Orange-red birefringence of gold particles.
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Antirheumatic Agents↗
Biomedical subjects
K Brady
Publications and source records attributed to K Brady.
Fat necrosis presenting as obscure abdominal mass: birefringent saponified fatty acid crystalloids as a clue to diagnosis.
AIMS: To describe the birefringent saponified fatty acid crystalloids seen in pancreatic fat necrosis. METHODS: A histological review, including polarising microscopy, of three cases of subacute or subclinical acute pancreatitis was performed. Histochemical analysis using Nile blue sulphate for lipid, Holczinger's copper rubeanate for fatty acids, and Alizarin Red S for calcium was performed in one case. Scanning electron microscopy and x-ray energy dispersive spectroscopic micro-analysis were performed in two cases. Necropsy pancreatic tissue, surgical archival tissue from cases of pancreatitis, and pancreatic and adipose tissue permitted to autolyse together in the laboratory, were also examined. The autolysed tissue was also examined histochemically. Stained and unstained sections were mounted in DPX and Canada balsam. Surgical material showing traumatic fat necrosis was reviewed. RESULTS: In each of the three cases there were subtle clues to subclinical pancreatitis. In neither surgical case was the true nature of the mass apparent to the operator. Histological analysis in all cases showed ghost adipocytes containing numerous polarising crystalloids, as well as some basophilic debris. Microanalysis showed calcium but no other substantial heavy element signals. Histochemical analysis showed a labile, polar, acidic lipid and the crystalloids behaved as calcium salts of free fatty acid. The crystalloids were not seen in archival material mounted in Canada balsam. No crystalloids were seen in traumatic fat necrosis. CONCLUSIONS: Little recognised, strongly birefringent, saponified free fatty acid crystalloids occurring in pancreatic fat necrosis may survive routine processing, and can point to the origin of obscure mesenteric masses related to subclinical pancreatitis.
Acute Disease↗
A rodent model for hemoglobin switching utilizing high performance liquid chromatography.
It has long been recognized that a treatment for beta hemoglobin chain anomalies could result if a way to reverse the Hb F to Hb A switch in humans were found. Studies of hemoglobin switching have been hampered by the fact that small animals normally used in the laboratory do not have a true Hb F. However, several small animal models which take advantage of a switch in minor beta chain proportions in certain strains of inbred mice and rats have been proposed and used. The use of these models has suffered from what, until now, could be considered technically demanding, time-consuming methodologies. In this study we report an effective, rapid and technically streamlined model of hemoglobin switching utilizing Fisher 344 rats and high performance liquid chromatography with a weakly cationic column.
Age Factors↗
Evaluation of the endocervical Cytobrush and Cervex-Brush in pregnant women.
OBJECTIVE: To compare, in pregnant women, the endocervical cell yield of the Cytobrush Cell Collector and the Cervex-Brush Cell Sampler with the standard cotton swab, and to determine the incidence of serious adverse events associated with the collection techniques. METHODS: In a randomized, controlled clinical trial, 352 pregnant women undergoing initial obstetric evaluation were randomly assigned to either the cotton swab and modified Ayers spatula, Cytobrush and modified Ayers spatula, or Cervex-Brush. The cytopathology laboratory, blinded to the Papanicolaou smear method, screened the smears using the Bethesda System guidelines. Statistical analyses were performed using the Pearson chi 2 and analysis of variance tests. RESULTS: There was an increased detection of endocervical cells in pregnant patients with both the Cytobrush and modified Ayers spatula (90.7%) and the Cervex-Brush (83.3%) methods, compared with the cotton swab and modified Ayers spatula (70.8%) (P = .0001 and P = .0233, respectively). There was no statistically significant difference between the Cytobrush-spatula and Cervex-Brush groups (P = .0956). Although there were more bloody Papanicolaou smears in the study groups, this was neither clinically nor statistically significant because all the samples were interpretable and repeat samples due to bloody specimens were not required. There were no serious adverse events associated with the study group methods. CONCLUSION: Performance of Papanicolaou smears using the Cytobrush and modified Ayers spatula and with the Cervex-Brush improved Papanicolaou smear adequacy as compared with the cotton swab and modified Ayers spatula. Despite an increased incidence of spotting following collection, these techniques were not associated with an increase in serious adverse events. Based on the cost per item and a clinically significant increase in endocervical cell yield, we recommend the Cytobrush and modified Ayers spatula for cytologic screening in pregnant women.
