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Biomedical subjects

J Condon

Publications and source records attributed to J Condon.

32 records · Page 2Linked to original sources

Prognostic significance of detection of monoclonality in remission marrow in acute lymphoblastic leukemia in childhood. Australian and New Zealand Children's Cancer Study Group.

Techniques based on the polymerase chain reaction (PCR) to detect rearrangement of the immunoglobulin or T-cell receptor genes can detect residual disease in leukemia and hence have the potential to improve prognosis and treatment. Such techniques may involve either detection of monoclonality, which is simple and quick but has limited sensitivity, or specific detection of the leukaemic clone, which is complex and time-consuming but has high sensitivity. The PCR was used to detect monoclonal rearrangements of the immunoglobulin heavy chain and/or T-cell receptor gamma chain genes in archival marrow specimens from 185 children with acute lymphoblastic leukemia who achieved remission during two consecutive Australasian trials of treatment. A monoclonal rearrangement was detected at diagnosis in 152 (84%) patients and in these patients detection of the same rearrangement in the remission marrow at the end of induction therapy was highly significantly correlated with outcome. There were nine patients in whom polymerase chain reaction showed only the monoclonal rearrangement and eight (89%) relapsed; there were 26 patients in whom PCR showed the leukemic monoclonal rearrangement as well as polyclonal rearrangements from normal lymphocytes and 12 (46%) relapsed; and there were 117 patients in whom only polyclonal rearrangements could be detected and only 29 (25%) relapsed. In patients who relapsed, remissions were shorter in those patients in whom the leukemic rearrangements had been detected in the remission marrow. Treatment in the later trial was more intensive than in the earlier trial, the results were better and the PCR detected the leukemic rearrangement in the remission marrow in significantly fewer patients. We conclude that detection by PCR of the monoclonal gene rearrangement of the leukemic clone in remission marrow indicates that numerous leukemic cells have survived induction therapy and is a good predictor of relapse. However, due to limited sensitivity of the test, failure to detect the leukemic clone by PCR is not a sufficiently good predictor of ultimate cure.

Bone Marrow↗

Quantitation of targets for PCR by use of limiting dilution.

We describe a general method to quantitate the total number of initial targets present in a sample using limiting dilution, PCR and Poisson statistics. The DNA target for the PCR was the rearranged immunoglobulin heavy chain (IgH) gene derived from a leukemic clone that was quantitated against a background of excess rearranged IgH genes from normal lymphocytes. The PCR was optimized to provide an all-or-none end point at very low DNA target numbers. PCR amplification of the N-ras gene was used as an internal control to quantitate the number of potentially amplifiable genomes present in a sample and hence to measure the extent of DNA degradation. A two-stage PCR was necessary owing to competition between leukemic and non-leukemic templates. Study of eight leukemic samples showed that approximately two potentially amplifiable leukemic IgH targets could be detected in the presence of 160,000 competing non-leukemic genomes. The method presented quantitates the total number of initial DNA targets present in a sample, unlike most other quantitation methods that quantitate PCR products. It has wide application, because it is technically simple, does not require radioactivity, addresses the problem of excess competing targets and estimates the extent of DNA degradation in a sample.

Base Sequence↗

Detection and quantitation of neoplastic cells in acute lymphoblastic leukaemia, by use of the polymerase chain reaction.

We report a simple and robust method for sensitive quantitation of leukaemic cells in acute lymphocytic leukaemia. Chain determining region 3 (CDR3) of the immunoglobulin heavy chain gene is a precise genetic marker for a patient's leukaemic clone. Quantitation of the leukaemic lymphocytes was achieved by use of the polymerase chain reaction to detect CDR3 at limiting dilution of DNA samples. Five patients were studied and high levels (1 in 1 to 1 in 10) of leukaemic cells were detected at diagnosis or relapse. Leukaemic cells were detected in remission marrows from three patients, at levels of 1 in 1000 to 1 in 100,000. All five patients showed a 1000 to 100,000-fold reduction in the levels of leukaemic cells after induction therapy. This technique should prove useful for monitoring therapy and may help predict outcome.

Adult↗

The RANZCP membership examination: a review of the relevant literature.

