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Biomedical subjects

P Hauser

Publications and source records attributed to P Hauser.

At least 19 recordsLinked to original sources
PubMed2006

Mutations of the transcription factor PU.1 are not associated with acute lymphoblastic leukaemia.

The transcription factor PU.1 plays a crucial role during normal haematopoiesis in both myeloid cells and B-lymphocytes. Mice with a disruption in both alleles of the PU.1 locus were found to lack macrophages and B cells and had delayed appearance of neutrophils. In addition, critical decrease of PU.1 expression is sufficient to cause acute myeloid leukaemia (AML) and lymphomas in mice. Recently, we reported that heterozygous mutations in the PU.1 gene are present in some patients with AML. Thus, we hypothesised that PU.1 mutations might also contribute to the development of acute leukaemias of the B-cell lineage. Here, we screened 62 patients with B-cell acute lymphoblastic leukaemia (B-ALL) at diagnosis for genomic mutations by direct sequencing of all five exons of the PU.1 gene. We found no genomic alteration of the PU.1 gene suggesting that PU.1 mutations are not likely to be common in B-ALL.

Adolescent↗
PubMed2005

[Osteoid osteoma and radiofrequency].

Osteoid osteoma and radiofrequency Osteoid osteoma relates to a benign skeletal neoplasm, smaller than 2 cm in diameter, composed of osteoid, highly vascularized connective tissue and surrounded by a ring of bone sclerosis. Its aetiology remains unknown. It affects twice more males than female patients and occurs usually between 5 and 40 years old. Long bones and spine are the most involved areas but the whole skeleton can be involved. Clinical manifestations can include local pain (increased at night and decreased by activity) and relief with salicylates administration. CT guided radiofrequency ablation of osteoid osteoma is in comparison to surgery less invasive, time saving and economic technique with excellent long term results.

Bone Neoplasms↗
PubMed2002

A prospective study of the incidence and open-label treatment of interferon-induced major depressive disorder in patients with hepatitis C.

Interferon (IFN) therapy has been associated with the development of Major Depressive Disorder (MDD) when given to patients with hepatitis C (HCV). The incidence, time course, risk factors, and treatment of IFN-induced MDD are poorly understood. The objectives of the present study were to determine the incidence of IFN-induced MDD, as well as to determine the efficacy of open-label antidepressant treatment, in particular selective serotonin reuptake inhibitors (SSRIs) for IFN-induced MDD. Thirty-nine HCV patients on IFN therapy were monitored weekly using the Beck Depression Inventory (BDI). Those who became depressed were treated with citalopram, a SSRI antidepressant. Main outcome measures included the incidence of IFN-induced MDD, as well as response rates to antidepressants in those patients who developed IFN-induced MDD. Our results showed that 13 of 39 patients (33%) developed IFN-induced MDD. There were no differences in age, gender, past history of MDD, or substance use between those who became depressed and those who did not. However, there were significantly fewer African American patients in the depressed group. Patients who developed IFN-induced MDD were on IFN therapy for an average of 12.1 weeks prior to the development of MDD. Eleven of 13 patients (85%) were responsive to antidepressant treatment. We conclude that IFN-induced MDD is common in HCV patients. Health care providers should follow IFN-treated HCV patients for the development of MDD, particularly between the 2nd and 5th months of IFN therapy. SSRIs, in particular citalopram, are an effective treatment for IFN-induced depression in HCV patients.

Adult↗
PubMed2001

Extreme thyroid hormone resistance in a patient with a novel truncated TR mutant.

