PubMed Health⌕ Search

Biomedical subjects

R David

Publications and source records attributed to R David.

At least 55 records · Page 3Linked to original sources
PubMed1998

Suppression of tobacco basic chitinase gene expression in response to colonization by the arbuscular mycorrhizal fungus Glomus intraradices.

A differentially displayed cDNA clone (MD17) was isolated from tobacco roots (nicotiana tabacum cv. Xanthi-nc) infected with the arbuscular mycorrhizal (AM) fungus Glomus intraradices. The isolated DNA fragment exhibited a reduced level of expression in response to AM establishment and 90% identity with the 3' noncoding sequence of two basic chitinases (EC 3.2.1.14) from N. tabacum. Northern (RNA) blots and Western blots (immunoblots), probed with tobacco basic chitinase gene-specific probe and polyclonal antibodies raised against the chitinase enzyme, yielded hybridization patterns similar to those of MD17. Moreover, the up-regulation of the 32-kDa basic chitinase gene expression in tobacco roots by (1,2,3)-thiadiazole-7-carbothioic acid S-methyl ester (BTH) was less effective in mycorrhizal roots than in nonmycorrhizal controls. Suppression of endogenous basic chitinase (32-kDa) expression was also observed in transgenic mycorrhizal plants that constitutively express the 34-kDa basic chitinase A isoform. When plants were grown with an increased phosphate supply, no suppression of the 32-kDa basic chitinase was obtained. These findings indicate that during the colonization and establishment of G. intraradices in tobacco roots, expression of the basic chitinase gene is down-regulated at the mRNA level.

Base Sequence↗
PubMed1998

Study of a kindred with classic congenital adrenal hyperplasia: diagnostic challenge due to phenotypic variance.

We sought to determine the concordance of the phenotype and genotype in a kindred with classic congenital adrenal hyperplasia due to 21-hydroxylase deficiency. The variation in phenotypic expression within this family underscores the difficulty of establishing the diagnosis in the absence of newborn screening, even with a heightened index of suspicion. Steroidogenic profiles were obtained for the three affected siblings. The available clinical history of the two affected aunts was retrieved. Genotyping was performed on several members of the kindred. Detailed sequencing of the entire CYP21 gene of two clinically dissimilar subjects in this family was undertaken to explore the possibility of other mutations or polymorphisms. PCR with ligase detection reaction analysis of CYP21 revealed that the affected family members III-2, III-3, III-4, II-3, and II-4, all were compound heterozygotes carrying the intron 2 point mutation known to interfere with splicing (nucleotide 656 A to G) and the exon 4 point mutation causing a nonconservative substitution of asparagine for isoleucine at codon 172 (I172N). Detailed sequencing of the gene was performed for the two most phenotypically dissimilar subjects. A single silent polymorphism was found in the third nucleotide for codon 248 in patient II-4, but not in patient III-4, and no additional mutations were found. Classic congenital adrenal hyperplasia remains a difficult diagnosis to make in the absence of newborn screening because of the variability of phenotypic expression. Likewise, the variable degree of genital ambiguity in affected females in this family serves to question universal advocacy of prenatal steroid treatment in pregnancies at risk for congenital adrenal hyperplasia. Extensive molecular exploration did not provide an explanation of the phenotypic heterogeneity and supports the possibility of influences other than the CYP21 gene for the observed divergence.

Adrenal Hyperplasia, Congenital↗
PubMed1998

Changing therapeutic paradigms in glaucoma management.

