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Biomedical subjects

J M Hawkins

Publications and source records attributed to J M Hawkins.

34 records · Page 2Linked to original sources

Karyotype and T-cell receptor expression in T-lineage acute lymphoblastic leukemia.

The relationship between karyotype and expression of the T-cell receptor (TCR) proteins was examined in 19 patients with T-lineage acute lymphoblastic leukemia (T-ALL). All patients expressed CD3 molecules in the cytoplasm or on the cell membrane. Patients were classified according to TCR expression thus: no TCR expression (TCR-), six cases; cytoplasmic expression of TCR beta chain (cTCRB) only, six cases; membrane expression of TCR alpha and beta chains (mTCRAB), five cases; membrane expression of TCR gamma and delta (mTCRGD), two cases. A chromosomally abnormal clone was detected in 15 cases. The most common site of chromosomal change was at 14q11 (seven cases), the chromosomal band to which TCRA and TCRD have been mapped; as a deletion (two cases); or as a translocation with reciprocal breakpoints in bands containing the TCRG (7p15); TCRB (7q35); or putative oncogenes HOXII (10q24), RBTN2 (11p13) or MYC (8q24) genes. Breakpoints were also seen in 6q (three cases), 9p (two cases), or 11q23 (two cases). The following observations were made: All four chromosomally normal cases lacked TCR expression (TCR-). Breakpoints at 14q11 were found in one of six TCR- cases, four of six cTCRB cases, and two of five mTCRAB cases. Abnormalities of 6q and of 9p were seen only in cases with full TCR expression (mTCRAB or mTCRGD).

Antigens, Differentiation, T-Lymphocyte↗

Isochromosome 1q in acute monocytic leukemia: a new nonrandom association.

We report a case of de novo acute monocytic leukemia in a 25-year-old man in whom the sole clonal cytogenetic abnormality was an additional isochromosome 1q. Cytogenetic polymorphisms indicate that, in addition to the formation of the isochromosome, a duplication of the remaining normal chromosome 1 had taken place. Other reported cases suggest an association between acute monocytic leukemia and i(1q).

Adult↗

Evaluation of cytogenetic samples and pertinent technical variables in adult acute lymphocytic leukemia.

Data on 200 bone marrow and peripheral blood samples received from 190 adults with acute lymphoblastic leukemia (ALL) were analyzed with respect to sample type (bone marrow or peripheral blood), sample cell count (concentration and total count), time in transit (days), and year of analysis. Each sample was assessed for 1) number and quality of metaphases, and 2) presence or absence of a clone. Sample type, concentration of cells, time in transit, and year of analysis all significantly affected the number and quality of metaphases and the detection of a clone. The chance of obtaining 10 or more cells for cytogenetic analysis in adult ALL was shown to be as low as 10% with a suboptimal sample (peripheral blood, low cell concentration) and as high as 70% with an optimal sample (bone marrow, adequate cell concentration, 1 day or less in transit). The likelihood of detecting a clone was smallest (0%) for the group (bone marrow, adequate cell concentration, 2 or more days in transit) and greatest (68%) in the optimal group (bone marrow, adequate cell concentration, 1 day or less in transit).

Bone Marrow Examination↗

Ewing's sarcoma t(11;22) in a case of acute nonlymphocytic leukemia.

Chromosome analysis of bone marrow cells from a patient with acute nonlymphocytic leukemia M2 revealed the translocation t(11;22)(q24;q12) usually associated with Ewing's sarcoma. Molecular investigations ruled out the possibility that this was a variant Philadelphia translocation with breakpoints in the major breakpoint cluster region. Although cytogenetic analysis was not available at diagnosis, this abnormality was found both pre- and postallogeneic bone marrow transplant.

Adolescent↗

Molecular investigation of 19p13 in standard and variant translocations: the E12 probe recognizes the 19p13 breakpoint in cases with t(1;19) and acute leukemia other than pre-B immunophenotype.

