Age-related changes in the articular cartilage of human sacroiliac joint

 Iliac and sacral articular cartilage of 25 human sacroiliac joints (1–93 years) are examined by light microscopy and immunohistochemistry in order to gain further insight into the nature and progress of degenerative changes appearing during aging. These changes can already be seen in younger adults as compared to cartilage degeneration known in other diarthrodial joints. Structural differences between sacral and iliac cartilage can already be observed in the infant: the sacral auricular facet is covered with a hyaline articular cartilage, reaching 4 mm in thickness in the adult and staining intensely blue with alcian blue at pH1. Iliac cartilage of the newborn is composed of a dense fibrillar network of thick collagen bundles, crossing each other at approximately right angles. A faint staining with alcian blue suggests a low content of acidic glycosaminoglycans. In the adult, iliac cartilage becomes hyaline and its maximal thickness reaches 1–2 mm. Both articular facets exhibit morphological changes during aging that are more pronounced in the iliac cartilage and resemble osteoarthritic degeneration; the staining pattern of the extracellular matrix becomes inhomogenous, chondrocytes are arranged in clusters and the articular surface develops superficial irregularities and fissures. Sometimes fibrous tissue fills up these defects. Nevertheless, large areas of iliac cartilage remain hyaline in nature. Sacral articular cartilage often remains largely unaltered until old age. The sacral subchondral bone plate is usually thin and shows spongiosa trabeculae inserted at right angles, suggesting a perpendicular load on the articular facet. Iliac subchondral spongiosa shows no definite alignment and joins the thickened subchondral bone plate in an oblique direction. The iliac cartilage therefore seems to be stressed predominantly by shearing forces, arising from the changing monopodal support of the pelvis during locomotion. The subchondral bone plate on both the iliac and sacral auricular facet is penetrated by blood vessels that come into close contact with the overlying articular cartilage. These vessels may contribute to the high incidence of rheumatoid and inflammatory diseases in the human sacroiliac joint. Immunolabelling with an antibody against type II collagen reveals a diminished immunoreactivity in the upper half of adult sacral cartilage and only a faint and irregular labelling in the iliac cartilage. Type I collagen can be detected in a superficial layer on the sacral articular surface and around chondrocyte clusters in iliac cartilage, as in dedifferentiating chondrocytes during the development of osteoarthritis. Accepted: 22 April 1998     

Shared Care: lessons from one model of shared care nursing in primary care

This paper is an exploration of the issues which arise when developing a model of shared care for substance misusers in primary care. A rural primary care group (PCG) developed a shared care nurse (SCN) role to provide improved care for substance misusing clients, and to support professionals in both primary and specialist care. The SCN was employed by the specialist drug service (SDS) and, for the purposes of the pilot project, the SCN held clinics at three general practitioner (GP) practices. An evaluation of this pilot project forms the basis of this paper. Semi-structured interviews were undertaken with clients of the shared care service and with professionals involved in the treatment of substance misusing clients. These interviews were recorded, transcribed and then analysed for salient themes. Questionnaires were distributed to members of the primary health care teams who had not been interviewed, and responses were also thematically analysed. This paper highlights the benefits and barriers encountered in developing a new model of care for substance misusing clients. It clearly illustrates improved satisfaction with service provision, both for service providers and clients. There continued to be difficulties, however, with waiting lists and clear referral pathways for the treatment of substance dependency.     

Breast cancer: prognostic factors. Apropos of 1000 conservative treatments

Prognosis was analyzed as a function of histologic grade, axillary gland spread and hormonal receptors in a consecutive series of 1000 patients with breast cancer (stages I and II) treated by conservative tumorectomy and axillary curettage, combined with radiotherapy, and followed up for between 3 and 12 years. The three factors analyzed are of major importance in that they constituted a veritable tumoral identity card. Grade I tumors, the absence of glandular spread and the presence of hormonal receptors are correlated with cancer of good prognosis, whereas grade III tumors, major axillary spread and absence of hormonal receptors are related to a poor prognosis. Their interactions are studied by comparing associations of good and poor prognostic factors, allowing determination of populations at low and high risk of therapeutic failure.     

