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Biomedical subjects

G Morgan

Publications and source records attributed to G Morgan.

At least 217 records · Page 12Linked to original sources

Successful allogeneic bone marrow transplantation in juvenile CML: conditioning or graft-versus-leukaemia effect?

Allogeneic BMT is the treatment of choice for juvenile CML (JCML). This has been successful following conditioning with cyclophosphamide (120 mg/kg) and total body irradiation (TBI) (10-15.75 Gy). However, busulphan (16 mg/kg) and cyclophosphamide (200 mg/kg) (Bu/Cy) conditioning has been reported to be insufficient to eradicate the malignant clone in JCML. We report successful BMT and eradication of the disease at 18 months follow-up in a child 15 months old at presentation, who was conditioned with busulphan 20 mg/kg and cyclophosphamide 200 mg/kg, with the addition of splenic irradiation. Despite using higher than conventional doses of busulphan, pharmacokinetic analysis revealed very low busulphan peak levels and rapid excretion. As a possible consequence, only partial chimerism was achieved, but full engraftment ensued following the discontinuation of cyclosporin A, rebound donor lymphocytosis and the onset of acute GVHD. We suggest that host resistance to engraftment and tumour elimination was overcome by removing a suppressive effect on donor lymphocytes, allowing a graft-versus-leukaemia effect.

Antineoplastic Combined Chemotherapy Protocols↗

Immunodeficiency presenting as hypergammaglobulinaemia with IgG2 subclass deficiency.

Recurrent bacterial infections, lymphadenopathy, and failure to thrive are unlikely to be attributed to immune deficiency if they occur in the presence of hypergammaglobulinaemia, and other explanations will usually be sought. We describe eight patients who presented with all these features in infancy or early childhood. Deficiencies of immunoglobulin and antibody production were initially discounted, and the children were referred for investigation of possible lymphoma, autoimmune disease, or chronic viral infection. The patients were later referred to us for more detailed immunological investigation, which revealed low levels of IgG2 and poor specific antibody production to common pathogens. Treatment with intravenous immunoglobulin resulted in resolution of signs and symptoms in all patients. Thus we have shown that hypergammaglobulinaemia does not preclude the presence of immunoglobulin/antibody deficiency. We suggest that investigation of children with high levels of IgG and features of immunodeficiency should include IgG subclass analysis.

Adolescent↗

Aboriginal and non-aboriginal perinatal deaths in Darwin: a comparative view.

OBJECTIVE: To compare perinatal deaths in Aborigines and non-Aborigines, and to identify the differences between the two groups in order to plan better prevention and bring about a reduction in perinatal deaths. DESIGN: A retrospective review of the records of 198 consecutive perinatal deaths (96 Aboriginal and 102 non-Aboriginal) in infants delivered in the maternity unit between 1984 and 1989. SETTING: Royal Darwin Hospital Maternity Unit. MAIN OUTCOME MEASURES: Stillbirth rate, neonatal death rate, perinatal mortality rate; classifying perinatal deaths by cause and birthweight. MAIN RESULTS: The Aboriginal perinatal mortality rate was 40.9 per 1000, three times that of the non-Aboriginal rate (13.4 per 1000). The stillbirth rate in Aborigines was 18.7 per 1000, 2.5 times that in non-Aborigines (7.2 per 1000). The Aboriginal neonatal mortality rate was 22.5 per 1000, 3.5 times the non-Aboriginal rate (6.2 per 1000). There was no significant difference in the distribution of Aboriginal and non-Aboriginal perinatal deaths when classified by cause, with the exception of pre-eclampsia. Aboriginal women appeared to be 2.5 times more likely than non-Aboriginal women (P = 0.002) to have pre-eclampsia causing perinatal death. Prematurity and the unexplained categories were the major causes of perinatal death in both Aboriginal and non-Aboriginal infants. MAIN CONCLUSION: The suboptimal perinatal outcome in Aborigines highlights the importance of antenatal care for Aboriginal mothers, and indirectly reflects the need for improving their standard of living.

Birth Weight↗

Relapsing illness due to Rochalimaea henselae in immunocompetent hosts: implication for therapy and new epidemiological associations.

Two previously healthy, immunocompetent men had persistent Rochalimaea henselae bacteremia with clinical relapses after courses of antibiotics to which the isolates were ultimately demonstrated susceptible in vitro. Both had sustained tick bites prior to their illnesses, thus demonstrating an association not previously identified, although suspected. The first patient had relapsing fever, constitutional symptoms, and an episode of aseptic meningitis despite therapy with amoxicillin, then with doxycycline, and then with ceftriaxone. Thereafter, he spontaneously became asymptomatic during a span of 2 months of persistent bacteremia. Finally, after 2 weeks of therapy with ceftriaxone plus gentamicin, followed by 4 weeks of therapy with oral ciprofloxacin, his bacteremia was cured. The second man had relapsing fever and constitutional symptoms after courses of tetracycline, then of chloramphenicol, and then of doxycycline. He became permanently asymptomatic after serial 2-week courses of chloramphenicol and erythromycin. The greater efficacy of lysis-centrifugation blood cultures in the recovery of R. henselae was noted.

