PubMed Health⌕ Search

Biomedical subjects

H Blacklock

Publications and source records attributed to H Blacklock.

10 recordsLinked to original sources
PubMed1991

Four different mutations in codon 28 of alpha spectrin are associated with structurally and functionally abnormal spectrin alpha I/74 in hereditary elliptocytosis.

Hereditary elliptocytosis (HE) Sp alpha I/74 is a disorder associated with defective spectrin (Sp) heterodimer self-association and an abnormal tryptic cleavage of the 80-kD alpha I domain of Sp resulting in increased amounts of a 74-kD peptide. The molecular basis of this disorder is heterogeneous and mutations in codons 28, 46, 48, and 49 (codons 22, 40, 42, and 43 in the previous nomenclature which did not include the six NH2-terminal amino acids) have been reported. In this study we present data on seven unrelated HE Sp alpha I/74 kindred from diverse racial backgrounds in whom we identified four different mutations all occurring in exon 2 of alpha Sp at codon 28. Utilizing the polymerase chain reaction we established a CGT----CTT; Arg----Leu 28 mutation in one kindred of Arab/Druze origin. In two unrelated white kindred of English/European origin the substitution is CGT----AGT; Arg----Ser 28 and in two apparently unrelated white kindred from New Zealand, the mutation is CGT----TGT; Arg----Cys 28. Finally, in one American black kindred and in a black kindred from Ghana the mutation involves CGT----CAT; Arg----His 28. Allele specific oligonucleotide hybridization confirmed that the probands are heterozygous for the respective mutant alleles. All four point mutations abolished an Aha II restriction enzyme site which allowed verification of linkage of the mutation with HE Sp alpha I/74. Our results imply that codon 28 of alpha Sp is a "hot spot" for mutations and also indicate that Arg 28 is critical for the conformational stability and functional self association of Sp heterodimers.

Base Sequence↗
PubMed1988

A randomized trial of empirical antibiotic therapy with one of four beta-lactam antibiotics in combination with netilmicin in febrile neutropenic patients.

Over a two year period 174 evaluable episodes of fever in neutropenic patients were treated in a randomized study comparing four beta-lactam antibiotics, each given in combination with netilmicin. Exclusions included episodes due to viral or fungal infection, and trial violations. Most patients were receiving treatment for leukaemia, including 18% undergoing bone marrow transplantation. The overall response rate (EORTC criteria) was 66%, ranging from 56% for cefoperazone to 76% for mezlocillin. Microbial documentation was obtained in 31% of episodes; Gram-positive isolates were most frequent but Pseudomonas aeruginosa was found in 18 patients. In patients with microbiologically documented infection 70% improved, overall--from 40% with cefoperazone to 80% with piperacillin (P less than 0.05). Nephrotoxicity was seen in 6.7% and was associated with severe documented sepsis. Hypokalaemia was seen in 29% and was most marked in patients receiving ticarcillin. Rashes occurred in 6.6% overall, with no difference between the groups. Ototoxicity, shown by serial audiograms, was seen in 4.7% of patients. No evidence of vestibular dysfunction was seen in 62 patients studied. Of thirteen deaths due to the primary infection, seven were caused by Ps. aeruginosa and five by fungi.

Agranulocytosis↗
PubMed1987

The effect of total body irradiation and bone marrow transplantation during childhood and adolescence on growth and endocrine function.

Seventeen children (11 M, 6 F) with acute leukaemia and myeloproliferative disorders were investigated for growth and endocrine dysfunction. All had undergone bone marrow transplantation prepared with cyclophosphamide and single fraction total body irradiation (900-1000 cGy) between 1.5 and 3.8 (mean 2.2) years previously. The majority of children exhibited growth failure, which was of multiple aetiology. Ten patients, of whom eight had had previous prophylactic cranial irradiation, had evidence of growth hormone deficiency based on the reduced growth hormone response to insulin induced hypoglycaemia. Three patients had evidence of hypothalamic damage as shown by their growth hormone response to 200 micrograms GHRH (1-29) NH2 intravenously. Gonadal failure was common, assessed clinically, and biochemically by basal gonadotrophin and sex steroid concentrations. All four girls of adolescent age (10.6-14.1 years) had ovarian failure requiring sex steroid replacement. Of the eight boys of adolescent age (12.3-18.3 years), two had testicular failure requiring sex steroid supplements. Both of these had had previous testicular irradiation. Five others had compensated gonadal failure, and one had normal Leydig cell function. Abnormalities of the TSH response to TRH occurred in 10 patients but only three had overt hypothyroidism. Unlike growth hormone deficiency, gonadal and thyroid dysfunction showed no correlation with previous cranial radiotherapy.

Adolescent↗
PubMed1986

Bone-marrow transplantation has a limited role in prolonging second marrow remission in childhood lymphoblastic leukaemia.

Fifty-three children with acute lymphoblastic leukaemia whose first complete remission ended in bone-marrow relapse received similar reinduction and consolidation therapy. Thirteen had an HLA-compatible sibling donor and were eligible to receive a bone-marrow transplant (BMT); five survive, all off treatment in continuing remission. Forty had no donor and received further chemotherapy; sixteen survive, twelve in remission and six off treatment. After 1-5.5 years' follow-up from relapse, there is no significant difference in survival between the groups. The major obstacle to success is marrow relapse which occurred in two eligible patients before BMT could be carried out. The lengths of first and second remissions in both groups were significantly correlated. Morbidity in survivors was substantial. The scope of BMT as retrieval therapy for ALL is limited by the instability of second remissions; this difficulty will not be overcome by increasing the number of potential donors or the use of autologous marrow.

Adolescent↗
PubMed1986

Salivary amylase and pancreatic enzymes in serum after total body irradiation.

Amylase increases in serum after total body irradiation (TBI). To investigate whether this increase is ascribable to pancreatic or salivary amylase, or both, we measured the post-irradiation activity concentration of the three major pancreatic enzymes (trypsin, amylase, and lipase) and of salivary-type amylase in serum from six leukemic patients given TBI before bone-marrow transplantation. Salivary amylase increased by as much as 50-fold after TBI, peaking on the first day after the irradiation. The increase was associated with the development of clinical parotitis. Pancreatic trypsin, total amylase, and lipase increased inconsistently and to a much smaller degree. There were no associated clinical features of pancreatitis. Our data show that, at the dose of radiation given to our patients, there is no danger of pancreatitis as a complication, but parotitis is a consistent development after TBI.

Amylases↗