Preliminary report of a new method of cleft palate repair.
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Biomedical subjects
Publications and source records attributed to C D Reid.
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The response of bone marrow and peripheral blood erythroid progenitors to human recombinant erythropoietin (rHuEPO) was studied in nine haemodialysed renal failure patients receiving this hormone for the correction of their anaemia. The haematocrit rose in all patients in response to thrice weekly injections of escalating rHuEPO doses (12-192 IU/kg). Both the numbers of CUF-e and BFU-e and their proliferative state in the bone marrow as well as BFU-e numbers in the peripheral blood were estimated before treatment and again after correction of the anaemia, at 16 h following an intravenous dose of rHuEPO. Following treatment bone marrow BFU-e numbers fell to a mean of 24.5% (P less than 0.01) of the pre-treatment values although there was no significant change in CFU-e or circulating BFU-e numbers. The mitotic rate (percentage S-phase cells) estimated by tritiated thymidine suicide rose from 45.2% to 68.4% (P less than 0.05) in the case of CFU-e and from 16.4% to 45.1% (P less than 0.05) for BFU-e following treatment with rHuEPO thus indicating in-vivo sensitivity of both the primitive as well as the mature erythroid progenitors to the hormone. The fall in BFU-e numbers in the bone marrow after several months of treatment may be due to a loss of cells from this progenitor pool by maturation that is uncompensated by replacement from the pluripotential stem cell compartment.
The growth in culture of circulating erythroid progenitors (BFU-e) from 34 patients with erythrocytosis was evaluated together with the clinical and bone marrow features at presentation and the subsequent response to treatment. Clonal erythroid growth in vitro in the absence of added erythropoietin (EEC) was observed in 17/18 patients with clinically unequivocal polycythaemia vera and in these patients bone marrow morphology was also abnormal. EEC were also present in three out of five patients with only a single minor criterion of that disease but none of the 11 patients without major or minor criteria or evidence of secondary polycythaemia were EEC positive. This group had a very low incidence of bone marrow abnormalities, was probably heterogenous in nature and included two patients with elevated serum immunoreactive erythropoietin of unknown cause. The reduction in haematocrit following treatment was assessed in EEC positive and negative patients and was found to be inferior in those lacking EEC. Thus both the poor therapeutic response and the low incidence of bone marrow abnormalities in patients lacking any other clinical features of polycythaemia vera correlated closely with the absence of EEC in in vitro culture. Myeloproliferative disorder may therefore be an unlikely cause of the erythrocytosis in such individuals.
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The myeloproliferative disorders are the result of an underlying abnormality of the pluripotential stem cell. One feature of this abnormality is a greatly increased sensitivity of the committed erythroid progenitors (BFU-E and CFU-E) to the hormone erythropoietin. Culture in vitro of these bone marrow or peripheral blood cells results in the growth of a proportion of colonies in the absence of added erythropoietin. These endogenous erythroid colonies (EEC) are seen in the great majority of cases of polycythaemia vera, as well as in some cases of thrombocythaemia, chronic myeloid leukaemia and idiopathic myelofibrosis. The presence of EEC appears to be a marker for the stem cell mutation and may serve to distinguish the neoplastic disorders from reactive increases of red cell mass or platelet numbers. Their absence in idiopathic erythrocytosis may also distinguish this condition from early polycythaemia vera and be useful in deciding on appropriate treatment. In patients with even a modest increase in the platelet count endogenous colonies provide firm evidence for a myeloproliferative disorder. Provision of myelosuppressive treatment can avert or improve vaso-occlusive or haemorrhagic complications. The mechanism of erythropoietin hypersensitivity is unknown but it has been shown to be a feature acquired rather late in maturation and by only a proportion of the progeny of the mutated clone. Normal erythroid progenitors co-exist with these abnormal cells in polycythaemia vera and the way in which their growth in vivo is inhibited has yet to be determined.
