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Biomedical subjects

J Harris

Publications and source records attributed to J Harris.

At least 235 records · Page 13Linked to original sources
PubMed1995

Skeletal unloading induces selective resistance to the anabolic actions of growth hormone on bone.

Loss of skeletal weight bearing or physical unloading of bone in the growing animal inhibits bone formation and induces a bone mineral deficit. To determine whether the inhibition of bone formation induced by skeletal unloading in the growing animal is a consequence of diminished sensitivity to growth hormone (GH) we studied the effects of skeletal unloading in young hypophysectomized rats treated with GH (0, 50, 500 micrograms/100 g body weight/day). Skeletal unloading reduced serum osteocalcin, impaired uptake of 3H-proline into bone, decreased proximal tibial mass, and diminished periosteal bone formation at the tibiofibular junction. When compared with animals receiving excipient alone, GH administration increased bone mass in all animals. The responses in serum osteocalcin, uptake of 3H-proline and 45Ca into the proximal tibia, and proximal tibial mass in non-weight bearing animals were equal to those in weight bearing animals. The responses in trabecular bone volume in the proximal tibia and bone formation at the tibiofibular junction to GH, however, were reduced significantly by skeletal unloading. Bone unloading prevented completely the increase in metaphyseal trabecular bone normally induced by GH and severely dampened the stimulatory effect (158% vs. 313%, p < 0.002) of GH on periosteal bone formation. These results suggest that while GH can stimulate the overall accumulation of bone mineral in both weight bearing and non-weight bearing animals, skeletal unloading selectively impairs the response of trabecular bone and periosteal bone formation to the anabolic actions of GH.

Analysis of Variance↗
PubMed1995

Reduced recurrence of orofacial clefts after periconceptional supplementation with high-dose folic acid and multivitamins.

To assess effects of periconceptional multivitamin and folic-acid supplementation on recurrence of cleft lip with or without cleft palate (CL +/- P), we prospectively evaluated 221 pregnancies in women at risk of a child with CL +/- P. The 10-step protocol included multivitamin supplementation with SPOFAVIT (A, B1, B2, B6, C, D3, E, nicotinamide, calcium pantothenicum) and folic acid (10 mg/day), beginning > or = 2 months before planned conception and continuing for > or = 3 months thereafter. A comparison group comprised 1,901 women at risk of a child with CL +/- P who received no supplementation and gave birth within the same period as the study group. In the supplemented group, 3 of 214 informative pregnancies ended with infants with CL +/- P, a 65.4% decrease (observed versus expected value -5.67; P = 0.031, Fisher's exact test); the expected value of 8.7 was calculated based on the incidence of cleft among first-degree relatives among the comparison group. Subset analysis by proband's sex, severity of CL +/- P, and both variables showed highest supplementation efficacy in probands with unilateral cleft (82.6% decrease, P = 0.024, Fisher's exact test). No efficacy was observed for female probands with bilateral CL +/- P. Generally, efficacy was greater for subgroups with unilateral than with bilateral cleft and for male than female probands.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Descriptive epidemiology of alimentary tract atresia.

A study has been made on certain epidemiological characteristics of infants with alimentary tract atresia: esophageal atresia, small and large gut atresia, and anal atresia. Data were collected from three malformation registries and represent a material of more than 4.5 million births. A total of 3,550 infants with alimentary atresia were identified corresponding to a total rate of about 8 per 10,000 births. In 167 infants (4.7%) more than one of the major atresia types were present simultaneously. Racial differences were found (based on data from California) for esophageal atresia where whites had a higher rate than other races. For gastrointestinal atresia, a high rate in blacks was found, while no differences between races were seen for anal atresia. Also, differences in registered rates between the three programs were found, at least partly explainable by different ascertainment. The different forms of atresia were compared from the point of view of sex ratio, twinning rate, maternal age and parity distribution, presence of chromosome anomalies, and types of associated malformations. The pathogenesis and etiology of the various types of atresia are discussed based on these observations. The conclusion is that although undoubtedly other pathogenetic mechanisms may exist for gastrointestinal atresia, a substantial proportion of all infants with alimentary atresia had their malformations as a result of early disturbances of intestinal morphogenesis. Within each subgroup, apparently different etiologies may exist, resulting in differences in epidemiological characteristics.