Hydroxylamine as an intermediate in ammonia oxidation by globally abundant marine archaea

The ammonia-oxidizing archaea have recently been recognized as a significant component of many microbial communities in the biosphere. Although the overall stoichiometry of archaeal chemoautotrophic growth via ammonia (NH₃) oxidation to nitrite (NO₂⁻) is superficially similar to the ammonia-oxidizing bacteria, genome sequence analyses point to a completely unique biochemistry. The only genomic signature linking the bacterial and archaeal biochemistries of NH₃ oxidation is a highly divergent homolog of the ammonia monooxygenase (AMO). Although the presumptive product of the putative AMO is hydroxylamine (NH₂OH), the absence of genes encoding a recognizable ammonia-oxidizing bacteria-like hydroxylamine oxidoreductase complex necessitates either a novel enzyme for the oxidation of NH₂OH or an initial oxidation product other than NH₂OH. We now show through combined physiological and stable isotope tracer analyses that NH₂OH is both produced and consumed during the oxidation of NH₃ to NO₂⁻ by Nitrosopumilus maritimus, that consumption is coupled to energy conversion, and that NH₂OH is the most probable product of the archaeal AMO homolog. Thus, despite their deep phylogenetic divergence, initial oxidation of NH₃ by bacteria and archaea appears mechanistically similar. They however diverge biochemically at the point of oxidation of NH₂OH, the archaea possibly catalyzing NH₂OH oxidation using a novel enzyme complex.Microbial oxidation of ammonia (NH₃) to nitrite (NO₂⁻), the first step in nitrification, plays a central role in the global cycling of nitrogen. Recent studies have established that marine and terrestrial representatives of an abundant group of archaea, now classified as Thaumarchaeota, are autotrophic NH₃ oxidizers (1–5). Despite increasing evidence that ammonia-oxidizing archaea (AOA) generally outnumber ammonia-oxidizing bacteria (AOB), and likely nitrify in most natural environments, very little is known about their physiology or supporting biochemistry (6, 7). Genome sequence analyses have pointed to a unique pathway for NH₃ oxidation, likely using copper as a major redox active metal, and coupled to a variant of the hydroxypropionate/hydroxybutyrate cycle (8). However, the only genome sequence feature that associates the archaeal pathway for NH₃ oxidation with that of the better characterized AOB is a divergent variant of the ammonia monooxygenase (AMO), which may or may not be a functional equivalent of the bacterial AMO. Thus, the supporting biochemistry of a biogeochemically significant group of microorganisms remains unresolved (8, 9).Among the AOB, as represented by the model organism Nitrosomonas europaea, NH₃ is first oxidized to hydroxylamine (NH₂OH) by AMO, an enzyme composed of three subunits encoded by amoC, amoA, and amoB genes (7). NH₂OH is subsequently oxidized to NO₂⁻ by the hydroxylamine oxidoreductase (HAO) (7), a heme-rich enzyme encoded by the hao gene (7). Of the four electrons released from the oxidation of NH₂OH to NO₂⁻, two are transferred to the terminal oxidase for respiratory purposes and two are transferred to AMO for further oxidation of NH₃ (7). Although all available genome sequences for the AOA contain homologs of the bacterial AMO (amoB, amoC, and amoA), there are no obvious homologs of AOB-like HAO, or cytochromes c554 and c_M552 critical for energy conversion in AOB (8–15). Thus, either the product of NH₃ oxidation is not NH₂OH or, alternatively, these phylogenetically deeply branching thaumarchaea use a novel biochemistry for NH₂OH oxidation and electron transfer (8).In an attempt to gain further insights into the biochemistry and physiology of these unique archaeal nitrifiers, we here investigated the role of NH₂OH in Nitrosopumilus maritimus metabolism. These studies were complicated by the extremely oligotrophic character of this organism contributing to very low cell densities in culture (16). To overcome the challenge of working with low cell density cultures of N. maritimus, we established a method to concentrate cells on nylon membrane filters such that the cells remained competent for NH₃-dependent NO₂⁻ formation and oxygen (O₂) uptake. This method enabled us to carry out relatively short duration physiological studies and stable isotope tracer experiments directed at determining if N. maritimus can oxidize exogenous NH₂OH to NO₂⁻ while consuming O₂ and producing ATP, and if NH₂OH is an intermediate in NH₃ oxidation pathway of N. maritimus.     

