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J D'Amaro

Publications and source records attributed to J D'Amaro.

At least 19 recordsLinked to original sources

Visual prognosis in immunocompetent patients with herpes zoster ophthalmicus.

PURPOSE: To determine the normal spectrum of ocular complications and associated visual outcome in patients with herpes zoster ophthalmicus. METHODS: This prospective observational cohort study included 73 immunocompetent adults with herpes zoster ophthalmicus, referred by their general practitioners within 7 days of skin rash onset. The follow-up period was 6 months. All patients received a 7-14-day course of systemic aciclovir treatment combined with longterm application of a lubricating ophthalmic ointment as long as the corneal epithelium was affected. Topical corticosteroids were strictly avoided in the acute phase of ocular disease. Acquired visual loss scores at 1, 2 and 6 months were based on best corrected visual acuity (BCVA) level and evaluation of the ophthalmological history and findings. RESULTS: Ophthalmic herpes zoster led to a variety of transient inflammatory reactions within the anterior eye segment of the involved side in 46 patients (63%), but did not seriously compromise their ultimate visual outcome. Mild to moderate visual loss, with corrected VA between 0.3 and 0.8, was found in 17 patients at 1 month (23%), in 10 patients at 2 months (14%) and in seven patients at 6 months follow-up (10%). None of the patients developed visual loss with a corrected VA of less than 0.3. CONCLUSION: Functional vision was retained in all ophthalmic zoster patients referred to the ophthalmologist in the acute phase of the disease by vigorous antiviral treatment and adequate prevention of corneal exposure.

Acyclovir↗

Histocompatibility and corneal transplantation.

BACKGROUND: HLA typing and matching have been poorly implemented in corneal transplantation, mainly because of inconclusive or contradictory analytical results. Consequently, we studied the immune response of corneal transplant recipients to HLA histoincompatibilities in a large homogeneous study. METHODS: All corneal transplantations were performed by a single surgeon in a single center between 1976 and 1996. Population genetic and other statistical analyses were performed. Simulation studies assessed the effects of HLA-DR mistypings on analytical results. RESULTS: Mono- and multivariate analyses identified retransplantation, degree of vascularization, HLA-AB and -DR match grades, endothelial cell count, graft size, recipient gender, storage method and panel-reactive antibodies as significantly influencing the survival of corneal transplants. Simulation studies showed that the beneficial effect of HLA-DR matching is abrogated by HLA-DR mistypings. CONCLUSIONS: Corneal transplant recipients have a normal immune response to HLA incompatibilities. Demonstration of that fact requires accurate HLA typings.

Cell Count↗

Longitudinal analysis of varicella-zoster virus DNA on the ocular surface associated with herpes zoster ophthalmicus.

PURPOSE: Longitudinal analysis of varicella-zoster virus DNA on the ocular surface of patients with herpes zoster ophthalmicus. METHODS: Clinical specimens were obtained from the bulbar conjunctival surface with a cotton-tipped swab at weekly intervals for 6 consecutive weeks from 21 patients with acute ophthalmic zoster with a skin rash duration of less than 7 days. All patients received oral valacyclovir 1000 mg three times daily for 10 days without additional corticosteroids. The swabs were analyzed by means of polymerase chain reaction for the presence of varicella-zoster virus and herpes simplex virus type 1 DNA. Conjunctival swabs were also obtained from a control group of 20 patients with cataract. RESULTS: On inclusion, varicella-zoster virus DNA was present on the ocular surface of 19 of the 21 patients. Six varicella-zoster virus DNA-positive patients had no signs of ocular inflammation. All control swabs were negative for both varicella-zoster virus and herpes simplex virus DNA. The duration of varicella-zoster virus DNA detection from rash onset varied from 2 to 34 days. The number of days between the onset of herpes zoster skin rash and the latest positive varicella-zoster virus DNA test was significantly longer in patients whose age was equal to or above the median age of 66 years than in the younger patients (Mann-Whitney test: P =.0004). At 6-week follow-up, all conjunctival swabs were negative for varicella-zoster virus DNA. However, at that time, the eyes of seven patients were still inflamed. CONCLUSION: The duration of varicella-zoster virus DNA shedding in herpes zoster ophthalmicus is highly variable and age dependent, and is probably related to the host immune response.