The design of any assessment system, as well as the way it is scored, must be intimately linked to the purpose it is to serve. Previous literature on the RANZCP membership examination has tended to focus exclusively on issues of reliability and validity at the expense of broader concerns. The present paper selectively reviews the literature on assessment in education highlighting the differences between normative and criterion referencing and their implications for the profession. Published studies of the reliability of post-graduate written and oral examinations are reviewed focussing particularly on those conducted in psychiatric settings. Finally, the arguments for and against continuous assessment are summarised. Greater familiarity with the literature may result in more informed and constructive debate about the assessment process than has hitherto been evident.

Australia↗

Abnormal beta and gamma sialoglycoprotein associated with the low-frequency antigen Lsa.

This paper describes the association of the low-frequency antigen Lsa with high-molecular-weight variants of beta- and gamma-sialoglycoproteins (beta-SGP, gamma-SGP). The variant beta-SGP, designated beta Lsa, carries the Ge3 epitope and the epitopes recognised by 3 murine monoclonal anti-beta-SGP antibodies. The variant gamma-SGP, designated gamma Lsa, carries the Ge2 and Ge3 epitopes. Both beta Lsa and gamma Lsa showed enhanced reactions in immunoblotting with anti-Ge3 sera--which may indicate the presence of 2 Ge3 epitopes on beta Lsa and gamma Lsa. These findings would be consistent with the proposed structure of the Lsa glycophorin C gene.

Epitopes↗

Immunocytochemical localization of a kallikrein-like serine protease (esterase A) in rat salivary glands.

Light and electron microscopic (EM) immunocytochemical methods have been used to localize arginine esterase A, a kinin-generating enzyme immunologically similar to tissue kallikrein, in rat salivary glands. Both polyclonal and monoclonal antibodies to arginine esterase A were used in these studies. By means of a polyclonal antiserum, esterase A was found in granular tubules of submandibular glands and in striated ducts of all three major salivary glands, in a distribution similar to that of tissue kallikrein. With recently developed specific monoclonal antibodies to esterase A, this enzyme was localized in the granules of some (but not all) granular convoluted tubule cells (GCT) and along the basal membranes (but not in apical granules) of striated ducts. By an EM immunoperoxidase method, esterase A was localized subcellularly in granules of some GCT cells and along the basal cell membranes of the tubule and duct system. Thus, this enzyme is found in some sites (GCT granules) shared with tissue kallikrein, but in some unique sites, i.e., basal membranes of striated ducts. The polyclonal antibody used in the present study cross-reacted with tissue kallikrein, but when absorbed with kallikrein, it gave the staining pattern characteristic of monoclonal antibody to esterase A.

Animals↗

Application of the avidin-biotin immunohistochemical method for the diagnosis of alveolar hydatid disease from tissue sections.

The avidin-biotin immunohistochemical (ABC) method was applied to the diagnosis of alveolar hydatid disease in patients from the hyperendemic region of western Alaska. The test was specific for larval cestodes of the genus Echinococcus, and exhibited high sensitivity. A negative reaction was obtained in all cases in which spontaneous death of the larval cestode had occurred. Results were inconsistent in sections of lesions from patients who had received long-term therapy with mebendazole, because of the persistence of antigens for a considerable time following the death of the parasite.

Animals↗

Chronicity of infection with Treponema paraluis-cuniculi in New Zealand white rabbits.

Popliteal lymph nodes from eight New Zealand white rabbits with clinical or serological evidence of naturally acquired infection with Treponema paraluis-cuniculi were transferred to rabbits that had not been exposed to this infection. Lymph nodes from two rabbits successfully transmitted infection. The nodes from one of these rabbits transmitted infection during both the acute and chronic stages of infection. Recipients that were successfully infected showed concomitant antibody responses in the Venereal Disease Research Laboratory (VDRL), rapid plasma reagin (RPR), and fluorescent treponemal antibody-absorption (FTA-ABS) tests six to 10 weeks after inoculation; recipients of uninfected nodes showed no change in serological state. Antibody responses were followed by the development of dark field positive genital lesions 14 to 15 weeks after inoculation.

Animals↗

Clinical course and treatment of venereal spirochaetosis in New Zealand white rabbits.