Glaucoma is a family of diseases commonly characterised by progressive optic neuropathy with associated visual field deficits for which elevated intraocular pressure (IOP) is one of the primary risk factors. For more than a century the main goal of glaucoma management has been to eliminate the risk associated with elevated IOP. In recent years, accumulating evidence of pressure-independent causes of glaucomatous optic neuropathy has led to the recognition that lowering IOP alone may often be insufficient for the long-term preservation of visual function. An innovative therapeutic approach is now emerging to prevent progression of glaucomatous optic neuropathy and preserve vision, irrespective of disease aetiology: direct protection of the optic nerve. In addition to reducing the risk associated with elevated IOP, this neuroprotective approach will augment the overall goal of preserving the optic nerve through direct promotion of retinal ganglion cell (RGC) survival and/or prevention of RGC death. Although no currently available compounds have been clinically demonstrated to provide neuroprotective benefit in glaucoma, recent preclinical studies have shown that alpha-adrenergic agonists, such as brimonidine, provide neuroprotective benefits, as well as excellent IOP lowering efficacy. In addition, new agents with promising neuroprotective utility that are emerging from other studies are now being investigated for efficacy in glaucoma. The review discusses recently introduced compounds and new drugs in development with regard to their potential value in conventional and/or neuroprotective strategies for vision sparing in glaucoma.

Journal Article↗
PubMed1998

Modelling the consultation process in a secondary referral unit for children.

This paper overviews a detailed study of a consultation service for children with severe and/or intractable speech and language difficulties. The Speech Therapy Clinical Unit at the University of Central England in Birmingham (UCE) offered multidisciplinary, in-depth assessment of such children to speech and language therapists, parents and other professions involved in their management. Documentary materials generated by the service were analysed using Grounded Theory to develop a model of the process of assessment and consultation employed in the Unit. The implications of this model for clinical education and practice are discussed.

Child↗
PubMed1998

Studies on control of visceral leishmaniasis: impact of dog control on canine and human visceral leishmaniasis in Jacobina, Bahia, Brazil.

To assess the effect of removing leishmania-infected dogs on the incidence of visceral leishmaniasis, a controlled intervention study was performed in northeast Brazil. The attempted elimination of seropositive dogs resulted in an initial significant decrease in the annual incidence of seroconversion among dogs from 36% to 6% over the first two years. In the following two years, the incidence increased to 11% and 14%, respectively. In a control area in which dogs were surveyed but seropositive dogs were not removed, the cumulative incidence did not vary significantly from year to year, ranging from 16% to 27%. In the intervention area, the prevalence of dog seropositivity decreased from 36% before the intervention to 10% and remained stable. These findings suggest that attempting to remove seropositive dogs is insufficient as a measure for eradicating visceral leishmaniasis in dogs. However, the force of transmission of infection among dogs can be reduced by such programs. Also, when the number of human cases before and after the start of the intervention was calculated, a significant decrease in incidence of disease in the intervention area was observed among children less than 15 years of age (P < 0.01). The results of this intervention study suggest that the elimination of the majority of seropositive dogs may affect the cumulative incidence of seroconversion in dogs temporarily and may also diminish the incidence of human cases of visceral leishmaniasis.

Adolescent↗
PubMed1997

Thyroid dysfunction as a late effect in survivors of pediatric medulloblastoma/primitive neuroectodermal tumors: a comparison of hyperfractionated versus conventional radiotherapy.

BACKGROUND: Primary hypothyroidism is a common sequela of craniospinal radiotherapy in the treatment of pediatric brain tumors. METHODS: The authors compared the incidence of primary hypothyroidism after hyperfractionated radiotherapy (HFRT) (n = 14 patients) versus conventionally fractionated radiotherapy (CRT) (n = 34 patients) in a group of pediatric patients with medulloblastoma/primitive neuroectodermal tumors (MB/PNET). RESULTS: The mean age at the time of tumor diagnosis was 7.9 years in the HFRT group and 8.4 years in the CRT group. The patients were followed for a mean of 4.6 years (HFRT) and 8.3 years (CRT) after diagnosis. Mean radiation doses to the thyroid were similar in both radiotherapy groups (29 gray [Gy] [HFRT] vs. 24 Gy [CRT]). Approximately 14% of the HFRT and 62% of the CRT patients developed primary hypothyroidism within a similar period after irradiation (3.2 years [HFRT] vs. 3.0 years [CRT]). Analysis by cumulative incidence function demonstrated a significant difference in the risk of developing thyroid dysfunction between these two groups of patients (P = 0.02). CONCLUSIONS: The current study findings suggest that the use of HFRT in the treatment of pediatric patients with MB/PNET is associated with a lower risk of these patients developing primary hypothyroidism.

