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Biomedical subjects

G Buchanan

Publications and source records attributed to G Buchanan.

At least 19 recordsLinked to original sources
PubMed1995

Neutrophil pool sizes and granulocyte colony-stimulating factor production in human mid-trimester fetuses.

We quantified neutrophils and neutrophil progenitors, and assessed granulocyte colony-stimulating factor (G-CSF) production in the liver and bone marrow of 20 human abortuses after elective pregnancy termination between 14 and 24 wk of gestation. Mature neutrophils were not observed in any of the liver specimens, but were present in the bone marrow as early as 14 wk. The concentrations of neutrophils in the fetal marrow were extremely low, by comparison with term infants and adults, with less than 5% of the nucleated cells being segmented neutrophils, band neutrophils, or metamyelocytes compared with 31-69% in term infants. Despite the low neutrophil populations, progenitors which had the capacity for clonal maturation into neutrophils in vitro were abundant in the fetal liver and fetal bone marrow. In addition, such progenitors had a dose-response relationship to recombinant G-CSF similar to that of progenitors from the bone marrow of healthy adults. At each gestational age tested, stimulation of mononuclear cells from fetal liver with IL-1 alpha generated less G-CSF protein and fewer G-CSF mRNA transcripts than did stimulation of mononuclear cells from fetal bone marrow. Mononuclear cells from the fetal bone marrow produced less G-CSF protein and mRNA than did mononuclear cells from the blood of adults. Thus, the liver of the mid-trimester human fetus is almost devoid of neutrophils, and the bone marrow contains a significantly lower proportion of neutrophils than does the marrow of term neonates or adults. These findings correlate with IL-1 alpha-induced production of G-CSF in these organs.(ABSTRACT TRUNCATED AT 250 WORDS)

Abortion, Induced↗
PubMed1992

A study of toxicity and comparative therapeutic efficacy of vindesine-prednisone vs. vincristine-prednisone in children with acute lymphoblastic leukemia in relapse. A Pediatric Oncology Group study.

Vindesine (des-acetyl Vinblastine) is a synthetic derivative of vinblastine, and was produced with the hope that it would have less neurotoxicity and hematopoietic toxicity than other vinca alkaloids. Phase I and II studies also demonstrated significant activity in lymphoid malignancies, especially Acute Lymphoblastic Leukemia (ALL). The present study was designed to compare therapeutic effectiveness of twice weekly vindesine (2 mg/M2/dose) plus Prednisone (60 mg/M2/dose) (Treatment 1) to weekly Vincristine (2 mg/M2/dose) plus Prednisone (60 mg/M2/day) (Treatment 2). All patients were less than 21 years of age, and had documented bone marrow relapse (blast count > 25%). In 39 patients presumed sensitive to vincristine, there were 11 complete responses out of 20 patients (55%) randomized to receive vindesine/prednisone and 7 complete responses out of 19 patients (37%) treated with Vincristine/Prednisone. In 37 patients resistant to vincristine, there were 7 complete responses (19%). Vindesine was more toxic than Vincristine. Major toxicities of vindesine included paraesthesias, peripheral neuropathy and ileus. Vindesine hematological toxicity appeared greater, but such toxicity is hard to assess in patients with bone marrow disease. In this study, vindesine and vincristine had similar efficacy, but vindesine use was associated with more toxicity.

Adolescent↗
PubMed1992

Metastatic cervical lymph nodes: general practitioner referral patterns.

Premature excision biopsy of a cervical lymph node infiltrated by metastatic carcinoma may compromise patient survival since it is associated with an increased incidence of local wound recurrence and distant metastases. Seventy per cent of such patients have an identifiable head and neck primary, obviating the need for an excision biopsy. It is important therefore that they are examined by surgeons who are experienced in inspecting the upper aerodigestive tract and who are competent in performing definitive head and neck surgery. A questionnaire sent to all general practitioners of an Inner London and a District Health Authority revealed that only 18% and 33% respectively referred patients who they suspected of having a metastatic neck node to a department with an experienced head and neck surgeon. We conclude that greater emphasis on the correct management of these patients at both an undergraduate and postgraduate level may encourage subsequent generations of general practitioners to review their referral patterns.

