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P Burke

Publications and source records attributed to P Burke.

At least 37 records · Page 2Linked to original sources

Systemic cytokine administration alters the histology of the eruption of lymphocyte recovery.

The eruption of lymphocyte recovery occurs after marrow ablative antineoplastic chemotherapy, with the earliest reappearance of lymphocytes in the peripheral circulation. The typical histopathologic findings are not specific, consisting of a perivascular lymphocytic infiltrate in the upper dermis with mild overlying epidermal changes. Since the initial report, 21 additional biopsy specimens from eruptions of lymphocyte recovery were obtained at our institution. Of these specimens, 18 displayed the expected findings while 3 specimens contained a relatively heavy lymphocytic infiltrate with nuclear pleomorphism and hyperchromasia. The majority of lymphocytes from the heavily inflamed tissues expressed CD3 and CD4; rare CD8+ cells were observed. The cells with large irregular nuclear contours displayed an "activated" phenotype, consisting of CD30, HLA-DR, and CD25, accounting for roughly 50% of the total infiltrate. The three patients from whom these specimens were obtained had received human recombinant cytokines in pharmacologic doses (2 granulocyte-macrophage colony stimulating factor, 1 interleukin-3). Three patients in this series also received human recombinant cytokines, but developed eruptions with the typical scant infiltrate of small lymphocytes. These findings extend the histologic spectrum of the eruption of lymphocyte recovery and suggest that the administration of human recombinant cytokines prior to marrow recovery may alter the appearance and phenotype of lymphocytes migrating into the skin.

Adult↗

Accuracy of immunohistochemistry and flow cytometry in estimating the proportion of leukemic cells in S phase in chronic myeloid leukemia patients.

We compared the proportion of S phase cells in bone marrow and peripheral blood samples obtained from 17 patients with chronic myeloid leukemia (CML). Before sampling all patients received a one hour i.v. infusion of iododeoxyuridine (IdUrd). The proportion of S phase cells was studied by immunohistochemistry (IHC) in bone marrow biopsies, and by flow cytometry (FCM) in bone marrow aspirates and peripheral blood samples. The IdUrd labelling index (LI) in bone marrow biopsy sections (27.5 +/- 1.8%) was significantly higher than the proportion of IdUrd labelled cells in bone marrow aspirate (15.1 +/- 2.0%). The percentage of S phase cells in peripheral blood was approximately the same as that in the aspirate (12.4 +/- 1.3%) and was correlated with that of bone marrow aspirate indicating a high degree of the aspirate dilution by peripheral blood. It is likely that the differences in % S phase cells in the aspirate and the biopsy result from this dilution. Estimates of the % S phase cells in the peripheral blood study by IHC and FCM were essentially the same. Samples labelled for one hour in vitro resulted in 1.5 fold higher LI than the same samples labelled in vivo. We conclude that estimates of the 8% S phase cells in the bone marrow of patients with CML should be made by infusing patients with IdUrd or BrdUrd with immunohistochemical evaluation of a marrow biopsy. Additionally in vitro labelling is not reflective of the percent S phase cells in vivo in patients.

Antibodies, Monoclonal↗

[Quality and homogeneity monitoring of radiologists in the Turin mammographic screening. Comparison of the pilot phase results].

The Turin mammographic screening program was designed to be carried out in several independent screening centers because of the large proportion of population involved (76,000 women aged 50 to 59 years). The first center began working in 1992 and the second center was opened in 1995. The latter center carried out an early pilot study in which 1024 women were examined to assess the homogeneity and the quality of the results. The results were then compared with European quality standards and with the results of both the pilot and the active screening periods in the first center. The results from the second center were very good as far as detection rate is concerned (7.8/1000-2.9/1000 in carcinoma < or = 1 cm). This rate is higher than the so-called "desirable" European standard. Recall rate and benign/malignant biopsy ratio were higher than the so-called "fair" European standard (recall rate: 7.1%; B/M biopsy ratio: 0.62). These results are slightly superior to those of the pilot period in the first center and slightly inferior to the results of active screening in the same center. The improvement relative to the pilot period in the first center (1991) is probably related to technical progress, such as the introduction of the double mammographic projection. The difference relative to the results from the active screening period in the first center (1992-1994) reflects different specific experience. Even though pilot periods have no statistical significance, they can be used for comparison, and in our experience they have proved, with positive results, the quality of the mammographic screening program provided to the Turin population.