Resistance to thyroid hormone (RTH) is a syndrome in which patients have elevated thyroid hormone (TH) levels and decreased sensitivity to its action. We describe a child with extreme RTH and a severe phenotype. A 22-month-old female presented to the NIH with goiter, growth retardation, short stature, and deafness. Additionally, the patient had hypotonia, mental retardation, visual impairment, and a history of seizures. Brain magnetic resonance imaging showed evidence of demyelination and bilateral ventricular enlargement. The patient had markedly elevated free T3 and free T4 levels of more than 2000 pg/dl (normal, 230-420 pg/dl) and more than 64 pmol/liter (normal, 10.3-20.6 pmol/liter), respectively, and TSH of 6.88 mU/liter (normal, 0.6-6.3 mU/liter). These are the highest TH levels reported for a heterozygous RTH patient. A T3 stimulation test confirmed the diagnosis of RTH in the pituitary and peripheral tissues. Molecular analyses of the patient's genomic DNA by PCR identified a single base deletion in exon 10 of her TRbeta gene that resulted in a frameshift and early stop codon. This, in turn, encoded a truncated receptor that lacked the last 20 amino acids. Cotransfection studies showed that the mutant TR was transcriptionally inactive even in the presence of 10(-6) M T3 and had strong dominant negative activity over the wild-type receptor. It is likely that the severely defective TRbeta mutant contributed to the extreme RTH phenotype and resistance in our patient.

Bone Development↗
PubMed2000

MRI-based measurements of temporal lobe and ventricular structures in patients with bipolar I and bipolar II disorders.

OBJECTIVE: There have been relatively few quantitative MRI studies of temporal lobe structures and the lateral ventricles in bipolar patients and a lack of agreement across studies as to whether these structures differ significantly in size from control subjects. Also there have been no quantitative MRI studies of bipolar II patients. The present study measured temporal lobe and ventricular structures in both bipolar I and bipolar II patients, as well as control subjects. METHOD: Twenty-five bipolar I patients, 22 bipolar II patients and 19 control subjects underwent MRI brain scans. The 5 mm coronal slices of each subject were coded and measured by a rater who was blind with respect to subject diagnosis. Volume estimates of the temporal lobe and hippocampus were calculated for each hemisphere by measuring the area of the structure in each slice in which it appears, multiplying by 5 mm and summing. In addition to these volume estimates, the area of the lateral ventricle and the inferior horn of the lateral ventricle, the lateral ventricle to cerebrum area ratio (LV/C) and the temporal lobe to cerebrum area ratio (TL/C), were calculated for each hemisphere in one reference slice only. The area of the third ventricle was also measured. Volume estimates and area ratios were then compared among diagnostic groups. RESULTS: There were no significant differences in temporal lobe or hippocampal volume estimates, in the third ventricle and inferior horn of the lateral ventricle area measurements, and in the TL/C area ratio among diagnostic groups. The lateral ventricle area and LV/C area ratio were significantly larger in bipolar I patients than either bipolar II patients or control subjects only in the left hemisphere. Furthermore, these measures were approximately twice as large in the bipolar I patients as the other groups. CONCLUSIONS: The current study adds to a growing literature that bipolar I disorder, particularly in males, may show different neurobiological alterations compared to bipolar II patients or control subjects. The pathophysiologic implications of this accumulating evidence of increased left ventricular size in bipolar I disorder remains to be further elucidated.

Adult↗
PubMed2000

Elevated sorbitol concentration in the cerebrospinal fluid of patients with mood disorders.

This study was undertaken to test the hypothesis that a specific pathophysiological mechanism of diabetic neuropathy, namely increased polyol pathway flux, could be operative in patients with bipolar and unipolar mood disorders. Numerous studies have shown abnormalities of carbohydrate metabolism, including high rates of diabetes mellitus, in patients with mood disorders. Several studies have found that peripheral neuropathy is a risk factor for depression in diabetics. Furthermore, increased polyol pathway flux results in elevated sorbitol concentrations in peripheral tissues and cerebrospinal fluid (CSF) of diabetics with neuropathy. The purpose of this study was to determine whether sorbitol concentration is elevated in the CSF of non-medically ill patients with mood disorders. Lumbar punctures were performed on 30 subjects - 10 with bipolar mood disorder, 10 with unipolar mood disorder, and 10 age-matched normal controls, and CSF sorbitol concentrations were measured, using a gas chromatographic-mass spectroscopic technique. The mean+/-standard deviation of CSF sorbitol concentrations differed among the three groups as follows: bipolar (22.9+/-4.6 micromoles/l) > unipolar (19.0+/-2.8 micromoles/l)>normal control (15. 6+/-1.9 micromoles/l). One-way ANOVA showed significant (P=0.0002) differences among the three groups. Post-hoc tests indicated a significant (P<0.05) difference between bipolars and normal controls, bipolars and unipolars, and unipolars and normal controls. Further investigation is needed to determine the pathophysiological significance of this novel finding of elevated sorbitol concentration in the CSF of patients with mood disorders.