Ten sporadic cases of venereal spirochaetosis, caused by Treponema paraluis-cuniculi, were seen in New Zealand white rabbits in two years. An equal number of males and females were affected. Females tended to have milder clinical signs than males. Lesions were usually found on the prepuce in males and the vulva in females, although the anus and skin of the perineum were also affected. Facial lesions were rare. Lesions healed in seven to 28 days in rabbits treated with penicillin. Eight rabbits had antibodies reactive in the Venereal Disease Research Laboratory (VDRL), rapid plasma reagin (RPR), and fluorescent treponemal antibody absorbed (FTA-ABS) tests when the disease was first diagnosed. In several rabbits followed longitudinally, RPR test results became negative two to four months after antimicrobial treatment, VDRL antibody titres diminished but usually persisted at low levels, while FTA-ABS antibodies declined slowly and were still evident 12 months after treatment.

Animal Diseases↗

Treponema paraluis-cuniculi infection in a commercial rabbitry: epidemiology and serodiagnosis.

The epidemiology of Treponema paraluis-cuniculi infection in a commercial rabbit breeding facility was described using several serologic tests. The Venereal Disease Research Laboratory, rapid plasma reagin, microhemagglutination and fluorescent treponemal antibody-absorption tests were used to detect antibodies to T paraluis-cuniculi. Young adult New Zealand white rabbits, tested prior to entry into the breeding program, were nearly always free of T paraluis-cuniculi infection. In adult females, the prevalence of T paraluis-cuniculi infection increased with parity; females para 6 or greater were usually seropositive. Most adult males seroconverted within 6 months of entering the breeding program; all males were seropositive after 12 months in the breeding program. This suggested that T paraluis-cuniculi spreads mainly by horizontal transmission during breeding in adult rabbits. Of the two nontreponemal antigen tests used, the Venereal Disease Research Laboratory test was more sensitive, whereas the rapid plasma reagin test was more specific in detecting T paraluis-cuniculi infection; the fluorescent treponemal antibody-absorption test was used as the confirmatory treponemal antigen test. However, neither nontreponemal antigen test was completely satisfactory. On the other hand, the sensitivity and specificity of the microhemagglutination test compared favorably with the fluorescent treponemal antibody-absorption test. Since the microhemagglutination test combines desirable features of both a screening and verification procedure, it should be the test of choice for detection of T paraluis-cuniculi infection.

Animals↗

Selective media for Pasteurella multocida and Bordetella bronchiseptica.

Easily prepared and inexpensive culture medium for the isolation of Pasteurella multocida and Bordetella bronchiseptica from the nares of laboratory rabbits was prepared by incorporating 2 micrograms/ml clindamycin into standard blood agar. Using this medium, the time and materials required to identify and isolate Pasteurella multocida was substantially reduced with only a slight loss in sensitivity. The combination of 2 micrograms/ml clindamycin and 4 micrograms/ml neomycin was effective in isolating Bordetella bronchiseptica from rabbits.

Animals↗

Ventricular septal defect due to septal infarction after repair of tetralogy of fallot.

A case is reported of ventricular septal defect resulting from septal infarction following repair of a tetralogy of Fallot. The infarct probably resulted from division of a septal coronary artery during resection of the hypertrophied infundibulum. The superficial position of the septal artery on the right side of the septum in tetralogy makes it surprising that this complication has not been previously reported.

Child↗

Inappropriate antihypertensive therapy in the elderly.

Six symptomless patients aged 64-84 (mean 72) years received antihypertensive therapy from their family doctors. Pretreatment systolic pressures ranged from 160 to 220 mm Hg and disastolic pressures from 80 to 120 mm Hg. Within one week of starting therapy all six patients were admitted as emergencies with epidoses of unconsciousness. Admission systolic pressures ranged from 80 to 150 mm Hg and diastolic pressures from 50 to 90 mm Hg. Before admission each patient had experiences symptoms of postural hypotension and had become housebound. After antihypertensive therapy was stopped, one patient had a residual left homonymous hemianopia but the others recovered completely. A raised systolic and distolic pressure is common in the elderly; potent antihypertensive treatment may seriously impair the quality of life and is often unecessary.

Age Factors↗