Adult↗
A slow clearing, fibrin-specific, PAI-1 resistant variant of t-PA (T103N, KHRR 296-299 AAAA).
Site directed mutagenesis was used to construct a t-PA variant that contains an additional glycosylation site in the first kringle domain (T103N) combined with a tetra-alanine substitution in the protease domain (KHRR 296-299 AAAA). This combination variant has a plasma clearance rate that is 4.5-fold slower in rats and 5.4-fold slower in rabbits than t-PA. It is also less than one tenth as active as t-PA towards plasminogen in the presence of fibrinogen, and has approximately twice the normal activity in the presence of fibrin. It shows substantial resistance to the fast acting inhibitor, plasminogen activator inhibitor-1 (PAI-1), requiring a 10-fold greater molar excess of PAI-1 to reduce its activity by 50%, compared to t-PA. This is the result of a reduction of nearly 100-fold in the second order rate constant for PAI-1 inactivation. These results show that it is possible to combine mutations in different domains of t-PA to construct a variant which is simultaneously slower clearing, less reactive towards plasminogen in the absence of a fibrin clot, and resistant to inactivation by PAI-1.
Animals↗
Intrauterine meconium aspiration in an extremely premature infant.
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Fatal Outcome↗
Gold in the dermis following chrysotherapy: histopathology and microanalysis.
Paraffin-embedded sections of skin from patients with rheumatoid arthritis treated with gold who had developed skin rashes were examined by light microscopy and scanning electronmicroscopy with microanalysis. Sparse, small, brown or black granules in plump, often elongated cells in the dermis were shown to contain gold by energy dispersive X-ray microanalysis. These cells expressed some macrophage markers. The amount of gold present showed some correlation with the total gold dose. Gold was not confined to lesional skin. In one case where uninvolved skin was examined, more gold was found there than in lesional skin.
Aged↗
The perioperative morbidity of scheduled cesarean hysterectomy.
OBJECTIVE: To compare the outcomes of patients undergoing scheduled cesarean hysterectomy with those of women treated with cesarean delivery and subsequent hysterectomy. METHODS: Through a retrospective review of 43 patients, we investigated the morbidity associated with scheduled cesarean hysterectomy and compared these findings with the combined morbidity of scheduled cesarean delivery and subsequent abdominal hysterectomy in a control population. Controls were included only if the subsequent hysterectomy was performed within 3 years of the index cesarean delivery. Each study subject was assigned two controls matched for age, parity, number of previous cesarean deliveries, and indications for procedures. The incidence of the following major morbidity events was compared between the groups: transfusion, urinary tract injury, fistula formation, cellulitis or endometritis, postoperative abscess or hematoma formation, ileus, pneumonia, and wound complications requiring prolonged therapy (seroma, hematoma, infection). RESULTS: The number of women receiving transfusions after scheduled cesarean hysterectomy was greater than among controls (39.5 versus 15.1%; P < .05). The proportion of patients with major morbidity, exclusive of transfusion, was significantly greater in the control population (44%) than in women with scheduled cesarean hysterectomy (16%) (P < .05). The cumulative number of women with a major complication, such as transfusion or a morbid event, was 22 of 43 in the study group versus 44 of 86 in the control population, a nonsignificant difference. CONCLUSION: We found no significant difference in the cumulative perioperative complication rates in women undergoing scheduled cesarean hysterectomy compared with a population of similar patients treated with cesarean delivery and subsequent abdominal hysterectomy.
