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Biomedical subjects

A Cant

Publications and source records attributed to A Cant.

At least 19 recordsLinked to original sources
PubMed2003

Long-term outcome of haematopoietic stem cell transplantation in autosomal recessive osteopetrosis: an EBMT report.

A retrospective analysis was made of 122 children who had received an allogeneic haematopoietic stem cell transplantation (HSCT) for autosomal recessive osteopetrosis between 1980 and 2001. The actuarial probabilities of 5 years disease free survival were 73% for recipients of a genotype HLA-identical HSCT (n=40), 43% for recipients of a phenotype HLA-identical or one HLA-antigen mismatch graft from a related donor (n=21), 40% for recipients of a graft from a matched unrelated donor (n=20) and 24% for patients who received a graft from an HLA-haplotype-mismatch related donor (n=41). In the latter group, a trend towards improvement was achieved at the end of the study period (17% before 1994, 45% after 1994, P=0.11). Causes of death after HSCT were graft failure and early transplant-related complications. Severe visual impairment was present in 42% of the children before HSCT. Conservation of vision was better in children transplanted before the age of 3 months. Final height was related to height at the time of HSCT and better preserved in children transplanted early. Most children attended regular school or education for the visually handicapped. At present, HSCT is the only curative treatment for autosomal recessive osteopetrosis and should be offered as early as possible.

Body Height↗
PubMed2000

Community acquired pneumonia--a prospective UK study.

BACKGROUND: There are few data on paediatric community acquired pneumonia (PCAP) in the UK. AIMS: To investigate the aetiology and most useful diagnostic tests for PCAP in the north east of England. METHODS: A prospective study of hospital admissions with a diagnosis of PCAP. RESULTS: A pathogen was isolated from 60% (81/136) of cases, and considered a definite or probable cause of their pneumonia in 51% (70/136). Fifty (37%) had a virus implicated (65% respiratory syncytial virus) and 19 (14%) a bacterium (7% group A streptococcus, 4% Streptococcus pneumoniae), with one mixed infection. Of a subgroup (51 patients) in whom serum antipneumolysin antibody testing was performed, 6% had evidence of pneumococcal infection, and all were under 2 years old. The best diagnostic yield was from paired serology (34%, 31/87), followed by viral immunofluorescence (33%, 32/98). CONCLUSION: Viral infection accounted for 71% of the cases diagnosed. Group A streptococcus was the most common bacterial infective agent, with a low incidence of both Mycoplasma pneumoniae and S pneumoniae. Pneumococcal pneumonia was the most common bacterial cause of pneumonia in children under 2 years but not in older children. Inflammatory markers and chest x ray features did not differentiate viral from bacterial pneumonia; serology and viral immunofluorescence were the most useful diagnostic tests.

Adolescent↗
PubMed1999

Combined immunodeficiency associated with increased apoptosis of lymphocytes and radiosensitivity fibroblasts.

Severe immunodeficiency characterized by lymphopenia was found in two siblings, one of whom was examined in detail. The calcium flux, pattern of tyrosine phosphorylation of proteins, and interleukin 2 (IL-2) production and proliferation in response to mitogens suggested that the peripheral blood T cells activated normally. The peripheral blood T cells were shown to have an activated phenotype with increased expression of CD45RO+ and CD95/Fas. Increased spontaneous apoptosis occurred in unstimulated lymphocyte cultures. The elevated apoptosis was not due to alterations in expression or to mutations in Bcl-2, Bcl-X(L), or Flip, nor could the spontaneous apoptosis be prevented by blocking Fas, suggesting that it was independent of Fas signaling. This is the first inherited combined immunodeficiency associated with impaired lymphocyte survival. Fibroblasts derived from the patient showed appreciable radiosensitivity in clonal assays, but apoptosis was not elevated. Our results show that the fibroblasts represent a new radiosensitive phenotype not associated with cell cycle checkpoint defects, V(D)J recombination defects, or elevated chromosome breakage. We suggest that the affected gene plays a role in an undetermined damage response mechanism that results in elevated spontaneous apoptosis in lymphoid cells and radiosensitivity in fibroblasts.