Acyclovir↗

Beneficial effect of HLA-DR matching on the survival of corneal allografts.

BACKGROUND: Although HLA typing and matching have been used for 3 decades, that practice has been poorly implemented in corneal transplantation, mainly because of inconclusive or contradictory analytical results. Consequently, we studied the immune response of corneal transplant recipients to HLA histoincompatibilities in a large homogeneous study. METHODS: All corneal transplantations performed by a single surgeon between 1976 and 1996 were studied. HLA-AB matching was used for recipient selection. All HLA typings were performed by a single experienced laboratory. Population genetic techniques were used to assess the validity of the HLA typings. Mono- and multivariate analyses were performed to identify the factors which significantly influence the survival of corneal allografts. Simulation studies were carried out to demonstrate the effects of mis-typed donor and recipient HLA-DR typings on analytical results. RESULTS: Retransplantation, degree of vascularization, HLA-AB and DR matching, endothelial cell count, graft size, recipient gender, and storage method were identified as significant factors by our monovariate analyses. A Cox proportional hazards survival analysis model identified degree of vascularization and HLA-AB and DR matching as significant prognostic factors when all immunological rejection episodes were used, P=0.000001. When only irreversible immunological rejection episodes were used, panel reactive antibodies, retransplantation, and number of rejection events were also identified, P=0.000001. Simulation studies showed that the effects of HLA-DR matching are abrogated by poor HLA-DR typings. CONCLUSIONS: Corneal allograft recipients have a normal alloimmune response to histoincompatibilities. Demonstration of that fact requires accurate HLA typings.

Adolescent↗

Risk and prognostic factors of postherpetic neuralgia and focal sensory denervation: a prospective evaluation in acute herpes zoster ophthalmicus.

OBJECTIVES: To determine the general risk and the prognostic factors of postherpetic neuralgia and focal sensory denervation in ophthalmic zoster disease. STUDY DESIGN: A prospective clinical study. SETTING: An ophthalmic practice participating in an eye-care network. PATIENTS: A cohort of 81 immunocompetent adult patients with herpes zoster ophthalmicus and referred by their general practitioner during the acute phase of the disease. METHODS: Various acute phase clinical parameters were determined via patient history and regular ophthalmic examinations. At a 2-month follow-up, the intensity of postherpetic neuralgia, rated on a 4-point verbal scale, and focal sensory denervation was determined. Skin tactile sensation within the ophthalmic dermatomes was tested with use of a cotton-wool tip, and corneal sensitivity was measured with use of a Cochet-Bonnet esthesiometer by comparing each eye. Statistical analysis was performed via chi2 analysis or Fisher exact test to identify prognostic factors of postherpetic neuralgia and focal sensory denervation at a 2-month follow-up. RESULTS: At a 2-month follow-up, pain of varying intensity was reported by 38 participants (47%). Of these patients, 25 patients (31%) rated their pain as mild, 8 patients (10%) rated their pain as moderate pain, and 5 patients (6%) rated their pain as severe. At that time, focal loss of normal skin or corneal sensation was detected in 49 patients (60%). Patient age, acute neuralgia score, manifestation and extent of acute skin rash, signs of ocular inflammation, and nontrigeminal cranial nerve involvement were all associated with prolonged pain and tactile sensory loss. CONCLUSIONS: The severity of acute skin rash, based on a specific manifestation of cutaneous herpes zoster eruptions, and the extent of infection to other neural pathways were clearly associated with postherpetic neuralgia and focal sensory denervation at a 2-month follow-up. These findings suggest that the inability of the immune system to control the spread of replicating varicella-zoster virus in the initial phase of the disease is an important factor in the pathogenesis of chronic zoster-related neuropathy.

Acute Disease↗

HLA-B8 and HLA-A3 coexpressed with HLA-B8 are associated with a reduced risk of the development of chronic myeloid leukemia. The Chronic Leukemia Working Party of the EBMT.

