The effect of tiletamine and zolazepam on isoflurane minimum alveolar concentration in goats.
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Administration, Inhalation↗
Biomedical subjects
H Schultz
Publications and source records attributed to H Schultz.
Primary thyroid lymphoma: a retrospective analysis of prognostic factors and treatment outcome for localized intermediate and high grade lymphoma.
Non-Hodgkin's lymphoma presenting in the thyroid gland is uncommon. A review of the King Faisal Specialist Hospital and Research Centre (KFSH & RC) experience was performed to assess treatment outcome and prognostic factors in this rare extranodal presentation of localized lymphoma. Sixty patients treated at KFSH & RC between 1975 and 1995 were identified, and their records were reviewed retrospectively. Eight patients who had stage III or IV disease, low grade, or did not complete their prescribed treatment were excluded from the study. There were 38 female and 14 male patients with a median age of 59.5 years at the time of diagnosis (range: 10-87 years). Thirty-five of the 52 patients underwent diagnostic partial or total thyroidectomy at other institutions based on a preoperative assumption of thyroid carcinoma. All 52 patients had non-Hodgkin's lymphoma of intermediate (94%) or high (6%) grade. Detailed staging was carried out in all patients; 16 patients (31%) had disease confined to the thyroid gland (stage IE), whereas 36 (69%) had associated disease in cervical lymph nodes and/or the mediastinum (stage IIE) disease. All patients were treated with curative intent. A total of 18 patients (35%) were treated with a single-modality treatment--radiotherapy alone in 2, chemotherapy alone in 13, and surgery alone in the remaining 3 patients. The majority of patients (34/52; 65%) were treated with a combined-modality approach. The overall relapse-free survival (RFS) and overall survival (OS) at 5 years were 72% and 88%, respectively. There were no significant differences in outcome between those treated with single-modality and those with combined-modality therapy. A univariate analysis showed that the presence of mediastinal lymph node involvement was the most important prognostic factor affecting both RFS and OS. Patients with Hashimoto thyroiditis and without "B" symptoms were found to have a significantly higher RFS without influence on the OS. However, patients who had a good performance status (PS) of 0, 1, and 2 were found to have a significantly higher overall survival in comparison to those with poor performance status. Age, sex, stage, histology, lactic acid dehydrogenase level, tumor bulk, and the treatment modality were not found to correlate with RFS or OS. Mediastinal involvement and PS were found to be the most important independent prognostic factors influencing RFS and OS.
Female↗
The endotoxin-binding bactericidal/permeability-increasing protein (BPI): a target antigen of autoantibodies.
The bactericidal/permeability-increasing protein (BPI) is an endotoxin-binding neutrophil leukocyte-granule protein with antibacterial and anti-endotoxin properties. A recombinant form of BPI (rBPI21) has been developed and is being tested as a therapeutic agent to treat gram-negative bacterial infections and exposure to gram-negative bacterial endotoxin. BPI is also a target antigen of anti-neutrophil cytoplasmic autoantibodies (ANCA). BPI-ANCA are present in cystic fibrosis, inflammatory bowel disease, vasculitis, and primary sclerosing cholangitis; presence of BPI-ANCA appears associated with a higher inflammatory disease activity and greater organ damage. BPI-ANCA as well as ANCA directed at other neutrophil-granule proteins may exacerbate inflammation by nonspecific effects of extracellular and cell-associated immune complexes. BPI-ANCA may further worsen inflammation by reducing the ability of BPI to promote clearance of gram-negative bacteria and bacterial-associated endotoxin.
Adult↗
Prognostic factors for medulloblastoma.
