Histological changes over time around the site of sustained release naltrexone-poly(DL-lactide) implants in humans.

In order to assess the histological tissue changes over time around the site of implant, tissue biopsies were taken at 1 to 38 months post-implant from 54 (34 male) consenting human subjects who had received the Australian subcutaneous naltrexone-poly(DL-lactide) implant for heroin dependence. The implant consists of multiple tablets containing compressed naltrexone-poly[trans-3,6-dimethyl-1,4-dioxane-2,5-dione] (DL-lactide) loaded microspheres. Assessment of tissue samples by pathologists showed an early phase (up to 12 months post-implant) of inflammation, foreign body reaction, and fibrosis. This subsided gradually over the next 12 months until tissue returned to normal by 25+ months. Sufficient evidence was not available to conclude that the poly(DL-lactide) implant matrix was totally biodegradable within the study period. While implant material was not identified in most of the latter biopsies, its presence was noted in one biopsy at 26 months post-implant. Nevertheless the study results did demonstrate the implant's biocompatibility by the lack of inflammation, foreign body reaction, and fibrosis detected by 25+ months. It seems highly probable that surgical technique rather than the implant itself was associated with the additional finding of fat necrosis. Moderate fat necrosis was observed as a common feature of biopsies carried out during the first 6 months following implant. It subsided to mild levels over the next 18 months, and was notably absent by 25+ months. The results of the study indicated that the Australian naltrexone-poly(DL-lactide) implant is well tolerated and may have a role for use in the management of medical conditions such as heroin dependence.     

Repeated measurements of mite and pet allergen levels in house dust over a time period of 8 years

BACKGROUND: Studies of the association between indoor allergen exposure and the development of allergic diseases have often measured allergen exposure at one point in time. OBJECTIVE: We investigated the variability of house dust mite (Der p 1, Der f 1) and cat (Fel d 1) allergen in Dutch homes over a period of 8 years. METHODS: Data were obtained in the Dutch PIAMA birth cohort study. Dust from the child's mattress, the parents' mattress and the living room floor was collected at four points in time, when the child was 3 months, 4, 6 and 8 years old. Dust samples were analysed for Der p 1, Der f 1 and Fel d 1 by sandwich enzyme immuno assay. RESULTS: Mite allergen concentrations for the child's mattress, the parents' mattress and the living room floor were moderately correlated between time-points. Agreement was better for cat allergen. For Der p 1 and Der f 1 on the child's mattress, the within-home variance was close to or smaller than the between-home variance in most cases. For Fel d 1, the within-home variance was almost always smaller than the between-home variance. Results were similar for allergen levels expressed per gram of dust and allergen levels expressed per square metre of the sampled surface. Variance ratios were smaller when samples were taken at shorter time intervals than at longer time intervals. CONCLUSION: Over a period of 4 years, mite and cat allergens measured in house dust are sufficiently stable to use single measurements with confidence in epidemiological studies. The within-home variance was larger when samples were taken 8 years apart so that over such long periods, repetition of sampling is recommended.     

Translocation of BCR to chromosome 9: A new cytogenetic variant detected by FISH in two Ph-negative,BCR-positive patients with chronic myeloid leukemia

Leukemic cells from two patients with Philadelphia-negative chronic myeloid leukemia (CML) were investigated: I) Cytogenetics showed a normal 46.XY karyotype in both cases, 2) molecular studies revealed rearrangement of the M-BCR region and formation of BCR-ABL fusion mRNA with b2a2 (patient I) or b3a2 (patient 2) configuration, and 3) fluorescence in situ hybridization (FISH) demonstrated relocation of the 5′ BCR sequences from one chromosome 22 to one chromosome 9. The ABL probe hybridized to both chromosomes 9 at band q34, while two other probes which map centromeric and telomeric of BCR on 22q 11 hybridized solely with chromosome 22. For the first time, a BCR-ABL rearrangement is shown to take place on 9q34 instead of in the usual location on 22q 11. A rearrangement in the latter site is found in all Ph-positive CML and in almost all investigated CML with variant Ph or Ph-negative, BCR-positive cases. The few aberrant chromosomal localizations of BCR-ABL recombinant genes found previously were apparently the result of complex and successive changes. Furthermore in patient 2, both chromosomes 9 showed positive FISH signals with both ABL and BCR probes. Restriction fragment length polymorphism (RFLP) analysis indicated that mitotic recombination had occurred on the long arm of chromosome 9 and that the rearranged chromosome 9 was of paternal origin. The leukemic cells of this patient showed a duplication of the BCR-ABL gene, analogous to duplication of the Ph chromosome in classic CML. In addition they had lost the maternal alleles of the 9q34 chromosomal region. The lymphocytes of patient 2 carried the maternal chromosome 9 alleles and were Ph-negative as evidenced by RFLP and FISH analyses, respectively. © 1993 Wiley-Liss, Inc.     

Primate endocrine function after pancreatico-duodenal-splenic allotransplantation

In this study the endocrine function following intraperitoneal hetero- and orthotopic pancreatico-duodenal-splenic allotransplantation (PDS) in hemipancreatectomized, non-immune-suppressed chacma baboons was assessed. Significantly reduced K-values and insulin release together with glucose intolerance during IVGTT were observed in hemipancreatectomized recipients (HPS) without grafts. Orthotopic and heterotopic PDS transplantation improved the glucose intolerance of HPS recipients; orthotopically sited grafts rendering the best curves. Normal glucose tolerance was not achieved. Both orthotopic and heterotopic PDS transplantation rendered suboptimal insulin release during IVGTT; heterotopically draining grafts released significantly more insulin than orthotopic grafts. Hyperglucagonaemia during IVGTT was a constant feature in both groups, heterotopic grafts releasing the most glucagon during stimulation. C-peptide release was significantly lower in orthotopic grafts compared to normal animals or heterotopically drained insulin. It is concluded that glucose tolerance was not directly related to insulin or glucagon release in this study as orthotopic grafts rendered near-normal IVGTT curves in the presence of hypoinsulinaemia, hyperglucagonaemia, and reduced C-peptide values. The hormonal response after PDS transplantation was variable and the advantages of portal vs systemic insulin drainage remain to be defined.     

HIV-antibody seroconversions in Dutch haemophiliacs using heat-treated and non heat-treated coagulation factor concentrates

A national multicentre study was performed to investigate the effects of donorselection and the use of heat-treated plasma products on seroconversion to HIV in 157 Dutch haemophiliacs. All patients included in the study were seronegative for HIV antibodies in 1983. Thirteen percent (20/157) seroconverted between 1983 and 1986. Nineteen of 20 seroconversions could be related to the use of non heat-treated products in the year preceding HIV antibody seroconversion. One seroconversion occurred in a person using heat-treated non donor screened product. Seroconversion rate decreased as a result of the policy to discourage high risk blood donors and no seroconversions were observed following the introduction of donor screening in 1985.     

Intracerebral bilateral symmetrical calcifications, demonstrated in a patient with pseudohypoparathyroidism

Bilateral Symmetrical Calcifications (B.S.C.) in cerebro represent calcium deposits usually found in the basal ganglia and/or dentate nucleus. They can be the result of diverse disorders, but can also present themselves without any underlying disease. Most often they are asymptomatic, but if the calcifications are extensive, extrapyramidal and cerebellar signs may arise. The following case concerns a patient with pseudohypoparathyroidism. Besides the usual signs and symptoms found in this disease, the patient also showed extensive B.S.C. The etiology and clinical symptoms of B.S.C. will be discussed. Furthermore, attention will be given to the syndrome of the pseudohypoparathyroidism and the effects of hypocalcemia.