Chronic myeloid leukemia (CML) is characterized by the chromosomal translocation t(9;22) resulting in the chimeric bcr-abl oncogene that encodes the P210 fusion protein, which contains a unique amino acid sequence. If peptides derived from the leukemia-specific part of P210 are expressed in HLA molecules on the cell membrane of leukemic cells, an immunological response may occur. Recent studies using synthetic peptides identical to the bcr-abl fusion region showed that some peptides are capable of binding to HLA-A3, -A11, and -B8 molecules. Cytotoxic T-cell responses have been induced against bcr-abl-derived synthetic peptides bound to HLA-A3 and -B8. We hypothesized that if antigen processing of the P210 fusion protein leads to presentation of peptides from the fusion region by major histocompatibility complex (MHC) molecules in vivo, this may be reflected in a diminished incidence of CML in individuals expressing HLA-A3, -A11, or -B8. Consequently, lower frequencies of these antigens would be expected in patients with CML compared with unaffected individuals. A case-control study and a meta-analysis were performed to test this hypothesis. The multicenter case-control study compared patients with CML from the data base of the European Group for Blood and Marrow Transplantation (EBMT) with unaffected individuals from the registry of Bone Marrow Donors Worldwide. Patients and controls were matched per country. The meta-analysis consisted of five studies reported in the literature. The multicenter case-control study consisting of 1,899 patients and 512, 363 bone marrow donors as controls yielded odds ratios (ORs) of 0.90 (95% confidence interval [CI], 0.80 to 1.00) for HLA-A3, 1.16 (95% CI, 1.02 to 1.33) for HLA-A11, and an OR of 0.73 (95% CI, 0.65 to 0. 82) for HLA-B8. Coexpression of HLA-A3 and HLA-B8 gave an OR of 0.51 (95% CI, 0.40 to 0.67). This can be translated in a protective effect of 27% for HLA-B8, 10% for HLA-A3, and 49% protection for the combination of HLA-A3 and HLA-B8. The meta-analysis comprising 463 CML patients and 4,912 controls showed a 29% risk reduction for individuals expressing HLA-B8 (OR of 0.71; 95% CI, 0.52 to 0.97), but an OR of 1.19 (95% CI, 0.90 to 1.56) for HLA-A3 and an OR of 1. 09 (95% CI, 0.80 to 1.50) for HLA-A11. In conclusion, these results indicate that HLA-B8 expression, in particular when HLA-A3 is coexpressed, is associated with a diminished incidence of CML. A biological mechanism may be that presentation of bcr-abl breakpoint peptides in these HLA molecules can induce a protective immune response.

Case-Control Studies↗

Validation of haplotype frequency estimation methods.

In order to investigate the performance of haplotype frequency estimation methods using unrelated individuals, we compared the results of three estimation methods with those from the haplotypes deduced from family pedigrees. To that end we used the HLA phenotypes of the parents of 1040 families as data for the estimation methods and the full pedigree information as data for the deductive method. We evaluated the results of the following estimation methods: the method using two by two tables described by Mattiuz et al., the maximum likelihood method described by Yasuda and Tsuji and a crude method that uses the information on homozygosity in the phenotypes. All estimation methods generate reliable haplotype frequencies for the more frequent haplotypes, but are unreliable for the less frequent haplotypes. The maximum likelihood estimation method shows the best overall correlation with the results of the deductive method.

Female↗

HLA gene haplotype frequencies in bone marrow donors worldwide registries.

To calculate reliable HLA gene and haplotype frequencies of bone marrow donors in various regions in the world, we have analyzed the HLA-A, -B, and -DR phenotype frequencies of 18 bone marrow donor registries with a total of more than 300,000 HLA-A, -B-typed donors. These registries were included in the 22nd edition of Bone Marrow Donors Worldwide. Maximum likelihood gene frequencies, Hardy-Weinberg equilibrium fit, and 2- and 3-locus haplotype frequencies were calculated as well as deltas, relative deltas, and their significance. Remarkable gene and haplotype frequency differences exist between the registries. The genetic distances between the different registries were used to draw phylogenetic trees that clearly show that the degree of similarity between registries is related to their geographic locations. The resulting frequencies can be used for the estimation of the probability of finding a hyplotypically identical related or unrelated bone marrow donor for an individual patient. Phylogenetic trees are useful representations of the similarity between donor pools and can also aid in the selection of donors.