Female↗

[Spermatic phlebography and sclerotherapy of the male varicocele].

Phlebographic sclerotherapy and embolization are better methods, from the biological and cost-effectiveness viewpoints, to treat male varicocele than conventional surgery. On the other hand, positive technical results are not always obtained and the rates of relapses and recurrences are high. A retrospective study was carried out on 70 (of 81) sclerotherapies performed in the Radiology Department of S. Anna Hospital, Turin, from 1993 to September, 1995. The results confirmed the feasibility of this treatment in a nonangiographic department, with technical success rates increasing with growing operators' experience (70% success rate in 1993, vs. more than 95% in 1994-95). Recurrence rate was 4.9% and the rate of limited persistence was 7.3% at clinical and Doppler follow-up ranging 6-24 months (mean: 10.2 months). Both rates appeared to be related to varicocele initial size, increasing progressively from grade I to grade III. Therefore, such new and expensive techniques as balloon or spiral embolization are justified only in the most severe cases. The follow-up showed improved or normalized sperm exams in 70.4% of treated and followed-up patients, with 5 full-term pregnancies. To conclude, sclerotherapy and embolization of the spermatic vein are very good tools to treat male varicocele with subfertility.

Adolescent↗

Abdominal aortic aneurysm in the Irish population: a familial screening study.

A pilot screening programme was undertaken in Ireland to determine the incidence of abdominal aortic aneurysm (AAA) (diameter 3 cm or greater) in the siblings of 120 patients known to have AAA. There were 621 siblings; 270 of them were dead, 32 were over 80 years old and 85 lived outside Ireland, leaving 234 under 80 years of age still living in Ireland who were invited to attend for ultrasonographic screening. Of the 270 siblings who had died, 102 were women and 168 men; eight men (4.8 per cent) had died from ruptured AAA. Only 125 (53.4 percent) of the 234 siblings agreed to participate in the screening programme, 60 brothers from 31 families and 65 sisters from 35 families. Fifteen (12.0 per cent) of the 125 siblings had an AAA (median size 4.2 (range 3.1-6.8) cm), 13 (22 per cent) of the 60 male siblings and two (3 per cent) of the 65 female siblings. The prevalence of AAA among siblings was not affected by the age or sex of the patient with aneurysm. Seven of the 14 male siblings with hypertension had an AAA, compared with only six of the 46 who were normotensive (P = 0.01). The high incidence of AAA in brothers of affected patients highlights the need to counsel this group on their risk of aneurysm. The relatively low participation rate by siblings in this screening programme indicates that a hospital-based unit is unlikely to be effective in recruiting all patient siblings at risk from an AAA.

Adult↗

New insights into the pathophysiologic condition of venous ulceration with color-flow duplex imaging: implications for treatment?

PURPOSE: This study was conducted to investigate the distribution of reflux in the veins adjacent to or within the venous ulcer (local) and to correlate it with the pattern of disease of the axial veins (all veins away from the ulcer area) of the affected limb. METHODS: Forty-three ulcers in 34 legs of 33 patients were examined with color-flow duplex imaging. The veins in the area of the ulcer were scanned with a sterile technique. RESULTS: In 17 legs (50%) there was documented past deep venous thrombosis. All of the 34 limbs had reflux in the superficial or deep axial veins either alone or in combination. Fifteen of these limbs (44%) also had perforating vein incompetence, but none had perforator incompetence alone. Six ulcers showed no evidence of reflux in the local veins when scanned through the ulcer bed despite the presence of reflux in the axial veins of the limb. In 13 limbs with 17 ulcers, either the superficial axial veins alone or the deep axial veins alone were affected (with or without associated perforator incompetence). Examination of the local veins associated with these 17 ulcers revealed a similar pattern of reflux to that seen in the axial veins in 13 cases, with the remaining 4 ulcers showing no local venous abnormality. The pattern of reflux was less predictable at the local ulcer level in limbs where both superficial and deep venous incompetence coexisted in the axial veins. Only 7 of the 26 ulcers (27%) in these limbs had similar evidence of combined superficial and deep reflux in the local ulcer veins, whereas 10 ulcers (39%) were associated with local reflux in the superficial or deep veins alone. CONCLUSIONS: These data show that 86% (37/43) of the ulcers has some degree of reflux in the local area, the pattern of which may differ from the axial vein disease. Treatment of the local hemodynamic abnormalities may be an important factor in the healing of the ulcers and in the prevention of their recurrence.

