Search PubMed⌕ Search

Biomedical subjects

M R Johnson

Publications and source records attributed to M R Johnson.

At least 73 records · Page 4Linked to original sources
PubMed2000

Longitudinal analysis of maternal plasma leptin concentrations during normal pregnancy and pre-eclampsia.

Leptin concentrations have been found to be elevated in cross-sectional studies of established pre-eclampsia. Circulating concentrations of leptin were measured in a cross-sectional study to confirm these findings (19 women with pre-eclampsia and 13 normal pregnant controls) and in a longitudinal study to establish the timing of the increase in leptin concentrations (samples obtained at 16, 20, 24, 28, 32, 36 and 38 weeks gestation from eight women who went on to develop pre-eclampsia and seven normal pregnant controls). In the cross-sectional study, plasma leptin concentrations were significantly greater in women with pre-eclampsia than in normal controls (P: = 0.001). In the longitudinal study, it was found that circulating leptin concentrations rose gradually to 32 weeks and thereafter declined slightly in normals. The concentrations in women destined to develop pre-eclampsia were consistently higher from 20 weeks gestation (P: = 0.04-0.003) and, in contrast to the normal controls, rose markedly from 32 weeks as pre-eclampsia developed. This study confirms that plasma leptin concentrations are increased in established pre-eclampsia and reports for the first time that leptin concentrations are elevated before pre-eclampsia is clinically evident.

Adult↗
PubMed2000

Detailed analysis of the oligodendrocyte myelin glycoprotein gene in four patients with neurofibromatosis 1 and primary progressive multiple sclerosis.

Neurofibromatosis 1 (NF1) is a common autosomal disorder with a wide range of neurological manifestations. The case histories of five patients, including two siblings, are reported who have both neurofibromatosis 1 and primary progressive multiple sclerosis (PPMS). A further patient with both NF1 and PPMS has since been identified. More recently, a systematic clinical review of 138 unselected adult patients with NF1 identified one patient with a slowly progressive spastic paraparesis and multiple high signal hyperintensities on T2 weighted MRI. Molecular genetic studies suggest a mechanism by which the clinical association of progressive white matter disease and NF1 might arise. The gene for NF1 is located on chromosome 17q, spans 350 kb of genomic DNA, and contains 60 exons. The gene for oligodendrocyte myelin glycoprotein (OMgp) is embedded within intron 27b of the NF1 gene. OMgp is a membrane glycoprotein that appears in the human CNS at the time of myelination. It can be detected immunohistochemically on CNS myelin and on the surface of cultured oligodendrocytes. Structurally, OMgp has the potential to function as an adhesion molecule and could contribute to the interactions between the plasma membranes of oligodendrocytes and axons required for myelination and/or axon survival. This study considers the specific hypothesis that PPMS in patients with NF1 results from concurrent mutation of the OMgp gene. The OMgp genes of four unrelated patients with NF1 and PPMS were examined using a combination of Southern blot, dosage polymerase chain reaction, and chemical cleavage of mismatch. The entire OMgp coding sequence, all intronic sequence, the intron-exon boundaries, and 1 kb of flanking sequence were screened. The DNA from two patients was found to contain an alteration in the OMgp gene resulting in an amino acid change of glycine to aspartic acid at codon 21. It is concluded that PPMS in patients with NF1 can occur without concurrent mutation of the OMgp gene. The glycine to aspartic acid polymorphic alteration at codon 21 is neither sufficient nor necessary for the development of PPMS.

Adult↗
PubMed2000

Quantitative atom-atom potentials from rotational tunneling: their extraction and their use.

Rotational tunneling of small molecular groups has been the subject of considerable theoretical and experimental activity for several decades. Much of this activity has been driven by the promise of exploiting the extreme sensitivity of quantum tunneling to interatomic potentials, but until recently, there was no straightforward means by which quantitative information about these potentials could be extracted. This review explains how a quantitative method, suitable for general application, was developed. It then goes on to show how this has been used to understand tunneling systems for which no previous satisfactory explanation had been found. The application of the methodology, and its results, to other disciplines is discussed.

Journal Article↗
PubMed2000

The role of pharmacogenetics and pharmacogenomics in cancer chemotherapy with 5-fluorouracil.