Localization of type I and II collagen during development of human first rib cartilage

The localization of fibrillar type I and II collagen was investigated by immunofluorescence staining with specific antibodies in order to obtain a better understanding of tissue remodelling during the development of first rib cartilage. In childhood and early adolescence type I collagen was found to be restricted to the perichondrium of first rib cartilage, while type II collagen was localized in the matrix of hyaline cartilage. However, in advanced age type I collagen was also found in the territorial matrix of intermediate and central chondrocytes of first rib cartilage. The matrix of subperichondrial chondrocytes was negative for type I collagen. This suggests that some chondrocytes in first rib cartilage undergo a modulation to type I collagen-producing cells. The first bone formation was observed in rib cartilages of 20- to 25-year-old adults. Interestingly, the ossification began peripherally, adjacent to the innermost layer of the perichondrium where areas of fibrocartilage had developed. The newly formed bone matrix showed strong immunostaining for type I collagen. Fibrocartilage bordering peripherally on bone matrix revealed only a faint staining for type I collagen, but strong immunoreactivity to type II collagen. The interterritorial matrix of the central chondrocytes failed to react with the type II collagen antibody, in both men and women, from the end of the second decade. These observations indicate that major matrix changes occur at the same time in male and female first rib cartilages. Thus, our findings indicate that ossification in human first rib cartilage does not follow the same pattern as that observed in endochondral ossification of epiphyseal discs or sternal cartilage.     

Bone uptake studies in rabbits before and after high-dose treatment with 153Sm-EDTMP or 186Re-HEDP.

The aim of this animal study was to measure the bone uptake of (99m)Tc-hydroxymethylene diphosphonate (HDP) before and after high-dose treatment with (153)Sm-ethylenediaminetetramethylenephosphonate (EDTMP) or (186)Re-(tin)1,1-hydroxyethylidene diphosphonate (HEDP) to prove or disprove post-therapeutic alterations of bone uptake of radiolabeled bisphosphonates. METHODS: Quantitative bone scanning using 100 MBq (99m)Tc-HDP was performed on 12 rabbits before and 8 wk after radionuclide therapy with 1,000 MBq of either (153)Sm-EDTMP or (186)Re-HEDP. Whole-body images were acquired at 3 min, 3 h, and 24 h after injection, and the activities for the whole body, urinary bladder, and soft tissue were measured by region-of-interest technique. From these data, bone uptake was calculated as initial whole-body activity minus urinary excretion and remainder soft-tissue activity. RESULTS: In animals treated with (153)Sm-EDTMP (n = 6), no differences could be proven for the bone uptake of (99m)Tc-HDP at 24 h after injection before and after therapy (51.1% +/- 5.5% vs. 48.0% +/- 6.1%, P > 0.05). There were also no significant differences for the remainder soft-tissue activities and the urinary excretion rates before and after therapy. Similar results were obtained in rabbits treated with (186)Re-HEDP: Bone uptake (44.8% +/- 6.7% vs. 40.4% +/- 4.9%, P > 0.05) and urinary excretion revealed no significant differences before and after treatment. CONCLUSION: No significant impairment of bone uptake of (99m)Tc-HDP could be observed 8 wk after high-dose radionuclide bone therapy. Because both the biokinetic data obtained for (186)Re-HEDP and (153)Sm-EDTMP and the myelotoxic effects were quite similar in rabbits to those in patients, it seems justifiable to expect the same result (i.e., no significant alteration of bone uptake of radiolabeled bisphosphonates) in patients undergoing a second radionuclide therapy within 2-3 mo after standard treatment with (186)Re-HEDP or (153)Sm-EDTMP.