PURPOSE: To evaluate prognostic factors for medulloblastoma. METHODS AND MATERIALS: One hundred and seventy-three consecutive patients with medulloblastoma, treated at King Faisal Specialist Hospital (KFSH) from 1988-1997, were reviewed. Eighty-four percent were children less than 15 years old. From 1988-1994, treatment was at the discretion of the investigator. From 1994-1998, patients entered a single-arm best practice protocol in which, in staged patients, the surgical intent was total resection, standard radiation treatment was defined, and adjuvant chemotherapy was given to a "high-risk" subset. RESULTS: For 150 patients who completed surgical and radiation treatment, the 5-year survival rate was 58%, compared with 0% for 16 patients who were unable to start or complete radiation treatment. For staged patients, the 5-year survival was M0 + M1, 78% and M2 + M3, 21% (p < 0.0001). Other favorable significant prognostic factors were age >14 years and gross cystic/necrotic features in the primary tumor. The size of the primary tumor, the degree of hydrocephalus at diagnosis, the presence of residual tumor in the post-operative CT/MRI, and the functional status of the patient prior to radiation treatment were not significant factors. CONCLUSIONS: Stage M0 + M1 was the most powerful favorable prognostic factor. In Saudi Arabia more patients present with advanced disseminated disease, 41% M2 + M3, than in the West, and this impacts adversely on overall survival. Total resection and standard radiation treatment were not sensitive prognostic factors in a treatment environment in which 78% of patients underwent at least 90% tumor resection and 60% received standard radiation treatment. In order to improve the proportion of patients able to complete radiation treatment, consideration should be given to limiting resection when the attainment of total resection is likely to be morbid, and to delaying rather than omitting radiation treatment in the patient severely compromised postoperatively.
Adolescent↗
Anti-neutrophil cytoplasmic antibodies directed against the bactericidal/permeability-increasing protein (BPI) in pediatric cystic fibrosis patients do not recognize N-terminal regions important for the anti-microbial and lipopolysaccharide-binding activity of BPI.
This study was performed to examine the prevalence and clinical correlates of bactericidal/permeability-increasing protein anti-neutrophil cytoplasmic antibodies (BPI-ANCA) in pediatric cystic fibrosis (CF) patients and to elucidate their possible role in CF pulmonary pathology. Sera of 27 CF patients were tested for ANCA by indirect immunofluorescence (IFT) and by enzyme-linked immunosorbent assay (ELISA) for ANCA sub-specificities. BPI-ANCA were examined by using standard ELISA for BPI, lipopolysaccharide-binding protein (LBP), and BPI/LBP fusion proteins to epitope map the main binding sites and look for cross-reactivity with LBP. Pulmonary function and serum concentrations of total immunoglobulin G (IgG) were measured and infections were diagnosed. In addition, release of reactive oxygen species (ROS) by neutrophil granulocytes was measured after stimulation with monoclonal BPI-ANCA. Using IFT, two patients showed atypical ANCA staining, six patients exhibited perinuclear ANCA staining, and no cytoplasmic ANCA staining was detected. Of 27 patients, 13 (48%) were BPI-ANCA (IgG) positive, and three were also immunoglobulin A (IgA) BPI-ANCA positive; one patient had ANCA against lactoferrin; and no proteinase 3 ANCA was detected in any of the patients. All BPI-ANCA bound to the C-terminal region of the molecule; none bound to the N-terminus or to LBP. There was no significant correlation between clinical data and the occurrence of BPI-ANCA in this cross-sectional study. Release of ROS from granulocytes was induced by monoclonal BPI-ANCA. Activation of neutrophils and possible modulation of BPI-mediated opsonophagocytosis and disposal of Gram-negative bacteria and lipopolysaccharides by BPI-ANCA raise the possibility that they contribute to pulmonary pathology in pediatric CF patients but intervention longitudinal studies in large groups of patients are needed to establish a causative association.
Adolescent↗
Comparative study of disomy and diploidy rates in spermatozoa of fertile and infertile men: a donor-adapted protocol for multi-colour fluorescence in situ hybridization (FISH).
Spermatozoa from seven healthy donors (two of whom had already fathered children) and five infertile patients taking part in the local programme of intracytoplasmic sperm-injection (ICSI) were investigated for the disomy rates of chromosomes 13/21, 18, X and Y as well as for the diploidy rates. Two- and three-colour fluorescence in situ hybridization (FISH) was applied after a donor-adapted decondensation pre-treatment: in a preliminary decondensation series the optimum fluorescence signals were individually determined by variation of the concentration of the decondensation reagents and the duration of incubation with these reagents. Strict scoring criteria were applied. The average disomy rates ranged from 0.10% (chromosomes 13/21) to 0.44% (disomy XY) in the infertile donors and from 0.07% (disomy XX) to 0.36% (disomy XY) in the controls. The average diploidy rates were 0.22% and 0.20% for the infertile donors and the controls respectively. There was no statistically significant difference between the two groups with respect to the disomy and diploidy rates. Within the two groups there were inter-individual differences which were partly statistically significant, indicating considerable inter-donor variation of the aneuploidy rates.