There is increasing evidence supporting the important role of genetics in determining the effect (response and toxicity) to cancer chemotherapy. This has included both pharmacogenetics, where the alteration of a gene coding for an important drug metabolizing enzyme results in increased toxicity (and occasionally altered efficacy), and pharmacogenomics, where knowledge of the expression of genes critical to the action of the cancer chemotherapy drug can be used to individualize therapy. This manuscript focuses on the widely used cancer chemotherapy drug 5-fluorouracil (5-FU) to illustrate the following concepts: (1) The effect of the pharmacogenetic syndrome known as dihydropyrimidine dehydrogenase (DPD) deficiency on 5-FU pharmacology; (2) the role of pharmacogenomics in individualizing 5-FU therapy, and (3) the potential value of pharmacogenomics in designing new drugs.

Animals↗
PubMed2000

Procedural and methodological issues in telepsychiatry research and program development.

OBJECTIVE: The authors reviewed the literature related to telepsychiatry-applications of videoconferencing technology for mental health care-which offers hope for an affordable means of solving long-standing workforce problems, particularly in geographical areas where specialist providers are not readily available. METHODS: To conduct a comprehensive review of the telepsychiatry literature, the authors searched the MEDLINE database (1970 to February 2000), using the keywords telepsychiatry, telemedicine, and videoconferencing. Studies were selected that included the use of videoconferencing technology for the provision of any form of mental health care services. RESULTS AND CONCLUSIONS: Psychiatric interviews conducted by telepsychiatry appear to be generally reliable, and patients and clinicians generally report high levels of satisfaction with telepsychiatry. A significant limitation of the literature is the lack of empirical research on telepsychiatry, especially cost analyses and clinical outcome studies. The authors outline a research agenda addressing the procedural and methodological issues that should shape future research: study design, outcome measurement, consideration of patient characteristics, and program design.

Consumer Behavior↗
PubMed2000

The relationship between leptin concentration and bone metabolism in the human fetus.

This study investigates the relationship between leptin and fetal bone metabolism by measuring fetal blood levels of leptin, carboxy-terminal pro-peptide of type I pro-collagen (PICP; a marker of bone formation) and cross-linked carboxy-terminal telopeptide of type I collagen (ICTP; a marker of bone resorption). The median gestational age at the time of sampling was 23 weeks (range, 18-35). There was a positive correlation between leptin concentration and gestational age (r = 0.543, P < 0.001) and a negative correlation between both PICP and ICTP and gestational age (r = -0.592 and r = -0.550, respectively, and P < 0.001 for both). Also, there was a negative correlation between the concentrations of leptin and both PICP (r = -0.260, P = 0.022) and ICTP (r = -0.622, P < 0.001). Using multiple regression analysis, fetal leptin concentration was positively correlated to the gestational age (r = 0.240, P = 0.042) and negatively correlated to ICTP (r = -0.420, P = 0.001). The increase in leptin concentration with gestational age is consistent with adipose tissue development and the subsequent accumulation of fat mass. The negative correlation between fetal leptin and ICTP suggests that leptin may decrease bone resorption with the overall effect of increasing bone mass. Therefore, leptin may play a role in fetal bone metabolism as part of its effect on fetal growth and development.

Adolescent↗
PubMed2000

Maternal thyroid function in multifetal pregnancies before and after fetal reduction.

