Lytic bone lesions in polycythaemia rubra vera.
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Biomedical subjects
Publications and source records attributed to H Goodman.
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Magnetic resonance (MR) scanning shows great promise as an imaging tool to evaluate the pelvis as a result of contrast resolution and lack of ionizing radiation. For these reasons, it is assuming an important role in staging gynecologic neoplasms, and evaluating diseases in the gravid pelvis. A case of uterine leiomyosarcoma is presented in which MR imaging was able to delineate the extent and tissue characteristics of the lesion more precisely than CT scan.
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To better understand the use of narcotic analgesics, the hydromorphone concentration was measured in serum samples from 43 patients with chronic severe pain who were receiving this drug. At the time of blood sampling, pain intensity, mood, and cognitive performance were assessed. There was large individual variation in the dose-drug level relationship. Seven patients with bone or soft tissue pain and drug levels of greater than or equal to 4 ng/ml had good pain control, whereas 10 did not. None of 15 patients with levels less than 4 ng/ml had pain control, despite drug doses similar to those given patients with higher levels. Thus 60% of the patients without control of their pain had hydromorphone levels below the lowest level that produced pain control. No patient with pain from nerve infiltration or compression had good pain control, irrespective of the drug level or dose. Poor mood correlated with high pain intensity and low drug level. Impaired cognitive performance was not related to drug level. Knowing that there is a low concentration of narcotic in the blood of a patient with chronic severe pain who is receiving high drug doses and who shows lack of both efficacy and side effects may reassure health care professionals that further narcotic dosage escalation is appropriate.
Pain and mental status were assessed in a series of 35 consecutive hospitalized patients with metastatic cancer receiving narcotics for pain that was difficult to control. Forty-five episodes of mental status impairment were detected in 27 of these patients. Fifteen patients had dose-related oversedation or organic brain syndrome. In only 4 could the narcotic dose be decreased without exacerbating the pain. Eleven patients had mental status impairment associated with factors other than the narcotic dose. These factors were: concurrent CNS-depressant drugs, presence of fever or infection, or changing from parental to average oral equianalgesic dose of narcotic. When these factors were corrected, mental function improved and remained stable despite resumption of the previous narcotic dose. Delirium occurred more frequently in patients over 65, while oversedation without delirium was more frequent in the younger group. For some patients with advanced metastatic cancer, pain relief and intact mental status cannot coexist. For others, correction of factors other than narcotics which can impair function can often lead to improved mental status without decreasing narcotic dose or decreasing the degree of pain control.
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The specificity of lysozyme determinations in human parotid and submandibular-sublingual salivas of two subjects was assessed by comparison of lysozyme concentrations in native acidified salivas with purified enzyme obtained by immunoadsorbent fractionation of the salivas. Lysozyme concentrations were measured by the turbidimetric catalytic method and by a newly developed enzyme-linked immunosorbent assay (ELISA). The validity of the assays was established by comparing assay results with enzyme concentration values determined from optical density-extinction coefficient calculations of the purified lysozyme peak. Values for purified enzyme were found to be similar, irrespective of the assay used to determine lysozyme concentrations, and were in agreement with extinction coefficient calculations. Based on the ELISA technique, recoveries of lysozyme from both parotid and submandibular-sublingual salivas were greater than 75 and 90%, respectively. Similar recoveries were noted for parotid saliva when determinations were based on the turbidimetric assay. However, the ELISA and turbidimetric assays differed with respect to lysozyme levels in submandibular-sublingual saliva because of the apparent presence of an enhancement factor which gave rise to higher lysozyme values in the catalytic assay and therefore resulted in low recoveries of purified enzyme. This catalytic enhancement factor was present in the nonadsorbed fraction of both subjects, as higher lysozyme activities were noted when nonadsorbed fractions were added to affinity-purified lysozymes. Lysozyme levels were also determined in the parotid and submandibular-sublingual salivas of caries-resistant and -susceptible adults. In general, levels of lysozyme in parotid saliva were lower in comparison to submandibular -sublingual saliva; however, significant differences in enzyme concentration were not evident between the caries-resistant and caries-susceptible subjects.
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Streptococcus mutans GS5 was grown in synthetic medium containing radioactive thymidine to monitor deoxyribonucleic acid release. At neutral pH, cell lysis of hen egg-white lysozyme- or lysozyme-protease-treated cells was dependent upon the nature and concentration of the additive inorganic anions, HCO-3, SCN-, Cl- or F-. At acidic pH, NaHCO3, but not NaSCN, NaCl or NaF, was effective in promoting cell lysis which was due not only to the change in pH but also to the new HCO-3 anion concentration at the new pH. In both pH 4 and 5.2 reaction mixtures, the lysozyme and trypsin acted synergistically with NaHCO3 and the amount of lysis produced was markedly greater than in reaction mixtures containing lysozyme and bicarbonate but no protease. At apparent sub-lytic concentrations of NaHCO3, lysis was achieved by adding an appropriate concentration of one of NaSCN, NaCl or NaF to the lysozyme-protease-damaged cells. Thiocyanate proved to be most effective among the anions requiring lower concentrations to elicit lysis compared to chloride or fluoride for a fixed sub-lytic concentration of bicarbonate. As the NaHCO3 concentration increased, the lysis in the presence of these other anions increased until maximum levels of released deoxyribonucleic acid (DNA) were attained. In addition, the higher the NaHCO3 concentration, the more marked was the change in the degree of cell lysis. At a selected concentration at which NaHCO3 was not effective with any one salt, lysis could be achieved by combining all four inorganic anions at this concentration. The results suggest that the various anions present in oral fluids may together be sufficient to trigger lysis of oral microorganisms.
