Graft-vs-host disease in the central nervous system.
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Biomedical subjects
Publications and source records attributed to E Hawkins.
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OBJECTIVE: To determine whether coagulation test results for blood samples obtained from heparinized jugular vein catheters in dogs are accurate. DESIGN: Prospective, controlled study. ANIMALS: Fourteen clinically normal dogs. PROCEDURE: Prothrombin time, activated partial thromboplastin time, concentration of fibrin degradation products, and fibrinogen concentration were measured in blood samples obtained by means of direct jugular venipuncture and through an indwelling jugular vein catheter 0, 2, 8, 24, and 48 hours after catheter placement. Blood samples were collected from the catheter by means of a 2-syringe technique, which involved discarding the first volume of blood collected. RESULTS: For all sample times, mean values for samples obtained from the jugular vein catheter were not significantly different from mean values for samples obtained by means of venipuncture. CLINICAL IMPLICATIONS: Blood samples for coagulation tests may be obtained from jugular vein catheters up to 48 hours after catheter placement in clinically normal dogs.
Autosomal recessive Alport syndrome can arise from a mutation in either of the genes COL4A3 and COL4A4 on chromosome 2, which encode, respectively, the alpha 3 and alpha 4 chains of Type IV collagen. This report describes a mutation in COL4A3 in a girl who presented at age 5 with hematuria and proteinuria, lacking any family history of renal disease. Renal biopsy at age 8 showed immunoglobulin A nephropathy and Alport syndrome. Sensorineural deafness developed during adolescence, and the patient's renal disease progressed to terminal renal failure by age 20. She received a living related donor renal allograft at age 20 and developed antiglomerular basement membrane nephritis of the allograft 8 months after transplantation. Amplification and sequencing of exon 5 of COL4A3 (counting from the 3' end of the gene) revealed a 7-base-pair deletion, producing a shift of the reading frame and the creation of a premature stop codon. Each parent was heterozygous for the normal and mutant exon 5 sequences. This mutation in COL4A3 would result in the loss of 222 amino acids from the carboxy-terminal noncollagenous domain of the alpha 3(IV) chain. The mutant chain would be unable to form trimers with other Type IV collagen alpha chains. In addition, the mutant chain would lack the Goodpasture epitope, which resides in the carboxy-terminal noncollagenous domain of the alpha 3(IV) chain. The absence of this epitope may underly the subsequent development of anti-glomerular basement membrane nephritis in the allograft.
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A questionnaire was circulated in 1990 by the Practice Committee of the Society for Pediatric Pathology to its membership to assess the involvement of pediatric pathology departments (PPDs) in quality improvement (QI) activities. Twenty-nine PPDs responded. Analysis of responses disclosed a wide variation in plans, although the majority (22 of 29) had developed or were in the process of developing (three of 29) a specific plan. The plans varied in sophistication and complexity. Pediatric pathologists (directors or designates) were heavily involved in assuming leadership roles for the QI activities in 25 of 28 PPDs. The PPDs with plans (25) had identified the QI indicators monitored either sporadically or on an ongoing basis. The respondents had several indicators in common, such as volume, technical, and clinical indicators, as well as indicators related to turnaround times, meetings, and internal and external consultations. The plurality of the monitors reported are related to indicators in the discipline of anatomic pathology. This review is therefore limited to QI issues in anatomic pediatric pathology. In conclusion, this survey functions to shed some light on the extent of involvement of PPDs in the management of QI. In addition, it provides a model for starting or improving the existing QI plans for PPDs.
PURPOSE: Six children who had mature or immature sacrococcygeal teratomas diagnosed in the newborn period have since been registered on a Pediatric Oncology Group/Children's Cancer Group germ cell study with recurrent malignant neoplasia [pure yolk sac tumor (YST) or teratoma with yolk sac elements]. RESULTS: Four of the children have responded to therapy, one has died, and one has been lost to follow-up. Review of the slides from five of the original tumors identified microscopic foci of YST in four. CONCLUSIONS: Detection of such foci in neonatal tumors is important because serum alpha-fetoprotein concentrations may not be helpful since they may normally be high in the newborn period due to fetal production.
