Biomedical subjects
S Schweitzer
Publications and source records attributed to S Schweitzer.
Colony-stimulating factors for neutropenia in glycogen storage disease Ib.
Explore the source record for details and available documents.
Granulocyte and granulocyte-macrophage colony-stimulating factors for treatment of neutropenia in glycogen storage disease type Ib.
Two children with glycogen storage disease type Ib associated with numerous recurrent bacterial infections as a result of neutropenia and neutrophil dysfunction were treated with recombinant human granulocyte colony-stimulating factor (G-CSF). One of the two patients was previously treated with recombinant human granulocyte-macrophage colony-stimulating factor (GM-CSF); therapy had to be discontinued because of severe local side effects. Both colony-stimulating factors at dosages of 3 and 8 micrograms/kg/per day, respectively, increased the average neutrophil counts from less than 300 cells/microliters to more than 1200 cells/microliters. Two subpopulations of neutrophils could be identified by their capacity to produce H2O2: one subpopulation generated H2O2 normally and a second was defective in H2O2 production. The doses of G-CSF effectively enhanced and maintained that subpopulation of neutrophils which produced normal amounts of H2O2. Moreover, these colony-stimulating factor-induced neutrophils demonstrated effective phagocytosis of zymosan particles and killing of staphylococci. Chemotaxis was decreased and could not be normalized by treatment with G-CSF. We conclude that maintenance treatment with G-CSF improved the quality of life in both patients: The number and severity of bacterial infections decreased markedly during treatment. Long-term treatment with G-CSF (12 and 10 months, respectively) was well tolerated, and no adverse clinical events were observed.
[Biotinidase deficiency. Results of neonatal screening 1985-1989 in Lower Saxony].
During a five-year-period (1985-1989) 420,000 newborns in Lower Saxony, FRG, were screened for biotinidase deficiency using biotinyl-para-amino-benzoic-acid as substrate. Three newborns with profound biotinidase deficiency (activity 1.1%, 2.1%, 2.3% of mean normal activity level) were detected. Nine newborns had partial biotinidase deficiency (activity 17-26% of mean normal activity level), thus giving an incidence of 1:140,000 with profound, and 1:46,667 with partial biotinidase deficiency, respectively. The infants with profound biotinidase deficiency are treated with biotin (2 x 5 mg/day) from the 3rd, 6th and 8th week of life and have developed normally so far. The children with partial biotinidase deficiency are not treated but followed up closely. The necessity of newborn screening for biotinidase deficiency is stressed.
Comparison of patients with complete and partial biotinidase deficiency: biochemical studies.
Seventeen partially biotinidase-deficient patients detected by neonatal screening or family studies were compared with four patients with classical biotinidase deficiency. Using a sensitive HPLC method for biotinidase in plasma (substrate: biocytin) the patients could be divided into two groups: one with residual biotinidase activity, and the second with undetectable biotinidase activity (0-activity). Biocytin excretion, characteristically elevated in 0-activity patients, decreased rapidly with increasing residual biotinidase activity and was almost normal when residual activity exceeded 2-3% of mean normal. In one patient with classical disease (0-activity) biotin deficiency, typical organic aciduria and multiple carboxylase deficiency were found as early as at the second week of life. In contrast, 13 infants with residual activities from 1.2% to 23% had no remarkable clinical or biochemical abnormalities. However, in three 5-, 14- and 15-year-old healthy siblings with residual biotinidase activities between 2.3% and 4.2%, biotin deficiency was proven by decreased activities of the mitochondrial carboxylases in lymphocytes (30-57% of mean normal) and, in the older siblings, also by subnormal plasma biotin concentrations. In biotinidase deficiency, biotin depletion presumably occurs earlier in the brain than in other tissues and may thus first affect the central nervous system. For this reason and because of discrete biochemical abnormalities found in a patient with residual biotinidase activity of 8%, we suggest that at least all patients with residual activities below 10% should be treated with biotin.
Antibiotic prophylaxis for dental patients with joint prostheses? A decision analysis.
A decision analysis was performed to assess the risks, costs, and effects of no prophylaxis, oral penicillin, and cephalexin regimens currently being debated for dental patients at risk for late prosthetic joint infection (LPJI). The analysis suggests that there is a very small risk of LPJI (29.3 cases per 10(6) dental visits), which is outweighed by a greater risk of death with an oral penicillin strategy than with a "no prophylaxis" strategy (2.31:1.93). An oral cephalosporin appears to spare life and limb but does so at an extremely high cost. Over $500,000 must be spent to spare one year of life, while $480,000 needs to be spent to prevent one case of LPJI. Some individual dental patients may still be at a much greater risk for LPJI than others. However, from the evidence to date, routine predental antibiotic prophylaxis for all prosthetic joint patients is a very expensive preventive strategy and is not cost-effective. However, clinical experience suggests that antibiotic prophylaxis may be appropriate in some situations.
