HLA-A, HLA-B and HLA-DRB1 allele and haplotype diversity among volunteer bone marrow donors from Croatia.

The determination of human leucocyte antigen (HLA)-A, HLA-B and HLA-DRB1 alleles in the routine procedure of a volunteer hematopoietic stem cell (HSC) donor's registration in the Croatian Bone Marrow Donor Registry (CBMDR) is performed to enhance the odds of finding a suitable HLA compatible donor for patients in need of a HSC transplantation worldwide. However, besides its original purpose, it also provides valuable information about the HLA polymorphism among Croats. The aim of the present study was to analyse the HLA allele and haplotype frequencies in a sample of 4000 donors from CBMDR. The distribution of HLA-A, HLA-B and HLA-DRB1 alleles did not demonstrate significant differences from the data reported for other European populations. The higher frequency of B*40:02 allele in comparison with B*40:01 and DRB1*11:04 in comparison with DRB1*11:01 is interesting because it represents a difference in comparison with the Western and Northern European populations which are a main source of donors for Croatian patients. The haplotype frequencies show a greater variation and difference in comparison with data from other registries and populations; however, due to a lack of high-resolution haplotype data, comparison was possible only with a very limited number of other populations.

[Twenty years of severe aplastic anemia treatment at Department of Hematology, University Department of Medicine, Zagreb University Hospital Center, Zagreb, Croatia]. / Dvadeset godina lijecenja teske aplasticne anemije u Zavodu za hematologiju Klinike za unutrasnje bolesti Klinickog bolnickog centra Zagreb.

Aplastic anemia is a bone marrow disease characterized by marrow aplasia and pancytopenia. Because hematopoietic stem cell transplantation (HSCT) cures severe aplastic anemia (SAA), it is the treatment of choice for younger patients. For many years, antithymocyte globulin (ATG) has been standard immunosuppressive therapy for those aplastic anemia patients that have no HLA matched related donor. ATG significantly improves aplastic anemia outcome, especially when combined with cyclosporine (CSP). The response rate varies from 40% to 70% and long-term survival is comparable with patients receiving marrow transplant. From 1983 until 2006, 46 SAA patients received HLA identical sibling marrow graft. In the same period, 50 patients received standard immunosuppressive therapy combined from horse or rabbit ATG, 6 methyl prednisolone and cyclosporine. Out of 46 transplant patients, 27 received a combination of cyclophosphamide and thoraco-abdominal irradiation. The overall probability of survival for SAA patients that underwent marrow grafting is 51%, and for patients receiving immunosuppressive treatment 20%. We analyzed a cohort of patients receiving treatment after 1990 and found the probability of survival to be 64% for bone marrow transplanted patients and 36% for patients receiving immunosuppression. Infection is the main cause of death in both groups. In conclusion, we documented improving results using ATG in patients with SAA.

IgH and TCRgamma gene rearrangements, cyclin A1 and HOXA9 gene expression in biphenotypic acute leukemias.

In this study we investigated IgH and TCRgamma gene rearrangements, cyclin A1 and HOXA9 gene expression as well as the in vitro growth of biphenotypic acute leukemia (BAL) blasts in relation to acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML). The aim of the study was to correlate BAL morphology and its biological parameters in order to get information that might be used for additional stratification of BAL. This rare form of AL was identified in a total of 10 patients, comprising 4.3% of adult and 3.0% of pediatric patients with de novo AL referred to our institution during the 1999-2003 period. Our results indicate that IgH and TCRgamma gene rearrangements correlated well with lymphoid BAL morphology, whereas the expression of cyclin A1 correlated with myeloid and undifferentiated BAL morphology. Surprisingly, HOXA9 expression, a marker associated with myeloid cell lineage, showed no strong correlation with BAL morphology. Finally, in vitro growth of blasts during a 7-day culture showed autonomous cell growth in 3/10 AML and 3/8 myeloid BAL samples tested, but not in any of the AL with lymphoid features. Further studies are needed to confirm these findings and to extend research to a broader spectrum of cell markers.

Multiple sclerosis: Part II. Common functional problems and rehabilitation.

Cognitive impairments, often unrecognized in multiple sclerosis, include memory loss, new learning problems, denial and depression. Spasticity and incoordination of the oropharyngeal and respiratory muscles create functional problems with speech and swallowing. Genitourinary problems include sexual dysfunction and neurogenic bladder. Specific measures can be used to alleviate these problems.

Multiple sclerosis: Part I. Common physical disabilities and rehabilitation.

Rehabilitation of the multiple sclerosis patient must be individualized because of the varied manifestations and fluctuating course of the disease. The activity schedule must be modified to compensate for muscle weakness and fatigability. Spasticity and the preventable complication of joint contractures may be treated with joint ranging, medications, motor-point blocks and surgical intervention. Mobility problems, such as foot drop, may be improved with an ankle-foot orthosis, but ultimately a patient may require a wheelchair. Measures to prevent pressure sores include position change, pressure release, incontinence management and special equipment.

Pressure ulcers. What to do if preventive management fails.

Tissue breakdown is a direct response to external pressure, friction, or shear. The key to management of pressure ulcers is prevention. With good nursing care, as well as education of medical personnel, the patient, and family members, such lesions should rarely occur. The axioms of treatment are to remove all pressure, debride necrotic tissue, keep the ulcer clean, and prevent further injury. There is only empirical evidence attesting to the effectiveness of the various dressings and physical and topical agents used in treatment. Most pressure ulcers can be classified as grade I or II and healed by conservative measures; however, the process can be very time-consuming. Surgery is warranted for some grade III and all grade IV and V pressure ulcers and for potential complications, such as fistulas.

Stroke rehabilitation: Part II. Recovery and complications.

Return of neurologic function after a stroke tends to be complete within six months after the insult. Initial flaccidity is superseded by spasticity, which is most prominent distally. Movements initially occur in synergistic patterns. Return of voluntary movements begins proximally in the lower extremity. In the upper extremity, proximal recovery usually occurs first, but finger movement occasionally is the earliest sign. Proper positioning and early, passive range-of-motion exercises help to avoid complications.

Stroke rehabilitation: part I. Cognitive deficits and prediction of outcome.

In many cases, the family physician will set the tone for rehabilitation of the stroke patient. It is imperative that the physician understand the recovery process, as well as the nature, benefits and limitations of rehabilitation. Since there are no precise predictors of individual outcome, no patient should be excluded from rehabilitation unless he is too ill or too cognitively devastated to participate.

Amyotrophic lateral sclerosis: comprehensive management.

The cause of amyotrophic lateral sclerosis remains unknown, and no curative treatment is available. From a rehabilitation perspective, however, comprehensive management and symptomatic treatment can minimize complications, increase function and improve the patient's quality of life. Quinine, diazepam (Valium) and phenytoin (Dilantin) may relieve muscle cramps, and orthoses may permit greater participation in daily activities. Problems with respiration and swallowing may require surgical procedures and the use of feeding tubes. Decisions regarding surgical intervention must be made in the context of the patient's overall status.

Clinical applications of a standardized mobility test.

Four patients with mobility problems were evaluated in relation to their performances on a standardized mobility test throughout the course of their rehabilitation programs. While each of the four cases demonstrates the value of an objective measurement of independent function, each also reflects individual points of merit. Clinical application demonstrated the test's ability to separate out areas of mobility deficit, evaluate forms of treatment, and indicate need for follow-up. Further, the sensitivity of the test in long-term follow-up of mobility problems was illustrated.