Biomedical subjects

R Paul

Publications and source records attributed to R Paul.

At least 37 records · Page 2Linked to original sources

PubMed2002

A solitary huge neurofibroma of the soft palate.

Neurofibroma of the soft palate, an extremely rare tumour, is probably not yet reported in the literature. We report the first case of an isolated neurofibroma of the soft palate not associated with von Recklinghausen's disease (VRD), which is also, probably, the first reported case of neurofibroma of the soft palate. The tumour was completely removed from the soft palate after performing tracheostomy, necessitated due to difficulties in intubation.

Female↗

PubMed2001

Expression of E. coli RecA targeted to mitochondria of human cells.

Mitochondrial DNA integrity is ensured by several nuclear-encoded proteins in vertebrates, and a number of mtDNA alterations in human diseases, including deletions and duplications, have been suspected to result from errors in the mitochondrial recombination pathway. However, the presence of the latter system is still a matter of controversy as RecA proteins display various functions in vitro. In Escherichia coli, RecA plays a central role in homologous recombination by pairing and transferring a single strand to a homologous duplex DNA. To address indirectly the issue of a mitochondrial recombination pathway in vivo, we have constructed a chimeric gene containing an N terminal mitochondrial targeting sequence and the E. coli RecA gene. Cells were transfected by the recombinant plasmid, then tested for their mtDNA repair upon bleomycin treatment. We found an increased repair rate of the mitochondrial DNA in cells expressing RecA as compared to control cells. These results indicate that the transfected cells display an improved mtDNA repair replication pathway due to the exogenous RecA, likely in synergy with an endogenous rate-limiting mitochondrial recombination pathway.

Anti-Bacterial Agents↗

PubMed2001

Neurocognitive performance enhanced by highly active antiretroviral therapy in HIV-infected women.

OBJECTIVE: To determine whether highly active retroviral therapy (HAART) is associated with better neurocognitive outcome over time among HIV-infected women with severely impaired immune function. METHODS: A semiannual neurocognitive examination on four tasks was administered: Color Trail Making, Controlled Oral Word Association, Grooved Pegboard and Four-Word Learning. This protocol was initiated in the HIV Epidemiological Research study (HERS) study when a woman's CD4 cell count fell to < 100 x 10(6) cells/l. Immune function (CD4), viral load status and depression severity (CESD) were also assessed semi-annually, along with an interview to determine medication intake and illicit drug use. RESULTS: HAART was not available to any participant at the time of enrollment (baseline), while 44% reported taking HAART at their most recent visit (mean duration of HAART 36.3 +/- 12.6 months). HAART-treated women had improved neurocognitive performance compared with those not treated with HAART. Women taking HAART for 18 months or more showed the strongest neurocognitive performance with improved verbal fluency, psychomotor and executive functions. These functions worsened among women not taking HAART. Substance abuse status, severity of depressive symptoms, age and educational level did not influence the HAART treatment effects on neurocognitive performance. Neurocognitive improvements were strongly associated with the magnitude of CD4 cell count increases. CONCLUSIONS: HAART appeared to produce beneficial effect on neurocognitive functioning in HIV-infected women with severely impaired immune systems. Benefits were greatest for women who reported receiving HAART for more than 18 months.

Adolescent↗

PubMed2001

Characterization of RNase P from Thermotoga maritima.

The protein subunit of RNase P from a thermophilic bacterium, Thermotoga maritima, was overexpressed in and purified from Escherichia coli. The cloned protein was reconstituted with the RNA subunit transcribed in vitro. The temperature optimum of the holoenzyme is near 50 degrees C, with no enzymatic activity at 65 degrees C or above. This finding is in sharp contrast to the optimal growth temperature of T.maritima, which is near 80 degrees C. However, in heterologous reconstitution experiments in vitro with RNase P subunits from other species, we found that the protein subunit from T.maritima was responsible for the comparative thermal stability of such complexes.

