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Biomedical subjects

N Mitchell

Publications and source records attributed to N Mitchell.

At least 37 records · Page 2Linked to original sources
PubMed1989

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↗
PubMed1989

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↗
PubMed1988

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↗
PubMed1987

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↗
PubMed1986

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↗
PubMed1986

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↗
PubMed1985

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↗
PubMed1985

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↗
PubMed1984

The sulphur content of chondrocyte nuclei.

The sulphur content as a measure of glycosaminoglycan content of growth plate cartilage was determined by energy dispersive x-ray analysis on fresh freeze dried unstained, unfixed ultra thin sections of rat growth plate. In the resting and proliferative zones, quantities of sulphur were found in the nuclei equal to that of the matrix. Less sulphur was present in the cytoplasm. In areas of cell degeneration nuclear and cytoplasmic content of sulphur fell to levels a fraction of that seen in the matrix. It was presumed that most of the sulphur was in glycosaminoglycans. Although glycosaminoglycans have been reported in small amounts in the nuclei of cells, no study of the glycosaminoglycan content of chondrocyte nuclei has been reported. The use of freeze dried unstained, unfixed sections presumably prevented the migration of sulphur and glycosaminoglycans from compartment to compartment.

Animals↗
PubMed1984

The selective impact of a cardiology data bank on physicians' therapeutic recommendations.

We asked the physicians and medical students caring for 60 patients with symptomatic coronary artery disease, immediately after reviewing cardiac catheterization data, to choose medical or surgical therapy and to estimate prognosis one and three years after either therapy. The next day, each participant was given prognostic estimates generated from a large coronary artery disease data bank and again asked to estimate prognosis and choose therapy. Participants unanimously chose medicine for 20 patients (Group I) and surgery for 21 patients (Group III). For 19 patients (Group II), participants were divided on their choice of therapy. After seeing data bank estimates, participants rarely changed recommendations for Group I or Group III, but changed ten percent (9/90, p less than 0.01) of their Group II recommendations. Changes of recommendations by far (9/12, p = 0.02) favored medicine, causing the majority recommendation to change to medicine for two Group II patients. Therapeutic recommendations were guided mostly by pathoanatomy and the chance of improving medical regimens. Computer-generated prognostic data selectively influenced choices among the Group II cases where recommendations had been divided, resulting in changes toward less costly therapy.

Cardiac Catheterization↗
PubMed1984

Developmental aspects of the hip in juvenile chronic arthritis. A radiological assessment.

The aim of this study in sero-negative juvenile chronic arthritis was to examine the radiological changes in the hip joints in relation to age and mode of onset of disease. Particular attention was paid to periods of complete immobilization or reduction in weightbearing, irrespective of clinical hip involvement. Twenty-two children with an early onset of disease (i.e. less than 5 years) with clinical hip involvement were compared with 12 similarly aged children without clinical hip involvement, and 22 children with a later onset but with clinical hip involvement. In all the children with an early onset of disease the initial radiographic findings were developmental rather than destructive. In those with clinical hip involvement, destructive changes supervened, while those with later onset had destruction as the first feature, often followed by the development of protrusio acetabula. The 12 children without clinical hip involvement who had prolonged periods of non-weightbearing in early life, usually because of knee involvement, showed developmental abnormalities. These findings suggest that weightbearing should be encouraged, to promote the normal development of the hips.

Acetabulum↗
PubMed1983

The dysvascular amputee: multidisciplinary management.

The authors describe 8 years of experience in the care of amputees with dysvascular diseases using a multidisciplinary team approach. They compare this method of amputee rehabilitation with one using similar personnel but no team approach. In the hospital using the team approach, there were many more below-knee amputees, a higher number of prosthetic fittings in a shorter period and more fittings in older patients than in the control hospital.

Amputation, Surgical↗
PubMed1982

Pitfalls in the serial assessment of cardiac functional status. How a reduction in "ordinary" activity may reduce the apparent degree of cardiac compromise and give a misleading impression of improvement.