Adult↗
PubMed2000

Study of chromosome rearrangements associated with the trpE26 mutation of Bacillus subtilis.

Chromosome rearrangements involved in the formation of merodiploid strains in the Bacillus subtilis 168-166 system were explained by postulating the existence of intrachromosomal homology regions. This working hypothesis was tested by analysing sequences and restriction patterns of the, as yet uncharacterized, junctions between chromosome segments undergoing rearrangements in parent, 168 trpC2 and 166 trpE26, as well as in derived merodiploid strains. Identification, at the Ia/Ib chromosome junction of both parent strains, of a 1.3 kb segment nearly identical to a segment of prophage SPbeta established the existence of one of the postulated homology sequences. Inspection of relevant junctions revealed that a set of different homology regions, derived from prophage SPbeta, plays a key role in the formation of so-called trpE30, trpE30+, as well as of new class I merodiploids. Analysis of junctions involved in the transfer of the trpE26 mutation, i.e. simultaneous translocation of chromosome segment C and rotation of the terminal relative to the origin moiety of the chromosome, did not confirm the presence of any sequence suitable for homologous recombination. We propose a model involving simultaneous introduction of four donor DNA molecules, each comprising a different relevant junction, and their pairing with the junction regions of the recipient chromosome. The resolution of this structure, resting on homologous recombination, would confer the donor chromosome structure to the recipient, achieving some kind of 'transstamping'. In addition, a rather regular pattern of inverse and direct short sequence repeats in regions flanking the breaking points could be correlated with the initial, X-ray-induced, rearrangement.

Bacillus subtilis↗
PubMed2000

Spontaneous apoptosis and retinoic acid receptor incidence in neuroblastomas and peripheral neuroectodermal tumors.

Twelve cases of neuroblastoma (NB) (7 boys and 5 girls) and 4 cases of primitive peripheral neuroectodermal tumor (PNET) (3 boys and 1 girl) were investigated for the presence of apoptosis and retinoic acid receptor (RAR) by immunhistochemical method. The apoptotic index in NB was zero or 1% in 8 children and relatively low (2-4.8%) in the other 4 cases, while it was higher (4.1-10.5%) in PNET. The RAR index determined by immunoperoxidase reaction in NB was zero or 3% in 5 cases and 9-34% in 7 children. RAR index in PNET was 16-68% in all the 4 cases. Good correlation (r = .47 according to Pearson-Bravis) was found between the number of RAR and spontaneous apoptosis. These results suggest that the RAR index in untreated NB and PNET shows great individual variation since its determination is necessary for the evaluation of the efficacy of retinoic acid treatment.

Apoptosis↗
PubMed2000

A preliminary study of the relation of neuropsychological performance to neuroanatomic structures in bipolar disorder.

OBJECTIVE: To investigate the relation between neuropsychological dysfunction and volumetric measures of neuroanatomic structures in patients with bipolar disorder. BACKGROUND: Previous research suggests that neuropsychological deficits are associated with neuroanatomic changes in patients with bipolar disorder. METHOD: Twenty-six outpatients who met Diagnostic and Statistical Manual, Third Edition-Revised criteria for bipolar disorder were administered a battery of neuropsychological tests that assessed memory, abstracting ability, psychomotor performance, sustained attention, and intelligence. Patients also received a magnetic resonance imaging scan, from which volumes of the temporal lobes, hippocampus, third ventricle, and areas of the lateral ventricles were calculated. Using multiple regression analyses, neuroanatomic structures were compared with neuropsychological test variables. RESULTS: Data suggest that a larger right hippocampal volume is associated with poorer neuropsychological functioning. CONCLUSIONS: Further studies are needed to both replicate and examine the relation between potential mechanisms of neuroanatomic alterations and neuropsychological dysfunction in patients with bipolar disorder.