The aim of the study was to investigate maternal thyroid function in pregnancy by monitoring the circulating concentrations of thyroid stimulating hormone (TSH), free thyroxine (fT(4)) and human chorionic gonadotrophin (hCG) in multifetal pregnancies before and after embryo reduction. We studied two groups of women: group 1 comprised singleton (n=12) and twin (n=12) pregnancies achieved after superovulation and in vitro fertilisation and embryo transfer (IVF-ET), and group 2 were multifetal pregnancies (n=39) undergoing selective fetal reduction to twin pregnancies. Blood samples were obtained initially at 10-12 weeks gestation (before fetal reduction) and then 4 and 8 weeks afterwards. Before fetal reduction, the circulating concentrations of fT(4) in multifetal pregnancies were significantly greater than those in singleton or twin pregnancies (singleton, mean 16.49 pmol/l (interquartile range 14.09-18.13 pmol/l); twins, 15.84 (15.36-16.95 pmol/l); multifetal, 21.08 (16. 64-26.29 pmol/l); P<0.005 for singleton and twins), and in a multiple regression analysis, fT(4) was significantly related to the number of fetuses (F=23.739, P=0.0001), but not to hCG. After fetal reduction to twins, the circulating concentrations of fT(4) in multifetal pregnancies decreased progressively towards those in control twin pregnancies, but remained significantly greater at both 4 (P=0.003) and 8 weeks (P=0.050). This pattern of change in the concentrations of fT(4) is similar to, but lags behind, that of hCG, which attains twin levels 4 weeks after fetal reduction. This may represent a delayed thyroid response to the decreasing concentrations of hCG, but the alternative is that the maternal thyroid function is controlled by a fetal factor in addition to hCG.

Chorionic Gonadotropin↗
PubMed2000

Panic disorder in primary care: patients' attributions of illness causes and willingness to accept psychiatric treatment.

OBJECTIVE: This study assessed the causes that primary care patients with panic disorder (PD) attribute to their panic symptoms, and their acceptance of various psychiatric treatment options. METHODS: In a cross-sectional assessment of 306 patients treated at two primary care clinics, 42 met criteria for DSM-IV PD in the past year. The authors classified these 42 PD-positive patients to one of two groups: those receiving both primary and specialty mental health care (PC+MH; n = 19) and those receiving only primary care (PC-only; n = 23). Patients rated the probability of four possible causes of their panic symptoms, and level of acceptability of three psychiatric and two medical treatments for PD. To place primary care patients' ratings into a broader context, a third contrast group of PD-positive patients, recruited from clinical trials of investigational PD pharmacotherapies (n = 31), also rated causes and treatment acceptability. RESULTS: Participants of the three treatment groups attributed psychiatric causes for their panic symptoms in approximately the same proportion (78 percent to 90 percent; p = ns). PC-only participants attributed medical causes for panic symptoms more frequently than PC+MH and PD Clinical Trials participants (48 percent vs. 5 percent and 32 percent; p = .01). Remarkably, the great majority of patients across all groups expressed willingness to see psychiatrists (84 percent to 94 percent) and psychotherapists (95 percent to 100 percent), and to take psychotropic medications (87 percent to 100 percent). CONCLUSIONS: In this study most patients attributed a psychiatric cause for panic symptoms and communicated strong acceptance of psychiatric treatment. Thus, we recommend that primary care clinicians more assertively inform their patients of PD diagnoses and recommend psychiatric treatments with less fear about stigmatizing and alienating them.

Adult↗
PubMed2000

A cancer gene therapy approach utilizing an anti-erbB-2 single-chain antibody-encoding adenovirus (AD21): a phase I trial.

The purpose of this Phase I study was to determine the feasibility of using an anti-erbB-2-encoding adenovirus (Ad21) to treat erbB-2-overexpressing ovarian cancer. Recurrent ovarian cancer patients were treated i.p. with Ad21 in dosages ranging from 1 x 10(9) to 1 x 10(11) pfu. Patients were monitored after treatment for evidence of clinical toxicity and efficacy. Peritoneal aspirates and serum samples were obtained to assess for evidence of gene transfer/expression, for generation of wild-type vector, and antiadenoviral humoral response. Fifteen patients were treated per study specifications. Treatment-specific grade 1/2 fever was experienced by 9 of 15 (60%) patients. Other transient grade 1/2 constitutional, pain, and gastrointestinal symptoms were also experienced. No dose-limiting vector-related toxicity was experienced. Of 13 patients evaluable for response, 5 (38%) had stable disease and 8 (61%) had evidence of progressive disease. One patient with nonmeasurable disease normalized her CA125 at the 8-week evaluation, and one patient with nonmeasurable disease remained without clinical evidence of disease for 6 months after treatment. PCR analysis of peritoneal aspirates demonstrated the presence of Ad21 in 84.6%, 84.6%, and 61.6% of evaluable specimens at days 2, 14, and 56 after treatment, respectively. No wild-type virus was detected. Reverse transcription-PCR analysis demonstrated expression of the anti-erbB-2 sFv-encoding gene in 10 of 14 evaluable patients at day 2. Five of six evaluable patients had an increase in antiadenovirus antibody titer. This study suggests that adenoviral-mediated gene therapy using an anti-erbB-2-directed intrabody is feasible in the context of human ovarian cancer.

