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Biomedical subjects

N Mitchell

Publications and source records attributed to N Mitchell.

At least 19 recordsLinked to original sources

Multiple phantom limbs in a child.

This case report describes multiple phantom feet in a child after amputation of a leg. The subject is a 16-year-old girl who was born with a right leg 10 cm shorter than the left and who at the age of 6 was amputated below the right knee so that she could wear a prosthesis that would give her normal mobility. The girl reports that she subsequently experienced 2 phantom feet and 3 sets of phantom toes which have persisted to the present time. Each phantom has a distinct size, length and position in relation to the others and each is also the site of vivid sensations such as heat, tickle, and fatigue as well as voluntary and involuntary movement. She also describes sensations that resemble sensations experienced before the amputation: one of her phantom feet feels flat and locked into a forward position which corresponds with the actual shape and position of her congenitally deformed amputated foot. The implications of multiple phantoms are discussed with reference to recent concepts of phantom limbs.

Adolescent

The clones of osteoarthritic cartilage.

We studied the early cartilage changes in osteoarthritis, examining the most normal appearing articular cartilage from the hips of 17 patients. Normal appearing cartilage from five patients treated for fractures was used as control material. Two different types of clone were found. The first had increased staining for proteoglycan and was thought to have been engaged in the synthesis of matrix. The other type was associated with a severe deficiency of proteoglycan, matrix streaks and evidence of degradation and phagocytosis of matrix components. Immunohistochemistry demonstrated large amounts of chondroitin 4 and 6 sulphate about the synthetic-type clones, and little or no reactivity about the degenerative clones which lay more superficially and were associated with matrix destruction. Clones appeared to be engaged in either matrix synthesis or its destruction. The disease process of osteoarthritis appeared to begin at the surface of the articular cartilage.

Aged

Permanent external striated sphincter stents in patients with spinal injuries.

Nine patients with complete quadriplegia underwent external striated sphincter stenting with the Wallstent in place of an external striated sphincterotomy. Although suprapubic catheters were placed to provide an outlet should problems develop with the stent, they were successfully removed within 6 weeks in all but 1 patient. Complete bladder emptying with reduced voiding pressures was achieved, together with a significant reduction in the duration of hyper-reflexic contractions. Epithelialisation of the stent was almost complete within 3 months and intermittent catheterisation or endoscopy (and resection) is possible through the stent. Although this is a preliminary report of this new technique, it is hoped that sphincter stenting will provide a rapid, safe and effective method of treating high pressure hyper-reflexia and detrusor sphincter dyssynergia in quadriplegic patients.

Adult

Routine admission urinalysis examination in pediatric patients: a poor value.

The urinalysis has long been considered an important screening test for hospitalized children. The value of the admission urinalyses, required by hospital bylaws, was assessed for detecting urinary tract disease in children admitted to a day-care unit or impatient medical or surgical services during the months of June and November 1987. Of 2695 admissions, urinalyses were considered essential for diagnosis or therapy in 543 patients (excluded from analysis). In the remaining 2152 patients eligible for screening, urinalyses were obtained in 145 (30%) of day-care unit and 587 (35%) of inpatient admissions. The results of 149 (20%) of screening urinalyses were abnormal (23% abnormal in inpatient and 10% abnormal in day-care unit admissions). The numbers of urinalyses with abnormal results were similar in surgical and medical admissions and between the months of June and November. Pyuria (90 patients) and hematuria (66 patients) were the most common abnormalities in initial urinalyses. Follow-up urinalyses and other diagnostic studies were obtained in 38% of patients with abnormal admission urinalysis results. In subsequent urinalyses, 58% showed persistent abnormalities; however, most subsequent abnormal results were not pursued with additional tests. Urinary tract infections were diagnosed in 6 patients. No other additional diagnoses were determined. The cost of initial urinalyses and subsequent diagnostic studies in these 732 patients during the 2 months was $23,465. The cost per diagnosis of urinary infection was $3911. It is concluded that when hospital bylaws require routine urinalyses at the time of admission, this requirement is frequently ignored and, in addition, abnormal results are often unappreciated or not pursued.(ABSTRACT TRUNCATED AT 250 WORDS)

Child

Improved chondrocyte morphology and glycogen retention in the secondary center of ossification following osmium-potassium ferrocyanide fixation.

