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Biomedical subjects

D David

Publications and source records attributed to D David.

At least 19 recordsLinked to original sources
PubMed2001

Rapid effect of interleukin-2 therapy in human immunodeficiency virus-infected patients whose CD4 cell counts increase only slightly in response to combined antiretroviral treatment.

Combined antiretroviral treatment in some human immunodeficiency virus-infected persons does not lead to a rapid increase in CD4 cell counts, and these patients may remain susceptible to opportunistic infections. A group of 13 patients with CD4 cell counts <200 cells/mm3 after > or =9 months of combined antiretroviral treatment received interleukin (IL)-2 immunotherapy (4.5x106 IU twice daily for 5 days every 6 weeks). After only 3 cycles, their CD4 cell counts increased from 123 cells/mm3 (range, 104-134 cells/mm3) to 229 cells/mm3 (range, 176-244 cells/mm3). A marked increase was noted in the naive CD45RA subpopulation of CD4 T lymphocytes. Furthermore, the magnitude of the CD4 cell count response correlated with the baseline expression levels of the antiapoptotic molecule Bcl-2. This study demonstrates that IL-2 immunotherapy can accelerate the recovery of CD4 lymphocytes in persons whose CD4 cell counts fail to increase rapidly in response to combined antiretroviral treatment.

AIDS-Related Opportunistic Infections↗
PubMed2001

Predictors of post-traumatic stress disorder following severe injury.

The chronicity and morbidity of established post-traumatic stress disorder (PTSD) has stimulated interest in recognizing and understanding the early development of the disorder. Acute stress disorder, a new diagnosis intended to facilitate early case detection, rests on the occurrence of dissociative reactions. It remains uncertain whether dissociation is a universal or unique early predictor of subsequent PTSD. Traumatic injury is an important and relatively understudied antecedent of PTSD. The objective of this study was to preliminarily identify which previously implicated early reactions and risk factors would apply to the prediction of PTSD following severe traumatic injury. Patients admitted to a regional Level I trauma center following life threatening events who had recall of the incident and did not have signs of traumatic brain injury or recent psychopathology were enrolled. Comprehensive assessments were conducted during hospitalization and after discharge approximately 2 months after the traumatic event. At follow-up, 24% of the available 50 subjects met full criteria for PTSD and an additional 22% met criteria for two of three symptom clusters. Early symptoms of heightened arousal and coping with disengagement were independent predictors of PTSD severity at follow-up. Relationships to initial dissociative reactions and a diagnosis of ASD were not significant. These early predictors found in a setting of severe injury only partially overlap findings from previous PTSD studies.

Adaptation, Psychological↗
PubMed2001

Are semantic errors actually semantic?: Evidence from alzheimer's disease.

Patients with Alzheimer's disease (AD) produce a high rate of semantic errors when naming to confrontation. This is considered to be one of the many consequences of their semantic memory deficit. However, it has been shown, in aphasic patients with focal lesions, that semantic errors could arise from impairment to any one of the levels in the naming process. To check this hypothesis in AD, we assessed in 15 patients the capacity to name and access semantic knowledge (by multiple-choice probe questions) about 14 objects presented successively in the visual, tactile, auditory, and verbal modalities. In the visual naming task, 33 errors were recorded: 26 (78.8%) were semantic and 7 (21.2%) were unrelated errors. Of the 26 semantic errors, 8 were related to a deficit of the semantic knowledge related to the item and 17 to a deficit in the retrieval of the phonological form of the word. One was associated with a deficit of access to semantic knowledge in the visual modality. The 7 unrelated errors were associated with a loss of semantic knowledge for 4 and deficit of access to the phonological form for 3. In conclusion, this study shows that semantic errors do not systematically reflect a deficit of semantic knowledge in Alzheimer's disease. It also seems that unrelated errors are more frequently related to semantic deficits than semantic errors in this population.

Aged↗
PubMed2001

[5-HT1B serotonin receptors and antidepressant effects of selective serotonin reuptake inhibitors ].