Serum from patients with juvenile chronic arthritis (JCA) was shown to inhibit colony formation by normal erythropoietic progenitor cells cultured in vitro. The inhibition was proportional to the degree of anaemia and to certain indices of activity of the arthritis and systemic disease. It occurred in a dose dependent manner with increasing serum concentration and was independent of previous blood transfusion or administered drugs. Erythropoietic progenitor cells from the bone marrows of anaemic patients with JCA showed normal requirements for accessory cells (T lymphocytes and macrophages) in culture, and autologous accessory cells were not deficient in providing normal growth requirements.
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Between February 1981 and December 1984 we treated 52 patients with chronic myeloid leukemia in the chronic phase and 18 patients with more advanced disease by high-dose chemoradiotherapy followed by allogeneic bone marrow transplantation using marrow cells from HLA-identical sibling donors. In addition, the 40 patients who had not previously undergone splenectomy received radiotherapy to the spleen. To prevent graft versus host disease, cyclosporine was given either alone or in conjunction with donor marrow depleted of T cells. Of the 52 patients treated in the chronic phase, 38 are alive after a median follow-up of 25 months (range, 7 to 50); the actuarial survival at two years was 72 percent, and the actuarial risk of relapse was 7 percent. Of the 18 patients with more advanced disease, 4 have survived; the actuarial two-year survival was 18 percent, and the actuarial risk of relapse was 42 percent. We conclude that the probability of cure is highest if transplantation is performed while the patient remains in the chronic phase of chronic myeloid leukemia. T-cell depletion may have reduced the incidence and severity of graft versus host disease. The value of irradiation to the spleen before transplantation has not been established.
A new free flap is described based on the deltoid vessels of the acromiothoracic axis. The flap is comprised of the clavicular head of pectoralis major muscle with overlying skin. It is also possible to harvest vascularised clavicular bone with the flap. The vascular anatomy is reviewed and the technique of raising the flap described. Its clinical application is illustrated with five cases. Four of these were intra-oral reconstructions and the fifth a composite osteo-musculocutaneous flap to a lower limb following trauma.
Secondary alveolar bone grafting in cleft palate patients has been popularised by the Oslo group. Harvesting of the bone graft has been carried out by techniques developed initially for cranio-facial surgery. This paper describes a more refined technique applicable to the requirements of alveolar bone grafting. The Craig bone biopsy set is used to trephine cores of autogenous particulate marrow and cancellous bone from the iliac bone. The method was tested in a cadaver and then applied in 10 clinical cases. The aesthetic and functional results of this technique proved to be superior to the conventional approach.
A retrospective questionnaire study, by post, revealed that 69% of patients, still living following first tumour recurrence, had detected the recurrence themselves prior to routine clinic appointments. Nearly 90% developed their first recurrence in the first 5 years following primary surgical treatment. Not only could the length of routine clinic follow-up after primary melanoma treatment be shortened, but with further education of the patient and involvement of the general practitioner it seems likely that patients can be trusted to detect their own recurrences and seek appropriate advice.
An inappropriate response of the bone marrow is implicated in the aetiology of the anaemia of chronic disease complicating rheumatoid arthritis. T lymphocyte subsets have been shown to inhibit early erythroid development in vitro in association with some cases of bone marrow failure, and an expanded peripheral blood pool of these cells is reported in rheumatoid arthritis. We have studied the role of peripheral blood T lymphocytes in erythroid bone marrow culture from seven normal volunteers and nine anaemic patients with rheumatoid arthritis and found comparable stimulation of growth in both groups.
Globin chain synthesis was studied in mature erythroid bursts cultured from the peripheral blood null cells of 21 normal individuals. Although coculture of autologous T-lymphocytes with null cells resulted in a fivefold increase in the yield of erythroid bursts, the proportion of gamma chains synthesized (gamma/gamma + beta) was not significantly different from that seen without T cells. Coculture with autologous monocytes also resulted in increased burst-forming unit (BFU-e) proliferation but the ratio gamma/gamma + beta (0.25 +/- 0.03) was significantly higher than that seen with null cells alone (0.08 +/- 0.006) or with T cells (0.10 +/- 0.008). The relative increase in gamma-chain synthesis correlated with the severity of megaloblastic changes in erythroid progeny of BFU-e (P less than 0.01) but showed no significant relationship to the extent of colony maturation assessed by erythroblast maturity.