Bone Marrow Transplantation↗

Changing patterns in organ donation in Eurotransplant, 1990-1994.

Organ transplantation has become the treatment of choice for patients with end-stage organ failure and has led to progressive increases in the size of waiting lists over the past decade. Unfortunately, from 1990 to 1994, the number of organ donors remained stable while the number of organs transplanted from these donors increased by only 10%. In view of the severity of the current organ shortage, elderly individuals are increasingly being accepted as organ donors. The graft survival rate with kidneys from donors older than 55 years is 5% lower than that with kidneys from younger donors at 1 years and 9% lower at 3 years post-transplantation. Graft survival is also significantly lower with organs from donors who die from cerebrovascular accidents than it is with organs from donors whose cause of death is cerebral trauma. The number of patients waiting for a nonrenal donor organ has increased rapidly in the past 5 years, and an increasing number of donor kidneys are now being provided by multiorgan donors. The favorable graft survival rate with multiorgan donor kidneys, which is significantly better than that obtained with single organ donor kidneys, confirms their suitability for renal transplantation.

Adult↗

The impact of HLA-A matching on long-term survival of renal allografts.

An important contribution of HLA-A antigen matching in renal transplantation was reported initially, hut later publications showed a minor or absent role. We analyzed the contribution of HLA-A locus matching to graft survival in 17,672 first renal transplants from unrelated, nonliving donors. We show that an independent HLA-A matching effect still exists. Due to its relative weakness and late appearance, large numbers and longer follow-up periods are required. The HLA-A matching effect is a significant factor in first renal allograft survival up to 6 years after transplantation, with an increasing effect over time. This is in contrast to the strong, short-lived, effects of HLA-DR and -B matching, which can only be detected up to 6 months and 2 years after transplantation, respectively. A clear additive beneficial effect of HLA-A matching is shown in the group without B and DR mismatches. Therefore, prospective matching for the HLA-A antigens remains important for renal allograft survival.

Graft Survival↗

The probability of finding a suitable related donor for bone marrow transplantation in extended families.

In bone marrow transplantation, the advantages of family donors over unrelated donors are threefold. (1) Family donors are better matched because they share complete haplotypes. (2) The time between the start of the search and the actual transplantation can be much shorter than for unrelated donors. (3) Related bone marrow transplantation is cheaper. We developed a procedure for calculating the probability of finding a suitable donor among cousins and blood-related aunts and uncles (the extended family). The procedure calculates the following probabilities (P): (1) P that any blood-related uncle or aunt is a suitable donor, (2) P that a suitable donor exists in all blood-related uncles/aunts (from [1]), (3) P that any cousin is a suitable donor (as in [1]), (4) P that a suitable donor exists in all cousins (from [3]), (5) P that a suitable donor exists in the entire extended family (from [2] and [4]). Additionally, we discuss the suitability of this procedure in the daily practice of donor procurement. The procedure is also suitable to search for family donors who have a single antigen mismatch with the patient. We also discuss the differences between our method and the one recently described by Kaufman (Bone Marrow Transplant 15:279, 1995).

Algorithms↗

Minimal phenotype panels. A method for achieving maximum population coverage with a minimum of HLA antigens.

Vaccination with peptides that induce a specific immune response is a potential prophylactic or therapeutic strategy against viral infections and tumors. Because of the extensive polymorphism of the HLA loci, synthetic peptide vaccines must consist of a cocktail of peptides that bind specifically to different HLA molecules. Such cocktails should be optimized for the target population as each population has its specific HLA gene frequencies. To achieve maximum population coverage with a minimum number of peptides, information is needed on the ranking of the most frequent HLA phenotypes. We introduce the minimal phenotype panel, which is the smallest combination of HLA antigens selected so that the proportion of individuals in a population that express at least one of the antigens in the panel exceeds a desired minimum value. We developed a method for assembling minimal phenotype panels based on known HLA class I gene frequencies. We give an example based on a set of 2446 well-defined HLA-typed, random, healthy, unrelated, Dutch Caucasoid individuals. In addition, we discuss the possibility of assembling minimal phenotype panels based on two-locus haplotypes, which enables the assembly of phenotype panels from the antigens of both loci.