Adult↗

Clinical and laboratory predictors of survival in Gambian patients with symptomatic HIV-1 or HIV-2 infection.

OBJECTIVES: To determine which clinical and immunological features of patients with symptomatic HIV-1 and HIV-2 infection best predict survival in The Gambia. METHODS: All patients presenting to two hospitals in The Gambia between January 1987 and June 1990 with symptoms or signs suggesting chronic HIV infection were tested for HIV-1 and HIV-2 antibodies. Eighteen HIV-1 and 31 HIV-2-infected patients were recruited to the study, investigated intensively on admission and followed up until the end of 1990. Presenting clinical features, such as Karnofsky score, diagnosis of AIDS according to World Health Organization Bangui or Centers for Disease Control criteria and number of associated infections, together with five immunological measurements, as well as type of HIV infection, were related to length of survival using proportional hazard models fitted to Kaplan-Meier plots of survival times. RESULTS: Karnofsky score and diagnosis of AIDS were the best clinical predictors of survival. Type of HIV infection or number of associated infections did not predict outcome. The most powerful laboratory predictors were log(e) serum neopterin level, CD4 cell count and log(e) serum beta 2-microglobulin (beta 2M) level. The estimated median survival times (90% confidence interval) of the HIV-1 and HIV-2-infected were six (4-11) and 13 (9-20) months, respectively. These survival times do not differ significantly. CONCLUSIONS: The Karnofsky score and measurements of serum neopterin or beta 2M, which are easier and cheaper to perform than CD4 counts, may prove to be useful guides to prognosis for HIV infection in Africa.

Acquired Immunodeficiency Syndrome↗

Lung dose rate and interstitial pneumonitis in total body irradiation for bone marrow transplantation.

The effect of dose rate to the lungs and development of interstitial pneumonitis (IP) was evaluated in 114 bone marrow transplant patients receiving fractionated total body irradiation (TBI) (1200 rads TD in 6 fractions twice daily over 3 days) as part of their pre-conditioning regimen. The tumour dose (TD) was calculated as the mean lung dose as previously described (1). A 6MV linear accelerator at a mid-line dose rate of 7.5 rads/minute was used between March 1981 and June 1985 and a Co-60 source at 5 rads/minute thereafter. This resulted in a range of dose rates to the lung of between 6.9 and 8.9 rads/minute and 2.9 and 6.5 rads/minute respectively. In the majority of patients the aetiology of IP was investigated by lung biopsy with histology and culture. There was no statistically significant difference in the incidence of IP over the two sets of dose rates. Our study suggest that the incidence of IP using fractionated TBI is not influenced by dose rates below 8.9 rads per minute.

Adolescent↗

Fetal T-lymphocyte subpopulations in normal pregnancies.

Peripheral blood T lymphocyte subpopulations were measured, using a fluorescence-activated cell sorter, in fetal blood samples obtained either by cordocentesis (n = 118) or at elective caesarean section (n = 14). Both the numbers and percentages of the total T lymphocytes (CD3+) and T-helper lymphocytes (CD4+) increased exponentially with gestation from respective means of 46% (1.15 x 10(9)/l) and 29% (0.70 x 10(9)/l) at 16 weeks to a plateau of 75% (3.11 x 10(9)/l) and 54% (2.10 x 10(9)/l) at 34 weeks. Similarly, the number of suppressor/cytotoxic T lymphocytes (CD8+) increased linearly with gestation from a mean of 22% (0.55 x 10(9)/l) at 16 weeks to 24% (0.96 x 10(9)/l) at 40 weeks; there were no natural cytotoxic T lymphocytes (CD3+CD56+) in any of the fetal blood samples. The helper-to-suppressor T lymphocyte ratio (CD4/CD8) increased exponentially with gestation from a mean of 1.22 at 16 weeks to 2.57 at 28 weeks. The alterations in T lymphocyte subpopulations were accompanied by changes in the expression of CD45RA, L-selectin, CD25 and HLA-DR. These alterations in T lymphocyte subpopulations with gestation reflect the pattern of maturation and development of the fetal cell-mediated immune system.

Antigens, Differentiation, T-Lymphocyte↗

Light and electron microscopic studies of cellular localization of oPL with monoclonal and polyclonal antibodies.

Accurate knowledge of placental lactogen localization is fundamental to any hypothesis of its synthesis and secretion. We used locally generated monoclonal and polyclonal antibodies from three separate sources to localize ovine placental lactogen immunoreactivity on light and electron microscope Lowicryl K4M sections of ovine placentomes of 97-145 days of gestation, using immunogold techniques. All antibodies demonstrated that immunoreactivity was exclusively localized in the trophoectoderm binucleate cell Golgi body and granules and in granules in the syncytium derived from binucleate cell migration. No evidence was found to support a recent claim that monoclonal antibodies to oPL that were produced in Canada indicated a predominant localization of ovine placental lactogen to uninucleate trophectodermal cells.

