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Biomedical subjects

K Paul

Publications and source records attributed to K Paul.

At least 73 records · Page 4Linked to original sources
PubMed1995

Minimally invasive diagnosis of renal artery stenosis by spiral computed tomography angiography.

We prospectively compared in a blinded fashion spiral computed tomography angiography (CTA) with arteriography in 62 consecutive patients with suspected renal artery stenosis (RAS). For CTA 150 ml of contrast material were injected intravenously. Arteriography was performed by DSA technique with selective catheterization of renal arteries. Of the 157 visualized renal arteries 155 could be evaluated with DSA and a total of 157 with CTA. Sensitivity of CTA for RAS > or = 50% was 98% and the specificity was 94%. Comparison of the grade of stenosis as evaluated by DSA versus CTA showed: identical gradation in 59 arteries (DSA > or = 50%/CTA > or = 50%), underestimation by CTA in one artery (DSA 50 to 75%/CTA < 50%), and overestimation by CTA in six arteries (DSA < 50%/CTA 50 to 75%). Factors that may contribute to these differences include impaired renal function and possibly "underestimation" of ostial RAS by arteriography. One artery not evaluable by arteriography showed a 70% stenosis by CTA. CTA showed no major side effects. We conclude that CTA has the same accuracy for the diagnosis of RAS > or = 50% as arteriography. However, CTA is only minimally invasive, safe, and causes less discomfort to patients.

Adult↗
PubMed1995

(n-6)-Fatty acids in plasma lipids of children with atopic bronchial asthma.

It has been suggested that atopy is associated with an impairment in the delta 6-desaturation of (n-6)-polyunsaturated fatty acids and subsequently low levels of eicosanoid precursors. To evaluate this hypothesis we analyzed the fatty acid composition of plasma phospholipids and plasma cholesterol esters in a well-defined group of children with atopic bronchial asthma (n = 17) and age-matched healthy controls (n = 10). Atopic children showed significantly higher levels of linoleic acid and lower proportions of arachidonic acid in plasma lipids. No differences were observed with respect to gamma-linolenic acid (GLA) and dihomo-gamma-linolenic acid (DHLA). It is concluded that there is no biochemical evidence for a delta 6-desaturation defect in atopic children and therefore no justification for the supplementation of GLA and DHLA; e.g., by the use of evening primrose oil preparations.

8,11,14-Eicosatrienoic Acid↗
PubMed1994

Mutations of an active site threonyl residue promote beta elimination and other side reactions of the enediol intermediate of the ribulosebisphosphate carboxylase reaction.

The side chain of residue threonine 65 within the active site of ribulosebisphosphate carboxylase participates in a network of hydrogen bonds and ionic interactions involving the phosphate moiety attached to C-1 of the substrate. This residue was replaced with serine, alanine, and valine in the enzyme from Synechococcus PCC 6301. The mutant enzymes were stable, expressed abundantly by Escherichia coli, and retained the ability to form gel-filterable complexes with the reaction-intermediate analog, 2'-carboxyarabinitol-1,5-bisphosphate. The substitutions reduced the kcat/Km(CO2) (where kcat is the substrate-saturated turnover rate) of the enzyme from 17- to 340-fold with the more radical substitutions causing more severe reductions. The CO2/O2 specificity also deteriorated progressively, the valine replacement causing a 2.3-fold reduction. In concert with these changes, a compound tentatively identified as 1-deoxy-D-glycero-2,3-pentodiulose-5-phosphate, the product of beta elimination of the 2,3-enediol(ate) intermediate of the catalytic reaction, appeared among the reaction products in progressively increasing amounts. In the case of the valine substitution, it comprised 13% of the ribulose bisphosphate consumed. The mutant enzymes also partitioned more of their reaction flux to pentulose bisphosphate isomers of ribulose bisphosphate. By contrast, the diversion of carboxylated product to pyruvate, as a result of beta elimination of the three-carbon aci-carbanion intermediate of the carboxylation reaction, was ameliorated by the replacements, the valine mutant showing a 5-fold improvement in this parameter. These observations focus attention on a geometric conflict which exists between the requirements for stabilization of the 5-carbon enediol(ate) and 3-carbon aci-carbanion intermediates. This conflict must be resolved by a change in the angle of the C-1/bridge oxygen bond during each catalytic cycle. The network of hydrogen bonds involving the side chain of threonine 65 must play a crucial role in facilitating reaction of the enediol(ate) with the gaseous substrate and in shepherding this subsequent movement.

