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Biomedical subjects

M R Johnson

Publications and source records attributed to M R Johnson.

At least 127 records · Page 7Linked to original sources
PubMed1996

Effectiveness and safety of diltiazem or lisinopril in treatment of hypertension after heart transplantation. Results of a prospective, randomized multicenter trail.

OBJECTIVES: The purpose of this study was to determine the effectiveness and safety of diltiazem or lisinopril for treatment of hypertension after heart transplantation. BACKGROUND: Systemic hypertension is common after heart transplantation, and to date there are no randomized, prospective multicenter treatment trials. METHODS: Members of the Cardiac Transplant Research Database Group developed and implemented a prospective, randomized multicenter trial of the effectiveness and safety of diltiazem or lisinopril in the treatment of hypertension in cyclosporine-treated patients after heart transplantation. RESULTS: One hundred sixteen patients with hypertension (blood pressure > or = 140/90 mm Hg) after heart transplantation were randomized for > or = 3 months of treatment. Of 55 diltiazem-treated patients, 21 (38%) were responders (diastolic blood pressure < 90 mm Hg), 23 (42%) were nonresponders (diastolic blood pressure > or = 90 mm Hg), and 11 (20%) were withdrawn from the study. Of 61 lisinopril-treated patients, 28 (46%) were responders, 22 (36%) were nonresponders, and 11 (18%) were withdrawn. There was no difference in baseline characteristics or percent responders between the two groups. Systolic pressure decreased from 157 +/- 2.3 to 130 +/- 2.0 mm Hg (mean +/- 1 SEM) in the diltiazem-treated responders and from 153 +/- 2.1 to 127 +/- 2.7 mm Hg in the lisinopril-treated responders (p < 0.0001). Diastolic pressure decreased from 100 +/- 0.9 to 85 +/- 1.6 mm Hg in the diltiazem-treated responders and from 100 +/- 1.0 to 84 +/- 2.0 mm Hg in the lisinopril-treated responders (p < 0.0001). There were a total of 35 reported adverse events, 22 of which led to withdrawal of the patient from the study. All drug-related side effects were considered minor and resolved with discontinuation of the drug. CONCLUSIONS: These results indicate that both diltiazem and lisinopril are safe for treatment of hypertension after heart transplantation, although titrated monotherapy with either drug controlled the condition in < 50% of patients.

Aged↗
PubMed1996

Endometrial thickness: individual and mean growth profiles for different hormone replacement regimens.

Currently, there is a paucity of data describing endometrial growth, with most studies concentrating on endometrial thickness immediately prior to implantation or embryo transfer. This study looked at the individual and combined growth profiles of 67 volunteers receiving three different hormone replacement regimens. Each treatment regimen was in excess of that considered necessary for optimal growth, and all promoted an endometrial thickness that would be considered satisfactory for embryo transfer. Three patterns of growth were identified, but overall there was a decrease in the rate of endometrial growth with duration of treatment. As expected, analysis of variance did not show a significant difference between the mean growth profiles for the three hormone replacement regimens. The correlation (r = 0.45, P < 0.0001) between rank order on day 3 and day 10 of treatment indicates that interim analysis during early treatment cannot accurately predict later thickness, but a doubling of endometrial thickness can be expected in most cases. A relationship between endometrial thickness and either the treatment dose or serum concentrations of oestradiol was not found. These findings suggest that manipulation of endometrial growth is not possible by adjustment of either the treatment dose or serum concentration. The findings indicate that treatment beyond 12 days does not promote either a clinically significant increase in endometrial thickness of an excessive thickness, suggesting that maintenance of an oocyte recipient in a pseudo-follicular phase is unlikely to be disadvantageous to implantation.

Adult↗
PubMed1996

The role of relaxin in the pregnancy associated reduction in plasma osmolality.