Adult↗
Stability of capillary gels for automated sequencing of DNA.
Recent interest in capillary gel electrophoresis has been fueled by the Human Genome Project and other large-scale sequencing projects. Advances in gel polymerization techniques and detector design have enabled sequencing of DNA directly in capillaries. Efforts to exploit this technology have been hampered by problems with the reproducibility and stability of gels. Gel instability manifests itself during electrophoresis as a decrease in the current passing through the capillary under a constant voltage. Upon subsequent microscopic examination, bubbles are often visible at or near the injection (cathodic) end of the capillary gel. Gels have been prepared with the polyacrylamide matrix covalently attached to the silica walls of the capillary. These gels, although more stable, still suffer from problems with bubbles. The use of actual DNA sequencing samples also adversely affects gel stability. We examined the mechanisms underlying these disruptive processes by employing polyacrylamide gel-filled capillaries in which the gel was not attached to the capillary wall. Three sources of gel instability were identified. Bubbles occurring in the absence of sample introduction were attributed to electroosmotic force; replacing the denaturant urea with formamide was shown to reduce the frequency of these bubbles. The slow, steady decline in current through capillary sequencing gels interferes with the ability to detect other gel problems. This phenomenon was shown to be a result of ionic depletion at the gel-liquid interface. The decline was ameliorated by adding denaturant and acrylamide monomers to the buffer reservoirs. Sample-induced problems were shown to be due to the presence of template DNA; elimination of the template allowed sample loading to occur without complications.(ABSTRACT TRUNCATED AT 250 WORDS)
Autoanalysis↗
Immunohistochemical localization of human immunodeficiency virus p24 antigen in placental tissue.
As human immunodeficiency virus (HIV) infection spreads into the heterosexual population, perinatally acquired HIV infection will increase in incidence, and knowledge of the mechanism of this transfer is important. We have used immunoperoxidase techniques to detect HIV p24 antigen in formalin-fixed, paraffin-embedded placental tissue from nine known HIV serologically positive mothers. In four of these cases we have detected evidence or viral antigen in placental Hofbauer cells, vascular endothelium, or intermediate trophoblast. The implications for understanding the mode of transfer of infection to the fetus are discussed.
Female↗
Involvement of residues 296-299 in the enzymatic activity of tissue-type plasminogen activator.
The tetra-alanine substitution variant KHRR 296-299 AAAA of tissue-type plasminogen activator (t-PA) was previously shown to have enhanced fibrin specificity and enhanced activity in the presence of fibrin compared with the wild-type form of the molecule. The structural requirements for these alterations in enzymatic activity were investigated by constructing several amino acid substitution variants at each of the positions from 296 to 299 and evaluating their activities under a variety of conditions. Effects on plasminogen activator activity were common among the point mutants at positions 296-299; nearly all had a phenotype similar to the KHRR 296-299 AAAA variant. The greatest effects on enzymatic function were found with multiple substitution variants, but some single charge reversals and proline substitutions had substantial effects. The enhanced fibrin specificity of KHRR 296-299 AAAA t-PA results in less fibrinogenolysis than seen with wild-type t-PA. Approximately four times greater concentration of KHRR 296-299 AAAA compared with wild-type t-PA was required to consume 50% of the fibrinogen in human plasma.
Alanine↗
A placebo-controlled trial of buspirone in anxious inpatient alcoholics.
The present study is a double-blind control trial of buspirone versus placebo in highly anxious alcoholics who recently completed inpatient detoxification for alcoholism. Subjects met DSM-III-R criteria for generalized anxiety syndrome and/or other nonpanic forms of anxiety disorders and alcohol dependence. Male veterans aged 21 to 65 were randomized to 45 to 60 mg/day of buspirone (n = 33) or placebo (n = 34). Anxiety scores, as measured by the Hamilton Anxiety Scale and other anxiety measures, declined significantly for both groups, but there were no differential group differences throughout the 6-month treatment period. Survival analysis measuring time to study drop out, time to first drink, time to 5 consecutive drinking days, and time to first intoxication indicated no significant differences between groups. The number of standard drinks per drinking day for nonabstainers also did not differ between groups. In the present study anxious alcoholics taking buspirone did not receive any benefit over placebo on a number of anxiety and alcohol use measures.
