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A Morell

Publications and source records attributed to A Morell.

At least 19 recordsLinked to original sources

Quality control of a national bone marrow donor registry: results of a pilot study and proposal for a standardized approach.

Unrelated hematopoietic stem cell transplantation (HSCT) is a recognized therapy for hematological diseases and over 8 million HLA-typed donors are ready to donate. Increased international exchanges and rapid requests through the Bone Marrow Donor Worldwide (BMDW) ask for standardized quality assurance. Since no such standards have been established to date, we tested a pilot program in order to evaluate donor availability and quality of HLA typing of the Swiss Registry. The 18500 donors of the registry have been analyzed by serology for HLA-AB and by molecular typing for HLA-DR. Through three successive annual quality control (QC) exercises, a total of 114 donor requests were sent to 13 blood transfusion centers responsible for donor recruitment asking for a blood sample. Donors were randomly selected according to recruitment periods (1988-1993; 1994-1997; 1998-2000), and to homozygosity for HLA-A and/or -B antigens. An additional 80 frozen blood samples from the repository corresponding to the three periods (n=26) and to the 2001 period (n=54) were also included in the HLA study. HLA-AB typings were done by polymerase chain reaction-sequence specific primers (PCR-SSP) and all discrepancies were retyped. The results showed that 79 samples provided by 69.3% of the requested donors were received within 14 days, and 19 samples (16.7%) were received in >14 days. Altogether, an 86% rate of donor availability was observed, independent of the recruitment period. Among the requested donors, 16 (14%) were not available: for medical reasons (two), for personal reasons (eight), for loss (one), and for an unknown reason (five). The HLA-A/B DNA typing results of 166 homozygous and 12 heterozygous blood samples showed that 437/439 (99.5%) of the assigned A/B antigens were correct. However in 36/178 donors (20.2%) an HLA-A or -B antigen had been missed (34 donors) or misassigned (two donors) by serology, with a decreasing discrepancy rate of 30% (1988-1993) to 18.5% in 2001. Assuming that HLA-A or -B homozygotes are found in 10-15% of the donors and that correct assignments have been observed in nearly 100% of the donors, an overall error rate of 4-5% would be expected for the national registry HLA-AB typing. These data show that standardized quality control for donor availability and HLA typing is feasible, and we propose that this model could be applied to the registries participating in bone marrow donor worldwide.

Bone Marrow Transplantation↗

Efficacy, tolerability, safety and pharmacokinetics of a nanofiltered intravenous immunoglobulin: studies in patients with immune thrombocytopenic purpura and primary immunodeficiencies.

BACKGROUND AND OBJECTIVES: A nanofiltration step with the capacity to reduce blood-borne pathogens was introduced into the manufacturing process of intravenous immunoglobulin (IVIG). In order to demonstrate the efficacy, safety and pharmacokinetics of the modified product, we conducted Phase II/III studies comparing the nanofiltered IVIG (IVIG-N) with its parent product, Sandoglobulin, in patients with chronic immune thrombocytopenic purpura (ITP) and primary immunodeficiencies (PID). MATERIALS AND METHODS: Patients with ITP (n = 27) with platelet counts of < 20 x 10(9)/l were treated with Sandoglobulin or IVIG-N infusions at a dose of 0.4 g/kg body weight on five consecutive days. The primary efficacy end-point was the number of patients with an increase in platelet counts to > 50 x 10(9)/l. Secondary end-points were time to and duration of response, and regression of bleeding. Patients with PID (n = 36) were treated for 6 months with Sandoglobulin or IVIG-N at doses of 0.2-0.8 g/kg, infused at 3- or 4-week intervals. The primary end-point was the number of days absent from school/work. Secondary end-points were hospitalization, use of antibiotics and feeling of well-being. In both studies, tolerability was assessed by recording of adverse events and laboratory determinations. Viral safety was ascertained by serology supplemented with nucleic acid detection methods. Pharmacokinetics were analysed in patients with PID using serum concentration-time data for immunoglobulin G (IgG), and IgG antibodies to hepatitis B surface antigen (anti-HBsAg). RESULTS: In the ITP study, the primary end-point was met by 12/16 patients on IVIG-N and by 10/10 patients on Sandoglobulin (P = 0.123). A shift towards lesser bleeding intensity was seen in both groups. In the PID study, seven of 18 patients on IVIG-N and six of 16 patients on Sandoglobulin missed days at work/school, with monthly mean absences of 0.4 and 0.5 days (P = 0.805). The feeling of well-being was comparable in both groups. In the ITP study, adverse events with a causal relationship to medication were suspected in six patients on IVIG-N and in seven on Sandoglobulin. In the PID study, three patients on IVIG-N and two on Sandoglobulin experienced possible drug-related adverse events. In both studies, serological and polymerase chain reaction (PCR) tests gave evidence for virus safety. Pharmacokinetics showed constant peak and trough serum IgG levels in all patients, indicating almost steady-state conditions for both formulations. The overall half-life (t1/2) for total IgG was 33 +/- 17 days in the IVIG-N arm and 25 +/- 16 days in the Sandoglobulin arm; for anti-HBsAg t1/2, values were 17 +/- 7 and 17 +/- 9 days, respectively. CONCLUSIONS: IVIG-N is efficacious, well tolerated and safe in patients with ITP and PID. Its pharmacokinetic properties were comparable to those of Sandoglobulin.

