Biomedical subjects

A K Taylor

Publications and source records attributed to A K Taylor.

At least 37 records · Page 2Linked to original sources

PubMed1999

Compound heterozygous female with fragile X syndrome.

We report on a 15-year-old compound heterozygous young woman with fragile X syndrome who has a full mutation of 363 repeats on one X chromosome and a premutation of 103 repeats on the other X chromosome. As predicted, subsequent testing demonstrated that her father carries a premutation (98 repeats) as does her mother (146 repeats). There is only one previous report of a compound heterozygous female with fragile X syndrome. By quantitation of Southern blot signals, the activation ratio for the premutation (the proportion of the premutation on the active X chromosome) was determined to be 0.78. Immunocytochemistry of blood smears showed fragile X mental retardation-1 protein (FMRP) expression in 63.5% of lymphocytes. Cognitively, this woman is functioning in the mid-range of involvement for fragile X females. She attends regular classes and receives supplemental assistance for her learning disabilities. She experiences behavior characteristics typical of females with fragile X syndrome including severe shyness, anxiety, panic episodes, mood swings, and attention deficits. She has responded very well to appropriate treatment including fluoxetine for anxiety, methylphenidate for attentional problems, and educational therapy.

Adolescent↗

PubMed1999

Tissue-specific methylation differences in a fragile X premutation carrier.

Methylation of a premutation was found in a small percentage of blood cells in a male premutation carrier for the FMR1 mutation. To investigate the inter-tissue heterogeneity and possible clinical implications of this finding, fibroblast cells from the subject were also studied. Although the premutation size was found to be the same in leukocytes and fibroblasts, the methylation pattern was different. In cultured fibroblasts, the premutation was completely unmethylated, as is typical of premutations, whereas methylation of the premutation was detected in a small percentage of lymphocytes. However, the change in methylation did not affect the FMR1 protein (FMRP) expression, as immunocytochemical analysis of FMRP performed on cultured skin fibroblasts and a blood smear revealed normal levels of expression in both tissues.

DNA↗

PubMed1999

Health insurance choices in two-worker households: determinants of double coverage.

Understanding how households make health insurance choices is of critical importance in evaluating issues of equity and efficiency in health care markets. We consider a largely neglected aspect of such decision making: the decision of families with two working spouses to obtain double coverage. Using data from the 1987 National Medical Expenditure Survey, we find that household decisions to obtain double coverage are especially sensitive to a couple's out-of-pocket premium costs. Our analysis also reveals that households with double coverage have more generous insurance, as reflected in their higher coverage rates for specific types of benefits. We also demonstrate that the presence of duplicate health benefits in double-covered households is not random, possibly reflecting a systematic attempt by working spouses to obtain more extensive coverage.

Adult↗

PubMed1998

Non-invasive assessment of bleeding pulmonary artery aneurysms due to Behçet disease.

Because of its ability to depict intravascular, intramural, and extramural pathology, non-invasive imaging is well suited to assessing life-threatening hemoptysis that may complicate Behçet disease. We made exclusive use of CT angiography supplemented by MR to identify pulmonary thromboembolism, mediastinal lymphadenopathy, and bilateral pulmonary artery aneurysms with signs of previous unilateral rupture. Two-dimensional reformatted CT images provided surgeons with a road map of upstream and downstream vascular relationships prior to aneurysm resection. Imaging findings were confirmed by surgery and pathology. Non-invasive imaging proved to be a useful alternative to standard catheter arteriography in the preoperative assessment of hemoptysis in this patient with Behçet disease.

Adult↗

PubMed1998

Phenotypic involvement in females with the FMR1 gene mutation.

Fragile X syndrome is the most common from of inherited mental retardation. Approximately half of females with the full mutation have significant cognitive deficits, whereas females with the premutation do not. Phenotypic effects seen in 281 females (IQs from 64 to 139) were analyzed. Results showed that females with the full mutation differ significantly from controls on selected anthropometric measurements, physical index score, and various behavioral features. Females with the premutation differed significantly from controls in regards to a few anthropometric measurements and the physical index score but not in behavioral features. These results suggest that phenotypic effects of the FMR1 mutation are not only common in females with the full mutation, but in females with the premutation as well.

Adolescent↗

PubMed1997

Drug migration from the adhesive matrix to the polymer film laminate facestock in a transdermal nitroglycerin system.