Although it has been suggested that cytomegalovirus (CMV) infection of the kidney might facilitate the development of human immunodeficiency virus-associated nephropathy (HIVAN) or other morphologic renal changes in patients with AIDS, no systematic study has been performed on kidneys from AIDS patients. We examined 75 autopsy kidneys, two renal biopsy specimens, and a nephrectomy specimen from 78 HIV-infected patients (five with HIVAN) for the presence of CMV. Immunocytochemistry (ICC) utilizing a monoclonal antibody against the late antigen of CMV and in situ hybridization (ISH) with a biotinylated DNA probe for CMV sequences were used. The detection system for both ICC and ISH was streptavidin-conjugated alkaline phosphatase with Fast Red TR chromogen. CMV was detected in only 10 of the 78 kidneys examined (12.8%): eight by both methods, one by ISH only, and another by ICC only. All 10 positive kidneys were obtained from autopsies of patients with AIDS. The average number of positive cells (in approximately 15 x 10 mm sections) was 22 with ICC and 10 with ISH. Glomerular intracapillary cells (possibly endothelial cells) were the most commonly stained, followed by positive cells in the interstitium and peritubular capillaries. Relatively few tubular epithelial cells were stained. The majority of positive cells by either ICC or ISH did not show nuclear or cytoplasmic inclusions; however, only two of the 10 positive kidneys did not contain cells with typical Cowdry type-A intranuclear CMV inclusions. The most frequent pathologic finding in the kidneys positive for CMV by either ICC or ISH was acute tubular necrosis (in six of 10, 60%).(ABSTRACT TRUNCATED AT 250 WORDS)
Our pilot study for neuroblastoma screening started in 1986. The study has progressed through several phases, with use of several analytical methods to a procedure based primarily on the use of automated gas chromatography mass spectrometry. The northern region of England has a relatively static population of approximately 3.5 million, with an annual birth rate of 41,000. The region consists of 16 administrative health districts. In 4 years, we have screened 20,829 infants from four health districts. In this program, we screen all children at 6 months of age. A urine sample is collected on filter paper by a health visitor, either at the time of the infant's routine clinic visit or during the health visitor's follow-up visit at home. In the laboratory, the sample is dried and processed for analysis of homovanillic acid (HVA) and vanillylmandelic acid (VMA), using a benchtop Hewlett Packard gas chromatograph mass spectrometer. The results are related to the creatinine content of the urine. Using cut-off limits of 39 micrograms/mg of creatinine for HVA and 25 micrograms/mg of creatinine for VMA, 2,537 infants (12.2%) required a second paper sample and 527 infants (2.5%) were observed with a liquid urine collection. Of these, the conditions of nine infants with elevated levels of HVA or VMA were investigated clinically for the possible presence of neuroblastoma. Two infants were found to have neuroblastoma; the other seven showed no evidence of tumor. In addition, there were three children who, when screened at 6 months of age, had normal levels of HVA and VMA but in whom neuroblastoma subsequently developed.
A 3-week-old girl who was born with club feet had signs of failure to thrive. On physical examination the child appeared normal; she had no abnormalities in the mucous membranes of the mouth, the eyelids, or in the neck, and her other systems, including heart, chest, abdomen, and neurologic systems, were clinically normal. Radiologically, the gastrointestinal tract was normal, but rectal biopsy showed neuromas. Her serum calcitonin level was measured both at basal and after pentagastrin stimulation at 5 weeks of age and found to be high, but whether it was consistent with the normal level at this early age or was caused by medullary thyroid carcinoma was not clear. At 3 months, the corneal nerves of both eyes were examined and showed considerable thickening, and multiple endocrine syndrome type IIb was suspected. The serum calcitonin level at 8 and 14 months was increased. A total thyroidectomy was done, and C-cell nodular hyperplasia and adenomatosis was found in the isthmus. The postoperative serum calcitonin level decreased to low normal and did not increase after pentagastrin stimulation. To the authors' knowledge, this case represents the youngest patient diagnosed with multiple endocrine syndrome type IIb in the absence of family history of the disease.
We report a 6-month-old male child with severe combined immunodeficiency who received an unirradiated blood transfusion and developed acute, severe graft-versus-host disease (GVHD), for which he received monoclonal anti-T cell (anti-T12) antibody treatment. The GVHD was manifested by a confluent maculopapular rash and increased liver function tests and was documented by skin biopsy. Separation of peripheral blood mononuclear cells forming rosettes with sheep red blood cells revealed engrafted T cells having the nonrelated HLA type of the blood donor. The patient was treated with intravenous monoclonal anti-T12 in a dose of 0.3 mg/kg/day for 5 days. An in vivo effect of the anti-T12 was suggested by clinical improvement of his skin rash and return of the liver transaminases to the normal range. Moreover, human complement components, activated C3 and C4, were detected by fluorescence microscopy on the surfaces of the engrafted CD8+ lymphocytes on the skin biopsy specimens. Also, with a biotin-avadin assay, the presence of the anti-T12 was detected on these same cells. These studies document not only the in vivo targeting of monoclonal anti-T12 antibody to cytotoxic T cells producing GVHD but also the activation of complement on these cells.