Adolescent↗
PubMed1997

A 1-year study of brimonidine twice daily in glaucoma and ocular hypertension. A controlled, randomized, multicenter clinical trial. Chronic Brimonidine Study Group.

OBJECTIVE: Brimonidin tartrate is a highly selective alpha 2-agonist. This study investigates the safety and efficacy of 0.2% brimonidine administered twice daily for 1 year in patients with glaucoma or ocular hypertension. METHODS: The study design was a multicenter, double-masked, randomized, parallel-group, active-controlled comparison clinical trial. Subjects instilled 0.2% brimonidine or 0.5% timolol maleate twice daily for 12 months. Subjects were examined at baseline, week 1, and months 1, 2, 3, 6, 9, and 12. A subset of subjects was examined at week 2. RESULTS: Of 443 subjects enrolled in this study, 374 met the entry criteria; 186 received brimonidine and 188 received timolol. Brimonidine-treated subjects showed an overall mean peak reduction in intraocular pressure (IOP) of 6.5 mm Hg; timolol-treated subjects had a mean peak reduction in IOP of 6.1 mm Hg. Brimonidine lowered mean peak IOP significantly more than timolol at week 2 and month 3 (P < .03); no significant difference was observed between the groups for this variable at other visits throughout the 1-year course of the study. No evidence of tachyphylaxis was seen in either group. Allergy was seen in 9% of subjects treated with brimonidine. Dry mouth was more common in the brimonidine-treated group than in the timolol-treated group (33.0% vs 19.4%), but complaints of burning and stinging were more common in the timolol-treated group (41.9%) than in the brimonidine-treated patients (28.1%). Headache, fatigue, and drowsiness were similar in the 2 groups. In general, the tolerance to medication was acceptable. CONCLUSIONS: Brimonidine is safe and effective in lowering IOP in glaucomatous eyes. Brimonidine provides a sustained long-term ocular hypotensive effect, is well tolerated, and has a low rate of allergic response.

Administration, Topical↗
PubMed1997

How Chlamydomonas keeps track of the light once it has reached the right phototactic orientation.

By using a real-time assay that allows measurement of the phototactic orientation of the unicellular alga Chlamydomonas with millisecond time resolution, it can be shown that single photons not only induce transient direction changes but that fluence rates as low as 1 photon cell(-1) s(-1) can already lead to a persistent orientation. Orientation is a binary variable, i.e., in a partially oriented population some organisms are fully oriented while the rest are still at random. Action spectra reveal that the response to a pulsed stimulus follows the Dartnall-nomogram for a rhodopsin while the response to a persistent stimulus falls off more rapidly toward the red end of the spectrum. Thus light of 540 nm, for which chlamy-rhodopsin is equally sensitive as for 440-nm light, induces no measurable persistent orientation while 440-nm light does. A model is presented which explains not only this behavior, but also how Chlamydomonas can track the light direction and switches between a positive and negative phototaxis. According to the model the ability to detect the direction of light, to make the right turn and to stay oriented, is a direct consequence of the helical path of the organism, the orientation of its eyespot relative to the helix-axis, and the special shielding properties of eyespot and cell body. The model places particular emphasis on the fact that prolonged swimming into the correct direction not only requires making a correct turn initially, but also avoiding further turns once the right direction has been reached.

Animals↗
PubMed1997

Endocrine late effects of childhood cancers.