Adolescent↗

Generic enteral formulas: a new idea for the 1990s.

Generic equivalent enteral formulas are now commercially available. The purpose of this article is threefold: (1) to define generic equivalents and compare both their nutritional and monetary differences with brand name products, (2) to provide the clinician with factors to consider when evaluating generic formulas--the source and distribution of macronutrients and micronutrients, and patient tolerance, nutritional status and outcome--and (3) to provide information on how to incorporate generic enteral formulas onto an institution's enteral formulary. In today's environment of diminishing health care budgets, generic enteral formulas can play a role in cost containment without sacrificing quality nutritional care.

Aged↗

Requirement for bowel preparation in colorectal surgery.

To determine whether mechanical bowel preparation influences the incidence of anastomotic dehiscence following colorectal surgery, 186 patients undergoing elective left colonic or rectal resection were randomized before surgery to bowel preparation (n = 89) or no bowel preparation (n = 97). Surgical technique was standardized and no patient had a defunctioning colostomy. Seventeen patients were excluded (seven with preparation, ten without). Indications for surgery in the remaining 169 patients were carcinoma (133 patients), diverticular disease (26), inflammatory bowel disease (six) and miscellaneous conditions (four). Operations performed were left colonic resection or reversal of Hartmann's procedure (26 with preparation, 28 without) and anterior resection (56 versus 59). The overall morbidity rate (18 per cent) was similar in the two groups. All seven clinical anastomotic leaks occurred after low anterior resection, in three of the 39 patients who had undergone bowel preparation and four of the 36 who had not (P > 0.9). Two deaths occurred, both of patients who had received bowel preparation, one being secondary to anastomotic leakage. Bowel preparation does not influence outcome after elective colorectal surgery.

Aged↗

Nitric oxide (endothelium-derived relaxing factor) attenuates revascularization-induced lung injury.

Aortic occlusion and revascularization (I-R) may lead to lung injury dependent on activated neutrophil adherence. Nitric oxide (NO) inhibits neutrophil adherence to endothelial cells. We studied the effect of increasing or decreasing NO levels with sodium nitroprusside (SNP) or N-nitro-L-arginine methyl ester (L-NAME) in an I-R lung injury model of 30 min ischemia followed by 120 min reperfusion. Sprague-Dawley rats (10/group) were randomized to controls, I-R, I-R treated with L-NAME (10 mg/ml/hr), and I-R treated with SNP (0.2 mg/ml/hr). Myeloperoxidase activity (MPO) was used as a measure of pulmonary neutrophil influx. Pulmonary endothelial permeability was measured by wet:dry weight ratio and bronchoalveolar lavage protein (BAL prot) and neutrophil counts (BAL PMN). Aortic occlusion and revascularization led to significant increases in pulmonary neutrophil influx (6.1 +/- 0.1 MPO u/g vs 3.05 +/- 0.4 MPO u/g in the control group, P < 0.001) and microvascular leakage; BAL prot (347 +/- 32 mg/ml in controls vs 454 +/- 16 mg/ml in the I-R group, P < 0.05); and BAL PMN (0.7 +/- 0.05 in controls vs 1.8 +/- 0.07 PMN/ml in the I-R group, P < 0.001). These changes were exacerbated further by administration of L-NAME (MPO = 8.9 +/- 0.7; BAL prot = 581 +/- 40 mg/ml; BAL PMN = 2.7 +/- 0.16 PMN/ml). Sodium nitroprusside therapy attenuated the I-R-induced lung injury (3.5 +/- 0.4 MPO u/g, P < 0.05 vs I-R; BAL prot = 330 +/- 61 mg/ml; BAL PMN = 0.9 +/- 0.1 PMN/ml).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Characterization and evaluation of a recombinant hepatitis B vaccine expressed in yeast defective for N-linked hyperglycosylation.