Recent data suggest that the ovarian peptide relaxin is responsible for the pregnancy-associated fall in plasma osmolality in the rat. In order to test whether relaxin has the same role during human pregnancy, plasma osmolality, electrolytes, urea and creatinine were measured in samples obtained at 10, 20 and 30 weeks gestation from singleton pregnancies conceived following ovum donation (OD, n = 12), spontaneously (N, n = 12) and following in-vitro fertilization and embryo transfer (IVF, n = 14). These groups were chosen, as relaxin concentrations throughout pregnancy are undetectable (OD), elevated (IVF) or normal (N). Thus, if relaxin alone is responsible for the fall in plasma osmolality associated with pregnancy in the human, then plasma osmolality would be expected not to fall during pregnancy in the OD group and to show a consistent decline from OD to N to IVF throughout pregnancy. Plasma osmolality fell significantly during pregnancy in both the OD and N groups, but not the IVF group. In addition, plasma osmolality was only significantly greater in OD when compared with IVF group at 10 weeks gestation; thereafter there were no significant differences between the groups with regard to plasma osmolality. Similarly, at 10 weeks the plasma concentrations of sodium and potassium were significantly higher in the OD than in either the N or IVF groups. Thus, although relaxin may be important in the initial control of plasma osmolality, other factors, probably derived from or regulated by the feto-placental unit, supersede it as pregnancy advances.

Blood↗
PubMed1996

A nonsense mutation in the cathepsin K gene observed in a family with pycnodysostosis.

Pycnodysostosis (MIM 265800) is a rare, autosomal recessive skeletal dysplasia characterized by short stature, wide cranial sutures, and increased bone density and fragility. Linkage analysis localized the disease gene to human chromosome 1q21, and subsequently the genetic interval was narrowed to between markers D1S2612 and D1S2345. Expressed sequence tagged markers corresponding to cathepsin K, a cysteine protease highly expressed in osteoclasts and thought to be important in bone resorption, were mapped previously in the candidate region. We have identified a cytosine to thymidine transition at nucleotide 862 (GenBank accession no. S79895) of the cathepsin K coding sequence in the DNA of an affected individual from a large, consanguinous Mexican family. This mutation results in an arginine to STOP alteration at amino acid 241, predicting premature termination of cathepsin K mRNA translation. All affected individuals in this family were homozygous for the mutation, suggesting that this alteration may lead to pycnodysostosis. Recognition of the role of cathepsin K in the etiology of pycnodysostosis should provide insights into the pathogenesis and treatment of other disorders of bone remodeling, including osteoporosis.

Blotting, Southern↗
PubMed1996

Head-to-cervix force: an important physiological variable in labour. 1. The temporal relation between head-to-cervix force and intrauterine pressure during labour.

OBJECTIVE: To investigate the relation between the rise in intrauterine pressure and rise in fetal head to cervix force in normal, slow and induced labour. DESIGN: Prospective observational study. SETTING: The labour ward of a London teaching hospital. PARTICIPANTS: Forty patients were recruited from the antenatal clinic and labour ward of a West London Hospital. Five had normal onset and progression of labour, 14 had slow progression of labour and 21 had induced onset of labour. METHOD: Intrauterine pressure and head-to-cervix force was measured simultaneously using an intrauterine pressure catheter and a specially designed four sensor head-to-cervix force probe. RESULTS: For each contraction of each labour, scattergrams of force by pressure were plotted. Three patterns were observed. When the rise in pressure preceded the rise in force, a positive 'loop' was generated. When the rise in pressure and force occurred simultaneously a linear pattern was generated (a neutral 'loop'). When the rise in pressure lags the rise in force, a negative 'loop' was generated. In normally progressive labour the distribution of loops was 29.1%, 22.6% and 48.3%, respectively, in slow labour the distribution was 26.1%, 14.1% and 59.8% and in induced labour the distribution was 33.8%, 14.4% and 51.8%. These distributions were not statistically different. However, a higher proportion of negative loops was observed in labours augmented with oxytocin compared to those receiving no oxytocin (MW-U = 87, P = 0.036). No differences were observed comparing parity, use of PGE2, epidural analgesia, or mode of delivery. Contraction frequency (number/10 minutes) was inversely correlated to the percentage of negative loops (rs = -0.34, P = 0.033) and positively correlated with percentage of positive loops (rs = 0.36, P = 0.027). CONCLUSIONS: This is the first report of the temporal relation between intrauterine pressure and head-to-cervix force in labour. The most common pattern is that the rise in pressure lags the rise in force, suggesting that a seal has to be created between the fetal head and cervix before a rise in pressure can occur. When oxytocin is given in labour, a higher proportion of loops are negative indicating that there is poor application of the fetal head and cervix in a greater proportion of contractions.