Apoptosis↗
PubMed1999

Influence of severe combined immunodeficiency phenotype on the outcome of HLA non-identical, T-cell-depleted bone marrow transplantation: a retrospective European survey from the European group for bone marrow transplantation and the european society for immunodeficiency.

We analyzed the outcomes of 214 HLA non-identical T-cell-depleted bone marrow transplantations (BMTs), performed in 178 consecutive patients for treatment of severe combined immunodeficiencies (SCID). Patients were treated in 18 European centers between 1981 and March 1995. SCID variants, that is, absence of T and B lymphocytes (B-) or absence of T cells with presence of B lymphocytes (B+) were found to have a major influence on outcome. The disease-free survival was significantly better for patients with B+ SCID (60%) as compared with patients with B- SCID (35%) (P =.002), with a median follow-up of 57 months and 52 months, respectively. Other factors associated with a poor prognosis were the presence of a lung infection before BMT (odds ratio = 2.47 [1.99-2.94]) and the use of monoclonal antibodies for T-cell depletion of the graft (odds ratio = 1.67 [1. 18-2.15]). Additional factors influencing outcome were age at BMT (<6 months) and period during which BMT was performed. Better results were achieved after 1991. Reduced survival of patients with B- SCID was associated with a higher incidence of early deaths from infection, a diminished rate of marrow engraftment, a trend to a higher incidence of chronic graft-versus-host disease, and slower kinetics of T/B immune function development. In both groups of patients, the use of busulfan (8 mg/kg total dose) and cyclophosphamide (200 mg/kg total dose) as a conditioning regimen provided the best cure rate (74% for patients with B+ SCID and 43% for patients with B- SCID, respectively), although results were not statistically significantly different from other regimens. This retrospective analysis should lead to the design of adapted measures to the performance of HLA non-identical BMT in patients with distinct SCID conditions.

Age Factors↗
PubMed1998

Long-term immune reconstitution and outcome after HLA-nonidentical T-cell-depleted bone marrow transplantation for severe combined immunodeficiency: a European retrospective study of 116 patients.

We have performed a retrospective analysis of the development of T- and B-cell functions after HLA-nonidentical T-cell-depleted bone marrow transplantation (BMT) performed in 193 patients with severe combined immunodeficiency (SCID) at 18 European centers between December 1982 and December 31, 1993. One hundred sixteen of 193 patients were alive with evidence of engraftment 6 months after BMT. Development of T-cell function occurred earlier than B-cell function and was achieved more frequently up to the time of last follow-up. The median time to achieve normal T-cell function was 8.7 months, whereas the median time to achieve normal B-cell function was 14.9 months. Twenty-four patients died later than 6 months post-BMT, mainly due to chronic graft-versus-host disease (cGVHD) and/or viral infection. Absence of T-cell reconstitution 6 months after BMT, unlike absence of B-cell reconstitution, was associated with a poor outcome. Two additional factors were associated with a poor outcome: presence of cGVHD 6 months after BMT and B- SCID versus B+ SCID. However, two of these three factors remained as significant prognostic factors in a multivariate analysis: the absence of T-cell function and the presence of cGVHD 6 months after BMT. Analysis of the factors influencing the development of immune reconstitution showed that T- and B-cell functions occurred earlier and more frequently in B+ SCID versus B- SCID patients. Acute GVHD was associated with a slower development of T-cell function at 6 months, and cGVHD had a negative influence on the development of T-cell function afterwards, but neither acute nor chronic GVHD was found to influence the development of B-cell function. Once engraftment occurred, whether patients had or had not received Busulfan in the conditioning regimen did not influence the kinetics and quality of T-cell function development. In a multivariate study, two factors were found to influence the T-cell function 6 months after BMT: type of SCID and acute GVHD. The results of this retrospective analysis should lead to new protocols adapted to SCID disease, considering that disease-related as well as BMT-related parameters influence the development of immune function and thereby long-term outcome after HLA-nonidentical T-cell-depleted BMT.