Amino Acid Sequence↗

PubMed2001

Overexpression and purification of Helicobacter pylori flavodoxin and induction of a specific antiserum in rabbits.

Flavodoxin from the gastric pathogen Helicobacter pylori has been shown to be the electron acceptor of the essential pyruvate-oxidoreductase enzyme complex and proposed to be involved in the pathogenesis of gastric MALToma. In order to obtain a sufficient amount for biochemical and structural studies, we overexpressed the protein either with a C-terminal His(6) -tag or as a fusion protein upstream of intein- and chitin-binding domains. With both expression systems we succeeded at purifying soluble and functional flavodoxin containing the cofactor FMN. When expressing with a His(6) -tag, we purified approximately 20 mg flavodoxin per liter of bacterial culture, while expression as an intein-CBD fusion protein with autocatalytic removal of the intein-CBD part rendered only approximately 1 mg of purified flavodoxin per liter of bacterial culture. Expressed as an intein-CBD fusion protein, flavodoxin copurified with a C-terminal degradation product, which was not observed for expression with a His(6) -tag. However, we were able to obtain protein crystals suited for X-ray structure determination from flavodoxin expressed as an intein-CBD fusion protein, but not from flavodoxin expressed with a C-terminal His(6) -tag. We further report the induction of a rabbit antiserum specific for H. pylori flavodoxin.

Animals↗

PubMed2001

Incidence and outcome of patients with adrenal metastases of renal cell cancer.

OBJECTIVES: To evaluate the outcome of patients with adrenal metastasis in renal tumors to establish the oncologic necessity of adrenalectomy in these patients. Radical nephrectomy for renal cell cancer includes simultaneous ipsilateral adrenalectomy. Recent reports suggest that adrenal involvement in renal cell cancer is rare and can be predicted by computed tomography or distinct algorithms. METHODS: In a retrospective analysis of 866 consecutive patients who underwent nephrectomy and adrenalectomy, we established the rate of adrenal metastasis and obtained follow-up information to evaluate disease outcome. RESULTS: We calculated an adrenal metastasis rate of 3.1% (n = 27); of these 27 patients, only 6 (0.7% of all patients) presented with a solitary adrenal metastasis. Kaplan-Meier analysis demonstrated that patients with solitary adrenal and multiple metastases have a poor outcome. The median survival of patients with localized renal cancer was 43.9 months compared with 21.3 months for patients with a solitary adrenal metastasis and 11.0 months for patients with multiple metastases. CONCLUSIONS: Ipsilateral, solitary, and synchronous metastases in renal cell cancer are rare and patients have a poor outcome despite surgical resection. Therefore, simultaneous adrenalectomy can be omitted during radical nephrectomy if the preoperative examinations or algorithms used do not predict adrenal metastasis in the patient with renal cell cancer.

Adrenal Gland Neoplasms↗

PubMed2001

A simulation modelling approach to evaluating alternative policies for the management of the waiting list for liver transplantation.

A shortage of donor liver grafts unfortunately results in approximately 10% of patients dying whilst listed for a liver transplant in Europe and the United States. Thus it is imperative that all available organs are used as efficiently as possible. This paper reports upon the application of a simulation modelling approach to assess the impact of several alternative allocation policies upon the cost effectiveness of this technology at one liver transplant centre in the UK. The impact of changes in allocation criteria on the estimated net life expectancy, average net costs and overall cost effectiveness of the transplantation programme were evaluated. The incremental cost effectiveness ratio (ICER) for the base case allocation policy, based upon the time spent on the waiting list (i.e., longest wait first) was 11,557 pounds sterling at 1999 prices. The ICERs associated with an allocation policy based upon age (lowest age first), and an allocation policy based upon the severity of the pre-transplant condition of the patient (with most severely ill patients given a lower priority) were lower than the base case at 10,424 pounds sterling and 9,077 pounds sterling, respectively. The results of this modelling study suggest that the overall cost effectiveness of the liver transplantation programme could be improved if the current allocation policy were modified to give more weight to the age of the patient and the reduced chances of success of the most severely ill patients.