Adenoviruses, Human↗
PubMed2000

Resting peripheral blood flow in normal pregnancy and in pre-eclampsia.

Multiple organ dysfunction followed by end organ failure occurs in pre-eclampsia. While one would intuitively reason that one of the factors contributing to the end organ failure is poor nutritional blood flow, this has yet to be demonstrated. The aim of the present study was to determine whether changes in resting nutritional blood flow occur in pre-eclampsia. We used strain-gauge plethysmography to study calf blood flow in 19 women with pre-eclampsia, 13 normal pregnant women and 17 non-pregnant controls. We reasoned that, since the calf comprises mostly skeletal muscle, without anastomotic channels, blood flowing through this region would primarily reflect nutritive flow. Calf blood flow was significantly reduced in women with pre-eclampsia (1.95+/-0.9 ml.min(-1).100 ml(-1)) compared with normal pregnant (3.9+/-1.4 ml.min(-1).100 ml(-1)) and non-pregnant (3.8+/-1.0 ml.min(-1).100 ml(-1)) women (P=0.0004 and P=0.0005 respectively; ANOVA). Blood flow in pre-eclampsia was also correlated significantly with platelet count as an index of disease severity. In addition, there was a significant negative correlation between blood flow and systolic blood pressure (r=-0.69, P=0.004) in the women with pre-eclampsia. These findings support the hypothesis that nutritional blood flow is reduced in pre-eclampsia. We suggest that measurement of resting calf blood flow could give a non-invasive index of deterioration of nutritive blood flow to vital organs in pre-eclampsia.

Adult↗
PubMed1999

Evaluation of sperm washing as a potential method of reducing HIV transmission in HIV-discordant couples wishing to have children.

OBJECTIVE: A number of discordant couples, in whom the man is HIV positive and the woman is HIV negative, wish to have children. To conceive they must abandon protected sex, posing a risk of HIV transmission to the woman and so to the child. In such circumstances purification of spermatozoa ('sperm-washing') to inseminate the woman artificially has been proposed as a method of reducing the risk of transmission. Here we evaluate whether this does represent a true risk reduction. METHODS: Semen samples from HIV-positive patients were separated into spermatozoa, non-sperm cells (NSCs) and plasma fractions. The amount of viral RNA present in each fraction was measured and compared with the level in the peripheral blood. Each fraction was also assessed for the presence of proviral DNA. The ability of spermatozoa to be infected was assessed by evaluating for the presence of HIV receptors, i.e. CD4, CCR5 and CXCR4 on the surface of the sperm, by flow cytometry. RESULTS: A poor correlation was found between the levels of HIV in blood and semen. Within the semen the virus was restricted to the plasma and/or NSCs. All spermatozoa were negative for viral RNA or proviral DNA. Spermatozoa did not express significant levels of CD4, CCR5 or CXCR4, suggesting that they are unlikely to be major targets for HIV infection. CONCLUSIONS: These data suggest that spermatozoa are not major targets of HIV infection. Purifying spermatozoa reduced the level of HIV RNA and proviral DNA to below the detection limit of the assays irrespective of the amount of virus present in the unfractionated semen. On the basis of these data we would recommend 'sperm-washing' followed by insemination as a safer alternative to natural conception for HIV-discordant couples wishing to have children.

DNA, Viral↗
PubMed1999

Relationship between symptom over-reporting and pre- and post-combat trauma history in veterans evaluated for PTSD.