Adult↗
PubMed1990

Teniposide (VM-26) and continuous infusion cytosine arabinoside for initial induction failure in childhood acute lymphoblastic leukemia. A Pediatric Oncology Group pilot study.

Twenty-six evaluable children with newly diagnosed acute lymphoblastic leukemia (ALL) who failed to achieve initial remission after receiving two to seven drugs for at least a 4-week period were given teniposide (VM-26) and continuous infusion cytosine arabinoside (Ara-C). Twenty-two received 150 mg/m2 of VM-26 on days 1 and 2 with 100 mg/2 of Ara-C as a continuous infusion on days 1 through 5; a second shortened course was given on day 14 to eight patients who had evidence of some antileukemic effect or were clinically judged able to tolerate a second course. The last four patients received three daily doses of VM-26 and a 7-day infusion of Ara-C at the same daily dosages. Twelve (48%) achieved complete remission (CR) of ALL. There was a trend toward decreasing response rates with an increasing number of drugs used in the initial induction regimen, i.e., five CR among seven patients with a prior two-drug induction attempt, six CR among 14 patients with a prior three- to four-drug induction attempt, and one CR among four patients with a prior five- to seven-drug induction attempt (P = 0.14). Ten of 17 non-T-cell patients and two of nine T-cell patients achieved remission (P = 0.10). The median time required to achieve a complete remission from the initiation of treatment was 26 days (range, 14-72 days). This period was shorter in those who required one course compared with those who required two induction courses, i.e., 25 days median vs. 44 days median. Toxicity was significant and due mainly to marrow aplasia and infection; one patient had severe prolonged VM-26-induced hypotension. Of the 12 patients entering remission, two were removed for marrow transplant and one was removed due to parental request. In the remaining nine patients, median remission duration was only 2 months (range, 1-18 months). All nine patients relapsed in the marrow. Among the entire group of 26 patients, only one patient is alive and a long-term event-free survivor (after allogeneic marrow transplant). Due to the current use of more aggressive initial induction regimens and the extremely poor prognosis in children who fail to achieve initial remission, more intensive regimens of continuation therapy or alternative therapies, such as bone marrow transplant, should be considered.

Adolescent↗
PubMed1990

Site-specific recombination of the tal-1 gene is a common occurrence in human T cell leukemia.

The tal-1 gene is altered as a consequence of the t(1;14) (p32;q11) chromosome translocation observed in 3% of patients with T cell acute lymphoblastic leukemia (T-ALL). tal-1 encodes a helix-loop-helix (HLH) domain, a DNA binding and dimerization motif found in a number of proteins involved in cell growth and differentiation. We now report that an additional 25% of T-ALL patients bear tal-1 gene rearrangements that are not detected by karyotype analysis. These rearrangements result from a precise 90 kb deletion (designated tald) that arises independently in different patients by site-specific DNA recombination. Since the deletion junctions resemble the coding joints of assembled immunoglobulin genes, tald rearrangements are likely to be mediated by aberrant activity of the immunoglobulin recombinase. Moreover, t(1;14)(p32;q11) translocations and tald rearrangements disrupt the coding potential of tal-1 in an equivalent manner, and thereby generate a common genetic lesion shared by a significant proportion of T-ALL patients.

Base Sequence↗
PubMed1990

The tal gene undergoes chromosome translocation in T cell leukemia and potentially encodes a helix-loop-helix protein.

We have analyzed t(1;14)(p32;q11) chromosome translocations from two patients with T cell acute lymphocytic leukemia. The chromosome 1 breakpoints of these patients lie within a kilobasepair of each other, and thus define a genetic locus (designated tal) involved in T cell oncogenesis. Moreover, we have identified sequences within tal that potentially encode an amphipathic helix-loop-helix motif, a DNA-binding domain found in a variety of proteins that control cell growth and differentiation. The homology domain of tal is especially related to that of lyl-1, a gene on chromosome 19 that has also been implicated in T cell oncogenesis. Hence, tal and lyl-1 encode a distinct family of helix-loop-helix proteins involved in the malignant development of lymphocytes.