The hepatitis B (HB) virus preS2 + 2 polypeptide (the M or middle envelope polypeptide) is N-glycosylated at the N4 residue of the preS2 domain when expressed in recombinant yeast. Hyperglycosylation at this amino acid residue (the addition of a large number of mannose residues to the core oligosaccharide), which occurs in common yeast strains, results in an HB vaccine with diminished immunogenicity. Hyperglycosylation can be prevented by expressing the preS2 + S polypeptide in mutant yeast strains (e.g. mnn9) which limit N-linked glycosylation to the addition of only core saccharide residues. An HB vaccine prepared from recombinant yeast expressing the non-hyperglycosylated preS2 + 2 polypeptide was of similar immunogenicity in mice to a licensed HB vaccine and was much more immunogenic in humans than the hyperglycosylated preS2 + 2 vaccine.

Adult↗

Biochemical and molecular genetic studies of abdominal aortic aneurysm in an Irish population.

Abdominal aortic aneurysm (AAA) is a common disease of the elderly exhibiting a complex aetiology. In a survey of 82 Irish aneurysm patients, compared to 79 age- and sex-matched control subjects, we have investigated a number of potential biochemical and molecular genetic markers which are amenable to analysis from blood specimens and which might have predictive value for AAA. No significant differences were observed between patients and control subjects in relation to serum lipids, leucocyte elastase activity or serum alpha 1-antitrypsin concentration. We have used the polymerase chain reaction to screen the patient and control groups in search of disease-associated genetic variation on chromosome 16, particularly in the region of the Cholesteryl Ester Transfer Protein (CETP) gene. Although variation in allele frequencies was detected between patients and controls at the four marker loci studied, no significant gene-disease associations were detected. The absence of gene-disease associations in our study may indicate that the genetic component in the aetiology of AAA in Ireland differs from that in the UK. Alternatively, it may indicate that the high degree of polymorphism at microsatellite loci may make them unsuitable as markers for the study of gene-disease associations in moderately sized populations. We therefore conclude that the biochemical and molecular genetic markers which we have examined are of no predictive value, and that ultrasonography remains the screening modality of choice for abdominal aortic aneurysm.

Aged↗

[Dosimetric and qualitative evaluations of the use of rhodium filtration in mammography].

The value of rhodium filtration in mammography was compared with that of conventional molybdenum; dosimetric and qualitative tests were performed on a phantom and in vivo on informed and consenting patients. Phantom dosimetric tests confirmed a dose reduction with rhodium filtration changing according to thickness and primary beam energy. With rhodium filtration the dose decreased by 40% on the average topping 67% in breasts thicker than 6.5 cm. No significant differences were observed between rhodium and molybdenum filtration in clinical and phantom qualitative tests. Four radiologists--three of them in double blind--studied 29 mammograms repeated in the same technical setting and expressed a very slight preference for molybdenum also in thick and dense breasts. The slight preference was not based on higher diagnostic yield and therefore clinically irrelevant. Preferences appeared to be subjective, differing from one radiologist to another. In conclusion, the authors suggest the use of rhodium filtration in thick breasts because of the lower administered dose and of shorter exposure time with direct magnification.

Breast Neoplasms↗

Optimisation of small-scale coupling of A5B7 monoclonal antibody to carboxypeptidase G2.

Conjugates of F(ab')2 fragment of the monoclonal antibody A5B7 coupled to carboxypeptidase G2 (CPG2) have been produced using the heterobifunctional reagents 2-mercapto-[S-acetyl]acetic acid, N-hydroxysuccinimide ester (SATA) and m-maleimidobenzoyl-N-hydroxysuccinimide ester (SMPB). The effect of various levels of modifying reagent on enzyme activity and antigen binding activity were determined, and it was shown that whilst CPG2 is relatively sensitive to modification, insertion of three maleimide groups per CPG2 resulted in the loss of 30% of enzyme activity; A5B7 F(ab')2 was insensitive to modification, little or no activity being lost. The coupling efficiency of the reaction was shown to be fairly constant over a wide range of substitution levels. There was thus no advantage to be gained in using high substitution levels, which may result in loss of enzyme activity. The formation of undesired high molecular weight aggregates could be controlled by adjustment of the protein concentration during the final coupling step.