Adolescent↗
PubMed1995

A phase II study of interleukin-2 with and without beta-interferon in the treatment of advanced renal cell carcinoma.

BACKGROUND: Biologic response modifiers have activity in renal cell carcinoma. The combination of interleukin-2 (IL-2) and beta-interferon (B-IFN) is synergistic in vitro. This trial was initiated to determine the efficacy of IL-2 alone and with B-IFN in advanced RCC. METHODS: Ambulatory patients with advanced RCC were randomly allocated to either IL-2 6 x 10(6) units/M2 intravenously (IV) three days a week for four weeks or IL-2 5 x 10(6) units/M2 IV plus B-IFN 6 x 10(6) units/M2 IV three days a week for 4 weeks. This induction phase was followed by a maintenance phase of the same drugs and doses administered for two weeks out of every four. RESULTS: 84 patients were entered onto this phase II trial with 75 considered eligible for response and survival. Toxicity is reported for the 81 patients on whom data was received, irrespective of eligibility. The overall response rate (RR) was 9.3% (7/75). Of the 3 responses in the IL-2 arm (RR = 8.3%), one was a complete response. 4 patients in the IL-2 + B-IFN arm (RR = 10.3%) achieved a partial response. Median survival was estimated to be 8.4 months for patients given IL-2 and 8.0 months for patients given the IL-2 and B-IFN combination. Multivariate analysis of survival data identified initial performance status, metastases of > 1 site, and weight loss as being important prognostic factors for survival. There were 2 lethal and 3 life threatening toxicities with the IL-2 treatment. While there were no lethal toxicities on the combination arm, there were 4 life threatening toxicities. CONCLUSIONS: The results of this study indicate that further investigation of IL-2 with or without B-IFN at this dose and schedule as treatments for renal cell carcinoma is probably not warranted.

Adult↗
PubMed1995

Oropharyngeal candidiasis in immunocompromised children: a randomized, multicenter study of orally administered fluconazole suspension versus nystatin. The Multicenter Fluconazole Study Group.

OBJECTIVE: To compare the efficacy, safety, and tolerance of fluconazole suspension versus nystatin in the treatment of oropharyngeal thrush in immunocompromised children. DESIGN: Multicenter, randomized, observer-masked trial. SETTING: Thirty-two centers participated, including hospitals and ambulatory care clinics. PATIENTS: We enrolled 182 immunocompromised infants and children, ages 5 months to 14 years, with signs of oral thrush and presence of yeasts on potassium hydroxide- or gram-stained preparations. Subjects were randomly assigned to receive a single daily dose of fluconazole suspension, 2 to 3 mg/kg per day, or nystatin, 400,000 units four times daily for 14 days; 159 patients, who had culture confirmation of thrush and received at least 7 days of study drug, were evaluated for efficacy; all patients were evaluated for safety. RESULTS: Clinical cure was demonstrated in 91% of the subjects in the fluconazole group and 51% of the subjects in the nystatin group (p < 0.001), and eradication of the organism cultured at entry occurred in 76% and 11% (p < 0.001), respectively. Gastrointestinal conditions developed in six patients who received fluconazole and in three who received nystatin; two fluconazole recipients were subsequently withdrawn from the study. Laboratory abnormalities occurred with equal frequency in both groups. Clinical relapse rates were similar in both groups at 2 weeks (18% and 24% for fluconazole and nystatin, respectively) and 1 month (28% and 27%, respectively) after the completion of study drug. CONCLUSIONS: Fluconazole suspension is more effective than nystatin in the treatment of thrush in immunocompromised children. Both regimens were well tolerated.