We examined the prevalence of pre- and post-combat traumatic events in the histories of 129 combat veterans referred to be evaluated for PTSD and examined the impact of these non-combat traumatic events on self-reported psychiatric symptoms. Participants were consecutive referrals to a Veterans Affairs outpatient post-traumatic stress disorder (PTSD) clinic who completed structured interviews, self-report measures (e.g., Minnesota Multiphasic Personality Inventory-2; MMPI-2), and a trauma history questionnaire as part of their routine clinical evaluations. Findings show that non-combat trauma was prevalent in this sample, with 65% (21% pre-combat) reporting physical assaults and 12% (11% pre-combat) reporting sexual assaults. Overall, history of sexual or physical assaults did not appear to be systematically related to reported symptom level. However, chi square analyses revealed a consistent over-representation of veterans who reported sexual trauma in the category suggestive of response exaggeration (i.e., MMPI-2 F-K validity index > or = 13). Finally, a hierarchical regression equation predicting F-K scores was computed, but accounted for only 15.9% of the variance in F-K. Presence of sexual assault history was the only predictor associated with a more pronounced response set suggestive of exaggeration or deception. These findings tentatively indicate that if history of sexual or physical assault has an impact on symptom reporting in combat veterans evaluated for PTSD, it is of modest magnitude.

Adult↗
PubMed1999

Feasibility of using fMRI to study mothers responding to infant cries.

While parenting is a universal human behavior, its neuroanatomic basis is currently unknown. Animal data suggest that the cingulate may play an important function in mammalian parenting behavior. For example, in rodents cingulate lesions impair maternal behavior. Here, in an attempt to understand the brain basis of human maternal behavior, we had mothers listen to recorded infant cries and white noise control sounds while they underwent functional MRI (fMRI) of the brain. We hypothesized that mothers would show significantly greater cingulate activity during the cries compared to the control sounds. Of 7 subjects scanned, 4 had fMRI data suitable for analysis. When fMRI data were averaged for these 4 subjects, the anterior cingulate and right medial prefrontal cortex were the only brain regions showing statistically increased activity with the cries compared to white noise control sounds (cluster analysis with one-tailed z-map threshold of P < 0.001 and spatial extent threshold of P < 0.05). These results demonstrate the feasibility of using fMRI to study brain activity in mothers listening to infant cries and that the anterior cingulate may be involved in mothers listening to crying babies. We are currently replicating this study in a larger group of mothers. Future work in this area may help (1) unravel the functional neuroanatomy of the parent-infant bond and (2) examine whether markers of this bond, such as maternal brain response to infant crying, can predict maternal style (i.e., child neglect), offspring temperament, or offspring depression or anxiety.

Adult↗
PubMed1999

Simultaneous intracoronary ultrasound and Doppler flow studies distinguish flow-mediated from receptor-mediated endothelial responses.

Abnormalities in vascular endothelial function, which occur early in atherosclerosis, may play an etiologic role in the development of the disease or represent a marker for the extent of atherosclerosis. Endothelial dysfunction, usually characterized by demonstration of decreased endothelium-dependent vasorelaxation, may be a sensitive and specific method to detect vascular disease in its earliest stages. In this context, separation of abnormalities in receptor-mediated and flow-mediated endothelium-dependent vasodilatory responses may allow for the most accurate characterization of endothelial dysfunction. In 35 patients undergoing routine annual cardiac catheterization after heart transplantation, changes in epicardial lumen area and coronary blood flow in response to intracoronary administration of adenosine, acetylcholine, and nitroglycerin were measured simultaneously using an intravascular ultrasound (IVUS) catheter positioned over a Doppler flow wire in the left anterior descending coronary artery. The combination of these techniques allowed for distinction between receptor-mediated and flow-mediated endothelium-dependent vascular responses. Peak flow with the endothelium-independent resistance vessel dilator adenosine occurred at 18+/-2 sec; the maximal lumen area response occurred later, at 43+/-11 sec (P < 0.001). Acetylcholine, an endothelium-dependent small- and large-vessel vasodilator, caused an immediate increase in both flow and lumen area, but a second peak of dilation was observed, and maximal area occurred 46 sec after maximal flow (54+/-14 vs. 100+/-26 sec, P < 0.001). Simultaneous IVUS and Doppler flow measurements after infusion of vasoactive agents allows for distinction between and evaluation of the relative contribution of agonist-mediated and flow-mediated responses, which may offer important and unique insights into coronary endothelial function.

Acetylcholine↗
PubMed1999

Increased maternal bone formation in type I diabetic pregnancies.