B-Lymphocytes↗
PubMed1997

B-cell-negative severe combined immunodeficiency associated with a common gamma chain mutation.

Severe combined immunodeficiency (SCID) is caused by a variety of underlying defects. Approximately 40% of cases are thought to be of the X-linked type (SCIDX1), which is phenotypically characterised by the absence, or very low numbers, of T cells, but normal or even high B cell numbers. The gene responsible for SCIDX1 is that coding for the common gamma chain (gamma c), a component of multiple cytokine receptors. Mutations in this gene have been demonstrated in a large number of boys affected by typical SCIDX1. We describe a sporadic case of a boy who had SCID with absent B cells and absent T cells, but in whom a mutation in the gamma c gene has been demonstrated. In the absence of a typical X-linked pedigree, the phenotype in this boy suggested an autosomal recessive form of SCID and the family would usually have been counselled accordingly. This family raises the question of the true frequency of SCIDX1 amongst sporadic male cases of SCID and highlights the need to screen these boys for gamma chain mutations.

Antigens, CD↗
PubMed1996

Bone marrow transplantation from genetically HLA-nonidentical donors in children with fatal inherited disorders excluding severe combined immunodeficiencies: use of two monoclonal antibodies to prevent graft rejection.

OBJECTIVE: For children with life-threatening inborn errors of metabolism without a matched related bone marrow donor, transplantation from an HLA genetically nonidentical donor is the only therapeutic option. To reduce the high risk of graft rejection in this setting without increasing the conditioning regimen, a protocol based on the infusion of an antiadhesion antibody directed against the CD11a (leukocyte function-associated antigen 1 [LFA-1]) molecule was performed by the European Bone Marrow Transplantation-European Society for Immunodeficiency group with promising results. To optimize engraftment, and thereby survival, further, the additional blockade of a second important leukocyte adhesion and signalization pathway mediated by the CD2 and LFA-3 interaction was attempted in a multicenter protocol conducted by the European Bone Marrow Transplantation-European Society for Immunodeficiency group. Results of this study (ie, engraftment and survival) were compared with a historical control group that received the anti-LFA-1 antibody alone. Factors that may have affected engraftment and survival were also considered in this study. METHODS: Forty-four children with inborn errors, including inherited immunodeficiencies (excluding severe combined immunodeficiencies), Chédiak-Higashi syndrome, familial hemophagocytic lymphohistiocytosis, and malignant osteopetrosis, received bone marrow from HLA-nonidentical related donors or from HLA-identical unrelated donors at 13 European centers between August 1990 and June 1993. Bone marrow was depleted of T cells by use of either erythrocyte (E) rosetting or monoclonal antibodies (MoAbs) to prevent graft-versus-host disease. The conditioning regimen consisted of busulfan and cyclophosphamide for all patients plus etoposide for patients with osteopetrosis, familial hemophagocytic lymphohistiocytosis, and Chédiak-Higashi syndrome. Infusions of MoAbs specific for the CD11a and the CD2 molecules were started 4 and 3 days, respectively, before and continued through the first 10 and 11 days, respectively, after bone marrow transplantation (a total of 14 injections). RESULTS: The overall sustained engraftment rate was 69.8%, with full chimerism in 80.6% of patients and no late graft rejection with the use of two MoAbs versus 65.7% and 58.1%, respectively, in the control group, in which only one MoAb was infused. The overall actuarial survival rate with a functional graft was 40.9%, with a mean follow-up of 39.3 months with two MoAbs versus 37.8% with one. The engraftment rate was significantly influenced by the T-cell depletion method, with better results for recipients of E rosette- depleted marrow (78.6% vs 20% for Campath 1-M plus complement-depleted marrows). Graft-versus-host disease and the kinetics of immune reconstitution were similar in both groups. CONCLUSIONS: The overall engraftment rate and overall survival rate with engraftment in patients treated with anti-LFA-1 and anti-CD2 were similar to those in patients treated with anti-LFA-1 antibody alone. However, although the number of patients is too small to draw definitive conclusions, results from the combined use of the two MoAbs indicates a trend toward better engraftment and survival after infusion of E rosette-depleted marrow. Further improvement in survival would demand additional strategies to hasten immunologic recovery.