Aneuploidy↗
BPI-ANCA is found in reactive arthritis caused by Yersinia and Salmonella infection and recognise exclusively the C-terminal part of the BPI molecule.
OBJECTIVE: To examine the prevalence, binding sites and functional interactions of antineutrophil cytoplasmic autoantibodies (ANCA) against the bactericidal/permeability increasing protein (BPI) in reactive arthritis (ReA). METHODS: Sera were analysed for the occurrence of ANCA by indirect immunofluorescence microscopy (IIF) and ELISA. Binding sites were determined using BPI, lipopolysaccharid binding protein (LBP), and fusion proteins of both proteins in ELISA. In addition, the effect of antibodies on the antibiotic activity of BPI was examined. RESULTS: BPI-ANCA was found in patients with Yersinia- and Salmonella-triggered ReA and directed against the C-terminal portion of BPI. Goat anti BPI antibodies recognising this part inhibited the antibiotic activity of BPI in vitro. CONCLUSION: BPI-ANCA was associated with ReA triggered by Salmonella and Yersinia infection. Directed against the C-terminal part of BPI, it can potentially inhibit its antibiotic activity and might be useful to identify patients with infectious bowel disease prone to extraintestinal sequelae.
Acute-Phase Proteins↗
Oligoarthritis mediated by tumor-specific T lymphocytes in renal-cell carcinoma.
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Arthritis↗
Radiological case of the month. Intrauterine stab wound to the head of a 29-week fetus.
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Adult↗
Evaluation of pannus and vascularization of the metacarpophalangeal and proximal interphalangeal joints in rheumatoid arthritis by high-resolution ultrasound (multidimensional linear array).
OBJECTIVE: To evaluate the extent of intraarticular vascularization and pannus formation in metacarpophalangeal (MCP) and proximal interphalangeal (PIP) joints of patients with rheumatoid arthritis (RA) by high-resolution ultrasound (US). METHODS: A newly developed, high-resolution multidimensional linear array US was utilized to obtain longitudinal and transverse scans of joints with active RA (n = 21), moderately active RA (n = 39), or inactive RA (n = 93), and of joints from healthy controls (n = 120). RESULTS: Healthy joints had no detectable pannus, whereas pannus could be detected in 52% of the joints with active RA, 82% of the joints with moderately active RA, and 67% of the joints with inactive RA. There was a significant difference in vascularization in the joints of all subgroups of RA patients and those of healthy subjects (P < 0.001). Moreover, vascularization differed significantly among the RA subgroups: inactive versus moderately active RA (P < 0.02) and inactive versus active RA (P < 0.05). Both pannus and vascularization appeared to be localized preferentially on the radial side of the joints. CONCLUSION: Evaluation of pannus and the extent of vascularization within the joints of patients with RA by high-resolution US might be helpful in the assessment of disease activity, and thus influence therapeutic strategies.
Adult↗
Stevens-Johnson syndrome in patients on phenytoin and cranial radiotherapy.
The use of phenytoin as a prophylactic anticonvulsant after brain surgery, particularly for brain tumors, is a common practice, regardless of whether the patient has a previous history of convulsions. This treatment policy assumes that the benefits exceed the risks. Four cases are described of adverse reactions to phenytoin during the concomitant use of cranial radiotherapy. In one patient this proved fatal. There is increasing anecdotal support in the literature for a synergistic effect between phenytoin therapy and cranial radiotherapy that can result in the life-threatening Stevens-Johnson syndrome. While the association is uncommon, four cases within 24 months in one department suggest that the routine use of postoperative phenytoin as a prophylactic anticonvulsant in the absence of a history of seizures may not be warranted, particularly if the patient is to receive cranial radiotherapy.
Adult↗
Low-grade astrocytoma--a retrospective analysis of 102 patients.
One hundred and two patients (57 males, 45 females, median age 17 years) with histologically proven low-grade astrocytoma (grades I, II) treated between 1978 and 1994 were retrospectively analyzed at the King Faisal Specialist Hospital & Research Center. Microscopic investigation showed 50 patients (48%) with grade I tumors as opposed to 52 patients (52%) with grade II tumors. Fifteen patients (15%) had complete surgical excision, 55 (52%) had partial excision and 32 (31%) had biopsy only; 68 patients (66%) received external radiotherapy with a median dose of 54 Gy (range 45-68.5 Gy). With a median follow-up of 3.3 years, the 5 and 10 years, overall actuarial survival rates were 78% and 62%, respectively while the progression-free survival rates at 5 and 10 years were 69%, and 35%, respectively. Age and performance status were significant prognostic factors in terms of overall survival on univariate (p = 0.05 and 0.05, respectively) and multivariate analysis (p = 0.005 and 0.006, respectively).
