The contribution of selected non-articular conditions to knee pain severity and associated disability in older adults.

OBJECTIVE: To estimate the contribution of selected non-articular conditions (NACs) to pain severity and functional limitation in community-dwelling older adults with knee pain. DESIGN: Population-based, cross-sectional study of 745 adults aged 50 years and over with knee pain. Self-complete questionnaires, clinical history and physical examination were used to identify the presence of selected NACs that could cause pain around the knee. Regression analyses were used to compare levels of knee pain severity (0-20) and functional limitation (0-68) (Western Ontario and McMaster Universities osteoarthritis index physical function subscale [WOMAC-PF]), between those with one or more NACs and those with none (NACs-absent). RESULTS: Two hundred and seventy-three (36.6%) participants had at least one NAC: widespread pain, n=159; low back pain with index leg referral, n=102; full-leg pain, n=88; hip arthritis, n=65; prepatellar, infrapatellar or pes anserine bursitis, n=35. The NACs group had significantly higher levels of pain severity and functional limitation than the NACs-absent group: 8.2(+/-4.6) vs 5.4(+/-3.8) and 27.9(+/-15.8) vs 16.8(+/-13.2), respectively. The groups did not differ with respect to severity of radiographic osteoarthritis (ROA). Having one or more NACs accounted for a significant proportion of the variance in WOMAC scores, above that which could be explained by age, gender, body mass index and severity of ROA. CONCLUSION: NACs appear to be common in older adults with knee pain. They make a significant contribution to knee pain severity and functional limitation and are likely to represent additional, rather than alternative, causes of knee pain/functional limitation to osteoarthritis (OA). These factors should be taken into account in epidemiological studies of knee pain and OA.

Knee osteoarthritis in community-dwelling older adults: are there characteristic patterns of pain location?

OBJECTIVE: To determine whether there are characteristic patterns of pain location associated with knee osteoarthritis (OA) among community-dwelling older adults. DESIGN: Population-based, cross-sectional survey of 697 adults aged 50 years and over reporting knee pain within the past 6 months. Pain at 13 individual sites at or around the knee was coded. Pain locations in participants with and without "symptomatic knee OA" (defined as symptoms on most days in the past month, at least a definite osteophyte on plain X-ray, and current pain intensity of at least 2 out of 10) were compared. Participants were then grouped by pattern of knee pain location, and their clinical and radiographic characteristics compared. RESULTS: Generalised knee pain (n=313) and medial knee pain (either in isolation or with peripatellar or lateral knee pain: n=175) were the most common patterns. Medial knee pain and distally radiating pain were significantly more likely in those with symptomatic knee OA. Individuals with generalised knee pain with radiation had more persistent, severe pain, and a relatively high proportion had moderate or severe radiographic disease. CONCLUSION: No single pattern of pain location is pathognomonic for knee OA. Attention towards the role of peripheral nociception and central sensitisation in producing medial knee pain and distally radiating knee pain is warranted.

C6 glioma-astrocytoma cell and fetal astrocyte migration into artificial basement membrane: a permissive substrate for neural tumors but not fetal astrocytes.

Cortically homografted C6 glioma-astrocytoma cells both invade the rat host brain as a mass and migrate as individual cells. In contrast, fetal astrocytes derived from homografted whole pieces of fetal cortex migrate only as individual cells throughout the brain of the rat but are not capable of invasion. Our experiment explored the migratory capacity (over 7 days) of cultured purified fetal astrocytes and C6 cells after seeding 10(6) cells on a hydrated artificial basement membrane wafer (Matrigel). The artificial basement membrane wafer was not a suitable substrate for the growth of cultured fetal astrocytes. In contrast, C6 cells migrated as individual cells from the surface of the wafer into the substrate. Individual C6 cells migrated 1.8 mm in the first 4 days and then ceased migration. The C6 cells were observed at the base of a digestion tube that extended from and was open to the surface of the wafer. At 3 days, micropockets were observed to form around each C6 cell at the base of each tube. By 7 days, the majority of pockets observed were large and contained several C6 cells. These multiple cell groups appeared to be progenitors of tumor masses. These data indicate that C6 glioma-astrocytoma cells, which in vivo appear to be a model for glioblastoma multiforme, primarily migrate as individual cells through artificial basement membrane and secondarily form tumor masses. Progenitor tumor masses form by coalescence of individual C6 cell micropockets or the division of a single cell in an individual micropocket.

C6 glioma cell invasion and migration of rat brain after neural homografting: ultrastructure.

