), bilateral temporo-occipital junction (BA19), and inferior temporal regions (BA36/37). Activation of right inferior temporal cortex (BA19 and BA37) was greater during naming of living versus nonliving category items. No category differences in activation strength in the left temporal lobe were observed. The authors conclude that visual semantic operations may involve visual association cortex in the right temporal lobe in women.

Brain Mapping↗
PubMed2000

Ovarian volume related to age.

OBJECTIVE: The goal of this study was to determine the relationship of ovarian volume to age, height, and weight in women undergoing transvaginal sonography. METHODS: Thirteen thousand nine hundred sixty-three women 25-91 years of age undergoing annual transvaginal sonography as part of the University of Kentucky Ovarian Cancer Screening Program were the subjects for this investigation. Each ovary was measured in three dimensions, and ovarian volume was calculated using the prolate ellipsoid formula (L x H x W x 0.523). Mean ovarian volume according to age was calculated for each decade of life. RESULTS: Data were obtained from 58,673 observations of ovarian volume. Mean ovarian volume was 6.6 +/- 0.19 cm(3) in women less than 30 years of age; 6.1 +/- 0.06 cm(3) in women 30-39; 4.8 +/- 0.03 cm(3) in women 40-49; 2.6 +/- 0.01 cm(3) in women 50-59; 2. 1 +/- 0.01 cm(3) in women 60-69; and 1.8 +/- 0.08 cm(3) in women >/=70. Mean ovarian volume was 4.9 +/- 0.03 cm(3) in premenopausal women and 2.2 +/- 0.01 cm(3) in postmenopausal women (P < 0.001). The use of exogenous estrogens was associated with a significant reduction in ovarian volume in women 40-59 years of age, but not in women >/= 60. Ovarian volume was unrelated to patient weight but was greater in tall women (>68 in.) than in short women (<58 in.). CONCLUSION: There is a statistically significant decrease in ovarian volume with each decade of life from age 30 to age 70. Mean ovarian volume in premenopausal women is significantly greater than that in postmenopausal women. The upper limit of normal for ovarian volume is 20 cm(3) in premenopausal women and 10 cm(3) in postmenopausal women.

Adult↗
PubMed2000

The efficacy of transvaginal sonographic screening in asymptomatic women at risk for ovarian cancer.

OBJECTIVE: The purpose of this study was to determine the efficacy of annual transvaginal sonography (TVS) as a screening method for ovarian cancer. METHODS: Annual TVS screening was performed on 14, 469 asymptomatic women from 1987 to 1999. Eligibility criteria included (1) all women >/= 50 years of age and (2) women >/= 25 years of age with a family history of ovarian cancer. Ovarian volume was calculated using the prolate ellipsoid (length x height x width x 0.523). An abnormal sonogram was defined by (1) an ovarian volume >10 cm(3) in postmenopausal women or >20 cm(3) in premenopausal women or (2) a papillary or complex tissue projection into a cystic ovarian tumor. All women with abnormal TVS had a repeat sonogram in 4-6 weeks. Patients with a persistently abnormal second screen had a serum CA-125 determination, tumor morphology indexing, and Doppler flow sonography, and were advised to have surgical tumor removal. RESULTS: One hundred eighty patients with persisting TVS abnormalities underwent exploratory laparoscopy or laparotomy. Seventeen ovarian cancers were detected: 11 Stage I, 3 Stage II, and 3 Stage III. Only three patients with Stage I cancers had a palpable ovarian mass on clinical examination. All patients with Stage I and II ovarian cancer are alive without recurrence 1.8-9.8 years (median, 4.5 years) after diagnosis. Two of the three Stage III patients have died of disease: one at 4.3 years and one at 7.7 years after detection. Four patients developed ovarian cancer within 12 months of a negative scan (FN): 2 Stage II, 2 Stage III. Three of these patients are alive with no evidence of disease 0.4, 1.9, and 5.5 years after diagnosis, and 1 patient has died of disease 0.7 years after diagnosis. Four patients developed ovarian cancer more than 12 months following a normal screen. All 4 presented clinically with Stage III disease. Two of these patients have died of disease and two patients are alive 1.5 and 2.1 years after diagnosis. TVS screening was associated with the following statistical variables: sensitivity, 81%; specificity, 98.9%; positive predictive value (PPV), 9.4%; and negative predictive value (NPV), 99.97%. After 46, 113 screening years, there have been 3 ovarian cancer deaths in the annually screened population and 2 ovarian cancer deaths in women receiving less than annual screening. The survival of ovarian cancer patients in the annually screened population was 95.0 +/- 4.9% at 2 years and 88.2 +/- 8.0% at 5 years. Excluding all cases of nonepithelial or borderline epithelial malignancies, the survival of patients with ovarian cancer in the annually screened population was 92.9 +/- 6.9% at 2 years and 83.6 +/- 10.8% at 5 years. CONCLUSIONS: (1) TVS screening, when performed annually, is associated with a decrease in stage at detection and a decrease in case-specific ovarian cancer mortality. (2) TVS screening does not appear to be effective in detecting ovarian cancer in which ovarian volume is normal.

Adult↗
PubMed2000

Continuing participation supports ultrasound screening for ovarian cancer.

The effect of ovarian cancer screening on survival is enabled by women who continue to actively participate in screening. In this report, factors that affect participation are examined. Participants included 13,963 Kentucky women who received 56,392 screens accounting for a 46,113 screening year experience. Background, health history and reasons for participating in transvaginal sonographic screening were collected via a self-reported questionnaire. Screening participants were characterized as > 50 years old, mostly married, well educated, medically insured, health conscious women, living in the vicinity of the screening centre or 51-150 miles away. Approximately 70% of the participants can be considered active in the study based upon a screening visit during the 1997-1998 2-year period. The probabilities of a return screen at 1, 2, 5 and 7.5 years were 77.8%, 72.0%, 58.7% and 50.6%, respectively. A total of 96% of return visits occurred within 2 years, with 33.7% having intervals of < 1 year. Perceived family history was not observed to affect continuation. However, abnormal findings were associated with a shortened participation. These high levels of continuation in ultrasound screening indicate that women take this disease seriously and demonstrate that this disease is of consequence to them.