Adult↗
Histopathological and microanalytical study of zirconium dioxide and barium sulphate in bone cement.
AIMS: To report the appearances of zirconium dioxide and barium sulphate in interface membranes, synovium, and other tissues around joint prostheses. METHODS: Histological sections from 23 specimens were reviewed by light microscopy and polarisation. Scanning electron microscopy and x ray microanalysis were performed on routinely processed paraffin wax sections. RESULTS: Polyethylene, metals, and polymethylmethacrylate cement debris were easily recognisable. Almost all the cement remnants contained either zirconium dioxide or barium sulphate, confirmed by microanalysis. The contrast media had characteristic light microscopic appearances. Zirconium was identified in macrophages away from cement remnants. CONCLUSION: The presence of radiographic contrast media in tissues around prosthetic joints is common but not widely recognised.
Adult↗
The effect of altitude on umbilical cord blood gases.
OBJECTIVE: Analysis of umbilical cord blood acid-base status has proven useful in the immediate care and resuscitation of the newborn and provides an objective measure of the intrapartum fetal environment. Our study was designed to determine whether there are any significant differences in the acid-base status of neonates delivered at a relatively high altitude of 6000 ft compared with sea-level controls. METHODS: Our study population consisted of 300 women who had undergone spontaneous vaginal delivery after uncomplicated labor; 150 delivered at an institution located at an elevation of 5900 ft and the remainder at an elevation of 87 ft. Exclusion criteria were hypertensive disease, diabetes, suspected fetal growth retardation, fetal distress, meconium-stained amniotic fluid, and chorioamnionitis. All patients received continuous electronic fetal monitoring, and tracings were reviewed by a physician blinded to the umbilical acid-base results. Umbilical cord arterial and venous samples were collected and analyzed within 30 minutes of delivery. RESULTS: Compared with sea-level controls, neonates delivered at high altitude had a significantly higher mean pH with lower mean carbon dioxide pressure values in both arterial and venous specimens (P less than .05). The difference between the mean arterial pH values was 0.026 (P less than .05, 95% confidence interval [CI] 0.015-0.037) and mean venous values was 0.037 (P less than .05, 95% CI 0.027-0.047). There were no significant differences in the arterial or venous oxygen pressure or oxygen saturation values between the study and control groups. There was a significant decrease in the mean birth weight of 320 g (P less than .05, 95% CI 199.5-441.3) and higher pre-delivery hematocrit values (2.4%; P less than .05, 95% CI 1.6-3.2) in the high-altitude population compared with the sea-level group. CONCLUSIONS: Neonates delivered at high altitude have significant alterations in umbilical blood acid-base measurements compared with neonates at sea level. Other significant differences include a lower infant birth weight and a higher maternal hematocrit relative to pregnant women at sea level.
Acid-Base Equilibrium↗
Risk of chromosomal abnormalities in patients with idiopathic polyhydramnios.
This prospective investigation was designed to assess the incidence of chromosomal abnormalities in patients with idiopathic polyhydramnios. Polyhydramnios was defined as 25 cm or greater in total vertical height in all four quadrants (amniotic fluid index) in any nonreferral patient (ie, primary care population) undergoing sonographic examination with a singleton pregnancy, normal fetal anatomical survey, normal glucose screening, and negative antibody screen. During the 2-year period from May 1, 1988 through April 30, 1990, 5038 gravidas delivered at Madigan Army Hospital Center. Unexplained polyhydramnios was detected sonographically in 125 patients, an incidence of 2.5%. After obtaining informed written consent, amniocentesis was performed in all patients. Within this group (N = 125), four chromosomal abnormalities (incidence of 3.2%) were detected. There were two trisomy 18 and two trisomy 21 fetuses. None of the four patients had maternal serum alpha-fetoprotein screening performed. The incidence of aneuploidy in patients with idiopathic polyhydramnios (3.2%) is much higher than the reported incidence of major karyotype abnormalities in live births (0.59%). We conclude that fetal chromosomal analysis should be considered in all obstetric patients with sonographic evidence of idiopathic polyhydramnios.