The gene E2A has recently been cloned, mapped to 19p13 and shown to be rearranged in cases of pre-B acute lymphoblastic leukemia (ALL) with t(1;19) (q23;p13). Nine cases with a 19p13 breakpoint, four having a phenotype other than pre-B, have been investigated with the E12 probe to the E2A gene. Five cases had t(1;19) (q23;p13) and C-ALL with pre-B phenotype in four out of four cases tested. Two cases had t(1;19) (q21;p13), one with Null cell phenotype, t(4;11), and 'jumping translocations' and the other with acute non-lymphocytic leukemia M5 following bone marrow transplantation for C-ALL. Variant translocations in patients with ALL were t(15;19) (q15;p13) and t(17;19) (q21;p13). Southern blotting with E12 showed rearrangement in the cases with t(1;19) (q23;p13) and t(1;19) (q21;p13), but not in other cases with variant 19p13 breakpoints. Thus rearrangement of the E2A gene is not restricted to cases with pre-B ALL but may also occur in acute leukemias with other immunological phenotypes. Failure to detect rearrangement in 19p13 variants may be due to an E2A breakpoint outside the E12 recognition region. Alternatively, there may be further genes in this location with relevance to leukemogenesis.

Adolescent↗

Philadelphia positive acute lymphoblastic leukemia in adults: age distribution, BCR breakpoint and prognostic significance.

Clonal karyotype, clinical and blast cell features were established in 113 adults, aged 15-68 (mean 31.2) years with acute lymphoblastic leukemia (ALL). The karyotypes were: Philadelphia positive (Ph+), 23 cases; t(4;11), six cases; other chromosome findings (group II), 84 cases. Ph+ patients were older (mean 39.7 years) at presentation than the group II patients (mean 28.3 years) (p less than 0.0001). Ph+ was less frequent than expected in teenagers (15-20 years) (10.3%) and patients aged 21-50 years (21.8%), and more frequent in patients over 50 years old (43.8%) (p less than 0.01). Follow-up (between 0.5 and 4.5 years) was obtained for 108 patients. Age and karyotype (Ph+ versus group II) were prognostically significant for event-free (EFS) and overall survival (S) (p less than 0.001 in each instance). Ph+ patients fared worse than group II cases in all age groups, but karyotype added prognostic significance to age only when Ph+ and t(4;11) cases were combined (group I) (group I versus group II: EFS, p = 0.054; S, p = 0.043). The Ph breakpoint location M-bcr+ (nine cases) and M-bcr- (14 cases) was irrelevant to age (mean 37.7 and 41.3, respectively) and to prognosis. The findings indicate a fundamental difference between the genetics of ALL in most older and the majority of younger patients which may partly explain the increasingly poor prognosis with age.

Adolescent↗

First intron and M-bcr breakpoints are restricted to the lymphoid lineage in Philadelphia positive acute lymphoblastic leukemia.

Knowledge of the level of commitment of the target cell in hematological malignancies may have important therapeutic and prognostic implications. Cell lineage involvement was investigated in two cases presenting with acute lymphoblastic leukemia diagnosed on clinical and immunological findings and having the Philadelphia translocation t(9;22)(q34;q11). DNA from cells separated into mononuclear (lymphoid) and granulocytic fractions was hybridized with Philadelphia breakpoint-specific probes. This revealed that the breakpoint giving rise to the Philadelphia chromosome in case 1 was within the major breakpoint cluster region and in case 2 was in the first intron of the BCR gene. Rearrangement was found in the lymphoid but not the granulocyte fraction in each case. It is therefore concluded that the target cell for chromosomal change in these cases was a lymphoid committed progenitor cell, irrespective of breakpoint location.

Adult↗

Potential hazard from spray cleaning of floors in hospital wards.

The potential hazard from using contaminated spray cleaning fluid to clean hospital floors was investigated. Eight of 10 sprays in daily hospital use failed the 'in-use' test of Kelsey & Maures. Contamination was due to Gram-negative bacilli, mainly Pseudomonas spp. An experiment showed that freshly diluted cleaning fluid in a new spray container became contaminated in 6 days, although the route of contamination of the fluid is not clear. Air samples and samples from bedding collected during spray cleaning with contaminated fluid showed the presence of Pseudomonas spp. Use of freshly diluted cleaning fluid and daily cleaning of spray containers is recommended.

Aerosols↗

Effects of pre-anaesthetic glycopyrrolate and cimetidine on gastric fluid acidity and volume in children.