The apparent loss of nitroglycerin in a prototype transdermal nitroglycerin system was investigated by attenuated total reflectance infrared (ATR-IR) microspectroscopy and high performance liquid chromatography (HPLC). Several transdermal nitroglycerin lots placed under controlled storage conditions exhibited loss of drug potency (up to 10%) along with the appearance of a defect in the polymer film laminate facestock. A significant loss of nitroglycerin from the transdermal drug/adhesive matrix may reduce the bioavailabilty of nitroglycerin to the patient. ATR-IR analysis confirmed that nitroglycerin migrated from the drug/adhesive matrix to the facestock polyester layer under storage conditions and that nitroglycerin was retained in the facestock polyester layer. An alternate sample extraction solution successfully removed the nitroglycerin from both the adhesive matrix and facestock polyester layer with nearly 100% labeled strength recovered. The relationship between the migration of nitroglycerin into the facestock polyester layer and the appearance of the defect in the facestock aluminum layer is discussed and a nitroglycerin-aluminum metal reaction mechanism is proposed.

Adhesives↗

PubMed1996

Molecular/clinical correlations in females with fragile X.

Females who are affected by fragile X syndrome (FXS) can have significant physical, neuropsychological and emotional involvement. This study was designed to explore the relationships between these three domains and to learn how the degree of involvement in each of these phenotypic areas relates to molecular parameters including CGG repeat length and activation ratio (the proportion of normal FMR1 alleles on the active X chromosome). Three groups of females were studied: 35 women who grew up in a fragile X family but do not carry an FMR1 mutation, 92 women with a premutation, and 29 women with a full mutation. Correlations between neurocognitive, physical and emotional traits were calculated for each of the three groups. Within the full mutation group significant correlations were seen between schizotypal traits and full scale IQ. The Lie scale was significantly correlated with the physical findings index. The activation ratio correlated significantly with the measure of executive function (r = .50, P = .01). There was a trend toward correlations of activation ratio with the physical index score, outer ear prominence and IQ. CGG repeat number significantly correlated only with the physical index (r = .44, P = .01). Thus, activation ratio may be the more pertinent molecular parameter in full mutation women in determining the degree of cognitive and physical phenotypic involvement.

Adolescent↗

PubMed1996

A controlled study of longitudinal IQ changes in females and males with fragile X syndrome.

The aim is this study is to compare the longitudinal changes in IQ scores of females and males with fragile X syndrome and controls and to assess the impact on IQ of molecular variations of the FMR-1 gene in males. Medical records from the child development unit at a university-affiliated children's hospital were retrospectively reviewed. Chart review yielded 35 males with fragile X (19 with a fully methylated full mutation, 9 with a mosaic pattern, and 7 with a partially unmethylated full mutation) 16 females with fragile X and a full mutation, 9 female controls, and 9 male controls who had repeated standardized IQ testing separated by 7 months to 13 years. The differences between the first and last IQ scores from the same IQ test were compared by t tests and subsequently by analysis of variance. Overall, a significant IQ decline was seen in 10/35 (28%) of fragile X males, 0/9 (0%) of control males, 6/16 (36%) of fragile X females, and 1/9 (11%) of control females. The initial t tests and analysis of variance showed a significant difference in IQ (p = 0.02) between fragile X males and control males but did not show a significant difference between males and females with fragile X syndrome or between fragile X and control females. When an analysis of covariance was carried out with the initial IQ as a covariable, a significant difference persisted between fragile X and control males, with a greater IQ decline in fragile X males. There were limitations in using the same IQ test. A comparison among the molecular subgroups of males yielded a significant IQ decline in 3/9 (33%) of mosaic males, 6/19 (32%) of fully methylated full mutation males, and 1/7 (14%) of partially methylated full mutation males. An analysis of covariance using the initial IQ and the intertest interval as covariables demonstrated significant differences between the fragile X molecular subgroups and the controls. Our findings show that a substantial percentage of both male and female fragile X patients and female control patients demonstrated significant IQ decline. There was a significant difference in the IQ change between fragile X and control males. There were no significant differences between fragile X and female controls. There were also significant differences in IQ decline among males with different molecular patterns compared with controls. Males with a mosaic pattern versus control males had the most significant decline of the molecular subtypes. Although the numbers were limited, there was no significant IQ decline in males with less than 50% methylation of the full mutation. This suggests that a small amount of FMR-1 protein production, which is often seen in males with less than 50% methylation, protects against significant IQ decline.

Adolescent↗

PubMed1996

Molecular-clinical correlations in males with an expanded FMR1 mutation.