Adult↗
PubMed2000

Whole grain foods and heart disease risk.

Coronary heart disease (CHD) is the leading cause of death in most developed nations and is rapidly increasing in prevalence in developing countries. Death rates from cardiovascular disease exceed 1 million annually in the United States and account for the largest disease-related cost to health with total costs estimated to exceed $120 billion per annum. Many dietary factors, including total and saturated fat consumption, fruit and vegetable intake and dietary fiber, have been shown to contribute to risk for CHD. We have systematically reviewed literature from the past 20 years evaluating an association between dietary fiber and CHD. Foods that are rich in dietary fiber, including fruits, vegetables, legumes and whole grain cereals, also tend to be a rich source of vitamins, minerals, phytochemicals. antioxidants and other micronutrients. Each of these factors may be independently contributing to the cardiovascular protective effects of fiber-rich foods.

Coronary Disease↗
PubMed2000

Risk factors for peripartum and postpartum stroke and intracranial venous thrombosis.

BACKGROUND AND PURPOSE: The study goal was to identify potential risk factors for peripartum or postpartum stroke and intracranial venous thrombosis. METHODS: Data from the Healthcare Cost and Utilization Project were analyzed for the years 1993 and 1994. Observed values were weighted with poststratification discharge weights to project to the universe of all discharges from community hospitals located in the United States. Nationally representative estimates of risk were calculated on the basis of age, race, mode of delivery, income, third-party payer, hospital size, hospital ownership, hospital location (rural versus urban), hospital teaching status, census region, and presence of specific complications. Multivariate models were developed with the use of logistic regression. RESULTS: Among 1 408 015 sampled deliveries, there were 183 observed cases of peripartum stroke and 170 cases of peripartum intracranial venous thrombosis in 17 states in the United States in 1993 and 1994. There were an estimated 975 cases of stroke and 864 cases of intracranial venous thrombosis during pregnancy and the puerperium in the United States among 7 463 712 deliveries during 1993 and 1994, for estimated risks of 13.1 cases of peripartum stroke and 11.6 cases of peripartum intracranial venous thrombosis per 100 000 deliveries. Multivariate analysis showed that the following were strongly and significantly associated with both peripartum and postpartum stroke: cesarean delivery; fluid, electrolyte, and acid-base disorders; and hypertension. Covariates that were strongly and significantly associated with both peripartum and postpartum intracranial venous thrombosis included cesarean delivery, hypertension, and infections other than pneumonia and influenza. CONCLUSIONS: Pregnancy-related hypertension and cesarean delivery are important risk factors for both stroke or intracranial venous thrombosis.

Acid-Base Imbalance↗
PubMed1999

Altered brain activation in cognitively intact individuals at high risk for Alzheimer's disease.

OBJECTIVE: To determine whether brain function is altered in cognitively normal individuals at high risk for AD several years before the typical age at onset for this illness. BACKGROUND: Neuropathologic alterations in AD precede cognitive impairment by several years. It is unknown whether functional alterations in neural circuitry accompany these neuropathologic changes, and if so, whether they may be detectable before onset of symptoms. METHODS: We used functional MRI to compare cortical activation between two groups of cognitively normal women differing only in their risk for developing AD. Visual naming and letter fluency tasks were used to activate brain areas subserving object and face recognition, previously described sites of hypometabolism and neuropathologic alteration in AD. The risk groups differed in family history of AD and apolipoprotein E allele status, but were matched in age, education, and measures of cognitive performance. Average age of the study participants was 52 years. RESULTS: The regional patterns of brain activation were similar between groups. However, the high risk group showed areas of significantly reduced activation in the mid- and posterior inferotemporal regions bilaterally during both tasks despite identical naming and letter fluency performance. CONCLUSIONS: Cognitively normal individuals at high risk for AD demonstrate decreased brain activation in key areas engaged during naming and fluency tasks. Decreased activation in the high risk group may be a consequence of the presence of subclinical neuropathology in the inferotemporal region or in the inputs to that region. If so, these findings provide evidence of a window of opportunity for disease-modifying treatment before the onset of symptomatic AD.

Adult↗
PubMed1999

Critical decline in fine motor hand movements in human aging.

BACKGROUND: Slowing of motor movements in human aging is a well-known occurrence, but its biologic basis is poorly understood. Reliable quantitation may refine observations of this phenomenon to better aid research on this entity. METHODS: A panel equipped with timing sensors under computer control was used to measure upper extremity movement times in two groups of healthy individuals: adults younger than 60 years of age (n = 56; range, 18-58 years) and adults older than 60 years of age (n = 38; range, 61-94 years). RESULTS: Fine motor performance was better in the dominant hand (p = 0.0007) regardless of age. Adult and aged groups differed on two basic timing measures, which reflect coarse motor and fine motor performance (p < 0.0001). There were no gender differences on either measure. There was a strong effect of task difficulty with age on coarse motor (p < 0.01) and fine motor (p < 0.0001) measures. The fine motor measure of hand performance in healthy individuals correlated in a nonlinear fashion with age for more difficult tasks (r2 = 0.63) but showed a simple linear relation for less-demanding tasks (r2 = 0.5). CONCLUSION: This technique sensitively detects age-related motor performance decline in humans. There may be a critical period in late midlife when fine motor performance decline either begins or abruptly worsens.

Adolescent↗