Adult↗
PubMed1996

Head-to-cervix force: an important physiological variable in labour. 2. Peak active force, peak active pressure and mode of delivery.

OBJECTIVE: To assess the relation between peak active (above baseline) head-to-cervix force (paHCF) and peak active (above baseline) intrauterine pressure (paIUP) in labour, and to compare the relation between labours progressing well and ending in vaginal delivery and those labours progressing slowly and ending in caesarean section. DESIGN: Prospective observational study. SETTING: The labour ward of a London teaching hospital. PARTICIPANTS: Forty women in labour who agreed to have an experimental head-to-cervix force probe and an intrauterine pressure catheter inserted. RESULTS: The relation was linear, with a correlation coefficient which ranged from 0.012 to 0.885 (mean value 0.438). The closeness of the relation did not correlate with the rate of cervical dilatation (r = 0.0192, P = 0.574) or the mode of delivery (r = 0.215, P = 0.183). However, in women who progressed well to a vaginal delivery, the mean slope of the paHCF to paIUP regression line was 0.72, significantly steeper than in women who progressed slowly and required delivery by caesarean section (mean slope = 0.45, t = 2.31, P = 0.02). Mean paIUPs were significantly higher in women progressing well and achieving a vaginal delivery than in those progressing slowly and requiring caesarean section (45.3 mmHg SD 7.5 vs 38.4 mmHg SD 11.4, t = 2.31, P = 0.02), but the overlap between the two groups was considerable. However, in keeping with their steeper paHCF/paIUP slope, women progressing well to a vaginal delivery had substantially higher head-to-cervix forces (46.4 gWt SD 11.8 vs 28.3 gWt SD 8.2, t = 5.22, P < 0.00001) than those progressing slowly and requiring caesarean section, and there was much less overlap between paHCF than paIUP. This resulted in paHCF being a much better discriminating variable than paIUP for mode of delivery. CONCLUSIONS: The relation between paHCF and paIUP is linear, but there is a wide variation in the degree of correlation between one woman and another. Women with a steep slope of paHCF relative to paIUP are more likely to achieve a high mean paHCF, progress rapidly in labour and achieve a vaginal delivery than women with a flap slope, although mean paIUPs do not differ substantially between the two groups. The level of paHCF was substantially better than cervical dilatation rate at predicting mode of delivery. These results suggest that head-to-cervix force is sensitive to factors determining mode of delivery which are not reflected in either the level of uterine activity as measured by intrauterine pressure, or cervical compliance as measured by cervical dilatation rates.

Adult↗
PubMed1996

cDNA cloning of bovine liver dihydropyrimidine dehydrogenase.

Dihydropyrimidine dehydrogenase (DPD), the initial and rate-limiting enzyme in pyrimidine catabolism, has recently been purified to homogeneity from several species. In the present study the molecular cloning of DPD with isolation of a cDNA coding for bovine liver DPD is reported using polymerase chain reaction (PCR) methodology. Known amino acid sequence from purified bovine DPD was used to initially design mixed oligonucleotide primers for amplification of a cDNA fragment (65 base pairs). Specific primers were subsequently designed and utilized in the amplification of the full-length cDNA (4422 base pairs). Sequence analysis demonstrated a 74 nucleotide 5'-nontranslated region, an open reading frame of 3075 bases, and a 1273 nucleotide 3'-nontranslated region. Comparison of the nucleotide and deduced amino acid sequences of Bovine DPD to Pig and Human liver DPD reveals 93% and 92% identity respectively.

Amino Acid Sequence↗
PubMed1996

Fluoxetine in the treatment of anger: an open clinical trial.