We used knockout mice and receptor antagonist strategies to investigate the contribution of the serotonin (5-hydroxytryptamine, 5-HT) 5-HT1B receptor subtype in mediating the effects of selective serotonin reuptake inhibitors (SSRIs). Using in vivo intracerebral microdialysis in awake mice, we show that a single systemic administration of paroxetine (1 or 5 mg/kg, i.p.) increased extracellular serotonin levels [5-HT]ext in the ventral hippocampus and frontal cortex of wild-type and mutant mice. However, in the ventral hippocampus, paroxetine at the two doses studied induced a larger increase in [5-HT]ext in knockout than in wild-type mice. In the frontal cortex, the effect of paroxetine was larger in mutants than in wild-type mice at the 1 mg/kg dose but not at 5 mg/kg. In addition, either the absence of the 5-HT1B receptor or its blockade with the mixed 5-HT1B/1D receptor antagonist, GR 127935, potentiates the effect of a single administration of paroxetine on [5-HT]ext more in the ventral hippocampus than in the frontal cortex. Furthermore, we demonstrate that SSRIs decrease immobility in the forced swimming test; this effect is absent in 5-HT1B knockout mice and blocked by GR 127935 in wild-type suggesting therefore that activation of 5-HT1B receptors mediate the antidepressant-like effects of SSRIs. Taken together these data demonstrate that 5-HT1B autoreceptors appear to limit the effects of SSRI on dialysate 5-HT levels particularly in the hippocampus while presynaptic 5-HT1B heteroreceptors are likely to be required for the antidepressant activity of SSRIs.

Animals↗
PubMed2001

Cognitive functioning and the early development of PTSD.

Cross-sectional studies of chronic PTSD reveal deficits in verbal memory. We studied cognitive functioning and its relationship to current and subsequent PTSD severity during an early phase of trauma response. Thiry-eight participants with traumatic injuries and only posttrauma incident psychopathology were evaluated shortly after admission to a Level I Trauma Center Neuropsychological measures were obtained at baseline and assessment of PTSD and other psychiatric disorders was conducted at baseline and follow-up, 6 weeks later. Significant negative correlations were found for follow-up PTSD severity with delayed recall and retroactive interference. These relationships were not significant for and were independent of baseline PTSD severity. Relative deficits in select areas of verbal memory after a trauma may confer greater risk for developing PTSD.

Adult↗
PubMed2001

Stable recombinant expression and characterization of the two haemophilic factor VIII variants C329S (CRM(-)) and G1948D (CRM(r)).

In haemophilia A, the functional defect at the molecular level of most factor VIII (FVIII) missense mutations remains unknown. Site-directed mutagenesis of B domain-deleted FVIII cDNA (FVIIISQ) was used to introduce two mutations associated with severe cross-reacting material (CRM)-negative (FVIII-C329S) or mild/moderate CRM-reduced (FVIII-G1948D) haemophilia A. Wild-type (FVIIISQ-WT) and variant FVIIISQ proteins were successfully expressed after stable transfection in Chinese hamster ovary (CHO) cells, and partially characterized at the intracellular, molecular and functional levels. Reverse transcription polymerase chain reaction analysis confirmed that both transcription and mRNA processing appeared normal in CHO cells transfected with both the wild-type and two variant constructs. In contrast to FVIIISQ-WT, immunofluorescence analysis of both CRM(-) and CRM(r) variants showed intracellular FVIII accumulation within the rough endoplasmic reticulum, suggesting secretion defects in transfected CHO cells. Immunoblot analysis of the FVIIISQ variant proteins that were secreted showed that they were expressed as mixed populations of uncleaved 170 kDa polypeptides, processed 90 kDa heavy chains and 80 kDa light chains, similar to FVIIISQ-WT. Phenotypic analysis of the B domain-deleted FVIIISQ variants expressed in CHO cells correlated well with the patients' reduced FVIII activity and, in addition, surface plasmon resonance studies demonstrated that both missense mutations were associated with increased rates of A2 domain dissociation following thrombin activation. We conclude that the mutations found are responsible for the haemophilia A phenotype, through intracellular retention and decreased stability of the active cofactor FVIIIa.