Adolescent↗

Merkel cell tumor presenting as a painful patch lesion on the right arm.

Primary small cell cutaneous neuroendocrine carcinoma (Merkel cell carcinoma) is an uncommon, highly malignant, primary cutaneous neuroendocrine carcinoma. Clinically it is seen as a 0.5- to 5.0-cm pinkish purple papule or nodule, usually not ulcerated, on the head, neck, or, less frequently, the roots of the limbs. We present the case of a woman with an atypical clinical presentation of a Merkel cell tumor.

Arm↗

Bone marrow transplantation with unrelated donors: what is the probability of identifying an HLA-A/B/Cw/DRB1/B3/B5/DQB1-matched donor?

Patients transplanted with marrow from an HLA-ABDR serologically matched unrelated donor suffer from more post-transplant complications than those who are transplanted with marrow from an HLA-identical sibling. This is most likely due to either HLA-ABDR incompatibilities not resolved by standard techniques and/or HLA polymorphisms not tested for by routine tissue typing (HLA-Cw,-DQ). By resolving these incompatibilities by molecular techniques combined with the in vitro cytotoxic T lymphocyte precursor frequency (CTLpf) test, we have shown that a high degree of HLA compatibility is associated with increased patient survival. However, higher requirements for HLA matching decrease the number of available donors. We have estimated the probability of finding an HLA-A/B/Cw/DRB1/DRB3/DRB5/DQB1 compatible donor based on 104 consecutive unrelated bone marrow donor searches initiated between January 1995 and December 1997, with December 1998 as the endpoint. For 96 patients (92.3%), one or more ABDR-identical donors were listed in the Bone Marrow Donor Worldwide Registry (BMDW). After contacting the registries, we obtained at least one (mean, 5.36; range, 1-20; total, 461) blood sample for 86 patients. A highly compatible donor was identified for 33/86 patients (38.4%), after testing an average number of 4.5 donors/patients (range, 1-13). However, by accepting an HLA-DRB3 or -DQB1 or -Cw incompatibility, this number would be as high as 68.6%. Approximately half of the patients (n = 40) for whom a search had been initiated have been transplanted: 22 patients with a perfectly matched donor, 15 patients with an HLA-DRB3 or -DQB1 or -Cw mismatch and three with other mismatches. The average time needed to identify the most compatible donor was 4 months. Extremely long searches seemed to be less useful, because after testing the first seven, a more compatible donor was seldom found. These results show that even when requirements for compatibility are high, the chances of finding a donor remain considerably low.

Bone Marrow Transplantation↗

Clinical use of intravenous immunoglobulins.

Prophylaxis and treatment with i.v. immunoglobulins must envisage preparations from normal or hyperimmunised human donors, animals (horses and rabbits) as well as monoclonal and genetically and proteomically engineered chimeric or recombinant antibodies. The latter group of antibody sources from the bioreactor source must be seen in the context of traditional antibody therapy, including passive immunization, general antibody substitution and provision of lost immune regulatory capacities such as downregulation of complement activation, attenuation of Fc receptor apparatus as well as anti-idiotypic potential. Beyond summarizing the present evidence based indications the present review is an outlook at the doorstep for future possibilities to improve precision of antibody dependent treatments and avoiding side effects which formerly compromised widespread use.

Animals↗

[10 years Swiss bone marrow donor registry].

The Swiss Bone Marrow Donor Registry was established 1988 as a project of Swiss Transplant. Up to the end of 1997, 13,500 unrelated volunteer donors have been added to the central registry in Bern in cooperation with the regional transfusion centers of Switzerland. During this period, the registry responded to over 15,000 international search requests. 67 matching Swiss donors were found for patients all over the world. On the other hand, 77 Swiss patients received unrelated bone marrow transplantation from international donors. In 1997, 24 donors were selected from the Swiss registry and 21 bone marrow transplantations were performed, which is more than in any year before. The most recent developments are peripheral blood stem cell donation and the creation of cord blood banks.

Bone Marrow Transplantation↗

Anti-D immunoglobulin in Rh(D) negative volunteers: clearance of Rh(D) positive red cells and kinetics of serum anti-D levels.

Properties of a new anti-D immunoglobulin were assessed in Rh(D) negative healthy male adults. Six volunteers received intravenous, and five volunteers intramuscular injections of 200 micrograms anti-D, 48 hours after pre-treatment with 5 mL of Rh(D) positive erythrocytes. Immediately after intravenous administration of anti-D, a rapid decrease of the Rh(D) positive erythroyctes was noted. After intramuscular injection of anti-D, there was a lag phase of 6 hours until the erythrocytes decreased, and the elimination rate was slower. Twenty-four hours after injection of anti-D, the Rh(D) positive erythrocytes were at the detection limit or no longer detectable in all volunteers. After intravenous administration, anti-D serum levels decreased from 45 ng/mL at 2 hours to 29 ng/mL at 24 hours, whereas after intramuscular administration, anti-D became detectable at 4 hours and increased to 11 ng/mL at 24 hours. During subsequent months, anti-D serum levels decreased at similar rates in both groups. After six months, anti-D was not detectable in any of the volunteers. Thus, the new anti-D immunoglobulin induced elimination of the Rh(D) positive erythrocytes and suggested that Rh(D) immunization of the volunteers was prevented.