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A 16-year-old girl had abdominal pain, hematemesis, and fever. Radiographic evaluation showed her to have an infarcted spleen and jejunum. Pathologic description revealed thrombi involving the vessels of both organs. A hypercoagulation evaluation of the patient and her family resulted in the diagnosis of hereditary protein C activity deficiency. She is unusual both in the diagnosis of protein C activity deficiency and in her appearance with mesenteric and splenic venous thrombosis. This appearance has not been previously reported in the literature and should be considered in the differential diagnosis of any thrombotic event, even in the face of a negative family history.
Autopsy specimens from a patient with infection-associated hemophagocytic syndrome (IAHS) were evaluated for the presence of Epstein-Barr virus DNA and RNA using in situ hybridization. Frozen sections of liver, lymph node, and spleen were probed with EBV Bam HI-H & W, gamma interferon, and SP-65 plasmid DNA as a negative control probe. Hybridization patterns before and after treatment with ribonuclease A were examined. Both EBV probes produced diffuse hybridization throughout the tissues; in addition, there were some foci of extremely heavy concentrations of silver granules. A gamma interferon probe showed evidence of hybridization, but the overall intensity was not as great as with EBV probes. Pretreatment with ribonuclease A dramatically decreased hybridization in all tissues to EBV probes, but hybridization with SP-65 was unaffected. The elimination of EBV hybridization with ribonuclease A pretreatment provides the first evidence of EBV gene expression in an IAHS patient.
The ability to use enhanced chemiluminescence (ECL) to detect horseradish peroxidase as a label for tissue antigens and cellular viral DNA was demonstrated. A liquid nitrogen-cooled charged-coupled device (CCD) was used to detect light output, which was visualized on a monitor or was quantitated using an attached microcomputer. In a tissue antigen model, equivalent sensitivity was observed between ECL and colorimetric detection.
Esmolol, administered as a bolus followed by continuous infusion, was used to treat the occurrence of transient tachycardia and hypertension or tachycardia alone before cardiopulmonary bypass in 45 patients. The study was conducted in two phases. Phase I (15 patients) was a dose-finding study and phase II (30 patients) was a randomized, double-blind, placebo-controlled efficacy study. All patients received the last dose of their usual beta-adrenergic blocker the night before the operation and were anesthetized with midazolam, vecuronium, and enflurane in oxygen. Treatment criteria were either a systolic blood pressure greater than 140 mm Hg and a heart rate greater than 70 or a heart rate greater than 80 beats/min. In phase I, graduated doses of esmolol were given to successive patients. A dose of 80 mg followed by a 12 mg/min infusion was declared effective. Phase II patients were randomized to receive esmolol (n = 16) or placebo (n = 14). Hemodynamic data were collected at baseline and 1, 3, 5, and 10 minutes after the administration of esmolol. Plasma norepinephrine was measured at baseline, 1, and 10 minutes. Esmolol significantly (p less than 0.05) reduced heart rate at 1, 3, 5, and 10 minutes but did not change blood pressure, pulmonary artery diastolic pressure, right atrial pressure, cardiac output, or systemic vascular resistance. Our results show that a bolus loading dose of esmolol is safe and effective in the treatment of tachycardia in patients with ischemic heart disease and that esmolol rapidly blocks the beta-adrenergic effects of norepinephrine associated with surgical stress.
A technique based on surface plasmon resonance is described which can be used to detect changes of refractive index that occur when one partner of a molecular binding pair diffuses from solution to bind the other partner which is immobilised on a silver surface. Results for the molecular binding pairs; protein-antibody, hapten-antibody and DNA-DNA are described. Instrumentation necessary for implementation of the technique is detailed. Immunoassay of proteins and haptens is possible in less than one minute with a sensitivity of 10(-9) mol/l. Hybridisation of 10 fmoles of a 97 base target sequence on the 1 mm2 area of detection to an immobilised oligonucleotide probe can be detected in less than five minutes. Advantages of the technique include the ability to record the kinetics of binding reactions in "real time" and the lack of labels in this simple assay format. Methods of improving the sensitivity are discussed.
Of 493 isolates of Streptococcus pneumoniae, 14 were found to have decreased penicillin susceptibility as determined by the oxacillin disk test. Of these 14 isolates, 4 were relatively resistant by quantitative susceptibility studies and 1 was penicillin resistant (MIC, 2 micrograms/ml). This is the first confirmed penicillin-resistant isolate in the Houston, Tex., area.