Administration, Oral↗
PubMed1995

Use of random PCR (RAPD) technology to analyse phylogenetic relationships in the Lolium/Festuca complex.

The RAPD PCR technique has been employed to investigate phylogenetic relationships between species of the genera Lolium and Festuca. Several decamer primers were used to generate patterns from groups of genotypes of several different species. The degree of band sharing was used to evaluate genetic distances between species and to construct a phylogenetic tree which is in good overall agreement with classical taxonomy, but contains a number of novel insights. The degree of homoplasy inherent in this approach has been investigated using Southern hybridization. These results are discussed in the context of current work in molecular biosystematics.

Base Sequence↗
PubMed1995

Double jeopardy and the veil of ignorance--a reply.

This paper discusses the attempt in this issue of the journal by Peter Singer, John McKie, Helga Kuhse and Jeff Richardson, to defend QALYs against the argument from double jeopardy which I first outlined in 1987. In showing how the QALY and other similar measures which combine life expectancy and quality of life and use these to justify particular allocations of health care resource, remain vulnerable to the charge of double jeopardy I am able to clarify some of the central issues concerning the value of life. In particular, the idea that the value of a life varies with its life expectancy and with its quality, understood in terms of its richness, variety, success etc, is subjected to special examination. It is shown how defenders of QALYs are committed to the view that so far from all lives being of equal value, all lives are necessarily of subtly different value. The paper then analyses the use to which the notorious 'veil of ignorance' has been put both by Singer et al and by others and shows how this device of John Rawls's cannot do the work so often assigned to it. The paper then considers the issue of hypothetical consent and the role that it can play in justifying disposing of the lives of people who have not in fact consented to their lives being disposed of in particular ways. Finally, the paper makes some points about the comprehensive nature of the data collection and storage which would be required by QALY advocates and points out the independent problems attaching to licensing such comprehensive collection and use of personal data.

Confidentiality↗
PubMed1995

The elimination of morality.

Anne Maclean has written a book which purports to identify and then definitively to reject the claims which she perceives to be the claims of bioethics. If she is right, then the enterprise to which this journal is dedicated is misconceived and worthless. In this paper, I attempt to show why so far from being not right she is comprehensively wrong, both in her understanding of the nature of bioethics and in the specific moral claims she makes about those she terms 'bioethicists'. Since much of her book-length study is devoted to a criticism of my own work, this paper analyses the extent to which Maclean's criticisms of me, and by extension, of other bioethicists, are sustainable.

Bioethics↗
PubMed1995

Water intake and activity of hypothalamoneurohypophysial system during osmotic and sodium stimulation in rats.

Intrajugular infusion (200 microliters/min for 10 min) of 0.85 M NaCl or 1.7 M mannitol in conscious adult male Sprague-Dawley rats increased plasma osmolality similarly and had an additive effect when combined. Plasma Na+ concentration, however, increased with infusion of 0.85 M NaCl, decreased with 1.7 M mannitol, and was not significantly altered by the combined solution. Irrespective of changes in plasma Na+ concentration, plasma vasopressin and oxytocin concentrations were elevated to a similar degree after independent infusion of 0.85 M NaCl or 1.7 M mannitol. With the combined infusion, the change in plasma vasopressin was additive but the change in oxytocin tended to be greater. Accordingly, glucose utilization increased throughout the hypothalamoneurohypophysial system after infusion of 0.85 M NaCl and 1.7 M mannitol. With the combined infusion, however, the change in glucose utilization in the paraventricular nucleus was additive but a synergistic effect occurred in the supraoptic nucleus and neural lobe. Drinking responses were similar in all groups receiving hypertonic solutions, with no additive effect after the combined stimulus. Although our results do not completely rule out the participation of cerebrospinal fluid sodium receptors, it is more likely that osmoreceptors regulate the activity of the hypothalamoneurohypophysial system and drinking behavior. Unlike the magnocellular system, however, drinking behavior seems to be negatively influenced by a stress component of the osmotic stimulation.