Amino Acid Sequence↗
PubMed1989

The chromosome translocation (11;14)(p13;q11) associated with T-cell acute lymphocytic leukemia: an 11p13 breakpoint cluster region.

The translocation (11;14)(p13;q11) was observed in karyotypes of leukemic cells from a 3-year-old boy with T-cell acute lymphocytic leukemia (T-ALL). Since this translocation is a recurrent marker of T-ALL, we undertook to investigate its mode of formation and role in leukemogenesis. The cytogenetic breakpoint on chromosome 14 occurs in 14q11, the same band wherein lies the T-cell receptor alpha/delta chain gene; and Southern hybridization analysis of peripheral blood and bone marrow DNA uncovered a tumor-specific rearrangement in the D delta-J delta region of this locus. DNA encompassing the rearrangement was isolated by molecular cloning, and further analysis revealed it to be the t(11;14)(p13;q11) junction. Nucleotide sequence determination of the junction indicates that the 14q11 breakpoint occurs immediately adjacent to the D delta 2 gene segment. Hence, the translocation arose as an aberrant rearrangement between the downstream recombination signal of D delta 2 and a pseudo recombination signal adjacent to the chromosome 11 breakpoint. Finally, comparison of the breakpoint in band 11p13 with those of other translocations (11;14)(p13;q11) identified a breakpoint cluster region of approximately 1.2 kilobase-pairs (kb), alterations of which may promote the development of T-ALL.

Base Sequence↗
PubMed1989

Isolated thrombocytopenia in children with acute lymphoblastic leukemia: a rare event in a Pediatric Oncology Group Study.

To determine how many children with acute lymphoblastic leukemia were initially referred to a pediatric hematologist because of isolated significant thrombocytopenia ([platelet count less than 50,000/mm3] and an otherwise normal complete blood cell count and physical findings), a retrospective review of the Pediatric Oncology Group's charts was undertaken. Review of the records of 2239 children enrolled in the past two acute lymphoblastic leukemia protocols showed that none of these children had significant thrombocytopenia with no other hematologic or physical manifestations of acute lymphoblastic leukemia when they were first seen by the hematologist. The results suggest that routine bone marrow aspiration in the child with isolated thrombocytopenia may be unnecessary to rule out acute lymphocytic leukemia.

Child↗
PubMed1989

Acute lymphocytic leukemia of childhood: the problem of relapses.

Developing improved therapy for the one-third or more of patients who can be expected to relapse after initial treatment for acute lymphoblastic leukemia would be less difficult if one could identify potential failures unequivocally at diagnosis. Subgroups of patients who should be considered candidates for highly experimental therapy include infants (less than 1 year of age), patients with the Philadelphia chromosome and perhaps patients with B-cell leukemia. The most important factor that determines the success of therapy after relapse is the length of the patient's initial remission. We recommend bone marrow transplantation for children whose first remission did not exceed 18 months. For all others, it appears that intensive chemotherapy affords as great a potential for cure as one could expect from transplantation. We favor intensive chemotherapy over transplantation in cases of late bone marrow relapse (greater than 18 months), because of the currently high peritransplantation mortality rate. It is not clear whether either modality will be adequate for patients relapsing on contemporary treatment programs.

Antigens, Neoplasm↗
PubMed1988

Tuberculous mastoiditis.

Two cases of aural tuberculosis in Caucasian adults are described. Stress is laid on the need to consider tuberculosis in cases of chronic otitis presenting unusual features. Lack of suspicion of tuberculosis frequently leads to long delays in diagnosis and subsequent needless disability.

Female↗
PubMed1986

Intensive retreatment of childhood acute lymphoblastic leukemia in first bone marrow relapse. A Pediatric Oncology Group Study.