Cost-Benefit Analysis↗

PubMed2001

Emotional and personality changes following cingulotomy.

The effects of bilateral anterior cingulate cortex (ACC) lesions on emotional and personality functioning were studied. Patients undergoing cingulotomy for chronic intractable pain were assessed on the Minnesota Multiphasic Personality Inventory (MMPI), the Profile of Mood States (POMS), cognitive tests, and pain ratings, pre- and postsurgically. Patients with intractable pain, not treated with cingulotomy, served as controls. Cingulotomy patients experienced reductions in POMS-Tension, POMS-Anger, and MMPI Scale 7 (Psychasthenia) compared with baseline and the controls. POMS-Tension was significantly correlated with attention-intention performance. The results indicate that the ACC modulates emotional experience, related to self-perceived tension, and that there is relationship between the emotional and the attentional effects of cingulotomy.

Adult↗

PubMed2001

Src deficiency or blockade of Src activity in mice provides cerebral protection following stroke.

Vascular endothelial growth factor (VEGF), an angiogenic factor produced in response to ischemic injury, promotes vascular permeability (VP). Evidence is provided that Src kinase regulates VEGF-mediated VP in the brain following stroke and that suppression of Src activity decreases VP thereby minimizing brain injury. Mice lacking pp60c-src are resistant to VEGF-induced VP and show decreased infarct volumes after stroke whereas mice deficient in pp59c-fyn, another Src family member, have normal VEGF-mediated VP and infarct size. Systemic application of a Src-inhibitor given up to six hours following stroke suppressed VP protecting wild-type mice from ischemia-induced brain damage without influencing VEGF expression. This was associated with reduced edema, improved cerebral perfusion and decreased infarct volume 24 hours after injury as measured by magnetic resonance imaging and histological analysis. Thus, Src represents a key intermediate and novel therapeutic target in the pathophysiology of cerebral ischemia where it appears to regulate neuronal damage by influencing VEGF-mediated VP.

Animals↗

PubMed2001

Psycholinguistic models of speech development and their application to clinical practice.

This article presents an introduction to psycholinguistic models of speech development. Two specific types of models are addressed: box-and-arrow models and connectionist or neural network models. We review some historical and some current models and discuss recent applications of such models to the management of speech impairment in children. We suggest that there are two ways in which a psycholinguistic approach can influence clinical practice: by directly supplementing a speech-language pathologist's repertoire of assessment and treatment approaches and by offering a new way to conceptualize speech impairment in children.

Brain↗

PubMed2001

Speech and prosody characteristics of adolescents and adults with high-functioning autism and Asperger syndrome.

Speech and prosody-voice profiles for 15 male speakers with High-Functioning Autism (HFA) and 15 male speakers with Asperger syndrome (AS) were compared to one another and to profiles for 53 typically developing male speakers in the same 10- to 50-years age range. Compared to the typically developing speakers, significantly more participants in both the HFA and AS groups had residual articulation distortion errors, uncodable utterances due to discourse constraints, and utterances coded as inappropriate in the domains of phrasing, stress, and resonance. Speakers with AS were significantly more voluble than speakers with HFA, but otherwise there were few statistically significant differences between the two groups of speakers with pervasive developmental disorders. Discussion focuses on perceptual-motor and social sources of differences in the prosody-voice findings for individuals with Pervasive Developmental Disorders as compared with findings for typical speakers, including comment on the grammatical, pragmatic, and affective aspects of prosody.

Adolescent↗

PubMed2001

Assessment of hemolysis related quantities in a microaxial blood pump by computational fluid dynamics.