Adolescent↗
[In Process Citation]
OBJECTIVE: The objective of this retrospective analysis was to compare the obstetrical procedures at premature birth and delivery at term. The aim was to show the influence of gestational time on mode of delivery and neonatal state. MATERIAL AND METHODS: 339 births from breech presentation between 1988-1990 were compared with premature births and deliveries at term. RESULTS: Frequency of breech presentation totalled 4.1%. 173 deliveries (51.7%) resulted vaginally, 26 cases (7.8%) with freeing of arms and 4 cases (1.2%) as extraction. Frequency of cesarean sections totalled 48.3%. The number of premature births reached in the group of breech presentation 23.1%. Births at term resulted with 58% predominantly vaginally (abdominally in 42%). Between the 31st and 36th gestational week the number of cesarean sections rose to 67.3%, in the 31st week it even reached 78.9%. The neonatal state was described with the help of Apgar-scores and umbilical cord-pH-values. The share of newborns with optimal Apgar-values after 1 minute (8-10) was in premature births with 36.5% only about half as large as in deliveries at term (77.6%). Only 9.6% of the children showed pH-values below 7.20. Number of newborns with these pH-values totalled in premature births in the 31st week 35.3%, for terms between the 31st and 36th week 15.6%, and declined in mature births to only 6.2%. CONCLUSIONS: Estimating the neonatal state of the group of breech presentations the vaginal birth should keep an equal rank in the delivery plan of a clinic. At the appraisal of the childlike early morbidity of a delivery group the number of premature newborns is decisive.
Journal Article↗
Analysis of the role of Hsp25 phosphorylation reveals the importance of the oligomerization state of this small heat shock protein in its protective function against TNFalpha- and hydrogen peroxide-induced cell death.
The role of murine Hsp25 phosphorylation in the protection mediated by this protein against TNFalpha- or H2O2-mediated cytotoxicity was investigated in L929 cell lines expressing wild type (wt-) or nonphosphorylatable (mt-) Hsp25. We show that mt-Hsp25, in which the phosphorylation sites, serines 15 and 86, were replaced by alanines, is still efficient in decreasing intracellular reactive oxygen species levels and in raising glutathione cellular content, leading the protective activity of mt-Hsp25 against oxidative stress to be identical to that of wt-Hsp25. To independently investigate the role of Hsp25 phosphorylation, we blocked TNFalpha-induced phosphorylation of wt-Hsp25 using SB203580, a specific inhibitor of the P38 MAP kinase. This treatment did not abolish the protective activity of Hsp25 against TNFalpha. The pattern of Hsp25 oligomerization was also analyzed, showing mt-Hsp25 to constitutively display large native sizes, as does wt-Hsp25 after TNFalpha treatment in the presence of SB203580. Our results, therefore, are consistent with the possibility that the hyperaggregated form of Hsp25 is responsible for the protective activity against oxidative stress and that the phosphorylation of serines 15 and/or 86 by interfering with this structural reorganization, may lead to the inactivation of Hsp25 protective activity.
Animals↗
Bactericidal/permeability-increasing protein for severe meningococcal sepsis.
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Adult↗
In vitro and in vivo biology of recombinant adenovirus vectors with E1, E1/E2A, or E1/E4 deleted.
Isogenic, E3-deleted adenovirus vectors defective in E1, E1 and E2A, or E1 and E4 were generated in complementation cell lines expressing E1, E1 and E2A, or E1 and E4 and characterized in vitro and in vivo. In the absence of complementation, deletion of both E1 and E2A completely abolished expression of early and late viral genes, while deletion of E1 and E4 impaired expression of viral genes, although at a lower level than the E1/E2A deletion. The in vivo persistence of these three types of vectors was monitored in selected strains of mice with viral genomes devoid of transgenes to exclude any interference by immunogenic transgene-encoded products. Our studies showed no significant differences among the vectors in the short-term maintenance and long-term (4-month) persistence of viral DNA in liver and lung cells of immunocompetent and immunodeficient mice. Furthermore, all vectors induced similar antibody responses and comparable levels of adenovirus-specific cytotoxic T lymphocytes. These results suggest that in the absence of transgenes, the progressive deletion of the adenovirus genome does not extend the in vivo persistence of the transduced cells and does not reduce the antivirus immune response. In addition, our data confirm that, in the absence of transgene expression, mouse cellular immunity to viral antigens plays a minor role in the progressive elimination of the virus genome.