We detected a large number of polymorphic insulin restriction fragments in black Americans. These different size fragments were probably generated by unequal recombination on both sides of the human insulin gene. Population genetic analysis indicates that recombination occurred 33 times more frequently than expected to generate this large number of polymorphic fragments. Specific properties of the unique repeated 14- to 16-base-pair sequences 5' to the insulin gene suggest that this sequence would promote increased unequal recombination. Additional pedigree analysis showed that the recombination rate between the structural insulin and beta-globin gene loci was 14% with strong evidence for linkage. Since both insulin and beta-globin have been mapped to the short arm of human chromosome 11, this study establishes that the genetic map distance between these genes is 14.2 centimorgans.
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When are Wormian bones significant is not an easy question to answer, but its relevance is important in relation to bone dysplasias such as osteogenesis imperfecta. Recognition will differ with age of patient, radiographic objectivity, and personal subjectivity. In order to attempt an answer, the skull radiographs of 81 cases of osteogenesis imperfecta of varying ages were examined for the presence of Wormian bones. These were compared against the incidence of Wormian bones in 500 skull radiographs of normal children. Significant Wormian bones as against normal developmental variants were considered to be those more than 10 in number, measuring greater than 6 mm by 4 mm, and arranged in a general mosaic pattern. They were found in all the cases of osteogenesis imperfecta but not in the normal skulls. The occurrence of significant Wormian bones in other bone dysplasias from our material and that of the literature was recorded. Other incidental findings in the skulls of the cases of osteogenesis imperfecta were also appraised.
Streptococcus mutans GS5 was grown in a synthetic medium containing radioactive thymidine to monitor cell lysis by assay of the release of DNA. Bacteriolysis was achieved by sequential treatment of the cells with either hen egg white lysozyme and sodium thiocyanate or a combination of hen egg white lysozyme and a proteolytic enzyme followed by addition of the thiocyanate. In the absence of sodium thiocyanate, a small percentage of the total macromolecular thymidine was released in control reaction mixtures during incubation. This amount of released DNA more than doubled in trypsin-treated cells, but the inclusion of lysozyme in reaction mixtures prevented assay of the DNA. Lysis was found to be optimal in the late log phase of growth and was dependent on the concentrations of both lysozyme and protease. Concentrations of trypsin or chymotrypsin as low as 0.01 microgram/ml were found to be effective in enhancing the lytic process. The addition of protease to lysozyme-inorganic salt reaction mixtures altered both the pH and ionic strength profiles of cell lysis. At pHs of 5.5 or lower, both the lysozyme-NaSCN and the lysozyme-trypsin-NaSCN systems were inactive in mediating lysis. The loss of insoluble cell wall peptidoglycan by lysozyme treatment was pH independent and did not appear to be affected by the addition of protease. Either diluted whole saliva or neutrophil extracts could replace trypsin to enhance cell lysis further.
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Streptococcus mutans BHT was grown in Todd-Hewitt dialysate medium containing N-acetyl[(14)C]glucosamine for 6 to 11 generations. After treatment with cold and hot trichloroacetic acid and trypsin, 52 to 65% of the radioactivity remained present in insoluble peptidoglycan-containing residues. Hen egg white lysozyme or mutanolysin treatment of the peptidoglycan residues resulted in the release of 80 and 97%, respectively, of the (14)C label to the supernatant fraction. Hydrochloric acid hydrolysates of such supernatants showed that essentially all of the radioactivity present in insoluble peptidoglycan fractions was present in compounds that comigrated on paper chromatography with glucosamine ( approximately 60%) or muramic acid ( approximately 30%). Treatment of whole cells with low and high concentrations of lysozyme alone resulted in losses of 45 and 70% of the insoluble peptidoglycan, respectively, yet release of deoxyribonucleic acid from cells was not detected. Sequential addition of appropriate concentrations of selected inorganic salts after lysozyme treatment did result in the liberation of deoxyribonucleic acid. Deoxyribonucleic acid release was correlated with a further release of peptidoglycan from the insoluble fraction. However, the total amount of peptidoglycan lost effected by the low concentration of lysozyme and NaSCN (lysis) was significantly less than the amount of peptidoglycan hydrolyzed by high concentrations of lysozyme alone (no lysis), suggesting that the overall amount of peptidoglycan lost did not correlate well with cellular lysis. The total amount of insoluble peptidoglycan lost at the highest salt concentrations tested was found to be greater than could be accounted for by lysozyme-sensitive linkages of the peptidoglycan, possibly implicating autolysins. The results obtained suggested that hydrolysis of peptidoglycan bonds in topologically localized, but strategically important, sites was a more significant factor in the sequence that results in loss of cellular integrity (lysis).