Fragile X syndrome is caused by an expansion of a CGG repeat in the FMR1 gene. The CGG repeat number of the FMR1 mutation and the percentage of cells with methylation of the gene were studied in 218 male patients. Physical and cognitive measurements were also performed. Patients were divided into three groups; those with full mutation and complete methylation (n = 160), those with full mutation and partial methylation (n = 12), and those with a mosaic pattern (n = 46). Statistical comparisons were made between males with the fully methylated full mutation and those with a mosaic pattern. Males having full mutation with complete methylation had the lowest IQ scores and greatest physical involvement. These significant differences were seen only in ages after puberty. CGG repeat length did not correlate with IQ or the physical index score in any group. These findings suggest that a partial production of FMR1 protein may predict milder clinical involvement in some males with fragile X syndrome.

Adolescent↗

PubMed1996

FMR1 fully expanded mutation with minimal methylation in a high functioning fragile X male.

Cytogenetic and molecular genetic analysis of a peripheral blood sample from a 31 year old, non-mentally retarded male with a family history of fragile X syndrome showed unexpected results. Nine percent of cells evaluated cytogenetically expressed a fragile X chromosome and molecular examination of the FMR1 gene showed a highly unusual pattern defined as a minimally methylated fully expanded mutation. This case illustrates the need to recognise exceptional variations of fragile X syndrome mutations.

Adult↗

PubMed1996

Clinical performances of galactosyl hydroxylysine, pyridinoline, and deoxypyridinoline in postmenopausal osteoporosis.

We have previously shown that galactosyl hydroxylysine (GHYL), pyridinoline (PYD), and deoxypyridinoline (DPD) have a better accuracy and discriminate power than hydroxyproline in distinguishing postmenopausal osteoporotic women from premenopausal controls. In this study, we evaluated the clinical performances of GHYL, PYD, and DPD, alone or in combination, in distinguishing postmenopausal osteoporotic women (OPBD, n = 26) from age-matched controls (CBD, n = 19). The diagnosis of osteoporosis was based upon the bone density (BD) of the lumbar spine measured by quantitative computed tomography (CBD: BD > 108 mg/cm3; OPBD: BD < 70 mg/cm3). Urinary excretion of GHYL, PYD, and DPD were measured by HPLC, and all data were expressed as the molar ratio with the creatinine excretion (GHYL/CR, PYD/CR, and DPD/CR). The clinical performances were tested by: Z score analysis (Z), Receiver Operated Characteristic curve analysis (%Acc) and logistic-regression analysis of the posterior probabilities for prediction from a logistic model (LOGIST). GHYL/CR, PYD/CR, and DPD/CR were significantly increased in OPBD compared with CBD. The clinical performances were similar for the three assays, with slightly better performances for GHYL/CR (GHYL/CR: Z = 3.14, %Acc = 70 +/- 8, LOGIST P = 0.01; PYD/CR: Z = 2.19, %Acc = 67 +/- 8, LOGIST P = 0.051; DPD/CR: Z = 2.13, %Acc = 65 +/- 8, LOGIST P = 0.06). None of the possible combinations of the three assays yielded better clinical performances than GHYL/CR alone. In conclusion, this study further confirms the validity of GHYL, PYD, and DPD as markers of bone resorption.

Aged↗

PubMed1996

Patient choice of physician: do health insurance and physician characteristics matter?

Generous health insurance coverage is widely believed to have contributed to both high and rising health care costs. This paper tests the hypothesis that better insured patients will demand higher "quality" by choosing more often to visit specialists rather than generalist physicians. We model the conditional decision to seek care from a specialist physician as a function of health insurance status, physician characteristics, and other socioeconomic factors. Analysis of data from the 1987 National Medical Expenditure Survey and the American Medical Association suggests that the presence of insurance coverage does not affect choice of physician. The results do show that people enrolled in health maintenance organizations (HMOs) see specialists less often than other patients.

Adolescent↗

PubMed1995

Comparison of mean cerebral transit time and single-photon emission tomography for estimation of stroke outcome.

Mean cerebral transit time (MCTT) scanning is a possible alternative to cerebral single-photon emission tomography (SPET) for early assessment of cerebral perfusion after acute ischaemic stroke. Although MCTT is rapid, inexpensive and does not require sophisticated equipment, the relationship between MCTT and functional outcome is unknown. This study aimed to compare the effectiveness of SPET and MCTT in the prediction of functional outcome. Sixty-three patients undergoing cerebral computed tomography (CT), technetium-99m MCTT, and technetium-99m-labelled hexamethylpropylene amine oxime SPET soon after acute ischaemic stroke had outcome assessed after 3 months. Cerebral CT, SPET and MCTT scans were interpreted without reference to the clinical data; a single independent observer assessed outcome using the Barthel Index. The 3-month Barthel score in survivors was significantly correlated with volume of lesion on SPET (Spearman's r=-0.425, P<0.005) and with the ratio of mean affected hemisphere transit times to mean unaffected hemisphere transit times (Spearmen's r=-0.356, P <0.01), but not with CT lesion volume (Spearman's r = -0.175, P >0.1). Stepwise logistic regression identified volume of lesion on SPET as the only significant predictor of good functional outcome (Barthel score>70). The overall predictive accuracy was 73%. It is concluded that MCTT, although significantly correlated with functional outcome, failed to predict good functional recovery in individual stroke survivors. Since SPET provides more detailed localisation of perfusion deficits, and since SPET lesion volume can be used to predict functional outcome, SPET remains preferable to MCTT when perfusion imaging is required.