BACKGROUND: Intense anger, easy irritability, and low frustration tolerance are frequently encountered in clinical practice and may occur as part of the constellation of symptoms associated with a number of Axis I and Axis II diagnoses. Recent studies have suggested the efficacy of fluoxetine in treating anger in depressed and borderline patients. The present study examines the treatment of anger as a target symptom regardless of accompanying psychopathology. METHOD: In this preliminary trial, 11 subjects experiencing intense anger were treated in an open-label fashion with fluoxetine over an 8-week period. Anger was measured by a clinician-administered Clinical Global Impressions-Severity (CGI-S) scale and a self-report anger inventory, the Multidimensional Anger Inventory (MAI). The Hamilton Rating Scale for Depression was administered at baseline and final visits. RESULTS: All 11 enrolled patients completed the study, and all patients demonstrated clinical improvement as measured by both the CGI-S and the MAI. Nine patients were rated as responders and 2 as nonresponders according to prospectively established criteria. Fluoxetine was well tolerated and showed rapid onset of action. CONCLUSION: This study is limited by small sample size and nonblinded, open-label design, but nonetheless suggests that fluoxetine may be useful in moderating anger as it occurs as part of the symptomatology of a number of Axis I and Axis II disorders. Controlled studies are warranted.

Adult↗
PubMed1995

Autosomal dominant optic nerve colobomas, vesicoureteral reflux, and renal anomalies.

We describe a father and 3 sons with optic nerve colobomas, vesicoureteral reflux, and renal anomalies. The youngest son had congenital renal failure and ultimately underwent renal transplantation. The father and one son had high frequency hearing loss. There were no other affected relatives. We conclude that the association of optic nerve colobomas, renal anomalies, and vesicoureteral reflux comprises a unique autosomal dominant syndrome. Molecular investigations have determined this disorder to be associated with a single nucleotide deletion in the PAX2 gene.

Abnormalities, Multiple↗
PubMed1995

Birth weight: nature or nurture?

OBJECTIVE: To investigate the relative role of environmental and genetic factors in the determination of birth weight following ovum donation. METHODS: Data from 62 cases of ovum donation were used to examine the relative influence of donor and recipient on birth weight. RESULTS: The only discernible factors that significantly influenced birth weight were gestational age and recipient's weight. Donor weight, her own birth weight, and the birth weight of the donor's own children were not significantly correlated with the birth weight of the child following ovum donation. CONCLUSIONS: It is concluded that the environment provided by the human mother is more important than her genetic contribution to birth weight.

Adult↗
PubMed1995

Insulin-related growth factor binding protein-1 levels in ovum donation pregnancies.

The finding that endometrial maturation may be delayed following hormone replacement therapy has suggested that a generalised endometrial dysfunction may exist in ovum recipients. In order to investigate this suggestion further, circulating levels of IGFBP-1 were measured in samples taken throughout pregnancies conceived either spontaneously or following ovum donation. When analysed at two-weekly intervals, the serum levels of IGFBP-1 in ovum donation pregnancies failed to show the expected peak towards the end of the first trimester and were significantly reduced at week ten (U = 364.5, p = 0.0002) and twelve (U = 138.0, p = 0.0047). For the remainder of pregnancy, circulating IGFBP-1 levels were similar in both groups. The birth weight of children born to the ovum donation group was not significantly different from a normal control group, suggesting that circulating levels of IGFBP-1 in early pregnancy do not reflect local function and that IGFBP-1 does not have an essential function (in relation to birth weight) in early pregnancy.

Birth Weight↗
PubMed1995

Superovulation, IGFBP-1 and birth weight.

In this study, the effect of superovulation on the circulating levels of insulin-like growth factor binding protein-1 (IGFBP-1) has been investigated. IGFBP-1 levels were measured in singleton pregnancies achieved either naturally (n = 203) or following superovulation, in-vitro fertilisation and embryo transfer (IVF-ET) with either pituitary desensitisation with buserelin and superovulation with human menopausal gonadotrophin (b/hMG) followed by IVF-ET (n = 15) or with clomiphene citrate and hMG (CC/hMG) followed by IVF-ET (n = 15, 1st trimester only). The circulating levels of IGFBP-1 were similar in all three groups during the first trimester, and in both normal and b/hMG pregnancies in the second, but were significantly higher during the third trimester in b/hMG pregnancies than in normal pregnancies (P = 0.0002). The birth weights were significantly lower in the b/hMG group (P = 0.04), but not in the CC/hMG group compared with natural conceptions. Gestational age at delivery was similar in control and b/hMG pregnancies, but significantly reduced in CC/hMG pregnancies (P = 0.04). These data suggest that pregnancies achieved following superovulation with b/hMG are associated with elevated levels of IGFBP-1 during the third trimester of pregnancy and reduced birth weight.