Chromosome Aberrations↗
Reproducibility of the oral glucose tolerance test in pregnancy.
This prospective investigation evaluated the reproducibility of the 100 gm oral glucose tolerance test. Sixty-four obstetric patients with greater than or equal to 135 mg/dl on the 50 gm oral glucose screening test were scheduled for the 100 gm test. All patients repeated the oral glucose tolerance test in 1 to 2 weeks. Both tests included a preparatory diet, and testing conditions were identical. There were no significant differences in the mean test values at each testing interval when the entire study population was considered. Patients were then divided into four groups according to the outcome of the two tests. Forty-eight of 64 (75%) had normal results at each testing period (group 1); 11 of 64 (17%) had initially normal results and abnormal results on retest (group 2); 3 of 64 (5%) had initially abnormal results and normal results on retest (group 3); 2 of 64 (3%) had abnormal results at both testing phases (group 4). There were no significant differences between oral glucose tolerance test results within groups 1 and 4. However, significant differences occurred within groups 2 and 3 between the two tests. Group 2 patients had a greater frequency of an abnormal 1-hour value on the test than group 1 patients (p = 0.001). Overall, the reproducibility of the oral glucose tolerance test was 78% (50 of 64). We recommend the oral glucose tolerance test be repeated when the 1-hour value is abnormal or when the fasting blood sugar, 1-hour, and 2-hour values are near the upper end of the normal range.
Adult↗
Role of amniotic fluid cytogenetic analysis in the evaluation of recent fetal death.
Chromosome abnormalities may be present in approximately 10% of cases of fetal death. Because of cell maceration and autolysis, the likelihood of successful karyotype analysis of fetal tissue varies inversely with the time between fetal death and delivery. In an attempt to reduce the influence of these postmortem changes, we obtained amniotic fluid cells for cytogenetic studies from 12 fetuses as soon as possible after the diagnosis of fetal death was confirmed. We also obtained fetal tissue for cell culture in ten of the cases immediately following evacuation of the uterus. Cell culture was successful in 11 of 12 amniotic fluid specimens and in only one of ten fetal tissue specimens (p less than 0.001). Since the results of cytogenetic studies are of such importance in counseling patients regarding recurrence risk for fetal death, we recommend that amniotic fluid cells be obtained for karyotype analysis at the time of diagnosis of fetal death rather than awaiting delivery of a potentially macerated and autolyzed fetus.
Amniotic Fluid↗
The predictive value of bone marrow morphologic characteristics and immunostaining in primary (AL) amyloidosis.
The authors previously demonstrated that bone marrow plasmacytosis in primary (AL) amyloidosis may be monoclonal or polyclonal. However, the clinical implications of the degree of plasmacytosis and its clonality have not been studied. The authors evaluated 62 patients with AL amyloidosis, 40 of whom had monoclonal medullary plasma cells. There was complete concordance between the light chain class of the plasma cells in the monoclonal cases and that of the circulating paraprotein in the 22 cases associated with a paraprotein. The remaining 22 patients had polyclonal plasma cells, although a paraprotein was detected in 6. The degree of plasmacytosis was significantly higher among patients with monoclonal plasma cells and correlated inversely with length of survival. The authors' findings indicate that the quantitation of bone marrow plasma cells in AL amyloidosis by immunoperoxidase studies may predict the clinical course.
Adult↗