Adult↗
PubMed1999

Intranasal murine model of Bordetella pertussis infection. I. Prediction of protection in human infants by acellular vaccines.

Bicomponent, tricomponent and pertactin DTPa vaccines were tested in sublethal aerosol, and lethal and sublethal intranasal murine Bordetella pertussis respiratory challenge models. Pertactin and bicomponent vaccines induced protective immunity against lethality but with little or no bacterial clearance. Intranasal challenge discriminated in a reproducible, statistically significant manner between the efficacies of bicomponent and tricomponent DTPa, in agreement with clinical trial data. This discrimination was not observed in the aerosol challenge. Pertactin had a synergistic effect with bicomponent DTPa. Intranasal challenge may be useful as part of the preclinical evaluation of new acellular pertussis formulations or DTPa-based combinations.

Administration, Inhalation↗
PubMed1999

Epithelial mesothelioma with deciduoid features.

A rare case of malignant mesothelioma in a 15-year-old girl is described. The patient presented with secondary amenorrhoea and clinical symptoms resembling those of an ovarian cyst. One large and multiple small peritoneal nodules were found at laparoscopy. Histologically the tumour was characterised by an unusual pattern with a superficial resemblance to decidual reaction, but because of significant mitotic activity the diagnosis of a malignant tumour, epithelial mesothelioma with deciduoid features, was made. The patient died 11 months after diagnosis. Post-mortem examination revealed extensive extraperitoneal spread.

Adolescent↗
PubMed1999

Screening methods for thyroid hormone disruptors.

The U.S. Congress has passed legislation requiring the EPA to implement screening tests for identifying endocrine-disrupting chemicals. A series of workshops was sponsored by the EPA, the Chemical Manufacturers Association, and the World Wildlife Fund; one workshop focused on screens for chemicals that alter thyroid hormone function and homeostasis. Participants at this meeting identified and examined methods to detect alterations in thyroid hormone synthesis, transport, and catabolism. In addition, some methods to detect chemicals that bind to the thyroid hormone receptors acting as either agonists or antagonists were also identified. Screening methods used in mammals as well as other vertebrate classes were examined. There was a general consensus that all known chemicals which interfere with thyroid hormone function and homeostasis act by either inhibiting synthesis, altering serum transport proteins, or by increasing catabolism of thyroid hormones. There are no direct data to support the assertion that certain environmental chemicals bind and activate the thyroid hormone receptors; further research is indicated. In light of this, screening methods should reflect known mechanisms of action. Most methods examined, albeit useful for mechanistic studies, were thought to be too specific and therefore would not be applicable for broad-based screening. Determination of serum thyroid hormone concentrations following chemical exposure in rodents was thought to be a reasonable initial screen. Concurrent histologic evaluation of the thyroid would strengthen this screen. Similar methods in teleosts may be useful as screens, but would require indicators of tissue production of thyroid hormones. The use of tadpole metamorphosis as a screen may also be useful; however, this method requires validation and standardization prior to use as a broad-based screen.

Animals↗
PubMed1998

Reliability and acceptability of psychiatric diagnosis via telecommunication and audiovisual technology.

The reliability of psychiatric diagnoses made remotely by telecommunication was examined. Two trained interviewers each interviewed the same 30 psychiatric inpatients using the Structured Clinical Interview for DSM-III-R. Fifteen subjects had two in-person interviews, and 15 subjects had one in-person and one remote interview via telecommunication. Interrater reliability was calculated for the four most common diagnoses: major depression, bipolar disorder, panic disorder, and alcohol dependence. For each diagnosis, interrater reliability (kappa statistic) was identical or almost identical for the patients who had two in-person interviews and those who had an in-person and a remote interview, suggesting that reliable psychiatric diagnoses can be made via telecommunication.

Alcoholism↗