Amino Acid Sequence↗
PubMed1994

Treatment of small cell lung cancer in the elderly.

OBJECTIVE: Since both the incidence of lung cancer and the proportion of the population over age 65 are increasing rapidly in North America, we undertook a retrospective review of elderly patients with small cell lung cancer (SCLC) in an attempt to assess the effect of age on treatment decisions, response, survival, and toxicity. DESIGN: Retrospective chart view. SETTING: Oncology Unit of a university-affiliated teaching hospital. PATIENTS: There were 123 patients age > 70 years treated from 1976-88. Chemotherapy consisted of either cyclophosphamide, doxorubicin, and vincristine, or etoposide and cisplatin. RESULTS: There were 74 patients aged 70-74, 35 aged 75-80, and 14 aged 80 years or older. No significant differences existed between the groups in sex, stage, performance status, or presence of co-morbid disease. Median survivals for patients with limited and extensive disease were 11.9 and 5.2 months, respectively (P = < 0.0001), with no significant difference for patients in any age group (P = 0.4). For both limited and extensive disease, survival correlated strongly with the treatment received. Twenty-five patients received no treatment (median survival 1.1 months), 20 had radiation only (median 7.8 months), and 27 patients had < 3 cycles of chemotherapy (median 3.9 months). Median survival for the 50 patients who had 4-6 cycles was 10.7 months (limited disease 15.0 months, extensive disease 8.61 months). In the Cox Model, survival correlated strongly with stage of disease and chemotherapy treatment (P < 0.0001), but only marginally with performance status (P < 0.077). Of the 77 patients who had chemotherapy, less than 50% in all age groups completed six cycles. Only two patients completed chemotherapy without a single dose reduction, and 76.7% required more than two reductions. CONCLUSIONS: Chemotherapy should not be withheld from elderly patients with SCLC on the basis of age. The survival of patients who receive chemotherapy is significantly longer than that of untreated patients even though frequent dose reductions for toxicity may be required. The survival benefit is due to treatment effect and is not due to a selection bias in the cohort of patients chosen for therapy.

Activities of Daily Living↗
PubMed1993

Amino-terminal truncations of the ribulose-bisphosphate carboxylase small subunit influence catalysis and subunit interactions.

The first 20 residues at the amino terminus of the small subunit of spinach ribulose-1,5-bisphosphate carboxylase form an irregular arm that makes extensive contacts with the large subunit and also with another small subunit (S. Knight, I. Andersson, and C.-I. Brändén [1990] J Mol Biol 215: 113-160). The influence of these contacts on subunit binding and, indirectly, on catalysis was investigated by constructing truncations from the amino terminus of the small subunit of the highly homologous enzyme from Synechococcus PCC 6301 expressed in Escherichia coli. Removal of the first six residues (and thus the region of contact with a neighboring small subunit) affected neither the affinity with which the small subunits bound to the large subunits nor the catalytic properties of the assembled holoenzyme. Extending the truncation to include the first 12 residues (which encroaches into a highly conserved region that interacts with the large subunit) also did not weaken intersubunit binding appreciably, but it reduced the catalytic activity of the holoenzyme nearly 5-fold. Removal of an additional single residue (i.e. removal of a total of 13 residues) weakened intersubunit binding approximately 80-fold. Paradoxically, this partially restored catalytic activity to approximately 40% of that of the wild-type holoenzyme. None of these truncations materially affected the Km values for ribulose-1,5-bisphosphate or CO2. Removal of all 20 residues of the irregular arm (thereby deleting the conserved region of contact with large subunits) totally abolished the small subunit's ability to bind to large subunits to form a stable holoenzyme. However, this truncated small subunit was still synthesized by the E. coli cells. These data are interpreted in terms of the role of the amino-terminal arm of the small subunit in maintaining the structure of the holoenzyme.

Amino Acid Sequence↗
PubMed1993

[Homozygous alpha 1-antitrypsin deficiency. Lung changes in children and adolescents].