The use of osmium-potassium ferrocyanide as the secondary fixative greatly improved chondrocyte preservation and stabilized the cartilage matrix proteoglycan. The proteoglycan was similar in appearance to that seen following fixation in the presence of cationic dyes. Extensive glycogen preservation was noted in these cells, occupying the area prior to and during the formation of the secondary center of ossification. The volume and organization of the glycogen within the cell cytoplasm were greater than that following buffered osmium fixation, and the cellular vacuoles within were greatly reduced. The cells forming the secondary center prior to the onset of mineralization were of greatest interest, because other studies compared them with the primary growth plate and described them as showing signs of hypertrophy as early as 5 days postnatally, as is found in the primary growth plate. Our observations indicate that glycogen is present in these cells, and cellular enlargement was not present. The cells do not resemble the hypertrophic chondrocytes of the primary growth plate, as far as cytoplasmic content is concerned, and we suggest that they may contribute to the development of the secondary center in a different fashion.

Animals

Phenotypical features of an unique Irish family with severe autosomal recessive osteogenesis imperfecta.

Severe Sillence type II/III Osteogenesis imperfecta (OI) is a lethal or severely crippling disease with either autosomal dominant or recessively inherited type I collagen mutations. Here we describe the detailed clinical features of a thin-ribbed OI variant with deformed limbs. The three consecutively affected children showed no genetic linkage with either of the two type I collagen genes, which implies that a novel mechanism causes this clinical phenotype. It can be prevented using ultrasound to diagnose affected foetuses.

Collagen

The deleterious effects of drying on articular cartilage.

Knee joints of mature rabbits were exposed to room air for periods of time ranging from thirty minutes to one hour in an attempt to mimic the human situation in the operating room. The animals were killed after the joint had been closed and activity in a cage had been allowed for twenty-four hours. When the animal was killed, cartilage was removed and was incubated with radioactive proline for four hours before light microscopy autoradiographs were made. Other samples were prepared for study by electron microscopy. The results in the animals that were killed immediately after the cartilage was exposed to room air and in those that were killed twenty-four hours after closure of the joint were identical. Both the ultrastructural and the autoradiographic findings indicated that the entire thickness of the articular cartilage was necrotic after sixty minutes of drying. Forty-five minutes of drying produced complete necrosis of the cartilage in half of the animals. In the other half, some cells survived, although many areas of the cartilage had complete necrosis, top to bottom. Thirty minutes of drying produced patchy necrosis that extended only to the middle zone of the cartilage. In joints that were exposed to room air for one hour, necrosis of the chondrocytes was completely prevented by irrigating the joint every five minutes with Ringer lactate solution.

Air

Periodic acid Schiff--p phenylenediamine staining of glycogen in chondrocytes. A new combination which improves both cellular detail and glycogen identification.

This study reports a method whereby glycogen is identified in the chondrocytes of the secondary center of ossification prior to mineralization. The use of new fuchsin rather than basic fuchsin on one micron Spurr sections of femoral head cartilage fixed with potassium ferrocyanide-reduced osmium produced excellent identification of glycogen and when followed by p phenylenediamine, intensified cellular detail.

Animals

Effect of patellar shaving in the rabbit.

Shaving of the articular cartilage on the undersurface of the patella was carried out in mature white New Zealand rabbits to determine whether the removed cartilage reformed or the shaving led to later evidence of degenerative arthritis. The animals were followed for as long as 15 months after surgery, at which time patellae were removed and examined by light and electron microscopy. The depth of shaving varied considerably; however, no evidence of repair and no evidence of degenerative arthritis was noted in either the superficial or deeply shaved patellae. It is concluded that such superficial cartilage defects neither repair or produce subsequent degenerative arthritis.

Animals

Mutagenesis originating in site-specific DNA damage.

Covalent monoadducts are the major types of gene damage after exposure to chemical mutagens and carcinogens. These and other damage structures together give rise to the spectrum of mutations that includes base-pair substitutions, insertions and deletions. In this study we introduced the bulky adduct guanine-8-aminofluorene into defined sites on one or both strands of the lactose operator. After insertion into plasmid pBR322 and replication in Escherichia coli COEC40, operator mutants were recognized on 5-bromo,4-chloro,3-indolyl-beta-D-galactoside plates and by hybridization probing. Out of ten randomly selected mutants, nine were single-base deletions and one was a two-base deletion. All mutations were at the site of modification or immediately adjacent to that site. If modifications were placed into both plasmid strands, preventing excision repair, operator mutants comprised close to 100% of operator-containing plasmids.

Base Sequence

The antigen induced arthritis model: the relevance of the method of induction to its use as a model of human disease.