C6 tumor cells (10(6] were grafted as suspensions into freshly made implantation pockets in rat host cerebral cortex. Specimens were prepared for transmission and scanning electron microscopy 1 to 7 days postimplantation (DPI). By 3 DPI vacuolated C6 cells had migrated on or invaded the host brain. C6 cells were observed on the glia limitans on the surface of the brain, in the corpus callosum, subependymal space, and perivascular space and had invaded the cortex under the implantation pocket. In addition to the tumor mass that was observed under the implantation pocket, by 7 DPI individual C6 cells had migrated into the corpus callosum and internal capsule. Migrated C6 cells were observed in a perineuronal position in the hippocampus and other gray matter structures inferior to the corpus callosum. Micropockets were found around each C6 cell and the processes of these cells had replaced host parenchyma. The preferred routes of migration were on basal lamina and parallel and intersecting nerve fiber bundles. Invasion occurred through gray and white matter. The movement of homografted C6 cells in the brain suggests that these cells actively migrate as individual cells in addition to invading as a mass.

Effect of gamma-irradiation on the healing of gastric biopsy sites in monkeys. An experimental model for peptic ulcer disease and gastric protection.

The acute effects of gamma-irradiation on the gastric mucosa have been studied in a primate model. Fiberoptic gastroscopies were performed in 6 rhesus monkeys in the basal state as well as 3 h and 3, 7, and 9 days after total body irradiation (800 rads). Gastric biopsy specimens (diameter 1 mm) obtained during each session were examined using light microscopy and scanning electron microscopy; in addition, subsequent healing of the biopsy sites was assessed visually. Gastric biopsy sites were completely healed in 3 days in the basal state; in contrast, ulcer craters (diameter 1 mm) were still present at the site of the biopsies 3, 7, and 9 days after the biopsies were performed in irradiated animals. Light microscopic examination of the biopsy specimens demonstrated only lymphocytic infiltration of the lamina propria. In contrast, scanning electron microscopic examination revealed that the size and number of microvilli of the gastric surface epithelial cells were increased on the day of irradiation compared to basal; 3-9 days later, numerous gastric surface epithelial cells were damaged or had disappeared so that bare areas of the lamina propria were visible in the specimens taken outside of the ulcer craters. These changes may reflect inadequate protection of insufficient regeneration of gastric mucosal cells which, in turn, would explain the persistence of ulcers after gastric biopsies were performed in irradiated monkeys.

Generation of anencephaly: 1. Aberrant neurulation and 2. Conversion of exencephaly to anencephaly.

An experimental model for anencephaly was used to focus on two important aspects of the development of anencephaly: neurulation and conversion of exencephaly to anencephaly. Vitamin A was administered to pregnant rats on gestational days nine and ten. The animals were killed on successive gestational days to allow study of the development of anencephaly. The scanning electron microscope revealed filopodia and lamellopodia as the predominant mode of initial neural fold contact in the controls. Intertwining and overlapping of filopodia and lamellopodia with fusion of the adjacent cutaneous ectoderm completed neurulation. In embryos developing anencephaly, filopodia and lamellopodia never made contact above the cervical region and exencephaly resulted. The first evidence of the conversion of exencephaly to anencephaly was profound, labyrinthine expansion of the extracellular space of the telencephalic mantle. In spite of normal vascular patency and intact vessel walls, the exencephalic malformation spontaneously disintegrated, converting the lesion to anencephaly. The causes for tissue disintegration other than infarction must be considered in reconstructing the pathogenesis of anencephaly.

Scanning electron microscopy of the stomach during modifications of acid secretion.

Acute stimulation of gastric acid secretion as well as intragastric instillation of physiological concentrations and volumes of HCl caused marked changes in the appearance of surface epithelial cells of the stomach. These changes could represent a damage of the gastric surface epithelial cells of the stomach. Pretreatment with the histamine H2-receptor-blocking drug cimetidine tended to reduce this damage, although the difference was not significant. In contrast, it was completely abolished by an analogue of prostaglandin E2. These observations suggest that gastric epithelial cells may be damaged under physiological conditions and that quick repair is needed to prevent ulceration of the gastric mucosa. Alternatively, endogenous release of prostaglandin under certain undefined conditions could prevent this damage.

Scanning electronmicroscopy of experimental anencephaly development.

The scanning electronmicroscope was used to study the development of anencephaly in an experimental model. Anencephaly was produced consistently, using vitamin A as the teratogen. Embryos destined to become anencephalic displayed failure of opposing sides of the rostral neural tube to fuse. Subsequently, the neural folds of the experimental embryos progressively curved laterally away from the midline, whereas the neutral folds of the control embryos fused in the midline by day 12. The anlage of the choroid plexus could be identified on the surface of the everting brain folds as early as gestational day 13. Thus, the abnormal eversion of the neural tube occurred before development of the choroid plexus. This study supports the view that anencephaly ultimately results from neural tube nonclosure.

SEM studies of gastric cell surface epithelium: an evaluation of various methods of preparation.

Observation of gastric surface epithelial cells using scanning electron microscopy is usually hampered by the presence of an opaque material coating the stomach mucosa. In the present report, we describe the results obtained with 3 different techniques of preparations. Enzymatic digestion followed by a mechanical action permitted effective and consistent removal of the opaque coating without apparent damage ot the cellular epithelium.