Long-term survival in children with cancer has increased markedly in the past 15 years. However, impaired linear growth and thyroid dysfunction that vary according to the age at diagnosis and treatment and to the dose and duration of radiation and chemotherapy have been described in these patients. The impact of cranial irradiation on the hypothalamic-pituitary-adrenal axis and on pubertal maturation has been less well studied. A positive correlation between the age at diagnosis and the age at onset of puberty in children who have been treated with high-dose cranial radiation therapy for central nervous system (CNS) tumors has been found recently. Frank adrenal insufficiency is uncommon after high-dose CNS irradiation, but alterations in the hypothalamic-pituitary-adrenal axis do occur. Assessments of the effects of newer modes of radiation therapy such as hyperfractionated craniospinal radiation suggest a lower incidence of primary hypothyroidism in the long term.

Adolescent↗
PubMed1997

Impaired early growth of infants perinatally infected with human immunodeficiency virus: correlation with viral load.

OBJECTIVE: To evaluate the effect of viral load on the early growth of infants infected with human immunodeficiency virus (HIV). METHODS: Plasma concentrations of p24-antigen and HIV ribonucleic acid were measured retrospectively and correlated with growth parameters for the first 18 months of life in a cohort of 47 term infants born to HIV-infected mothers prospectively enrolled in a study of perinatal HIV transmission. Comparisons of the mean weight and length of the 18 HIV-infected and 29 uninfected infants for each interval and across intervals were made. Viral load was correlated with standard deviation scores. Infants were stratified by high and low viral load during the first 6 months of life. RESULTS: At birth, no difference in weight and length was observed between HIV-infected and uninfected infants. Between birth and 6 months of age, the infected infants grew less rapidly than the uninfected infants, a finding temporally associated with an exponential increase in HIV viremia. The linear growth of infected infants remained consistently less than that of the uninfected infants after 6 months of life, although the differences were no longer statistically significant and tended to decrease with age in parallel with declines in viral load. The median plasma concentration of HIV ribonucleic acid was significantly higher at 3, 6, 12, and 18 months in infected infants in whom growth failure developed. Infants who had a high viral load in the first 6 months of life were significantly more likely to have severe growth failure. Though the mean SD for weight of the infected infants was always less than that of the uninfected infants, the differences were small and not significant. CONCLUSIONS: Our results confirm the observation that stunting is an early frequent finding in perinatal HIV infection. The deleterious effect of HIV on linear growth appears to be correlated with the level of postnatal HIV viremia, although the exact mechanism of this association remains to be elucidated.

Birth Weight↗
PubMed1997

Delayed postburn blisters: an immunohistochemical and ultrastructural study.

This study was performed in an attempt to further elucidate the pathogenesis of delayed postburn blistering. Two cases were studied ultrastructurally and immunohistochemically, 1 with blisters on the recipient site of autologous split-thickness skin grafts and the other on the donor site. Ultrastructurally, the basement membrane was on the roof of the blisters in both cases, except for a single small blister in the first case where it was on the dermal floor. In the blister roofs, the basement membrane showed small or marked segments of discontinuity. In the adjacent non-blistered healed skin, the basement membrane was usually continuous, and anchoring fibrils were present. Immunoperoxidase staining on frozen sections, using antibodies to laminin, laminin 5, collagen IV, and collagen VII, showed a mostly continuous linear pattern in the adjacent non-blistered skin, which often became discontinuous near the blisters and markedly discontinuous in the blister roofs. In the blister floors, weakly stained linear or granular deposits of some of these components were sometimes also present. The results of this study support discontinuity of the basement membrane as the main anomaly in delayed postburn blistering. Disturbance in the reassembly or local breakdown of the basement membrane components might be the underlying defect.

Adult↗
PubMed1997

Hypothalamic-pituitary-adrenal function following cranial irradiation.

