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Biomedical subjects

D Simon

Publications and source records attributed to D Simon.

At least 55 records · Page 3Linked to original sources

Non-Hodgkin's lymphoma related eosinophilic endomyocardial disease.

Two patients with eosinophilic endomyocardial disease related to peripheral T-cell lymphomas are reported. Both patients were free of cardiac symptoms at presentation and during follow-up. Routine two dimensional echocardiography revealed bi-apical ventricular obliteration, which was also seen on MR imaging. On the T1-weighted sequence, the thickened endocardium appeared with an isointense signal. Gadolinium DOTA provided an enhanced contrast of the internal part of the left ventricular wall. On T2-weighted sequence, a thin hypointense curvilinear structure drew a dividing line between the internal, endocardial, and the external, myocardial area. Left-ventricular systolic and diastolic functions remained unaltered during subsequent follow-up.

Adult

Inhibition of human T cell leukaemia virus type I long terminal repeat expression by DNA methylation: implications for latency.

Human T cell leukaemia virus type I (HTLV-I) provirus DNA was found to be methylated in patients with adult T cell leukaemia. We have therefore examined the possibility that DNA methylation might contribute to HTLV-I latency. In vitro methylation of HTLV-I long terminal repeat (LTR)-chloramphenicol acetyltransferase or LTR-Luciferase constructs at eight HpaII sites, a subset of the eukaryotic methylation site CpG, resulted in a three- to fourfold inhibition of transcription in transfected cells. Inhibition of transcription by methylation of all CpG methylation sites using SssI methylase was much more pronounced (50- to 80-fold). As partial methylation of the LTR showed, methylation of the promoter region was responsible for most of the effect. Whereas cellular stimulation by a combination of phorbol 12-myristate 13-acetate and Tax was able to reverse the HpaII methylation effect, the inhibition by SssI methylation was not suppressible under these conditions. The results are in line with a possible function of DNA methylation in HTLV-I latency.

Adult

Feminist method and qualitative research about midlife.

This paper identifies criteria seen as essential to feminist research. In light of these criteria, issues which have arisen during our current research on women and their experiences of midlife and menopause are discussed. Issues considered include the researchers' responsibilities to participants when exploring sensitive and highly personal issues relating to participants' life experiences, and less clear cut issues such as knowledge construction, power and control. In relation to the latter the balance of power in the research-participant relationship, and the role and responsibilities of the researcher in knowledge construction, are explored. Foucault's notions of knowledge construction and power and control and the feminist researcher's position, are considered in terms of rigour in feminist research and dissemination of research reports. Issues which are seen as problematic and worthy of further debate are: the relations between interviewer and interviewee; the intellectual (the researcher) as the bearer of universal values and as truth teller; and the level of critical activism possible in research studies of this nature.

Age Factors

Longitudinal study of brainstem auditory evoked responses in 87 normal human subjects.

We evaluated the reproducibility of brainstem auditory evoked responses (BAERs) in 87 normal individuals in a longitudinal study by estimating the correlation coefficients and variability of the interpeak intervals and the V/I amplitude ratio between trials on the same day and between sessions spaced 2 years apart. The highest correlation coefficients occur for the I-V interpeak interval between trials on the same day. The coefficients for the I-III and III-V intervals are lower, due to the variability of wave III. The correlations between ears done on the same day are lower still and are similar to measures obtained from the same ear at a 2-year interval. BAERs are more variable than previously believed between ears and over time, but not in a manner that is clinically significant and can be used longitudinally as a measure of neurologic disease. Finally, we provide the sample size required to detect a significant change in interpeak intervals.

Acoustic Stimulation

Negative correlation between plasma GHRH values and growth velocity in short prepubertal children.

Numerous data suggest that impaired growth hormone secretion in short children is usually related to abnormal regulation of the hormone at the hypothalamic level. In order to improve our understanding of neurohypothalamic dysfunction in short children, we measured basal and peak (after L-dopa stimulation) plasma growth hormone-releasing hormone levels in 43 prepubertal children. Among them, in 23 children suspected of having hypothalamic growth hormone dysregulation, growth hormone-releasing hormone values were significantly higher than those observed in normal short stature children (n = 20), no longer correlated with peak growth hormone following L-dopa, and negatively correlated with growth velocity. This suggests that a predominant inhibitor of growth hormone secretion, such as an increase in somatostatin tone, might be prevalent in a large number of children with partial growth hormone deficiency and suspected hypothalamic growth hormone dysregulation.