Homozygous alpha 1-antitrypsin deficiency can lead to pan-lobular emphysema early in adulthood. Based on own studies and a review of the literature the article dates up the knowledge about risk factors (especially smoking), the variable clinical pattern (relationship to bronchial hyperreactivity) and pulmonary function (30% pulmonary hyperinflation) of children and adolescents with homozygous alpha 1-antitrypsin deficiency (PIZZ). It discusses diagnostic (selective screening, regular lung function tests) and therapeutic possibilities (substitution) as well as preventive aspects (passive and active smoking cessation).

Adolescent↗
PubMed1993

[Behavior of neonates with hyperbilirubinemia treated with blue light].

Two groups of fullterm newborns were polygraphically examined. The first group consisted of 10 newborns with hyperbilirubinemia treated by phototherapy, the second group was a control one and consisted also of 10 newborns. The polygrams were made at the age of four days. The length of the sleep cycle, the length of quiet and paradoxical sleep, respiratory rate during both sleep states, the frequency of rapid eye movements during paradoxical sleep, the frequency of EMG discharges during paradoxical sleep, the number of sleep apneas during paradoxical sleep and the incidence of body movements during the whole recording time (100 minutes) were assessed. There were no significant differences in majority of parameters, only the length of paradoxical sleep and the number of sleep apneas were significantly higher in infants with hyperbilirubinemia. Infants with higher levels of bilirubin had longer sleep cycle, longer paradoxical sleep and lower incidence of body movements. Large individual differences in all parameters studied were observed, especially in infants with hyperbilirubinemia. This indicates that special observational care should be given to these infants.

Humans↗
PubMed1992

A phase I dose escalation trial of yttrium-90 microspheres in the treatment of primary hepatocellular carcinoma.

METHODS: Ten patients with primary hepatocellular carcinoma were treated with intraarterial instillation of yttrium-90 (Y-90) microspheres, including eight men and two women (median age, 52 years; range, 29-69 years). Four patients were treated at a targeted hepatic dose of 50 Gy, two at 75 Gy, and four at 100 Gy. RESULTS: In 8 of the 10 patients, there was a significant concentration of Y-90 in localized tumor masses with tumor-to-liver perfusion ratios from 1.0:1-10.0:1. No patient had a complete or partial response, but 10 patients had stable disease (median duration, 10 weeks; range, 5-64 weeks). The median survival was 18 weeks (range, 2-150 weeks), and three patients lived longer than 1 year. Significant bone marrow or hepatic toxicity was not seen. One patient had a radiation-induced duodenal ulcer that required surgical management. CONCLUSIONS: Intraarterial instillation of Y-90 microspheres appears to be safe and deserves additional evaluation to determine whether there is meaningful activity in patients with primary hepatocellular carcinoma.

Adult↗
PubMed1992

Validity and reliability of the Neurobehavioral Assessment Scale.

The Neurobehavioral Assessment Scale (NAS) was developed to measure the full range of behavioral functioning from fully alert to deep coma. This investigator-rated scale was evaluated in 60 patients undergoing conscious sedation for maxillofacial procedures. The results obtained on the NAS were reliable, as evidenced by high correlations between the rating of the two raters. The scale is also valid as determined by high correlations between the NAS and a standard scale, the Glasgow Coma Scale (criterion validity) and between the NAS and the Digit Symbol Substitution Test (behavioral validity). The NAS clearly distinguished between two levels of sedation (heavy and light). Furthermore, the NAS appears to be better able to discriminate among the different degrees of sedation in lightly sedated patients than the Glasgow Coma Scale.

Adolescent↗
PubMed1992

Ifosfamide, cisplatin, and etoposide (ICE) in the treatment of advanced non-small cell lung cancer.

