Expression profiling of metalloproteinases and inhibitors in cartilage

Objective   To profile the expression of all known members of the matrix metalloproteinase ( MMP ), a disintegrin and metalloproteinase with thrombospondin motifs ( ADAMTS ), and tissue inhibitor of metalloproteinases ( TIMP s) gene families in normal cartilage and that from patients with osteoarthritis (OA).
Methods   Human cartilage was obtained from femoral heads at joint replacement for either osteoarthritis or following fracture to the neck of femur. Total RNA was purified and expression of genes assayed using quantitative real-time PCR.
Results   Several members of the above gene families were regulated in OA. Genes increasing in expression in OA were: at P  < 0.001, MMP-13 , MMP-28 , ADAMTS-16 ; at P  < 0.01, MMP-9 , MMP-16 , ADAMTS-2 , ADAMTS-14 and at P  < 0.05, MMP-2 , TIMP-3 , ADAMTS-12 . Genes decreasing in expression in OA were: at P  < 0.001, MMP-1 , MMP-3 , ADAMTS-1 ; at P  < 0.01, MMP-10 , TIMP-1 , ADAMTS-9 and at P  < 0.05, TIMP-4 , ADAMTS-5 , ADAMTS-15 . Correlation analysis revealed that groups of genes across the gene families are co-expressed in cartilage.
Conclusion   This is the first comprehensive expression profile of all known MMP , ADAMTS and TIMP genes in cartilage. Patterns of expression provide a foundation on which to understand mechanisms of gene regulation in OA and potentially for refining the specificity of anti-proteolytic therapies.     

Improving survival and limb salvage in patients with aortic graft infection

A 15-year experience with 38 aortic graft infections, including 15 patients with graft enteric fistulas, is reviewed in order to analyze modern-day surgical results utilizing extra-anatomic bypass and aortic graft excision. Perioperative mortality was 14% during the most recent 7-year interval, which was a notable improvement compared with the earlier time interval (p = 0.06). Extended follow-up of the perioperative survivors demonstrated a 77% cumulative 5-year survival and a 76% cumulative 5-year limb salvage rate. Subsequent axillofemoral graft infection occurred in 22% of survivors and resulted in a significantly higher amputation rate compared with those patients with no axillofemoral graft infection (p less than 0.001). The results suggest good perioperative and long-term survival in patients with aortic graft infection, with excellent limb salvage if subsequent axillofemoral graft infection can be avoided.     

Micronutrient Supplementation and Infection in Institutionalized Elders

A randomized, double-blind, placebo-controlled clinical trial was conducted to determine the effects of a low-dose (<2 times the Recommended Dietary Allowance) micronutrient supplement containing trace minerals (zinc and selenium) and/or vitamins/provitamins (vitamin C, α-tocopherol, and β-carotene) on the incidence of respiratory and urogenital infections in institutionalized elderly. After 2 years, there was a significant decrease in the mean number of infections in elders given trace elements (p < 0.01) but not vitamins.     

Relations between upper limb soft tissue disorders and repetitive movements at work

To make a preliminary assessment of whether upper limb soft tissue disorders might be associated with activities at work, we have conducted a case-control study of subjects attending orthopedic clinics in three cities. All subjects between the ages of 16 and 65 years, in whom defined soft tissue conditions of the upper limb were diagnosed by the participating orthopedic surgeons, were invited to take part. Controls were subjects attending the same clinics within the same age range whose clinical diagnosis did not include disease of the upper limb, cervical or thoracic spine. Information concerning repetitive movements of the upper limbs at work was elicited by questionnaire. Five hundred eighty cases and 996 controls were studied, representing 96% and 93%, respectively, of those invited to participate. The diagnoses of the cases included soft tissue conditions affecting the shoulder, elbow, forearm, wrist, thumb, hand, and fingers. The diagnoses of the controls included traumatic, degenerative, and inflammatory conditions, mostly of the legs and lower back. Women predominated among the cases (70%) and men among the controls (56%). Of 221 female cases with injury to the wrist and forearm, 32 were cleaner/domestics (14.5%) compared to 35 of 439 controls (8%), a difference statistically significant at the 2 1/2% level. Other jobs significantly overrepresented (5% level) among female cases with injuries at various anatomical sites included hairdressers, secretary/temps, assembly line workers, and machine operators (type unspecified). Among male cases, electricians were significantly overrepresented (5% level). Jobs for which there was a suggestion (p < 0.1) of overrepresentation among cases included butchers and teacher/ lecturers (both males only) and the combined job groups (chosen a priori for analysis) of keyboard operators, machine operators, and music teachers (all three jobs, females only).     

Effects of Pravastatin on Plasma Lipid Concentrations in Poloxamer 407-Induced Hyperlipidemic Rats

A new animal model of hyperlipidemia is being developed using the nonionic surfactant poloxamer 407 (P-407). We investigated the impact of pravastatin on P-407-induced hyperlipidemia. Twenty rats received P-407 300 mg intraperitoneally to induce hyperlipidemia, and 20 control rats received saline injection. Pravastatin was administered orally to an equal number of rats in both groups using three different regimens. A fourth group did not receive pravastatin. At 24 hours after injection, total cholesterol levels in two of the pravastatin groups were 28% and 34% lower than those in animals that did not receive pravastatin (p≤0.01). At 48 hours, triglyceride levels were significantly lower in all pravastatin groups (21–44%) versus animals not receiving pravastatin. Pravastatin diminished the effects of P-407 on lipoproteins. This new animal model may be useful in screening for investigational antihyperlipidemic agents.     