Adolescent

[Minor aplasia of the ear: anatomical findings and results of functional surgery].

We report a retrospective study of 57 cases of minor aplasia of the ear. Each case was analyzed according to the clinical presentation, audiometric results and preoperative radiography. Intra-operative classification of the malformation was obtained in 56 of the 57 cases. The post-operative anatomic and functional results were analyzed. Stapedectomy in type II malformations (stapedo-vestibular ankylosis) gave the best results but this procedure also carries the highest risk for the inner ear. Globally, functional results were good or average in 48% of the patients. These results may appear unsatisfactory but must be appreciated in light of the fact that half of the patients benefited from the operation (particularly in eliminating further use of an external hearing aid). Nevertheless, the long-term stability of these audition results is unknown.

Adolescent

Esophageal motility in AIDS patients with symptomatic opportunistic infections of the esophagus.

OBJECTIVES: In patients with AIDS, esophageal symptoms are commonly due to opportunistic esophageal infection with Candida, cytomegalovirus (CMV), herpes simplex virus (HSV), and HIV. Despite apparently appropriate therapy against these pathogens, some patients continue to complain of dysphagia or odynophagia. This study was designed to determine whether such complaints were associated with a motility disorder of the esophagus. METHODS: Sixteen patients underwent esophagoscopy and biopsy followed by esophageal manometry, performed using a 5-channel water perfused system (Synectics Medical, Inc., Irving, Texas). All patients had odynophagia, and eight had dysphagia. RESULTS: Identified infections included: Candida (11), HSV and Candida (1), CMV (3), and a giant ulcer presumably caused by HIV (1); one patient also had lymphoma. Seven patients had normal esophageal motility, and in nine patients, a nonspecific motility disorder was found. After therapy, one of 10 patients had persistent odynophagia and dysphagia, and two had odynophagia only. At follow-up endoscopy, complete healing was demonstrated in six of eight patients with Candida. One of two patients with CMV and the patient with HSV also showed complete healing of the esophagus. Repeat esophageal motility studies were performed after therapy in 10 patients. Five had a persisting abnormality despite eradication of the pathogen (three Candida, one HSV, one CMV); in four, the previously identified motor abnormalities resolved after eradication of the infection (three Candida, one CMV). CONCLUSIONS: These findings suggest that a nonspecific motility disorder exists in AIDS patients with esophageal symptoms and may contribute to the persistence of symptoms despite appropriate therapy of esophageal opportunistic infections.

AIDS-Related Opportunistic Infections

Pharmacokinetics and bioavailability of bemoradan, a long-acting inodilator in healthy males.

Bemoradan is a potent, long-acting orally active inodilator. The pharmacokinetics and bioavailability of bemoradan were studied in twelve normal males following oral administration of single, ascending doses of the bemoradan HCL salt in capsules. Plasma and urine levels of bemoradan were determined by HPLC (detection limits: approximately 0.5 ng/ml for plasma and 5 ng/ml for urine). Bemoradan was rapidly absorbed from the capsule formulation at all doses (Cmax occurred at 2.1-2.4 hours). Bemoradan was slowly eliminated from the body (harmonic mean t1/2 16-23 hours). There was a dose-proportional increase in the AUC (0-48) values of bemoradan in humans following the administration of 0.5, 1, 1.5 and 2 mg of bemoradan. The AUC (0-48) values increased to 2.3, 3.4 and 4.0 times when the dose was increased to 2, 3 and 4 times. Urinary excretion of unchanged bemoradan accounted for approximately 5-12% of the dose. Results from this study and previous studies in rats and dogs indicate that bemoradan is well and rapidly absorbed after oral dosing, has linear pharmacokinetics and long elimination half-lives across species.

Administration, Oral

Intestinal permeability in patients infected with the human immunodeficiency virus.