Antibodies, Monoclonal↗
PubMed1991

The incidence of abnormal morphology and nucleocytoplasmic ratios in 2-, 3- and 5-day human pre-embryos.

Human cleaving pre-embryos at 2 and 3 days and cavitated pre-embryos at 5 days post-insemination have been examined for cell number and the incidence of mononucleated cells. At least 60% of polynucleate or anucleate cells have been detected at all these stages and regardless of morphological grading at day 2. It is concluded that even by the time at which pre-embryo replacement would occur therapeutically, the majority of pre-embryos are unlikely to have full developmental potential. The possible origins of the abnormalities of nucleocytoplasmic ratios are discussed.

Blastocyst↗
PubMed1991

Erythroderma, palmoplantar keratoderma and profound failure to thrive in an infant.

The case is reported of a female infant, who at the age of 3 months developed severe erythroderma, marked hyperkeratosis of the palms and soles and subsequently extreme growth failure and intermittent diarrhoea. Her course was complicated by life-threatening infections but detailed investigation revealed no recognized underlying metabolic or immune abnormality.

Dermatitis, Exfoliative↗
PubMed1991

The effect of maternal supplementation with linoleic and gamma-linolenic acids on the fat composition and content of human milk: a placebo-controlled trial.

Total fat content and therefore total energy content and the content of essential fatty acids (EFAs) in milk are known to decline with prolonged breast feeding. In a placebo-controlled study a variety of evening primrose oil (Efamol) rich in linoleic and gamma-linolenic acids, or a matching placebo were given to 39 women for a period of 8 months starting between the 2nd and 6th months of lactation. Total fat and EFA contents of the milk declined in the placebo group but rose in the primrose oil supplemented group. A surprisingly high proportion of the supplemented dietary fatty acids could be accounted for by appearance in the milk. The milk composition can be readily manipulated by changing the fatty acid composition of the maternal diet.

Dietary Fats, Unsaturated↗
PubMed1990

Acid Tyrode's solution can stimulate parthenogenetic activation of human and mouse oocytes.

Fresh and aged (24 hours after ovulation) human oocytes and recently ovulated mouse oocytes may be activated by exposure to acidified Tyrode's solution. No activation of either type of human oocyte was observed after exposure to hyaluronidase or pronase, but significant numbers of fresh mouse oocytes were activated after exposure to pronase but not to chymotrypsin. The implications of these results for the manipulation of human and mouse eggs in vitro are discussed.

Animals↗
PubMed1990

Transient cooling to room temperature can cause irreversible disruption of the meiotic spindle in the human oocyte.

The effect on the microtubule system of human oocytes of cooling to room temperature for either 10 or 30 minutes has been investigated. Changes in spindle organization were found in all oocytes cooled for 30 minutes compared with control oocytes kept at 37 degrees C throughout. These changes included reduction in spindle size, disorganization of microtubules within the spindle itself, and sometimes a complete lack of microtubules. In some oocytes, chromosome dispersal from the metaphase plate was associated with these changes. Cooling the oocyte to room temperature for only 10 minutes produced a similar pattern of disruption to spindle structure in many cases. The spindles in oocytes that were cooled for either 10 or 30 minutes and then allowed to recover at 37 degrees C for either 1 or 4 hours were found to resemble those in noncooled control oocytes in less than one half of the cases examined, although in only a few cases did the chromosomes remain dispersed. The significance of these findings for the handling of oocytes during gamete intrafallopian transfer and in vitro fertilization procedures is discussed in relation to the levels of aneuploidy detected in early human embryos.

Chromosomes↗