Because the New York Heart Association (NYHA) classification system categorizes patients based on subjective impression of the degree of functional compromise, a reduction in exercise might make a patient seem improved because the new lower level of ordinary activity produced fewer symptoms. To test this hypothesis, we studied three different sets of patients and compared their NYHA classes to their functional classes as determined by a new Specific Activity Scale (SAS) that is based on the metabolic equivalents of oxygen consumption required for activities the patient actually performs. Among ambulatory patients referred for exercise tests, the NYHA class was higher (i.e. indicated the patient was more limited) in 28% of patients and the SAS class was higher in 14% (p less than 0.001). Among patients interviewed at or near the time of catheterization for chest pain, the NYHA was higher in 20% and the SAS class was higher in 20% (p = NS). In both medically and surgically treated patients interviewed 1--3 yr after cardiac catheterization, the NYHA class was higher in only 4%, whereas the SAS class was higher in 28% (p less than 0.001). The SAS class was significantly more likely to be higher in patients who were not working full time and in patients who described their present activity level as sedentary or light. When the NYHA and SAS systems disagreed as to whether a patient was improved, SAS was significantly more likely to correlate with the patient's self-assessment. These findings suggest that some patients restrict their activity as their cardiac disease progresses; the resultant change in the definition of ordinary activity may reduce the apparent degree of cardiac compromise and thus give a false impression of improvement by NYHA criteria.

Activities of Daily Living↗
PubMed1982

An intercellular network artefact in glycol methacrylate dehydrated neonatal cartilage.

A striking network thought to consist of glycosaminoglycan in neonatal cartilage has recently been reported following glycol methacrylate (GMA) dehydration and embedding. This study attempted to learn why the network was not seen in other preparations previously reported. Comparative light and transmission electron microscopy of the network structures was carried out to determine their biological significance. We have shown the networks to be reproducible artefact, attained only following GMA dehydration of glutaraldehyde fixed neonatal cartilage.

Acrylates↗
PubMed1982

Interaction between a Bacillus cereus spore hexosaminidase and specific germinants.

A purified coat-associated hexosaminidase from spores of Bacillus cereus was studied to determine whether it could promote germination of dormant spores. Spores of a coat-deficient mutant as well as chemically extracted spores were used as substrate. Both of these spore preparations responded poorly to most germinants. However, absorbance loss was accelerated when the hexosaminidase was added in the presence of L-alanine. Enzyme alone was not effective. The addition of D-alanine inhibited completely the absorbance loss caused by hexosaminidase and L-alanine. Calcium dipicolinate and L-alpha-aminobutyric acid activated the hexosaminidase to some extent, but these chemicals were much less effective than L-alanine. In addition to the absorbance loss, the spores treated with enzyme and germinants released hexosamine and lost heat resistance and phase whiteness. The results suggest that this particular enzyme might have a role in germination.

Alanine↗
PubMed1982

Incremental value of the exercise test for diagnosing the presence or absence of coronary artery disease.

To determine the incremental value of the exercise test (ETT) for diagnosing coronary artery disease (CAD), we derived a multivariate logistic regression model for the pre-ETT prediction of CAD using data from 3840 patients at Duke University. We then applied the model to 324 patients at the Brigham and Women's Hospital. Using seven clinical factors, the multivariate model had an 84% overall predictive accuracy on both the training (Duke) and the validation (Brigham) sets of patients. Three ETT factors (ST-segment change in patients not taking digitalis, absence of ST-segment change in patients taking digitalis, ETT stopped because of ECG or blood pressure changes) had incremental, significant predictive power, but overall predictive accuracy based on both clinical and ETT factors improved only to 87%. When the ETT result was important enough to move the probability of CAD across a potential therapeutic threshold, the direction of the change in probability was correct only two-thirds of the time. Thus, the ETT was of limited value in predicting the presence or absence of CAD after other easily obtainable clinical data were taken into account.

Adult↗