Forty-seven previously untreated patients with histologically or cytologically proven non-small cell lung cancer were treated with ICE (ifosfamide/cisplatin/etoposide). Patients received ifosfamide 4 g/m2 with mesna uroprotection on day 1, and cisplatin 25 mg/m2/d and etoposide 100 mg/m2/d on days 1, 2, and 3; courses were repeated every 28 days. Premedication with prochlorperazine, dexamethasone, and high-dose metoclopramide was given to prevent nausea; lorazepam was added on days 2 and 3 only. Thirty-four men and 13 women (median age, 60 years) received a total of 146 treatment cycles. One patient had stage IIIA disease, seven had IIIB disease, and 39 had hematogenous metastases. Forty-six patients were evaluable for response and toxicity. One patient suffered a myocardial infarction on day 7 that was judged unrelated to treatment. Two patients suffered early death from toxicity and have been classified as nonresponders. Three patients achieved complete response (median, 42+ weeks) and 14 patients achieved partial response (median, 29+ weeks; range, 10 to 82+), for an overall response rate of 37% (95% confidence limits, 23% to 51%). The median survival of the entire group is 26 weeks (1 to 82+). The median nadir granulocyte count was 0.275 x 10(9)/L (range, 0 to 2.3 x 10(9)/L), and there were 14 episodes (in 11 patients) or neutropenia-associated fever, one of which resulted in death. Seven of these patients had not had the required protocol dose reduction for nadir neutrophil count in the preceding cycle. The median nadir platelet count was 120 x 10(9)/L (range, 13 to 385 x 10(9)/L), and three patients required platelet transfusions. Eleven patients had RBC transfusions. Only ten patients had grade 2 gastrointestinal toxicity. Five patients had microscopic hematuria, and one patient had central nervous system toxicity.

Adult↗
PubMed1992

Comparative efficacy of fluoroquinolones, aminoglycosides, ureidopenicillins & newer cephalosporins against Pseudomonas species.

A total of 74 strains of Pseudomonas aeruginosa and 18 strains of Ps. putrefaciens were tested for sensitivity to 14 different antimicrobial agents. Ps. aeruginosa were mostly sensitive to netilmicin (81%), piperacillin (78%), amikacin (73%), azlocillin (70%), ceftazidime (69%) and pefloxacin (65%). Only 66 per cent strains of Ps. putrefaciens were sensitive to netilmicin, ceftazidime and ceftriaxone. The MIC values of the different drugs for the sensitive strains were comparable with the results of susceptibility testing. The Ps. putrefaciens strains showed greater resistance than Ps. aeruginosa.

4-Quinolones↗
PubMed1991

Mutations in the small subunit of ribulosebisphosphate carboxylase affect subunit binding and catalysis.

Fully functional Synechococcus PCC 6301 ribulose 1,5-bisphosphate carboxylase-oxygenase (kcat = 11.8 s-1) was assembled in vitro following separate expression of the large- and small-subunit genes in different Escherichia coli cultures. The small subunits were expressed predominantly as monomers, in contrast to the large subunits which have been shown to be largely octameric when expressed separately [Andrews, T. J. (1988) J. Biol. Chem. 263, 12213-12219]. This separate expression system was applied to the study of mutations in the amino-terminal arm of the small subunit, which is one of the major sites of contact with the large subunit in the assembled hexadecamer. It enabled the effects of a mutation on the tightness of binding of the small subunit to the large-subunit octamer to be distinguished from the effects of the same mutation on catalysis carried out by the assembled complex when fully saturated with mutant small subunits. This important distinction cannot be made when both subunits are expressed together in the same cell. Substitutions of conserved amino acid residues at positions 14 (Ala, Val, Gly, or Asp instead of Thr) and 17 (Cys instead of Tyr), which make important contacts with conserved large-subunit residues, were introduced by site-directed mutagenesis. All mutant small subunits were able to bind to large subunits and form active enzymes. A potential intersubunit hydrogen bond involving the Thr-14 hydroxyl group is shown to be unimportant. However, the binding of Gly-14, Asp-14, and Cys-17 mutant small subunits was weaker, and the resultant mutant enzymes had reduced catalytic rates compared to the wild type.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗
PubMed1991

Alteration of the lung parenchyma associated with autoimmune hepatitis.