Animals↗
PubMed2001

An Indonesian child with orofacial duplication and neurocristopathy anomalies: case report.

The parents of an Indonesian patient were concerned with the facial appearance of their child. A medical, family and social history was taken for the patient with the detection of no specific, systemic abnormalities or unusual conditions, although it was noted that the family lived in an area associated with pollutants. On examination, the facial appearance was asymmetric with inferior displacement of the right eye. The zygomatic-maxillary region appeared to be enlarged and deformed. There was unilateral macrostomia with the upper lip appearing elongated. Intra-oral examination revealed that there was duplication of the maxilla and associated structures. The maxilla had a normal complement of deciduous teeth but gross caries was noted. A supernumerary maxilla appeared to be responsible for the extra-oral, zygomatic-maxillary deformation, and its deciduous dentition was incomplete intra-orally. For the mandibular structures, the tongue was abnormally small, giving the appearance of microglossia. The mandibular dentition appeared to be incomplete with gross caries. Further posteriorly, there appeared to be clefting of the individual soft palates. Photographs and radiological examinations were undertaken but CAT scans were not possible. For patient management, a comprehensive surgical strategy is indicated with full family support, education and cooperation.

Child, Preschool↗
PubMed2001

Is a capacity for negative priming correlated with hypnotizability?: a preliminary study.

Hypnotic responsiveness may depend upon the ability to inhibit the irrelevant stimuli that evoke responses that are incompatible with current goals (or the mapping between an irrelevant/disruptive stimulus and its response) in order to actively maintain task-relevant information. In a simple correlation design, the authors investigated the relationship between cognitive inhibition (negative priming) and hypnotic responsiveness. A statistically significant correlation was obtained between the extent of negative priming (measured in time latency) and hypnotic responsiveness (r = .491). Limitations of this preliminary study and implications for future work are discussed.

Adult↗
PubMed2001

Superior written over spoken picture naming in a case of frontotemporal dementia.

Two main hypotheses have been proposed regarding the role of phonology in written word production. According to the phonological mediation hypothesis, the retrieval of the lexical phonological representation of a word is an obligatory prerequisite to the retrieval of its spelling. Therefore, deficits to the phonological lexicon should affect both spoken and written picture naming. In contrast, the orthographic autonomy hypothesis posits that the lexical orthographic representations of words can be accessed without any necessary phonological mediation. In support of this view, cases of preserved written naming despite impaired lexical phonology have been reported following brain damage. In this report, we replicate this basic pattern of performance in case YP, a 60-year-old woman with a pattern of frontotemporal dementia. As her disease progressed, YP's ability to write down the names of pictures remained very good despite a severe decline in oral naming. Further testing indicated that this deficit was not primarily due to an articulatory or post-lexical phonological deficit. YP's case provides strong additional support for the orthographic autonomy hypothesis. The significance of this case with respect to the characterization of dementia syndromes is discussed.

Agraphia↗
PubMed2001

Serum leptin levels increase following acute myocardial infarction.

Leptin is secreted into the circulation and communicates the peripheral nutritional status to specific hypothalamic centers. Recent studies suggest that leptin may be involved in the acute response to stress, and that its interaction with the hypothalamo-pituitary-adrenal axis and the inflammatory cytokine system may be of clinical importance. Since these systems are activated during acute myocardial infarction (AMI), we studied leptin and cortisol levels during hospitalization in 30 consecutive patients admitted for AMI. The results show that leptin reached its peak on the second day of hospitalization, with a 2-fold increase from its baseline level on admission (p < 0.02). On day 3, leptin levels declined, and were 46%, 9%, and 6% above baseline on days 3, 4 and 5, respectively. The mean cortisol level was elevated on day 1 and decreased toward normal levels thereafter (p < 0.001). The cortisol level did not correlate with leptin concentration throughout the study. These findings suggest that leptin may have a role in the metabolic changes taking place during the first days after an AMI.