Adult↗
PubMed1995

Coronary angioplasty, atherectomy and bypass surgery in cardiac transplant recipients.

OBJECTIVES: This study sought to analyze the outcomes of revascularization procedures in the treatment of allograft coronary disease. BACKGROUND: Allograft vasculopathy is the main factor limiting survival of heart transplant recipients. Because no medical therapy prevents allograft atherosclerosis, and retransplantation is associated with suboptimal allograft survival, palliative coronary revascularization has been attempted. METHODS: Thirteen medical centers retrospectively analyzed their complete experience with percutaneous transluminal coronary angioplasty, directional coronary atherectomy and coronary bypass graft surgery in allograft coronary disease. RESULTS: Sixty-six patients underwent coronary angioplasty. Angiographic success (< or = 50% residual stenosis) occurred in 153 (94%) of 162 lesions. Forty patients (61%) are alive without retransplantation at 19 +/- 14 (mean +/- SD) months after angioplasty. The consequences of failed revascularization were severe. Two patients sustained periprocedural myocardial infarction and died. Angiographic restenosis occurred in 42 (55%) of 76 lesions at 8 +/- 5 months after angioplasty. Angiographic distal arteriopathy adversely affected allograft survival. Eleven patients underwent directional coronary atherectomy. Angiographic success occurred in 9 (82%) of 11 lesions. Two periprocedural deaths occurred. Nine patients are alive without transplantation at 7 +/- 4 months after atherectomy. Bypass graft surgery was performed in 12 patients. Four patients died perioperatively. Seven patients are alive without retransplantation at 9 +/- 7 months after operation. CONCLUSIONS: Coronary revascularization may be an effective palliative therapy in suitable cardiac transplant recipients. Angioplasty has an acceptable survival in patients without angiographic distal arteriopathy. Because few patients underwent atherectomy and coronary bypass surgery, assessment of these procedures is limited. Angiographic distal arteriopathy is associated with decreased allograft survival in patients requiring revascularization.

Adolescent↗
PubMed1995

Serum concentrations of luteinizing hormone and progesterone in ovum recipients: their relationship with pregnancy and miscarriage.

Our objective was to test the hypothesis that the association between elevated luteinizing hormone (LH) concentrations and miscarriage is mediated via an effect of LH on the maternal environment, rather than on the oocyte. The impact of maternal age, ovarian function, previous IVF attempts, therapeutic (buserelin) and hormonal (LH, oestradiol, progesterone) effects occurring on the day of zygote intra-Fallopian transfer (ZIFT) or embryo transfer, and of oocyte or embryo numbers, whether they were fresh or frozen, and their mode of transfer on the occurrence of pregnancy and miscarriage following ovum donation (n = 57) were investigated. The cycles were divided by outcome into non-pregnant (n = 26), miscarriage (n = 19) and normal term pregnancy (n = 12). The circulating concentrations of LH were greater in miscarriage cycles (P = 0.046) and cycles ending in pregnancy (P = 0.04) than in non-pregnant cycles, while the concentrations of progesterone were greater in non-pregnant (P = 0.029) and miscarriage (P = 0.015) cycles than in cycles ending in pregnancy. Frozen embryos were used more frequently in non-pregnant compared to cycles ending in pregnancy (P = 0.016). Multiple regression analysis was used to investigate which factors are associated with miscarriage and identified progesterone concentrations at the time of transfer as being the only significant variable (r = 0.48, F = 8.5, P = 0.007).(ABSTRACT TRUNCATED AT 250 WORDS)

Abortion, Spontaneous↗
PubMed1995

Clinical follow-up of the heart transplant recipient.

Long-term survival of heart transplant recipients is now commonplace, due to improved perioperative care. It is thus appropriate to review recent studies concerning immunosuppression-related clinical problems in heart transplant recipients, including infections, malignancies, hypertension, hyperlipidemia, and osteoporosis. Hormonal and peripheral vascular responses of the denervated heart, exercise tolerance, pulmonary function, and parenting are also discussed.

Follow-Up Studies↗