Aged↗

PubMed1995

Cavitation of mesenteric lymph nodes: a rare complication of coeliac disease, associated with a poor outcome.

Five cases are presented, all of which showed peculiar cavitation of mesenteric lymph nodes. Clinically, three presented with abdominal symptoms, a mass or obstruction, warranting laparotomy. Two patients showed cavitating mesenteric lymph nodes at autopsy. Lymph nodes were enlarged with central, partly cystic degeneration; milky fluid exuded from the cut surface. In each case, investigation showed intestinal villous atrophy and splenic atrophy; coeliac disease was confirmed by response to gluten withdrawal. Three patients died, two from cachexia and the other from pneumonia; the other two are alive and well one year and six years after presentation. Review of the literature shows 12 previously reported cases, with a mortality of about 50%. The diagnosis is made by the histopathologist, alerting appropriate treatment. The pathogenesis is unknown.

Adult↗

PubMed1995

Who belongs to HMOs: a comparison of fee-for-service versus HMO enrollees.

As employers have turned to managed care to curtail the rising cost of health care benefits, the number of HMO enrollees has proliferated. Between 1984 and 1994, HMO enrollment increased from approximately 15 million to over 49 million individuals. Although research has indicated that HMOs have been effective in limiting medical costs, there is mixed evidence in the literature on how they achieve these savings. This article uses data from the 1987 National Medical Expenditure Survey to examine one hypothesis for these patterns: that HMOs enroll a healthier population than fee-for-service plans. To test this hypothesis we examine HMO and fee-for-service enrollees with respect to socioeconomic variables such as age, race, sex, income, education, health status, and location. Our results indicate that HMOs tend to enroll a younger but not much healthier population than traditional fee-for-service plans, suggesting that self-selection is not a major contributor to HMO cost savings.

Adolescent↗

PubMed1995

Phenytoin increases markers of osteogenesis for the human species in vitro and in vivo.

Phenytoin therapy is a well recognized cause of gingival hyperplasia, a condition characterized by increased gingival collagen synthesis, and may also cause acromegalic-like facial features. Based on these clinical findings suggestive of anabolic actions, we sought to test the hypothesis that phenytoin acts on normal bone cells to induce osteogenic effects. To test the direct actions of phenytoin on human bone cells, we measured the dose responses to phenytoin for [3H]thymidine incorporation, cell number, alkaline phosphatase specific activity, and collagen synthesis in human hip bone-derived cells. Phenytoin significantly and reproducibly increased [3H]thymidine incorporation, cell number, alkaline phosphatase specific activity, and collagen synthesis in a biphasic manner with optimal stimulatory doses between 5-10 mumol/L. Thus, micromolar concentrations of phenytoin can act directly on human bone cells to stimulate osteoblast proliferation and differentiation. We next sought to test the hypothesis that phenytoin stimulates bone formation in humans in vivo. Accordingly, three serum biochemical markers of bone formation, i.e. osteocalcin, skeletal alkaline phosphatase, and procollagen C-terminal extension peptide, were measured in 39 male epileptic patients, 20-60 yr of age, with an average duration of phenytoin therapy of 10.5 +/- 1.62 yr (mean +/- SEM). In this group of patients, the mean serum phenytoin level was 9.56 +/- 0.90 mg/L (mean +/- SEM; equivalent to 34.9 +/- 3.3 mumol/L). Thirty apparently healthy male subjects of similar age and taking no medication were included as controls. Serum calcium, 25-hydroxyvitamin D3, and PTH levels in the phenytoin-treated patients were not significantly different from those in the age-matched controls and were within the clinical laboratory normal range of our hospitals, indicating that the patients did not develop hypocalcemia, vitamin D deficiency, or secondary hyperparathyroidism. Serum levels of osteocalcin, skeletal alkaline phosphatase, and procollagen peptide in the phenytoin-treated patients were significantly increased compared to those in the age-matched subjects; in each case these biochemical markers were significantly correlated with the serum phenytoin level, but not with the dose or duration of phenytoin treatment. These findings are consistent with the interpretation that phenytoin increases the bone formation rate in humans in vivo.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗

PubMed1994

Molecular predictors of cognitive involvement in female carriers of fragile X syndrome.