Aged↗
PubMed2001

Functional MRI assessment of the hemispheric predominance for language in epileptic patients using a simple rhyme detection task.

This study assesses the interest of a simple fMRI rhyme detection paradigm to determine hemispheric predominance for language in epileptic patients. Nineteen patients were examined. The findings derived from the fMRI examinations were compared with those obtained on the same patients using the Wada test, stereotactic intracerebral EEG stimulations and recordings, and/or video-EEG recordings. For the seventeen patients for whom language dominance could be assessed by means of at least one of the latter procedures, the fMRI examination provided concordant results in sixteen. In two patients, the hemispheric predominance for language could only be determined by fMRI. Nine patients underwent surgery subsequent to the fMRI examination. None of them exhibited any aphasic problems following surgery. The rhyme detection task used in the fMRI examination generates robust responses in the language areas, permits easy monitoring of the patient's task performance and can be easily undertaken by the epileptic patients. Thus, this study demonstrates that the fMRI rhyme detection paradigm is particularly well-suited for determining hemispheric language predominance in epileptic candidates for surgery.

Adult↗
PubMed2001

Autonomic response to hypobaric hypoxia assessed by time-dependent frequency decomposition of heart rate.

BACKGROUND: Acute hypoxia tolerance varies substantially among healthy individuals. We hypothesized that this variability results from a difference in autonomic (ANS) response to hypoxic stress. METHODS: Peripheral oxygen saturation, respiration and ECG were recorded from 21 healthy subjects (age, 29 +/- 7 yr) in an altitude chamber during normoxia, severe hypoxia (282 mm Hg), and mild hypoxia (360 mm Hg). Cardiovascular control was assessed by time-frequency decomposition of the heart rate signal applying the Selective Discrete Transform Algorithm (SDA). This procedure uses a variable time window, thus providing reliable physiological data even during transient states. Autonomic activity was quantified by power spectral density integrals over a 3-dimensional time-dependent spectral distribution of heart rate fluctuations. RESULTS: Subjects who had slower peripheral oxygen desaturation during severe hypoxia onset (mean 92.9 vs. 58.4 s) were those who displayed higher ANS activity in all ambient states, namely normoxia and hypoxia. These same subjects withstood hypoxia for significantly longer time periods (mean 313 vs. 244 s). CONCLUSION: Improved hypoxia tolerance is linked to enhanced autonomic activity, involving a better management of peripheral blood flow.

Adult↗
PubMed2000

Bacillary angiomatosis affecting the oral cavity. Report of two cases and review.

Bacillary angiomatosis (BA) is an infectious disease characterized by proliferative vascular lesions; it mainly affects HIV-positive patients. Multiple cutaneous nodular lesions together with fever, chills, malaise, anorexia, vomiting and headache are the most important clinical manifestations. It may also involve the heart, liver, spleen, bones, lung, muscles, lymph nodes, central nervous system and other organs. Erythromycin, 500 mg four times a day, is the drug of choice. The importance of this lesion lies in its clinical and histological similarity with other diseases. Cutaneous and oral lesions of BA clinically resemble Kaposi's sarcoma (KS). Histopathologically, BA may be confused with angiosarcoma, pyogenic granuloma and epithelioid hemangioma. We report two HIV-positive men with BA lesions in the oral mucosa. Diagnosis was confirmed by biopsy and Warthin-Starry silver staining.

AIDS-Related Opportunistic Infections↗
PubMed2000

Mutations in ARHGEF6, encoding a guanine nucleotide exchange factor for Rho GTPases, in patients with X-linked mental retardation.