We devised a plan of intensive chemotherapy to address the problem of inadequate results of treatment in children with acute lymphoblastic leukemia in first bone marrow relapse. Immediately after remission was induced with four conventional drugs, a two-week intensification course of teniposide and cytarabine was given to eradicate subclinical leukemia. Patients in remission were then treated for two years with rapid rotation of pairs of drugs that were not cross-resistant and periodic courses of the same agents used to induce remission. A second complete remission was induced in 31 of the 39 patients in whom response to chemotherapy could be assessed. The probability of maintaining bone marrow remission in these patients for one year was 0.38 +/- 0.19 (95 percent confidence interval); the two-year probability was 0.29 +/- 0.17. Seven patients completed the treatment program, five of whom have been in continuous second complete remission 17 to 20 months after the cessation of therapy. Children whose initial bone marrow remission lasted less than 18 months had significantly poorer responses to retreatment than did those with a longer first remission (P = 0.004). Intensive chemotherapy, as described here, may save half of the children with acute lymphoblastic leukemia in whom bone marrow relapse occurs after a relatively long initial remission.

Adolescent↗
PubMed1986

Merkel cell tumour of the skin.

Two cases of a rare neuroendocrine skin tumour (Merkel cell carcinoma) are reported. The tumour affects mainly old women and men. It has a great tendency to metastasize to lymph nodes and distant sites. The primary treatment is surgical but radiotherapy has an important role to play. Merkel cell tumours are capable of producing NSE and have also been documented to secrete calcitonin and ACTH. Difficulties in histological diagnosis are frequent. The definitive diagnosis can only be made by electron microscopic examination.

Adenocarcinoma↗
PubMed1984

Light fantastic.

Explore the source record for details and available documents.

Adult↗
PubMed1982

The Mondini defect in Turner's syndrome. A temporal bone report.

The histopathology of the right temporal bone of a 47 year old deaf woman with Turner's Syndrome (gonadal dysgenesis) is described. The appearances are of the Mondini deformity, the cochlea consisting of a single basal turn with a bulbous apical dilatation. The organ of Corti was absent. The remainder of the bony labyrinth save for the cochlear aqueduct was normal. The patient's death was due to a cerebral astrocytoma. Previous reports concerning the co-existence of gonadal dysgenesis, congenital deafness and non-gonadal neoplasia are discussed.

Astrocytoma↗
PubMed1981

Radical resection for cancer of the hypopharynx and cervical oesophagus with repair by stomach transposition.

The results of 58 consecutive cases of pharyngolaryngo-oesophagectomy and pharyngogastric anastomosis are presented. The Grey Turner technique is used, but modified by adding bilateral chest drainage established by guidance from below the diaphragm and a jejunostomy. The immediate postoperative therapy management of hypocalcaemia with calcium gluconate and long term control with calciferol is described. An overall 3-year survival rate of 29 per cent has been obtained. Seven patients survived longer than 7 years, the longest living over 10 years. The authors conclude that, with careful management this technique is within the compass of competent surgeons with good facilities and should be the surgical treatment of choice for these difficult tumours.

Adult↗
PubMed1977

Unexplained infertility. A reappraisal.

During a 30-month period 229 couples were evaluated for infertility at the Naval Regional Medical Center, Oakland. Laparoscopy was used in all cases of otherwise unexplained infertility. The resulting laparoscopic examination of the female partner of 24 such couples demonstrated abnormal findings in 18 (75%). Of these 18 subjects, unsuspected endometriosis was found in 11 (46%) and peritubal adhesions in 7 (29%). Of the 229 couples evaluated, only 8 (3.5%) failed to show some etiologic factor associated with infertility. Thus, the previously reported 10 to 20% incidence of unexplained infertility is too high an estimate in view of the additional information made available through pelvic endoscopy.

Adnexal Diseases↗
PubMed1975

Research opportunities at the Institute of Laryngology and Otology, London.

Emphasis is placed on the need to encourage original research in our training programs. This implies an obligation to help trainees inexperienced in research to bridge the gap between theory and practice. Four examples of patterns of research at a postgraduate institute are presented. All are in areas in some way relevant to carcinoma of the larynx: a) the effect of experimental hypothermia on transplanted tumors in rats; b) isotope detection of deep vein thrombosis following head and neck surgery; c) stomal calibre after laryngectomy related to airflow, esophageal voice and cineradiographic appearances; d) a case-controlled study of the etiologic role of asbestos in laryngeal cancer. These studies are still in progress but some preliminary observations can be reported.

Academies and Institutes↗