Animals↗

Influence of dietary cation-anion balance during the dry period on the occurrence of parturient paresis in cows fed excess calcium.

Our objective was to evaluate the effectiveness of a low dietary cation-anion balance (DCAB) in preventing milk fever and udder edema in dry cows consuming a high-Ca diet and to evaluate the effect of this diet on calves delivered by these cows. Seventy primiparous or multiparous cows and 50 pregnant heifers were offered alfalfa hay-based diets beginning 4 wk before their projected calving date. Diets contained 1.6% Ca and a DCAB of -3 or +9 mEq/100 g of diet DM. Blood and urine samples were collected weekly from 3 wk prepartum until 3 wk postpartum. Blood samples were collected from calves at parturition and weekly thereafter for 3 wk. Feeding a low vs high DCAB in a high-Ca diet for 3 wk prepartum did not reduce the incidence of milk fever; this lack of response may have been attributable to the relatively low DCAB of each diet and the small difference in DCAB between the two diets. Udder edema seemed to regress more rapidly postpartum for cows that had consumed the low DCAB during the dry period. Test diets fed to prepartum cows did not affect systemic acid-base status or plasma mineral content of their calves, although plasma Ca was somewhat lower for calves from cows consuming a low DCAB and was higher for calves from primigravid cows. Correlations of plasma mineral concentration of the cows with those of their calves were highest for plasma Ca (r = .75; P less than .001). We conclude that the prophylactic effects on the occurrence of milk fever of feeding a low DCAB during the dry period may be absent when diets contain greater than 1.6% Ca and DCAB is greater than or equal to -3. The cation-anion balance of the diet consumed by dry cows did not affect the acid-based status or plasma mineral content of their calves.

Acid-Base Equilibrium↗

Smoking prevalence and attitudes of Gwynedd Health Authority staff towards passive smoking and the Authority's non-smoking policy.

In 1989, a postal survey was undertaken to investigate the smoking prevalence and attitudes of Gwynedd Health Authority employees towards the Authority's non-smoking policy, passive smoking and other related issues. The results show a smoking prevalence rate of 22% for those participating in the survey, with over half of all smokers expressing a wish to stop. Although the rate was similar for males and females, it was marginally higher amongst nursing staff and young employees. Smoking prevalence was highest among the ancillary staff, and lowest among the medical and dental professions. Most employees were in broad agreement with the Authority's non-smoking policy, and a majority thought it about right or favoured extending it. Most non-smokers and ex-smokers believed passive smoking to be a health hazard, with an increased number rating it anti-social. Attitudes towards these issues were similar for males and females, with marked differences between the groups employed in different areas of the service. Younger employees were more aware of the dangers of passive smoking, but less sympathetic towards the policy than the older ones. The findings of this study highlight the differences between smokers and non-smokers on all smoking issues. The implications for health education and the Authority's non-smoking policies are discussed.

Attitude of Health Personnel↗

Quantitative immunogold ultracryomicrotome studies of the distribution of periimplantation proteins in the sheep.

Several mammalian uterine and conceptus proteins are produced at specific stages of implantation. Ovine trophoblast protein-1 (OTP-1) is only synthesised in vitro by conceptus tissue from between 13 and 21 days of pregnancy (dpc). This immunogold ultracryosection study shows that, during this period, OTP-1 immunoreactivity is only found in the Golgi body of the trophectodermal cells. A second protein, of 14 kD molecular weight (14 K protein), has a more varied distribution being found in membrane-bounded crystals in uterine epithelium and trophectodermal cells, and distributed throughout the cytosol and nucleoplasm of the uterine epithelium. There are only trace amounts of the 14 K protein in the fetomaternal syncytium which replaces the uterine epithelium during implantation, and no crystals are found in the trophectoderm after cotyledonary villus formation is initiated at 24-25 dpc. The crystals containing 14 K protein persist throughout pregnancy in the intercotyledonary areas. The narrow time window of OTP-1 occurrence reinforces the suggestion that this represents an important developmental signal, whereas the distribution of the 14 K protein indicates a more general nutritive function.

Animals↗

Successful bone marrow transplantation and treatment of BCG infection in two patients with severe combined immunodeficiency.

We report successful bone marrow transplantation (BMT) in two patients with severe combined immunodeficiency (SCID), who had developed BCG infection following neonatal vaccination. Patient 1 had Omenn Syndrome, associated with hypertrophic non-obstructive cardiomyopathy. Patient 2 had SCID due to adenosine deaminase deficiency. This communication demonstrates that with appropriate anti-mycobacterial cover, immunological reconstitution together with full recovery from BCG infection can be achieved by BMT. As demonstrated by persistent negative Mantoux tests, specific cell-mediated immunity to BCG was not acquired following BMT. We suggest that these children may continue to be at risk from mycobacterial infection.

Adenosine Deaminase↗