The effects of pre-anaesthetic glycopyrrolate and cimetidine on gastric fluid pH and volume were studied in 96 paediatric patients from ages 6 months to 12 years undergoing elective surgery. They were randomly allocated into six groups with 16 patients in each group. Patients in group I received neither glycopyrrolate nor cimetidine and served as controls. Group II patients received glycopyrrolate, 5 micrograms kg-1 intramuscularly in a.m. Patients in group III received cimetidine 5 mg kg-1 orally in a.m. Group IV patients received cimetidine 5 5 mg kg-1 orally in a.m. and glycopyrrolate 5 micrograms kg-1 in a.m. Patients in group V received cimetidine 5 mg kg-1 orally h.s. and a.m. Group VI patients received cimetidine as in group V and also received glycopyrrolate as in group II. Patients with gastric pH 2.5 or less and volume of gastric contents 0.4 ml kg-1 or greater were defined to be at risk of pulmonary damage if aspiration should occur. The patients in the control group had a mean gastric pH of 1.91 +/- 0.074 and mean gastric volumes of 0.52 +/- 0.06 ml kg-1. Ninety-four per cent of patients in this group had gastric pH less than or equal to 2.5 and 69% of patients had gastric volumes greater than or equal to 0.4 ml kg-1. Glycopyrrolate (group II) reduced patients with pH less than or equal to 2.5 to 50% and volumes greater than or equal to 0.4 ml kg-1 to 44%. Cimetidine markedly reduced both gastric acidity (gastric pH less than or equal to 2.5 in 0-13% of patients in groups III-VI) and gastric volume (greater than or equal to 0.4 ml kg-1 in 19-38% of patients in groups III-VI). Only a maximum of 13% of the patients presented with combination of both risk factors in groups III-VI.(ABSTRACT TRUNCATED AT 250 WORDS)

Child↗

Colonisation of babies and their families by group B streptococci.

A high incidence of group B streptococcal disease of the newborn in West Berkshire led to a prospective study of the condition. Cultures taken from 1090 babies shortly after birth showed that 65 (6%) were colonised with the streptococcus. Thirty of these babies were assigned to group 1. Bacteriological samples were taken from babies and mothers at birth and at four, eight, and 12 weeks, and also from fathers and siblings. Fifty uncolonised babies and their families were similarly studied and served as controls (group 2). In group 1,28 of the 30 mothers and 14 of the 28 fathers examined were colonised by group B streptococci. In group 2 the streptococci were isolated from three babies, 12 mothers, and 11 out of 45 fathers during follow-up. These findings suggest that group B streptococci are carried predominantly in the lower gastrointestinal and genitourinary tracts. Most families are lightly colonised, but in others maternal colonisation is stable and heavy and the incidence of paternal colonisation high. Results of serotyping suggest that sexual transmission occurs, which may explain the difficulty in eradicating the organism during pregnancy.

Adult↗

Anaphylaxis after sesame seed ingestion.

Four patients with histories of systemic anaphylaxis or angioedema and urticaria after ingestion of sesame seed or sesame oil-containing products were studied for anti-sesame seed extract IgE by the radioallergosorbent test (RAST). Three of four were found to be positive. RAST inhibition after density-gradient ultracentrifugation of sesame seed extract indicates that the most active allergens appear to have molecular weights between 8,000 to 62,000 daltons.

Adult↗

Clinical placements by computer program.

A computer allocation and recording system was developed and implemented to permit an integrated, sequesntial and, to some extent, individually tailored clinical experience for occupational therapy students. Necessary technical information is described for those who may wish to adapt the program to their needs. A difficult administrative task was solved by a machine well known for its speed and accuracy, extensive memory, and copy-typing capabilities.

Clinical Competence↗

The pharmacology of local anesthetics.

As practitioners of dentistry we are truly fortunate to have these wonder agents which we tend to use like water everyday. It is estimated that over 11,000,000 cartridges of local anesthetics are administered every year in Ontario. The incredible safety record speaks for itself. However, we must caution ourselves that a local anesthetic is a drug and as such demands our ongoing skill, care and judgment for each individual case.

Anesthetics, Local↗