Antibodies, Monoclonal↗

Ankle fracture is associated with prolonged venous dysfunction.

Leg swelling is a significant problem following ankle fracture. Venous pump function and femoral and popliteal venous patency were assessed prospectively in 26 patients with ankle fractures requiring open reduction, internal fixation and immobilization in plaster. Functional venous volume, venous filling index (VFI), ejection volume fraction (EVF) and residual volume fraction (RVF) were measured using air plethysmography at 5 days and at 6, 12 and 18 weeks after fracture. The uninjured leg was used as a control. Popliteal and femoral venous patency was determined using duplex ultrasonography. No patient developed deep vein thrombosis during the study. At 5 days after fracture there was a significant reduction in mean(s.d.) EVF, 18.2(12.1) versus 55.9(19.5) per cent, and increase in RVF, 87.0(14.3) versus 42.5(22.2) per cent (both P < 0.001). Analogous values were similar at 6 weeks, EVF 28.5(21.2) versus 55.6(21.9) per cent, RVF 82.2(16.8) versus 48.5(23.8) per cent (both P < 0.001), and at 12 weeks, EVF 39.1(16.0) versus 60.3(14.9) per cent, RVF 64.7(18.8) versus 38.8(13.2) per cent (both P < 0.001). However, by 18 weeks there was no significant difference in venous function between fractured and control limbs. It is concluded that there is a significant and prolonged impairment in venous pump function following ankle fracture.

Ankle Injuries↗

Selective cholangiography in laparoscopic cholecystectomy.

Laparoscopic cholecystectomy is now the method of choice for removing the diseased gallbladder. Asymptomatic common bile duct stones occur in approximately 6 per cent of patients. Controversy exists, however, as to whether selective or routine peroperative cholangiography should be performed during laparoscopic cholecystectomy. Over a 21-month period 300 consecutive laparoscopic cholecystectomies without routine cholangiography were attempted. There were 28 conversions. In all, 229 patients did not undergo cholangiography and in this group there were two common duct injuries. These were both identified and dealt with by open operation. Five patients underwent peroperative cholangiography, none of whom was found to have common duct pathology. Endoscopic retrograde cholangiopancreatography was performed in 38 patients. Of 27 who had this investigation performed before operation, common duct stones were diagnosed in seven (26 per cent). Two common duct stones were discovered in 11 patients who underwent the investigation after operation. Thus only two of 240 patients (0.8 per cent) who did not undergo preoperative or peroperative cholangiography subsequently had symptomatic duct stones. Peroperative cholangiography may be indicated in selected patients who have had symptoms of common bile duct stones or in those in whom the biliary anatomy is unclear. However, routine preoperative or peroperative cholangiography is unnecessary during laparoscopic cholecystectomy.

Adolescent↗

How much heparin? A simple in vitro test.

A simple in vitro test to calculate the dose of heparin required to achieve optimal in vivo anticoagulation during surgery has been assessed in 15 patients who subsequently underwent vascular surgery. Heparin was added to four aliquots of patients blood in vitro to give five solutions with heparin concentrations ranging from 0-0.8 units/ml of plasma. The activated partial thromboblastic times (APTT) of each of these samples was then measured and the natural log (ln) of the APTT calculated. The natural log of the APTT in vitro was then plotted against the in vitro heparin concentration. From this linear correlation the concentration of heparin required to achieve an APTT 2.5 times the normal in vitro (Hc) for the 15 different patients was calculated and ranged from 0.4-0.75 units/ml (median 0.47). Based on an estimate of the plasma volume (PV), the bolus dose of heparin given intravenously to each patient to produce an equivalent anticoagulant response in vivo was calculated (Hc x PB). Heparin boli administered ranged from 1000-2000 units (median 1500). The mean in vivo APTT achieved was 77% of the predicted value (range 62%-123%). Such an estimation of an in vivo response, by means of an in vitro test, should help to more accurately predict the effects of heparin in vivo and individualise anticoagulation dosage.

Aged↗