OBJECTIVE: The etiology of acquired immunodeficiency syndrome (AIDS) enteropathy is unknown. This condition has been associated with malabsorption and villous atrophy. Other disorders with similar findings, including celiac disease, are characterized by altered intestinal permeability. Our objective was to confirm (or reject) our hypothesis that processes that cause increased permeability may occur in patients with AIDS, and thus be a cause of idiopathic diarrhea. METHODS: A lactulose-mannitol differential intestinal permeability test was performed in healthy controls, asymptomatic human immunodeficiency virus (HIV)-positive patients, and AIDS patients with and without diarrhea. RESULTS: Asymptomatic HIV-positive patients lactulose and mannitol recoveries were no different than healthy control patients. AIDS patients without diarrhea had lactulose recovery similar to healthy controls and decreased mannitol recoveries; their mean lactulose:mannitol ratio was no different from that of controls, and less than that of AIDS patients with diarrhea. AIDS patients with diarrhea had increased lactulose recovery and decreased mannitol recovery; their mean lactulose:mannitol ratio was significantly greater than the ratios in all the other groups. CONCLUSIONS: Patients with AIDS and diarrhea have altered intestinal permeability. The decreased absorption of mannitol suggests that the functional absorptive surface of the intestine decreases as HIV disease progresses.

AIDS-Related Opportunistic Infections

Sequence specific binding of the transcription factor c-Ets1 to the human immunodeficiency virus type I long terminal repeat.

Human immunodeficiency virus type I (HIV-1) long terminal repeat (LTR) driven transcription is regulated by a variety of cellular transcription factors. Most work has focused on the two nuclear factor kappa B (NF-kB) elements indispensable for HIV-1 LTR enhancer function. We demonstrate here the specific binding of the transcription factor c-Ets1 to an U3 region of the HIV-1 LTR (nt -141 to -149) using electrophoretic mobility shift analysis with T-cell nuclear extract and in vitro translated protein. This previously not identified Ets binding site is highly conserved among different HIV-1 isolates and maps to an U3 region recently shown to be necessary for viral growth in vitro. The c-Ets proto-oncogene family of transcription factors has yet been associated with HTLV-I and HIV-2 transcription. Our present analysis suggests an important role of c-Ets proteins in HIV-1 transcription.

Base Sequence

Sequence of the cDNA encoding bovine uridine monophosphate synthase.

A 1869-bp cDNA encoding bovine UMP synthase (UMPS), including the 3'-untranslated and 34 bp of the 5'-untranslated regions, was isolated and sequenced. The deduced amino acid sequence shows a high degree of homology to UMPS sequences reported from other species, namely for regions corresponding to the putative catalytic sites. The sequence information will be used to analyse the molecular basis of the deficiency of UMPS (DUMPS) in cattle.

Amino Acid Sequence

Surgical reintervention for differentiated thyroid cancer.

Reoperation was performed in 110 of 185 patients with a differentiated thyroid carcinoma. In 25 patients (23 per cent) the indication for reintervention was a large thyroid remnant and in the other 85 (77 per cent) persistent or recurrent cancer was suspected. In 32 (29 per cent) of the 110 patients undergoing reoperation no evidence of cancer tissue was found. Tumour tissue in 33 patients (30 per cent) was resectable. Of 45 patients (41 per cent) with residual tumour after operation 24 showed only occult thyroid carcinoma with a raised serum thyroglobulin level. Eight of 21 patients with macroscopically persistent tumour died from the disease during a mean follow-up of 2.3 years. In 13 of 38 patients the investigated recurrent tumours were histologically less differentiated than the primary lesions, stressing the importance of total tumour clearance. The treatment of choice for persistent and recurrent differentiated thyroid carcinoma is surgical reintervention, if feasible, before radioiodine and radiation therapy are considered.

Adenocarcinoma, Follicular

DUMPS cattle carry a point mutation in the uridine monophosphate synthase gene.

Deficiency of uridine monophosphate synthase (DUMPS) is a monogenic autosomal recessive disorder in cattle, resulting in early embryonic death of homozygous offspring. To identify the mutation responsible for DUMPS, liver RNA from identified, DUMPS heterozygous animals from the Holstein and Red Holstein breeds was reverse transcribed. Amplification of cDNA with sequence-specific primers and subsequent sequencing of the PCR products revealed a mutation (C-->T) with the loss of an AvaI site at codon 405, resulting in a premature stop codon with a truncated C-terminal catalytic subunit of the protein. A direct DNA test based on PCR was developed and subsequently tested on 102 animals. Complete concurrence of deficiency of UMPS and the presence of the described point mutation in heterozygous animals was observed, thus confirming this point mutation as the basic defect in DUMPS cattle.

Animals