Adenovirus E1 Proteins↗
GFRalpha-2 and GFRalpha-3 are two new receptors for ligands of the GDNF family.
The receptor for glial cell line-derived neurotrophic factor (GDNF) consists of GFRalpha-1 and Ret. Neurturin is a GDNF-related neurotrophin whose receptor is presently unknown. Here we report that neurturin can bind to either GFRalpha-1 or GFRalpha-2, a novel receptor related to GFRalpha-1. Both GFRalpha-1 and GFRalpha-2 mediate neurturin-induced Ret phosphorylation. GDNF can also bind to either GFRalpha-1 or GFRalpha-2, and activate Ret in the presence of either binding receptor. Although both ligands interact with both receptors, cells expressing GFRalpha-1 bind GDNF more efficiently than neurturin, while cells expressing GFRalpha-2 bind neurturin preferentially. Cross-linking and Ret activation data also suggest that while there is cross-talk, GFRalpha-1 is the primary receptor for GDNF and GFRalpha-2 exhibits a preference for neurturin. We have also cloned a cDNA that apparently codes for a third member of the GFRalpha receptor family. This putative receptor, designated GFRalpha-3, is closely related in amino acid sequence and is nearly identical in the spacing of its cysteine residues to both GFRalpha-1 and GFRalpha-2. Analysis of the tissue distribution of GFRalpha-1, GFRalpha-2, GFRalpha-3, and Ret by Northern blot reveals overlapping but distinct patterns of expression. Consistent with a role in GDNF function, the GFRalphas and Ret are expressed in many of the same tissues, suggesting that GFRalphas mediate the action of GDNF family ligands in vivo.
Amino Acid Sequence↗
[Bactericidal permeability increasing protein (BPI-ANCA marked chronic inflammatory bowel diseases and hepatobiliary diseases].
BACKGROUND: Bactericidal permeability increasing protein (BPI) is an antibacterial product of neutrophilic granulocytes that can serve as target antigen for antineutrophil cytoplasmic antibodies (ANCA). The clinical associations of autoantibodies against BPI (BPI-ANCA) are essentially unclear. PATIENTS AND METHODS: 587 sera from patients with chronic inflammatory bowel diseases, inflammatory hepatobiliary diseases, primary systemic vasculitides and other rheumatological diseases were examined for BPI-ANCA by mono-specific ELISA and a standard indirect immunofluorescence test for ANCA. (ACD-CPR versus S-CPR). The treatment groups were similar with respect to age, sex, time interval from collapse to CPR, defibrillation and first epinephrine medication. There was no difference between the ACD group and the standard CPR group in terms of survival rates and neurologic outcome. No differences occurred concerning complications of CPR. CONCLUSION: In our two-tiered EMS system with physician-staffed ambulances ACD-CPR neither improved nor impaired the survival rates and the neurological prognosis in patients with out-of-hospital cardiac arrest. Our results are in accordance with other studies carried out in EMS systems, with first tier call-response intervals between 4 and 6 min. RESULTS: The prevalence of BPI-ANCA was 43% in ulcerative colitis, 23% in Crohn's disease, 35% in primary sclerosing cholangitis, 25% in primary biliary cirrhosis and 29% in autoimmune hepatitides. In a spectrum of systemic vasculitides, inflammatory joint diseases and collagen vascular diseases the prevalence was only 3 to 11%. In contrast to PR3-ANCA and MPO-ANCA, BPI-ANCA was not associated with a particular pattern of fluorescence in the immuno-fluorescence test on ethanol- and formalin-fixed neutrophils. CONCLUSION: This study shows that BPI-ANCA is the third ANCA specificity, besides PR3-ANCA and MPO-ANCA, with a limited spectrum of clinical associations. The diagnostic and prognostic relevance of BPI-ANCA in the above clinical conditions is being examined prospectively.
Antibodies, Antineutrophil Cytoplasmic↗