Adult↗

Orifices at the lower neck: heterotopic salivary glands.

Heterotopic islands of salivary-gland tissue are rare and have been described in a number of sites in the head and neck. We describe a patient with salivary-gland fistulas in the lower third of the neck, without evidence of any other congenital abnormalities. The appearance of sinuses in association with heterotopic salivary-gland tissue suggests that its embryologic origin may be from the branchial clefts. Surgical treatment is recommended.

Child↗

Aerosolized immunoglobulin treatment of respiratory syncytial virus infection in infants.

BACKGROUND: Recent studies in animals with experimental respiratory syncytial virus (RSV) infection indicate that passive immunization by intranasal or intratracheal application of gamma-globulins (immunoglobulins) may be beneficial for treatment of infants with lower respiratory tract infection caused by RSV. METHODS: We conducted a placebo-controlled, randomized multicenter study involving 68 infants with proven RSV infection admitted to 5 pediatric centers in Switzerland from November 1, 1992, through April 30, 1993. Treatment was carried out with aerosolized human IgG (Sandoglobulin) by assisted ventilation. On the day of hospital admission a single dose of 0.1 g of IgG per kg of body weight in a 5% solution or an identical amount of placebo, each delivered in 2 parts, was given. RESULTS: The two groups did not differ substantially in their response to the aerosol received. The rate of improvement for symptoms of respiratory tract infection, oxygen requirement and length of hospital stay were comparable for both groups. There was a significant reduction (P < 0.05) in the frequency of apneic spells observed in the treatment group by Day 3 posttreatment. Aerosol therapy was generally well-tolerated in nonintubated infants, but some severe side effects (increased oxygen requirements in two patients, pneumothorax in one patient) were observed in two of three intubated and ventilated infants treated with IgG. CONCLUSIONS: Aerosolized immunoglobulin in the dosage used had no substantial beneficial effect on RSV bronchiolitis. Despite these findings passive immunotherapy for treatment of RSV-induced lower respiratory tract infection deserves further evaluation before being discarded as ineffective.

Aerosols↗

Livedo reticularis and thrombotic purpura related to the use of diphenhydramine associated with pyrithyldione.

We describe the case of a young woman who habitually took large doses of a combination of diphenhydramine and pyrithyldione. She complained of arthralgia, painful recurring plaques and nodules, together with persistent reticular purpuric mottling and areas of necrosis on her legs. There were positive antinuclear antibodies and rheumatoid factor and histologically massive thrombosis of the dermal vessels without signs of vasculitis. Other cases of similar adverse reactions attributed to this drug combination used as a hypnotic have been described.

Adult↗

Tricoadenoma of Nikolowski.

The patient, aged 50 years, with no relevant clinical history, complained of a symptomless, soft tumor of the right buttock that had been present for many years. On examination, it was found to be pediculate, oval, somewhat erythematous, firm on palpation, and with a central keratin plug. The greatest diameter of the lesion was 1.2 cm (Fig. 1). On surgical removal of the lesion, it was seen to be composed of a symmetric intradermal proliferation of cystic formations, uniformly distributed throughout and made up of flat, pluristratified epithelium with laminated keratin. There was little difference in the thickness of the walls of the cysts (Fig. 2). Some cysts were attached to a short tadpole-shaped, epithelial cord and surrounded by a scanty fibroblastic stroma. No hairmatrix-like differentiation nor basaloid structures were seen, nor were atypical cells present. There was hardly any inflammatory infiltration.

Buttocks↗

Mucosal-associated lymphoid tissue lymphoma of the conjunctiva.

The recognition of mucosal-associated lymphoid tissue as a distinct entity has lead to the separate classification of tumors arising in this tissue, ie, the mucosal-associated lymphoid tissue lymphoma. Five patients with mucosal-associated lymphoid tissue lymphoma of the conjunctiva are described herein; four of the five patients had bilateral tumors. Laboratory analysis was done using microscopy, immunophenotyping, gene rearrangement analysis using both Southern blot and polymerase chain reaction techniques, and oncogene (bcl-1, bcl-2, and c-myc) rearrangement studies. Typical mucosal-associated lymphoid tissue lymphoma features were seen in all patients; three of four patients who underwent testing with immunphenotyping had light-chain restriction, four of five patients had a clone detected using Southern blot analysis, and all five patients showed clones on polymerase chain reaction analysis. No patient demonstrated oncogene rearrangement. In all patients, complete physical examinations and laboratory tests did not detect any evidence of systemic spread. After treatment, no evidence of local recurrence or dissemination was found during follow-up ranging from 2 to 3 years.

Adult↗