There is evidence that infants of insulin-dependent diabetics have increased intrauterine bone resorption and reduced bone mineral content at birth. The aim of this study was to determine if type I diabetes is associated with abnormal maternal bone metabolism. We measured the circulating levels of carboxyterminal propeptide of type I procollagen (PICP) and cross-linked carboxyterminal telopeptide of type I collagen (ICTP) in the third trimester of pregnancy in samples obtained from 19 pregnant women with type I diabetes and 19 pregnant controls, to monitor the rate of bone formation and degradation, respectively. Diabetic control was considered to be good as the mean hemoglobin A(1) level was less than 8.5%. The circulating levels of PICP were significantly higher in pregnant women with insulin-dependent diabetes than in controls with uncomplicated pregnancy (median IDDM 147 microgram/liter, control 115 microgram/liter, P = 0.0014), but there was no significant difference in the circulating levels of ICTP between the two groups (median IDDM 4.6 microgram/liter, control 4.6 microgram/liter, P = 0.907). Therefore, our findings suggest that there is an increase in bone formation in pregnant women with type I diabetes which may be related to the increased amount of insulin administered and the improvement in diabetic control associated with pregnancy.

Adolescent↗
PubMed1999

Comparison of functional capacity in patients with end-stage heart failure following implantation of a left ventricular assist device versus heart transplantation: results of the experience with left ventricular assist device with exercise trial.

BACKGROUND: Use of a permanent left ventricular assist device (LVAD) has been proposed as an alternate treatment of patients with end-stage heart failure. The purpose of this study was to compare the functional capacity of patients following implantation of a LVAD vs heart transplant (HTx). METHODS: Eighteen patients from 6 centers who received an intracorporeal LVAD as a bridge to HTx underwent treadmill testing 1 to 3 months post-LVAD and again post-HTx. Baseline and peak measurements, including oxygen consumption, blood pressures, and respiratory rate were made during each treadmill test. RESULTS: Peak oxygen consumption was 14.5+/-3.9 ml/kg/minute post-LVAD and 17.5+/-5.0 ml/kg/minute post-HTx (p < .005). The percentage of the predicted peak oxygen consumption based on gender, weight, and age was 39.5%+/-5.5% post-LVAD and 47.7%+/-10.9% post-HTx (p < .005). Exercise duration was lower post-LVAD than post-HTx (10.3+/-4.2 minute vs 12.5+/-5.4 minute, p < .05). After LVAD implantation, peak total oxygen consumption correlated with peak LVAD rate and output. Eight patients reached an LVAD rate of 120 beats per minute (bpm) before the conclusion of exercise, the maximum rate for the outpatient electric device. The peak respiratory exchange ratio post-LVAD was 1.15+/-0.22 and post-HTx was 1.15+/-0.18, consistent with a good effort in both groups. CONCLUSIONS: Patients demonstrated a lower functional capacity post-LVAD than post-HTx. For some patients functional capacity post-LVAD may be improved by a higher maximum LVAD rate and output.

Adult↗
PubMed1999

Effect of antenatal dexamethasone therapy on maternal plasma human chorionic gonadotrophin, oestradiol and progesterone.

The aim of this study was to determine whether the current regimen of dexamethasone administration to induce fetal lung maturation affected the circulating concentrations of placental hormone. A standard regimen of dexamethasone that comprised two doses of 12-mg intramuscular injections, 12 h apart was administered to 12 pregnant women to promote fetal lung maturation in anticipation of premature delivery before 34 completed weeks of gestation. Blood samples were collected before starting the dexamethasone therapy, 24 h, and 48 h after completing therapy for the measurement of the plasma concentrations of human chorionic gonadotrophin (HCG), oestradiol and progesterone. There was a progressive fall in the plasma concentrations of HCG following dexamethasone therapy (P = 0.049 and P = 0.034, 24-h and 48-h post therapy respectively). There was an initial fall in the plasma concentrations of oestradiol after dexamethasone therapy (z = 3.059; P = 0.002, 24-h post therapy), which recovered by 48 h (P = 0.239). There was no difference between the plasma concentrations of progesterone at the three time points. The effect of dexamethasone on HCG concentrations suggests that it has a direct inhibitory effect on placental hormone synthesis or secretion. Further studies are needed to define the mechanism of action of dexamethasone on placental HCG production.

Adult↗