A computational assessment or even quantification of shear induced hemolysis in the predesign phase of artificial organs (e.g., cardiac assist devices) would largely decrease efforts and costs of design and development. In this article, a general approach of hemolysis analysis by means of computational fluid dynamics (CFD) is discussed. A validated computational model of a microaxial blood pump is used for detailed analysis of shear stress distribution. Several methods are presented that allow for a qualitative assessment of shear stress distribution and related exposure times using a Lagrangian approach and mass distribution in combination with shear stress analysis. The results show that CFD offers a convenient tool for the general assessment of shear-induced hemolysis. The determination of critical regions and an estimation of the amount of blood subject to potential damage in relation to the total mass flow are shown to be feasible. However, awareness of limitations and potential flaws in CFD based hemolysis assessments is crucial.

Computational Biology↗

PubMed2001

Antiphospholipid antibodies in women at risk for preeclampsia.

OBJECTIVE: The aim of this study was to determine whether positive results of tests for any of 5 antiphospholipid antibodies are associated with recurrent preeclampsia among women with a history of preeclampsia in a previous pregnancy. STUDY DESIGN: Second-trimester serum samples were obtained from 317 women with preeclampsia in a previous pregnancy who were being followed up in a prospective treatment trial. The serum samples were measured by enzyme-linked immunoassay for immunoglobulin G and immunoglobulin M antibodies against 5 phospholipids. Positive results were analyzed with regard to preeclampsia, severe preeclampsia, intrauterine growth restriction, and preterm delivery. RESULTS: Sixty-two of the 317 women (20%) had recurrent preeclampsia develop, 19 (6%) had severe preeclampsia, and 18 (5.8%) were delivered of infants with growth restriction. Positive results of tests for immunoglobulin G or immunoglobulin M antiphospholipid antibodies were not associated with recurrent preeclampsia. Positive results for immunoglobulin G or immunoglobulin M antibodies at the 99th percentile were also not associated with preterm delivery. Positive results at the 99th percentile for immunoglobulin G antiphosphatidylserine antibody were associated with severe preeclampsia, and positive results at the 99th percentile for immunoglobulin G anticardiolipin, antiphosphatidylinositol, and antiphosphatidylglycerol antibodies were associated with intrauterine growth restriction. The positive predictive values for these outcomes all were approximately 30%. CONCLUSION: Positive results of testing for antiphospholipid antibodies in the second trimester were not associated with recurrent preeclampsia among women at risk because of a history of preeclampsia. Positive results for immunoglobulin G antiphosphatidylserine antibody were associated with severe preeclampsia, and positive results for immunoglobulin G anticardiolipin, antiphosphatidylinositol, and antiphosphatidylglycerol antibodies were associated with intrauterine growth restriction. However, the positive predictive values for all these associations were modest. Testing for antiphospholipid antibodies during pregnancy is of little prognostic value in the assessment of the risk for recurrent preeclampsia among women with a history of preeclampsia.

Adult↗

PubMed2001

Lack of endothelial nitric oxide synthase aggravates murine pneumococcal meningitis.

Nitric oxide (NO) plays a central role in the pathogenesis of bacterial meningitis. However, the role of NO produced by endothelial NO synthase (eNOS) in meningitis is still unclear. We investigated the influence of eNOS depletion on the inflammatory host response, intracranial complications, and outcome in experimental pneumococcal meningitis. Leukocyte accumulation in the cerebrospinal fluid was more pronounced in infected eNOS-deficient mice than in infected wild type mice. This effect could be attributed to an increased expression of P-selectin, macrophage inflammatory protein-2, keratinocyte-derived cytokine, and interleukin (IL)-1beta in the brain of infected eNOS-deficient mice. However, no differences in the cerebral expression of intercellular adhesion molecule-1, tumor necrosis factor-alpha, and IL-6 as well as of neuronal NOS and inducible NOS could be detected between infected wild type and mutant mice. In addition to enhanced leukocyte infiltration into the CSF, meningitis-associated intracranial complications including blood-brain barrier disruption and the rise in intracranial pressure were significantly augmented in infected eNOS-deficient mice. The aggravation of intracranial complications was paralleled by a worsening of the disease, as evidenced by a more pronounced hypothermia, an enhanced weight reduction, and an increased death rate. The current data indicate that eNOS deficiency is detrimental in bacterial meningitis. This effect seems to be related to an increased expression of (certain) cytokines/chemokines and adhesion molecules; thus leading to increased meningeal inflammation and, subsequently, to aggravated intracranial complications.