The much favoured ovalbumin antigen induced model of arthritis in rabbits is widely used in rheumatoid arthritis (RA) research. When examined histologically, it was found to have important deficiencies as parallels to the human disease. After sensitization to ovalbumin, 2 intraarticular challenge doses of a magnitude at each end of the spectrum used by investigators were used in 152 rabbits. The effects of the high and low dose challenges were examined histologically with particular attention to the articular cartilage. With high doses, the gross and histological changes in the knee joint were remarkably akin to acute cartilage necrosis rather than RA1. In the low dose, a milder smoldering arthritis was produced. These observations suggest that, depending on the challenge dose used, there is a tremendous variability in the kind of arthritis produced by the antigen induced arthritis model. Furthermore, it is suggested that previous conclusions about the pathophysiology and immunology of RA drawn from the models that produce a rapid and severe arthritis should be reexamined.

Animals

Osteitis condensans ilii or sacro-iliitis?

Eight patients with a radiological diagnosis of Osteitis condensans ilii (OCI) had clinical features similar to those of 8 patients with sacro-iliitis (SI). The X-ray appearances may be very difficult to differentiate on standard films and discrimination between the two conditions has to be made from a combination of clinical and radiological findings. The term OCI should be regarded with suspicion when applied to young people with a history of backache.

Adult

Ultrastructural modifications of proteoglycans coincident with mineralization in local regions of rat growth plate.

We carried out histochemical and electron-microscopic studies to examine the relationship between mineral deposition and changes in the organization of proteoglycans during mineralization in the cartilaginous growth plate of the rat. To preserve the distribution and organization of proteoglycans in the extracellular matrix and to stain proteoglycans, acridine orange was included in the solutions that were used for fixation and demineralization. In undecalcified sections, mineral crystals that initially appeared at the level of the penultimate hypertrophic chondrocyte grew into dense, spherical mineral clusters, roughly one micrometer in diameter, in the longitudinal septa of the lowermost hypertrophic zone. Following the removal of mineral with EDTA in the presence of acridine orange, proteoglycan structures with a characteristic rosette-like architecture were revealed within the matrix of the longitudinal septa of the lower hypertrophic zone. The location of these rosette-like proteoglycan structures was identical to that of the dense, spherical mineral clusters in the undemineralized controls, and they were remarkably similar in morphology and size. In the electron micrographs stained with uranyl acetate and lead citrate, the greatly increased density of the rosette-like structures and large diameter of the proteoglycan structures located in mineral clusters contrasted sharply with the slender strands of more faintly stained proteoglycan that was diffusely distributed throughout most of the extracellular matrix. X-ray microprobe analysis for sulphur confirmed the existence of proteoglycans in the rosette-like structures and demonstrated that the concentration of proteoglycans was selectively increased in these regions. The cores of the metaphyseal calcified cartilage also exhibited rosette-like proteoglycan structures, which before demineralization were totally obscured by the diffuse, dense homogeneous deposition of mineral. Without stabilization of the proteoglycans in the extracellular matrix with acridine orange, the rosette-like proteoglycan structures could not be demonstrated. These results clearly indicate that there is a selective increase in the concentration of proteoglycans in exactly the same regions where mineral clusters are formed in the hypertrophic zone of the cartilaginous growth plate.

Acridine Orange

The localization of articular cartilage proteoglycan by electron microscopy.

Rabbit articular cartilage was fixed with glutaraldehyde containing Ruthenium Red or Safranin O proteoglycan localization is easily obtained. Ruthenium Red stained proteoglycan is easily visualized by electron microscopy. Previous digestion with papain prevented staining by either technique confirming that the material was indeed proteoglycan. Using these methods of proteoglycan identification the sites of attachment to collagen are shown as well as the deposition of proteoglycan about cells of differing vitality and the relationship of proteoglycan to cell membranes.

Animals

The use of ruthenium and p-phenylenediamine to stain cartilage simultaneously for light and electron microscopy.

p-Phenylenediamine was incorporated during the dehydration of cartilage blocks fixed with ruthenium red, glutaraldehyde and osmium. The addition of p-phenylenediamine permitted the visualization by light microscopy of cellular detail not obtained with ruthenium red alone. Ruthenium red is a widely used method for retaining and localizing proteoglycan for electron microscopy but its inability to produce sufficient density within the cells for light microscopy prevented simultaneous visualization by these two modes. The addition of p-phenylenediamine staining overcame this shorcoming without interfering with the ultrastructural detail and both stains can also be used before the making of radioautographs.

Animals