X-linked forms of mental retardation (XLMR) include a variety of different disorders and may account for up to 25% of all inherited cases of mental retardation. So far, seven X-chromosomal genes mutated in nonspecific mental retardation (MRX) have been identified: FMR2, GDI1, RPS6KA3, IL1RAPL, TM4SF2, OPHN1 and PAK3 (refs 2-9). The products of the latter two have been implicated in regulation of neural plasticity by controlling the activity of small GTPases of the Rho family. Here we report the identification of a new MRX gene, ARHGEF6 (also known as alphaPIX or Cool-2), encoding a protein with homology to guanine nucleotide exchange factors for Rho GTPases (Rho GEF). Molecular analysis of a reciprocal X/21 translocation in a male with mental retardation showed that this gene in Xq26 was disrupted by the rearrangement. Mutation screening of 119 patients with nonspecific mental retardation revealed a mutation in the first intron of ARHGEF6 (IVS1-11T-->C) in all affected males in a large Dutch family. The mutation resulted in preferential skipping of exon 2, predicting a protein lacking 28 amino acids. ARHGEF6 is the eighth MRX gene identified so far and the third such gene to encode a protein that interacts with Rho GTPases.

Base Sequence↗
PubMed2000

Significant beat-to-beat hemodynamic changes in fetal circulation: a consequence of abrupt intrathoracic pressure variation induced by hiccup.

During routine fetal echocardiographic studies, we incidentally observed abrupt beat-to-beat changes in blood flow velocity and direction during bouts of hiccups in fetuses with a normal heart and regular and synchronized atrioventricular cardiac rhythm. The effect of hiccups on blood flow velocity and direction varied depending on the time of occurrence of hiccups during the cardiac cycle. In systole, a significant transient reduction of peak flow velocity occurred at the aortic and pulmonic valves, and brief tricuspid regurgitation appeared synchronously with each hiccup. In diastole, a transient reversal of flow direction was recorded simultaneously with the hiccup at the aorta and ductus arteriosus, and acceleration of peak flow velocity was observed across the tricuspid and mitral valves. Throughout the entire cardiac cycle, marked blood flow acceleration was observed in the superior vena cava, inferior vena cava, and ostium secundum simultaneously with the hiccup. A direct transmission of briefly augmented, negative intrathoracic pressure to a compliant aorta and systemic veins appears to be a reasonable explanation for most of our observations.

Blood Flow Velocity↗
PubMed2000

The impact of posthypnotic amnesia and directed forgetting on implicit and explicit memory: new insights from a modified process dissociation procedure.

The authors describe a study investigating the relationship between posthypnotic amnesia (PHA) and directed forgetting (DF) and their impact on implicit and explicit memory. This study adopted a recent modification of the process dissociation procedure to accommodate the cross-contamination of memory test performance by implicit and explicit memorial factors. Forty high and 40 low hypnotically susceptible participants were compared in PHA, DF, and control conditions on estimates of voluntary conscious (VCM), involuntary conscious (ICM), and involuntary unconscious memory (IUM) performance. Both groups showed significant decrements in VCM and ICM following instructions for DF, whereas only high susceptibles showed this decrement in the PHA condition; neither DF nor PHA affected IUM. Moreover, there was no relationship between forgetting in PHA and DF. Although both PHA and DF seem to prevent the conscious (i.e., explicit) expression of memorial information while leaving implicit memory intact, the mechanisms underlying these phenomena may nevertheless be different.

Adult↗
PubMed2000

Molecular epidemiology of rabies virus isolates from Israel and other middle- and Near-Eastern countries.

A total of 226 isolates of rabies virus from different areas of Israel, including three human isolates and one sample from South Lebanon were identified between 1993 and 1998 by direct immunofluorescence using monoclonal antibodies to the viral nucleoprotein (N). An epidemiological survey based on nucleotide sequence analysis of 328 bp from the C terminus of the N coding region and the noncoding region between the nucleoprotein and the phosphoprotein (NS gene) was performed. Phylogenetic analysis of the isolates from Israel showed that they were related geographically, but not according to host species. Five variants, related groups distributed among four geographical regions, were identified. In each region, rabies virus was isolated from more than one animal species. A comparison of the sequence analysis of rabies virus samples from the rest of world revealed a 2-nucleotide change that distinguished the Middle East variants from the rest.

Adult↗