Animals↗

PubMed2001

Mutations of the Helicobacter pylori genes rdxA and pbp1 cause resistance against metronidazole and amoxicillin.

To investigate amoxicillin and metronidazole resistance of Helicobacter pylori, we compared putative resistance genes between resistant strains obtained in vitro and their sensitive parent strain. All metronidazole-resistant strains had rdxA mutations, and an amoxicillin-resistant strain had pbp1 and pbp2 mutations. By transforming PCR products of these mutated genes into antibiotic-sensitive strains, we showed that rdxA null mutations were sufficient for metronidazole resistance, while pbp1 mutations contributed to amoxicillin resistance of H. pylori.

Amino Acid Sequence↗

PubMed2001

Giant malignant mesenchymoma of the spermatic cord with bidirectional differentiation.

BACKGROUND: Spermatic cord neoplasms are a rare tumor entity and, moreover, of benign behavior. Malignant tumors of the spermatic cord are mostly of mesenchymal origin. We present the unusual case of a giant malignant mesenchymoma of the spermatic cord with bidirectional differentiation into a liposarcoma and a leiomyosarcoma. CASE REPORT: A 84-year-old male patient presented with a scrotal mass on the left side which was observed growing since 1 year and misdiagnosed as scrotal hernia or testicular hydrocele. Ultrasound and computed tomography demonstrated a solid tumor suggesting a spermatic cord tumor. The patient underwent hemiscrotectomy, and the histological examination of the 2,500-gram specimen revealed a malignant mesenchymoma originating from the spermatic cord with two distinct histopathological compartments of liposarcoma and leiomyosarcoma. Because an adjuvant therapy protocol is of questionable effect and because of the patient's age no further therapy was applied. The patient was closely followed and is now, 5 years after surgery, still free of disease. CONCLUSION: Even in older patients, scrotal masses should be considered malignant tumors as long as no benign diagnosis has been proven. Although malignant mesenchymomas are rare tumors with poor prognosis, in selected cases even large tumor masses, as presented, can be cured by surgery.

Aged↗

PubMed2001

Impairments of attention and effort among patients with major affective disorders.

Impairments of attention are common among people with major affective disorders, yet the influence of effortful task demands on attentional performance in unipolar and bipolar illness has been little studied. The authors compared psychiatric inpatients with primary diagnoses of unipolar or bipolar affective disorder (n=27) and age-matched normal control subjects (n=20) on a battery of eight neuropsychological tasks designed to measure different attentional functions. There were low-effort and high-effort versions of each task. Significant group differences were consistently observed on tasks demanding sustained and focused attention, but not on tasks requiring visual selective attention. Although affective disorder patients showed impairments on most tasks regardless of level of task effort, group differences were greatest on high-effort conditions. Results indicate that patients with major affective disorders show significant attentional impairments on most measures of effortful attention, and the magnitude of these impairments increases as the effortful demands of the task increase.

Adult↗

PubMed2001

Dementia severity and pattern of cognitive performance in vascular dementia.

We evaluated the influence of dementia severity on cognitive performance in two groups of individuals with vascular dementia (VaD). Performance on the Mini-Mental State Exam (MMSE) was used to determine dementia severity. Tests of executive function, psychomotor speed, memory, language, and visuospatial function were administered. As expected, individuals with severe VaD (MMSE < 18) performed significantly more poorly than individuals with mild VaD (MMSE > or = 18) on most tests. More important, deficits were evident for both groups in each cognitive domain when compared to normative data. These results indicate that multiple cognitive domains are affected even in mild cases of VaD. Clinicians should be aware that although the presence of "patchy" cognitive deficits may indicate stroke, general cognitive dysfunction may occur in mild cases of VaD.

Aged↗