The precise vascular territory and the variations of the acromio-thoracic axis were investigated in a series of 60 fresh cadavers and 50 formalin fixed specimens using dissection, ink injection and barium radiographic studies. The sternocostal portion and the clavicular head of the pectoralis major were found to have virtually independent vascular and nerve supplies. The pectoral artery supplied the former, whereas the deltoid artery nourished the latter. The dominant supply from the pectoral artery to the rib cage was found to enter around the fourth rib in the mid clavicular line. This supply is associated with a previously undescribed origin of the pectoralis major muscle in this region. The supply to the sternum was determined as indirect via the captured territory of the internal mammary system. The dominant supply to the skin from the pectoral artery arose laterally along the free lower border of the muscle as fasciocutaneous branches. The deltoid artery supplies the skin over the shoulder by numerous small branches which emerge from the intramuscular septa of the deltoid muscle. In addition a large axial artery was noted. In most cases this arose from the deltoid artery or its acromial branch and coursed laterally. It is noteworthy that the majority of skin paddles of the pectoralis major myocutaneous flap currently used in clinical practice are designed medially and inferiorly around the perimeter of the muscle and onto the rectus sheath. In these situations such flaps are not supplied directly by the pectoral artery. In fact, they are supplied indirectly by cutaneous branches belonging to the internal mammary/superior epigastric system which are captured by arterial connections with the pectoral artery. These occur predominantly in the pectoralis major muscle. Suggestions, based on these anatomical studies, are offered to improve the versatility and safety of flaps designed in this area.
Clonal assays for erythroid progenitors (BFU-e and CFU-e) were used to study 20 patients with rheumatoid arthritis, 15 of whom had anaemia of chronic disease and five of whom were haematologically normal. The numbers of bone marrow BFU-e and CFU-e in the anaemic patients did not differ significantly from those in normal controls. Macrophages were removed from the bone marrow by a combination of adherence and buoyant density centrifugation over a sucrose gradient and the resulting fractions were cultured alone or together with autologous adherent cells in BFU-e assays. Co-culture with adherent cells significantly increased colony growth in both the controls and in seven of eight anaemic patients studied. Serum from 14 anaemic patients and from five non-anaemic patients was added to cultures of bone marrow or to control peripheral blood 'null' cells. Anaemic serum uniformly either inhibited or failed to stimulate BFU-e growth under these conditions. Serum from non-anaemic patients and from 10 healthy controls stimulated BFU-e growth from 'null' cells to an equal degree.
A one-stage flap repair is described for complicated dorsal injuries of the hand involving loss of skin and tendon based on the principle of the "Chinese" radial artery forearm flap in which vascularised tendons are transferred to reconstruct the missing extensor tendons.
The myeloproliferative disorders, including polycythaemia rubra vera, arise as a result of a single-cell mutation. A characteristic of the abnormal haemopoietic clone is that it can form erythroid colonies in vitro in the absence of added erythropoietin. Such endogenous erythroid clones were consistently found in two of seven patients with peripheral vascular disease. These two patients had mean platelet counts of 600 X 10(9)/l and 630 X 10(9)/l. Culture of blood and bone-marrow cells from patients with raised platelet counts secondary to a variety of other disorders failed to yield such colonies. The presence of endogenous erythroid clones provides early evidence of a myeloproliferative disorder.
Colony assays in methylcellulose of primitive erythroid precursors (BFU-E) were carried out from the null cell fraction of normal human peripheral blood lymphoid cells. There was little proliferation or maturation of BFU-E as assessed by both the number and the size of colonies formed, when null cells alone were cultured. Culture of null cells with up to 8 X 10(5) autologous T-lymphocytes per ml led to considerable stimulation of colony growth and maturation. Culture of null cells with peripheral blood monocytes also resulted in the indication of BFU-E growth, although the response was inferior to the seen with T-cells. Co-culture of null cells together with both T-cells and monocytes resulted in a uniformly greater response than with either alone, and this was shown to be due to a positive interaction between these two cell types.