Animals↗
PubMed1995

Analysis of the role of angiotensinogen in spontaneous hypertension.

Allelic variants at the human angiotensinogen locus have recently been reported to increase susceptibility to the development of essential hypertension. In this study we analyzed the role played by angiotensinogen in the elevated blood pressure of the spontaneously hypertensive rat (SHR). The SHR angiotensinogen locus (on chromosome 19) cosegregated with a significant (P = .003) and specific increase in pulse pressure in F2 rats derived from a cross of the SHR with the normotensive Wistar-Kyoto rat (WKY), accounting for 20% of the genetic (10% of total) variance in this phenotype. To identify potential mechanisms underlying the effect of the locus, we further examined angiotensinogen structure and expression in the two strains. Sequence analysis of the respective coding regions revealed no differences in the primary structure of angiotensinogen between the strains. Likewise, plasma angiotensinogen level did not differ in adult rats of the two strains. However, gene expression studies showed tissue-specific, age-related differences in angiotensinogen mRNA levels between SHR and WKY, particularly in the aorta. The findings suggest that pulse pressure, which significantly influences cardiovascular risk, has independent genetic determinants. They further suggest that the effect of the angiotensinogen locus on this phenotype in the SHR may be mediated through a tissue-specific abnormality of angiotensinogen gene expression.

Angiotensinogen↗
PubMed1995

Serum cardiac troponin T levels during treatment of early-stage breast cancer.

PURPOSE: To measure serum troponin T concentrations in patients with early-stage left breast cancer during breast-conserving radiation therapy. Troponin T has been introduced recently as a sensitive and specific marker for acute myocardial injury. PATIENTS AND METHODS: We compared pretreatment and posttreatment serum troponin T values in 50 patients undergoing radiation therapy to the entire left breast following conservative surgery for stage I and II breast cancer. RESULTS: No changes in troponin T concentrations were found after 45 to 46 Gy whole-breast irradiation. All women had undetectable or normal troponin T on the first and last day of treatment. There was no evidence of an upward trend during treatment. CONCLUSION: Radiation therapy to the left breast does not affect serum cardiac troponin T levels, despite the fact that a portion of the myocardium lies within the high-dose region. This suggests that the acute effects of radiation on the myocardium are minor. Long-term evaluation of these patients is necessary to rule out the possibility of late cardiac morbidity due to accelerated atherosclerosis. This study also suggests that an elevated troponin T level during or shortly after left breast irradiation should not be attributed to treatment.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1995

Short-course FAC-M versus 1 year of CMFVP in node-positive, hormone receptor-negative breast cancer: an intergroup study.

PURPOSE: To compare 1 year of therapy with continuous cyclophosphamide, methotrexate, fluorouracil (5-FU), vincristine, and prednisone (CMFVP) with a short course of treatment with a doxorubicin-based regimen in the postsurgical adjuvant treatment of patients with hormone receptor-negative, node-positive breast cancer. PATIENTS AND METHODS: Five-hundred thirty-one eligible women with hormone receptor-negative, node-positive breast cancer were randomized to receive either 1 year of therapy with CMFVP or 20 weeks of therapy with four 5-week courses of treatment with 5-FU, doxorubicin, cyclophosphamide, and methotrexate (FAC-M). RESULTS: At a median follow-up time of 4.9 years, the two treatment arms cannot be demonstrated to be different with respect to overall survival (stratified log-rank, P = .27). The 5-year survival rate is 64% on the CMFVP arm and 61% on the FAC-M arm. CMFVP produces marginally superior disease-free survival (P = .06). The estimated 5-year disease-free survival rate is 55% for patients treated with CMFVP as opposed to 50% for patients treated with FAC-M. CONCLUSION: Neither regimen was shown to be superior in terms of overall survival. Because the disease-free survival produced by CMFVP is marginally superior to that produced by FAC-M, we do not recommend FAC-M for further investigation or for routine use. Possible implications of this study are discussed in the context of other adjuvant chemotherapy trials.