Combined epidural and general anesthesia versus general anesthesia in patients having colon and rectal anastomoses.
Three retrospective studies were conducted at St. Vincent's Hospital to compare the outcomes of colorectal anastomoses, with and without resections, with respect to anesthetic technique. Operations were performed upon patients anesthetized with either combined regional (epidural) and general anesthesia (CRAG) or general anesthesia alone (GA). Postoperative pain relief was achieved with either continuous epidural analgesia (CEA) in the CRAG group or with postoperative narcotics in the GA groups (GA/PN). In one group, a different regimen was introduced: combined epidural and general anesthesia with postoperative epidural morphine (CRAG/EDM). Overall, anastomotic leak rates and death rates were lower in the CRAG group, and the lowest incidence of anastomotic leak was reported in the patients receiving CEA. Thus the reduced leak rate was associated more with the postoperative analgesia regimen than with the anesthetic technique. An increased incidence of wound dehiscence occurred with postoperative epidural morphine analgesia.
The utility of cytodiagnostic urinalysis for monitoring renal allograft injury. A clinicopathological analysis of 87 patients and over 1,000 urine specimens.
Cytodiagnostic urinalysis was tested to determine its utility in the evaluation of allograft dysfunction in renal transplant patients. Specimens were prepared using the Papanicolaou stain on cytocentrifuge preparations of standardized quantities of urine. Differential counts of blood cells (neutrophils, lymphocytes, red cells), renal tubule cells (convoluted, collecting duct, necrotic), and casts (i.e. hemoglobin, renal tubule cell) were included in the sediment evaluation. Receiver operating characteristic curves demonstrated collecting duct cell exfoliation at 20 per 10 hpf to be a more sensitive and specific reflector of acute rejection than lymphocytes at their optimum decision point of 13 per 10 hpf. Sixty-four percent of cytodiagnostic urinalysis diagnoses preceded the clinical diagnoses. Ciclosporin nephrotoxicity was differentiated by the exfoliation of renal tubule convoluted cells in excess of collecting duct cells. The advantages of this technique over membrane-filter or phase-microscopic techniques for examining urine sediment of both transplant and nephrology patients include improved sensitivity and specificity in identification of sediment elements and reliable quantitative data for use in detecting renal disease and for monitoring therapy.
Accidental salicylate intoxication in a hemodialysis patient.
A 61-year-old woman receiving long-term hemodialysis presented with symptoms of tinnitus, insomnia, malaise, and disequilibrium. On close questioning, it was discovered that she had received a prescription for salsalate (Disalcid) from a consulting physician who had evaluated her for joint pain. This tablet was similar in appearance to a dried aluminum hydroxide gel preparation (Alu-tab) that the patient was taking as a phosphate binder. She had mistakenly been taking six Disalcid tablets with each meal. Her salicylate level was 5.86 mmol/L, but she had no change in her serum electrolyte levels or acid-base status. When the salsalate treatment was stopped and regular dialysis treatments were continued, the symptoms of salicylism resolved. This case illustrates one of the potential dangers of polypharmacy in patients with chronic disease. The midl course was probably due to ongoing hemodialysis, which prevented the appearance of the usual acid-base abnormalities of salicylate intoxication.
Chemoprophylaxis of dental patients with prosthetic joints: a simulation model.
A computer simulation model was created to assess the risks and effects of no prophylaxis, oral penicillin, and oral cephalexin regimens for dental patients at risk for late prosthetic joint infection (LPJI). Given the assumptions made, this analysis suggests that there is a very small risk of LPJI (29-68 cases per 10(6) dental visits), which is outweighed by a greater risk of death from a fatal antibiotic reaction. Thus, routine predental antibiotic prophylaxis for all dental patients with prosthetic joints may lead to higher mortality. However, clinical experience suggests that antibiotic prophylaxis may be appropriate in "high risk" patients.
The clinical efficacy of cytodiagnostic urinalysis in the diagnosis of acute renal allograft rejection: a clinical-pathologic correlation of 122 urine specimens.
Explore the source record for details and available documents.
The hypervariable region in the genes coding for entomopathogenic crystal proteins of Bacillus thuringiensis: nucleotide sequence of the kurhd1 gene of subsp. kurstaki HD1.