Epitopes↗

Validation of large data sets, an essential prerequisite for data analysis: an analytical survey of the Bone Marrow Donors Worldwide.

Large data sets like the Bone Marrow Donors Worldwide (BMDW) data set can be used for population genetic analyses. The qualities of such data sets are unique. To be able to use the BMDW data for analyses, several problems, like limited size and selective DR typing, of the data have to be solved and the quality of the registry data subsets has to be examined. We describe these problems and methods to overcome them. Also, we give an overview of the qualities of the different registry subsets. Sixteen of the twenty-nine examined subsets contain data that can be used for population genetic analysis. We will deal with these analyses in the future. Additionally, we present a method to calculate the minimum number of individuals required for reliable haplotype frequency estimation.

Bone Marrow Transplantation↗

HLA gene and haplotype frequencies in Dutch blood donors.

We analyzed the HLA-A, -B, -C, -DR and -DQ phenotypes of 2,440 healthy, unrelated, Dutch Caucasoid blood donors and of 20,814 Dutch blood donors who were registered as volunteer bone marrow or platelet donors. Phenotype and gene frequencies, Hardy-Weinberg equilibrium fit and homozygosity were calculated as well as 2- and 3-locus haplotype frequencies, deltas, relative deltas and significance levels of the deltas. The population appears to be in Hardy-Weinberg equilibrium. Many haplotypes are in strong positive linkage disequilibrium. A phylogenetic tree, based on the HLA-A, -B and -DR gene frequencies of blood donors in different Dutch regions, reflects the limited but manifest heterogeneity of the Dutch population. Additionally we introduce a stepwise test for Hardy-Weinberg equilibrium and discuss the applicability of this test and of the single test for Hardy-Weinberg equilibrium for tissue typing quality control and for selection of split antigens prior to gene and haplotype frequency analyses.

Blood Donors↗

Some contemporary ethical considerations related to organ transplantation.

With the increasing number of transplantable organs and tissues, as well as improvements in transplantation results, has come a severe shortage of organ donors. Consequently, new ethical dilemmas, related to the fair allocation of available organs and the use of alternative sources of donor organs, are of growing concern. Establishing fair allocation priorities is a serious problem in organ transplantation. Ethically, they should be defined by society as a whole rather than exclusively by the medical profession. Proposed solutions for the organ donor shortage, each with their unique ethical constraints, include the use of related donors, partial organ transplantation, cell transplantation using fetal tissue, and the use of animal organs "xenotransplantation ". Commercial trading in donor organs must be regarded as an unethical activity rather than an ethical dilemma since the donors are motivated by monetary rather than by humanitarian reasons. These ethical dilemmas could be largely avoided by an effective reduction in the severe shortage of postmortal organ donations.

Ethics, Medical↗

Irregular polymerase chain reaction-sequence-specific oligonucleotide hybridization patterns reveal seven new HLA-DRB1 alleles related to DR2, DR3, DR6, DR8, and DR11. Implications for sequence-specific priming.

In the past 3 years we have typed over 7000 individuals for HLA-DRB using a nonradioactive PCR-SSO method. The use of locally developed computer programs simplified data input and the interpretation of the DRB PCR-SSO readings. In this way we detected a number of samples with unexpected hybridization patterns. DRB1 exon 2 segments of these samples were amplified, cloned, and sequenced and appeared to identify seven new DRB alleles: DRB1*0304, a DRB1*0301 variant, was observed in three unrelated Caucasoid individuals; DRB1*1606, which is very similar to *1603; DRB1*1113 is a *1101 variant with some *1401 sequences; DRB1*1310 is *1301-like; DRB1*1311 is similar to *1305 and *1307; DRB1*1416 is a *1401 sequence with a HV3 derived from *1301; DRB1*0808 was found in an Ethiopian individual. Next, we studied the effectiveness of PCR-SSP typing of the newly defined DRB1 alleles. Only two variants were distinguished as odd by PCR-SSP and two were typed as regular specificities. Three alleles were not amplified by the primer sets used. As compared to PCR-SSO, the PCR-SSP typing method using currently available typing kits clearly has limitations as far as the recognition of new and variant alleles is concerned. The products of some of these new alleles may be distinguished using conventional serology.

Alleles↗