Adult↗
PubMed1995

The molecular response of bone to growth hormone during skeletal unloading: regional differences.

Hind limb elevation of the growing rat provides a good model for the skeletal changes that occur during space flight. In this model the bones of the forelimbs (normally loaded) are used as an internal control for the changes that occur in the unloaded bones of the hind limbs. Previous studies have shown that skeletal unloading of the hind limbs results in a transient reduction of bone formation in the tibia and femur, with no change in the humerus. This fall in bone formation is accompanied by a fall in serum osteocalcin (bone Gla protein, BGP) and bone BGP messenger RNA (mRNA) levels, but a rise in bone insulin-like growth factor-I (IGF-I) protein and mRNA levels and resistance to the skeletal growth-promoting actions of IGF-I. To determine whether skeletal unloading also induced resistance to GH, we evaluated the response of the femur and humerus of sham and hypophysectomized rats, control and hind limb elevated, to GH (two doses), measuring mRNA levels of IGF-I, BGP, rat bone alkaline phosphatase (RAP), and alpha 1(1)-procollagen (coll). Hypophysectomy (HPX) decreased the mRNA levels of IGF-I, BGP, and coll in the femur, but was either less effective or had the opposite effect in the humerus. GH at the higher dose (500 micrograms/day) restored these mRNA levels to or above the sham control values in the femur, but generally had little or no effect on the humerus. RAP mRNA levels were increased by HPX, especially in the femur. The lower dose of GH (50 micrograms/day) inhibited this rise in RAP, whereas the higher dose raised the mRNA levels and resulted in the appearance of additional transcripts not seen in controls. As for the other mRNAs, RAP mRNA in the humerus was less affected by HPX or GH than that in the femur. Hind limb elevation led to an increase in IGF-I, coll, and RAP mRNAs and a reduction in BGP mRNA in the femur and either had no effect or potentiated the response of these mRNAs to GH. We conclude that GH stimulates a number of markers of bone formation by raising their mRNA levels, and that skeletal unloading does not block this response, but the response varies substantially from bone to bone.

Analysis of Variance↗
PubMed1995

Retinoic acid inhibits both the basal activity and phorbol ester-mediated activation of the HIV long terminal repeat promoter.

OBJECTIVE: To establish whether the steroid hormone retinoic acid (RA) was able to modulate the activity of the HIV-1 promoter. DESIGN: The effect of RA and nuclear factor (NF)-kappa B on HIV-1 promoter activity was investigated using HIV-1 long terminal repeat (LTR)-based reporter constructs. METHODS: The activity of wild type and mutant LTR sequences was compared in a variety of stably and transiently transfected human cell lines. RESULTS: It was shown that RA treatment inhibits both the basal activity of the HIV-1 LTR and its stimulation by phorbol ester treatment. This inhibition is observed in both HeLa cells (in the presence of exogenously supplied RA receptors) and the naturally RA-responsive U937 monocyte cell line. RA can also inhibit the stimulation of the HIV-1 LTR by overexpression of NF-kappa B subunits, while linkage of the NF-kappa B sites in the HIV promoter to a heterologous promoter results in its inhibition by RA. CONCLUSIONS: The data presented clearly demonstrate a negative effect of RA on HIV-1 LTR activity that may contribute to its effect on viral replication.

Base Sequence↗
PubMed1995

Correlation of pain with temperature and blood-flow changes in the lower limb following chemical lumbar sympathectomy in reflex sympathetic dystrophy. A case report.

Temperature and microcirculatory blood flow studies have been measured before and after chemical sympathectomy in a patient with reflex sympathetic dystrophy of the left leg present for at least three years following surgery for glomus tumour. Normalisation of temperature and blood flow was associated with the relief of pain, present initially when the limb was hypothermic and vasoconstricted and recurring when the limb was hyperthermic and vasodilated. It is possible that such objective measurement may be used to determine the optimal management of RSD.

Aged↗