One of the genes for the entomophatogenic crystal protein of Bacillus thuringiensis (subsp. kurstaki strain HD1) has been cloned in Escherichia coli, and its nucleotide sequence determined completely. The gene is contained within a 4360-bp-long HpaI-PstI DNA restriction fragment and codes for a polypeptide of 1,155 amino acid residues. The protoxin protein has a predicted Mr of 130,625. The E. coli-derived protoxin gene product is biologically active against Heliothis virescens larvae in a biotest assay. Extensive computer comparisons with other published B. thuringiensis subsp. kurstaki strains HD1, HD73, and B. thuringiensis subsp. sotto gene sequences reveal hypervariable regions in the first half of the protoxin coding sequence. These regions are responsible for the biological activity of the protein product of the cloned gene, and may explain the different biological activities of these different protoxins.
Cloning and expression in Escherichia coli of a synthetic DNA for hirudin, the blood coagulation inhibitor in the leech.
A 235-bp DNA coding for the leech blood coagulation inhibitor, hirudin, was chemically synthesized. The synthesis involved preparation of seven long oligodeoxyribonucleotide pairs which were assembled and cloned using a rapid and simple procedure. More than half of the transformed Escherichia coli cells expressed a biosynthetic polypeptide having biological properties which were very similar to authentic hirudin from the leech Hirudo medicinalis. To achieve efficient expression, we fused the hirudin DNA to a truncated C1 repressor gene of bacteriophage lambda to create a hybrid protein. An additional methionine at the fusion point allowed the active hirudin to be cleaved off by cyanogen bromide.
Introduction of plasmid pC194 into Bacillus thuringiensis by protoplast transformation and plasmid transfer.
The Staphylococcus aureus plasmid pC194 which codes for resistance to chloramphenicol was introduced into six Bacillus thuringiensis strains representing five varieties by protoplast transformation. Six other varieties could not be transformed. pC194 could be identified in transformed strains as autonomous plasmid. The transformed clones contained in addition a new extrachromosomal element of somewhat lower electrophoretic mobility hybridizing with pC194, and pC194 in multimeric forms. pC194 was also transferred from one B. thuringiensis variety to another and from Bacillus thuringiensis to Bacillus subtilis and vice versa by a conjugation-like process, requiring close cell-to-cell contact.
Expression of Ti-plasmid DNA in E. coli: comparison of homologous fragments cloned from Ti plasmids of Agrobacterium strains C58 and Ach5.
Fragments of two Ti plasmids from Agrobacterium tumefaciens were cloned and studied for cross-hybridization. Homologous fragments were further investigated for areas of strong homology and mapped with various restriction enzymes. The fragments were inserted in two directions and the recombinant plasmid was brought into E. coli strains producing minicells. About five proteins were found to be coded by those fragments of the Ti plasmids.
Identification of two novel mutations in OCTN2 of three patients with systemic carnitine deficiency.
Systemic carnitine deficiency is a potentially lethal, autosomal recessive disorder characterized by cardiomyopathy, myopathy, recurrent episodes of hypoketotic hypoglycemia, hyperammonemia, and failure to thrive. This form of carnitine deficiency is caused by a defect in the active cellular uptake of carnitine, and the gene encoding the high affinity carnitine transporter OCTN2 has recently been shown to be mutated in patients suffering from this disorder. Here, we report the underlying molecular defect in three unrelated patients. Two patients were homozygous for the same missense mutation 632A-->G, which changes the tyrosine at amino acid position 211 into a cysteine (Y211C). The third patient was homozygous for a nonsense mutation, 844C-->T, which converts the arginine at amino acid position 282 into a stop codon (R282X). Reintroduction of wild-type OCTN2 cDNA into fibroblasts of the three patients by transient transfection restored the cellular carnitine uptake, confirming that mutations in OCTN2 are the cause of systemic carnitine deficiency.
Seventeen novel mutations that cause profound biotinidase deficiency.
We report 17 novel mutations that cause profound biotinidase deficiency. Six of the mutations are due to deletions, whereas the remaining 11 mutations are missense mutations located throughout the gene and encode amino acids that are conserved in mammals. Our results increase the total number of different mutations that cause biotinidase deficiency to 79. These additional mutations will undoubtedly be helpful in identifying structure/function relationships once the three-dimensional structure of biotinidase is determined.
[Psychosocial aspects of the treatment of phenylketonuria].
The psychosocial aspects of phenylketonuria (PKU) were investigated retrospectively in the families of 25 children and adolescents with classical PKU. With the help of a semistructurated questionnaire the parents were asked in interviews what impact the birth, the diagnosis of PKU in their child and the treatment itself had on them. 19 of the children had been detected by newborn screening and given early treatment. With one exception they all showed adequate intellectual development. Six other children were diagnosed late and only three of them had been given dietary treatment with some degree of success. Many of the parents reacted with shock and disbelief after being informed that their child was abnormal. In many ways the parents expressed retrospectively the wish that they had been better informed about their childs disease and had more intensive support from the medical professionals. They believed that with these prerequisites they would have been more competent in the case of their children. The data demonstrate the necessity of psychological care for the entire family of the chronically sick child.