The clinical history, radiological and histomorphological alterations of the lung parenchyma associated with chronic active autoimmune hepatitis are described. A 6-month-old female infant developed chronic active autoimmune hepatitis associated with autoimmune haemolytic anaemia. She was treated with immunosuppressive drugs, including steroids, for more than 6 years and developed symptoms and radiological signs of interstitial pneumonitis 4 years after onset of the autoimmune hepatitis. Associated bronchiectasis was detected 1 year later. No abnormalities of lung defence mechanisms could be demonstrated. Resection of the sixth left segment and of the basal parts of the left lower lobe revealed honeycombing with changes in the lung parenchyma which included chronic interstitial pneumonitis with multinucleate giant cells, seen predominantly in the distal airways, marked diffuse interstitial mononuclear infiltrates and mild diffuse interstitial fibrosis as well as bronchiectasis and organizing pneumonia. Granulomatous lesions, angiitis and necrotic areas were absent. Immunohistochemistry for immunoglobulins was negative for IgA, IgG and IgM and positive for IgD in the multinucleate giant cells. A strong positive reaction to HLA-DR-specific monoclonal antibody was noted, whereas no specific sugar receptors (endogenous lectins) could be detected by use of biotinylated glyconeoproteins.

Autoimmune Diseases↗
PubMed1991

Pulmonary function in children with chronic renal failure.

Lung volumes were measured in 45 children with chronic renal failure and compared to 10 healthy controls. Six patients were receiving conservative treatment (CT), 11 were undergoing regular haemodialysis (HD), 8 were on continuous ambulatory peritoneal dialysis (CAPD) and 20 were post transplantation (TP). We measured vital capacity (VC) and forced expiratory volume in 1 s (FEV-1) with a bell spirometer. In addition residual volume (RV) was determined in CAPD patients. VC and FEV-1 values below the lower limit of predicted normal values from healthy children with the same body height were found in 38% and 52% of all patients respectively (P less than 0.05). Median values of VC and FEV-1 were lowest in CT and highest in TP patients. Median FEV-1 was significantly reduced to 79% of predicted values in CT and to 82% in HD patients (P less than 0.05). No correlation was found between FEV-1 and haemoglobin levels or the concomitant use of beta-blocking agents. During a HD session mean FEV-1 increased significantly. In CAPD patients the routine filling of the abdomen was followed by an 11% decrease of RV (non significant) while the other parameters remained stable. It is concluded that lung volumes are frequently reduced in chronic renal failure but remain essentially stable during the dialysis procedures.

Adolescent↗
PubMed1991

Pulmonary alveolar lipoproteinosis in a seven-year-old girl. A follow-up over six years.

Alveolar lipoproteinosis is a rare disease in childhood, and its outcome is considered unfavourable compared to adults. We report on the spontaneous improvement of the disease over a six-year period in a child now 13 years of age. At the time of diagnosis the vital capacity was reduced to 65% of the mean predicted for her height, but deteriorated to 40% during the following year. A bronchoalveolar lavage was performed with small amounts of fluid but it did not immediately reverse the pulmonary alterations. Contrary to expectation, in the following years there was a continuous and gradual increase of the vital capacity to 70% of the mean predicted without specific therapy. This observation underlines the importance of an individual approach to prognosis in this disease and contributes to discussion of therapeutic procedures in the paediatric age group.

Bronchoalveolar Lavage Fluid↗
PubMed1991

[Fibrosing alveolitis in a 7-year-old girl with autoimmune hemolytic anemia and autoimmune hepatitis].

A Coombs-positive haemolytic anaemia with proof of heat autoagglutinins and autoantibodies against cell nuclei was diagnosed in a girl, now 7 1/2 years of age, in the sixth month of her life as a sequel to jaundice. Shortly afterwards liver biopsy yielded a confirmed diagnosis of giant cell hepatitis. The signs of the disease receded under treatment with decortin and imurek. An attempt to discontinue the medication at 5 1/2 years of age resulted in a histologically confirmed recurrence of autoimmune hepatitis. When the patient was 5 years old, the x-ray revealed a mainly interstitial pneumonia; at 6 years of age, bronchiectases in the region of the left lower lobe were confirmed by bronchography. Resection of the lower lobe was performed after occurrence of atelectasis. Histopathological findings confirmed fibrotic alveolitis associated with giant cells. Based on the overall clinical course and the histological and immunological findings, autoimmune etiology of fibrotic alveolitis must be discussed. Progression of the disease could be avoided during the past 6 months by intensifying the immunosuppressive prednisolone therapy.

Anemia, Hemolytic, Autoimmune↗