We assessed the effect of cranial irradiation on hypothalamic-pituitary (HP)-adrenal function in 17 patients (12 females, 5 males) treated with cranial/ craniospinal irradiation for acute leukemia (2 patients) or tumors distant from the hypothalamus and pituitary (8 medulloblastoma, 3 astrocytoma, 3 rhabdomyosarcoma, 1 ependymoma). Estimated doses of radiation (RT) to the HP region ranged from 18 to 72 Gy. Thirteen of seventeen patients were also treated with chemotherapy. Patients were a median of 3.75 years of age (1.5-19 years) at diagnosis and were studied at a median of 5 years (0.1-20 years) after RT. Patients received corticotropin-releasing factor (oCRF, 1 microgram/kg i.v.), and sampling for cortisol and ACTH levels was performed at -15, 0, 15, 30, 60, 90 and 120 min. The-5- and 0-min levels were combined for a standardized baseline value (Base). Cortisol levels at 0, Base, 30 and 120 min, as well as the peak cortisol response, were significantly lower in the patients. Twelve of seventeen patients' peak cortisol levels fell below the normal range. The patients' mean integrated values for cortisol (area under the curve) were not, however, different from controls. The ACTH responses to oCRF did not differ between patients and controls. No relationship was observed between ACTH or cortisol responses and the time elapsed from treatment or dose of HP RT. Further, in 10 of 12 patients, 0-min dehydroepiandrosterone sulfate levels were lower than the expected normal mean levels for age, sex and pubertal status, and in 4 of these 10 patients the values were below the normal range. These data suggest that some patients treated with HP RT may be at risk for adrenal insufficiency.

Adolescent↗
PubMed1997

Testicular arginine vasopressin in the developing rat: a possible physiological role.

Testicular immunoreactive arginine vasopressin (irAVP) has been shown to inhibit testosterone production by the Leydig cell in vitro. We studied pre- and postpubertal rats and the results are in agreement with the notion that such inhibition might occur in vivo and, therefore, could have physiological significance. Testicular irAVP and serum testosterone levels were measured in 14-, 21-, 28-, 35-, 42-, and 70-day-old rats. The testicular irAVP concentration was lowest in early prepubertal rats, increased significantly to the highest level at 35 days, then decreased at 42 days, and plateaued at 70 days of age. A pubertal increase in serum testosterone was observed at 42 days when AVP was decreasing. Thus, an inverse relationship was observed at the onset of pubertal maturation. These parameters were also measured in 3 groups of rats 1 week after hemicastration which was performed at the ages of 28, 35 and 70 days. In the 28-day-old rats there was a significant decrease in irAVP 1 week later, in contrast to the intact animal, whereas hemicastration performed at 35 and 70 days of age had no impact on irAVP. Our data suggest that the role of AVP may be physiologically relevant during the peripubertal period of testicular maturation in the rat.

Age Factors↗
PubMed1997

Menstrual bleeding in a female infant with congenital adrenal hyperplasia: altered maturation of the hypothalamic-pituitary-ovarian axis.

Vaginal bleeding during the neonatal period is commonly related to the withdrawal of maternal estrogens. Vaginal bleeding has also been reported in female infants with congenital adrenal hyperplasia and has been proposed to be due to a treatment-induced activation of the hypothalamic-pituitary-ovarian axis. We report a female infant with the salt-losing form of congenital adrenal hyperplasia due to 21-hydroxylase deficiency, who had the onset of vaginal bleeding at 3 months of life. Adrenal steroid suppression had been achieved by 2.5 weeks of age. At the time of bleeding, imaging studies revealed an enlarged right ovary with a dominant 3-cm cyst and additional small cysts that had not been seen on the newborn sonogram. The uterus was enlarged and stimulated. Three weeks later (1 week after the cessation of bleeding), repeat ultrasound demonstrated a marked decrease in the size of the right ovary, and the dominant cyst was no longer seen. The patient had a heightened FSH response to GnRH and elevated levels of estradiol for age. At 5 months of age, no further episodes of sustained vaginal bleeding were observed. Repeat hormonal levels were prepubertal, and pelvic sonogram demonstrated no evidence of stimulation. The findings in our patient suggest that a decline in adrenal androgens after glucocorticoid treatment resulted in an increase in gonadotropin levels, which then triggered a transient and augmented end-organ response (menses). Further, we suggest that our infant's hormonal findings may reflect a delay in the timely development of the negative restraint by sex steroids on gonadotropins that is normally observed in infancy.