OBJECTIVE: Fragile X syndrome is caused by a mutation involving expansion of a CGG trinucleotide repeat segment in the fragile X mental retardation-1 (FMR1) gene on the long arm of the X chromosome. This study was undertaken to determine the relative impact of three molecular characteristics of the FMR1 mutation--number of CGG repeats, methylation status, and X inactivation ratio--on the cognitive involvement of female carriers of fragile X syndrome. DESIGN: Retrospective study with new DNA analysis of known female carriers of fragile X syndrome. SETTING: Molecular studies were conducted in a university-based DNA diagnostic laboratory. Patients were originally ascertained through a regional fragile X clinic in a university-affiliated pediatric hospital. PATIENTS: Forty-eight female carriers of fragile X syndrome were studied, including 22 with a premutation (a small expansion to approximately 50 to 200 CGG repeats), 23 with a full mutation (a full expansion to > 200 CGG repeats), and three with both types of mutations (mosaics). RESULTS: Median IQ score was significantly lower for females with a full mutation than for females with a premutation. No significant relationship was found between IQ score and number of CGG repeats or percentage methylation of the mutant allele within each mutation category. In addition, no significant relationship was found between IQ score and the proportion of normal FMR1 alleles on the active X chromosome in the carrier female group as a whole or in either mutation subgroup. Comparisons of leukocytes and saliva-borne epithelial cells in certain full-mutation carriers revealed striking differences in FMR1 mutation sizes. CONCLUSIONS: Mutation category remains the most important predictor of affectedness in female carriers of fragile X syndrome. Our data do not support use of the proportion of normal FMR1 alleles on the active X chromosome as a predictor of cognitive involvement in female carriers with full mutations. Individual tissue-specific differences exist in the heterogeneous sizes of full mutations and in the presence of premutation/full-mutation mosaicism.

Adolescent↗

PubMed1994

Biochemical markers of bone turnover for the clinical assessment of bone metabolism.

Despite these potential problems, biochemical bone markers are the single most sensitive method for monitoring acute changes in bone metabolism. For example, subcutaneous injections of recombinant human insulin-like growth factor I cause a measurable increase in both procollagen and urinary DPD in as little as 1 day. Similarly, it is possible to measure a significant decrease in bone formation as determined by decreases in serum levels of ALP, OC, and C-PCP within 12 hours after the beginning of a PTH infusion study. Additionally, an increase in DPD/cr was determined within 24 hours of the start of bed rest. These changes, seen within 24 hours, are far earlier than could be detected by any other method of monitoring bone metabolism. Thus, biochemical assays have opened a new era where changes in bone metabolism can be detected in hours to days. This acute detectability should be especially helpful to the development of new drugs and the optimization of the use of approved drugs. Accordingly, definite dose-response studies can now be done in a reasonable time. For osteoporosis therapy there are reasons to consider cyclic drug administration, such as avoiding drug resistance (PTH or calcitonin), avoiding overtreatment (bisphosphonates), or avoiding a possible mineralization defect (fluoride). By using biochemical assays, we can determine the optimum amount of "on time" and "off time" in cyclic therapy. Of the bone formation assays, ALP, OC, and PCP, we recommend for routine use the OC assay because of its high discriminant power and because it has been better characterized, in terms of clinical application, than the PCP assays and the ALP IRMA. If, however, the serum cannot be drawn at a specific time in all patients to be studied, we recommend the ALP assay because, unlike the OC assay, it shows no diurnal variation. Of the bone resorption assays, HYP, TRAP, GHYL, and PYD/DPD, we recommend the urine PYD/DPD assay (adjusted for creatinine) because it is commercially available and because, along with the urine GHYL assay, it is the most sensitive bone resorption assay. Established guidelines for the use of assays in patient care is not yet available, largely because of the large intrapatient variation seen with most assays. Once this problem is resolved, it should be possible to apply biochemical assays to routine clinical practice. For example, if the patient has a urine DPD/cr (indicating a high bone resorption rate), the patient would be selected for antiresorptive therapy, and subsequently the urine DPD/cr assay would be repeated during therapy to determine the effective dose of the drug.(ABSTRACT TRUNCATED AT 400 WORDS)

Acid Phosphatase↗