Giardia transmission in a swimming pool.

In the fall of 1985, an outbreak of giardiasis occurred among several swimming groups at an indoor pool in northeast New Jersey. Nine clinical cases were identified, eight of whom had Giardia positive stool specimens. All were female; seven were adults (greater than 18 years) and two were children. The attack rate was highest (39 per cent, 5/13) for the ladies lap group who had exposure on one day. These cases had no direct contact with children or other risk factors for acquiring Giardia. Infection most likely occurred following the ingestion of swimming pool water contaminated with Giardia cysts. The source of Giardia contamination was a handicapped child who had a fecal accident in the pool. He was a member of a group that swam at the same time as the ladies lap group. A stool survey of the handicapped group showed that of the 20 persons tested, nine were positive for Giardia, including the specimen from this child. Examination of the pool records showed that no chlorine levels had been taken on the day of the fecal accident and that on the following day the chlorine level was zero. This is the second report of Giardia transmission among swimming pool attendees. It emphasizes the need to maintain appropriate chlorine levels in swimming pools and to institute measures to clear pools after a fecal accident.     

Gliadin antibody detection in gluten enteropathy

Circulating antigliadin antibody has been described in patients with gluten enteropathy although the prevalence varies in different studies. It has been suggested that the investigation for antigliadin antibody might be useful as a screening test. The object of the present study was to evaluate two different techniques for assaying these antibodies — an indirect immunofluorescent method and an enzyme-linked immunosorbent assay (ELISA). Antibodies were assayed in the sera of 102 patients in whom jejunal biopsies were also obtained. The specificity of both tests was greater than 95%, and the correlation between the presence of antibody and histology was significant (p < 0.005), though the sensitivity of each test was less than 70%.     

Maturation of myocardial capillaries in the fetal and neonatal rat: An ultrastructural study with a morphometric analysis of the vesicle populations

The ultrastructural morphology of the cellular and extracellular components of the developing myocardial capillary wall—from the 16-day-gestation fetus of the rat to the 21-day neonate—was examined. A morphometric analysis of plasmalemmal vesicles and of coated vesicles and pits of capillary endothelial cells was performed during the same developmental period. As the lateral extensions of the capillary endothelial cells change from irregular to regular in their thickness during development, there is an increase in the number of plasmalemmal vesicles and a progression from clusters of plasmalemmal vesicles to a uniform distribution in the endothelial cell. The ratio of vesicles which are open to the luminal front, which are “free” in the cytoplasm, or which are open to the abluminal front of the endothelial cell was consistent throughout development. The numerical density of plasmalemmal vesicles demonstrates a gradual and significant increase. In contrast, the numbers of coated vesicles and pits are variable within a very narrow range, and no pattern of increase or decrease is discernible during development. Similarly, there is no change in interendothelial cell junctions, which consist of occluding and primitive adhesive junctional types, during development. The lamina densa of the basal lamina gradually develops from discontinuous, patchy densities along the abluminal surface of the endothelial cells to a continuous and distinct layer by 21 days gestation. The presence of the proteoglycan species in the developing basal lamina was assessed with the cationic dye ruthenium red (RR), and the appearance of RR-marked proteoglycans was found to parallel the appearance of lamina densa material. The RR sites appear discontinuously in patches; and later, the RR sites appear in a continuous and regular planar lattice in the lamina rara interna and externa at 21 days gestation. A complete array of RR-stainable anionic sites outside a continuous lamina densa near birth indicates that the basal laminae of developing capillaries in the heart are morphologically, and in part biochemically, mature by the end of the first neonatal week. Our results show that the endothelial cells and the subtending basal lamina of myocardial capillaries gradually mature morphologically during the final days of gestation and the first neonatal week. The finding of tight junctions and small areas of vesicle concentration in fetal endothelial cells could indicate that sites of permeability are limited early in myocardial capillary development and that these vesicular sites increase as gestation proceeds and as the myocardial capillaries mature.     

Musculoskeletal problems and driving in police officers

The Occupational Health Department of a rural police force inthe UK had concerns regarding sickness absence levels due tomusculoskeletal problems, particularly in officers who droveas part of their job. It was decided to conduct an interviewsurvey comparing two groups of police officers with differinglevels of exposure to driving, recording sickness absence andprevalence data related due to musculoskeletal troubles. Theresults indicate that exposure to car driving, both in termsof distance and hours driven, had a significant effect on self-reportedlow back trouble. Officers whose job mainly involved drivingalso experienced more low back trouble over the last 12 monthsthan those whose job primarily involved sitting (not driving),standing and lifting tasks. Police motorcyclists had significantlyhigher prevalence figures for reported shoulder trouble thanpolice car drivers.