Adrenal Hyperplasia, Congenital↗
PubMed1997

Treatment of open tibial fractures with primary suture and Ilizarov fixation.

Thirty-two open tibial fractures were treated by irrigation, debridement, antibiotic therapy, primary closure when possible, and fixation with Ilizarov device. In the Gustilo classification, 11 were Grade I, 10 Grade II, 8 Grade IIIA, and 3 were Grade IIIB. No Grade IIIC fractures were treated in the period studied. Fifteen were in patients with multiple trauma, and in 17 patients the fracture was a single injury. All fractures healed with good anatomic alignment, except for 1 with 5 degrees angulation and another with 1-cm shortening. The healing time was 21.9 weeks in the single injury and 25.7 weeks in the patients with multiple trauma. Eleven patients had pin tract infection, and in 4 the pin had to be replaced. One patient had dermatitis near the fracture site. This treatment of open tibial fractures proved to be successful for anatomic restoration of the tibia and had a low complication rate. Primary closure should be considered a possible method of treatment in Types I to IIIA open fractures, together with the Ilizarov external fixator, if the wound edges can be approximated easily with no tension at the suture line.

Adolescent↗
PubMed1996

[Screening for scoliosis in western Galilee schools].

Scoliosis screening is still under debate. It is generally agreed that it is not cost-effective, but some still favor it as integral to preventive medicine. Among 2940 school children, aged 9 - 13, from several Moslem-Arab villages in the western Galilee, 55 (1.9%) were found to have some deformity on physical examination and were referred for spinal X-ray. Of these, 24 were X-rayed and in 20 of them there was a scoliosis of more than 7 degrees. The prevalence of in-family marriage in those with deformities was 31%, not significantly different from the 35% found in their communities. Using the worst-case analysis, the Moslem-Arab population of western Galilee cannot be regarded as a population at risk for scoliosis. Considering the poor cooperation of the parents with further investigation, we conclude that scoliosis screening should not be performed in this community.

Adolescent↗
PubMed1996

Age at onset of puberty following high-dose central nervous system radiation therapy.

OBJECTIVE: To determine if a relationship exists between age at irradiation, sex of the patient, and age at onset of puberty and pubarche in children treated with high-dose radiation to the central nervous system. DESIGN: Case series. SETTING: Tertiary care institutional practices and clinics. PATIENTS: Thirty-six children treated with high-dose irradiation (hypothalamic pituitary dose, 30-72 Gy) by conventional (n = 29) or hyperfractionated (n = 7) schedules. Girls were treated before age 8 years and boys before age 9 years. Twenty-six of the 36 children also received chemotherapy. All tumors were distant from the hypothalamic-pituitary region. MAIN OUTCOME MEASURE: Age at onset of puberty and pubarche. RESULTS: In girls, the median age at onset of puberty was 9.3 years vs 10.9 years for controls (P < .01); pubarche occurred at 9.4 years vs 11.2 years for controls (P < .01). In boys, the median age at onset of puberty--genital II--was 11.0 years vs 11.5 years for controls (P = .30); pubarche occurred at a median age of 10.5 years vs 12 years for controls (P = .25). A censored-data normal linear regression model was used to account for children (n = 6) who had not reached puberty. Age at diagnosis (P < .01) and sex (P = .01) were significant predictors of age at onset of puberty. Body mass index SD score (z score) was inversely related to age at onset of puberty (r = -0.77) and was greater at onset of puberty in girls than in boys. CONCLUSION: In children who have received high-dose cranial radiation therapy, a significant positive correlation exists between age at diagnosis and age at onset of puberty in boys and girls.

Adolescent↗