Myoadenylate deaminase (MADA) deficiency has been associated with symptoms of postexertional aches, cramps, weakness, and skeletal muscle dysfunction. Measurement of plasma lactate and ammonia concentrations after forearm ischemic exercise has been suggested as a screening test for this disorder. We performed forearm ischemic tests on 3 patients with histochemically defined MADA deficiency and 13 healthy control subjects, in a standardized fashion. Our results demonstrated that subject effort and/or performance during the exercise portion of testing is a critical variable. In addition to lactate and ammonia, plasma purine compounds (adenosine, inosine, and hypoxanthine) were measured. The finding of decreased purine release after exercise in MADA-deficient patients compared with that in normal individuals increases the specificity of the test and supports the hypothesis that disordered purine metabolism occurs in MADA deficiency.

AMP Deaminase↗

PubMed1986

Myoadenylate deaminase deficiency: diagnosis by forearm ischemic exercise testing.

These results indicate that measuring venous ammonia concentrations after forearm ischemic exercise is an effective means of screening for MADA deficiency but that submaximal exercise performance, whether due to weakness, pain or poor effort, can provide false positive results. Measurements of purine compounds released after exercise may increase the specificity of forearm ischemic exercise testing for MADA deficiency. The low level of purines released after exercise in MADA-deficient subjects supports the hypothesis that disordered purine metabolisms occurs when MADA activity is absent.

AMP Deaminase↗

PubMed1986

Adenosine deaminase deficiency and chondro-osseous dysplasia.

An in vitro model of ADA deficiency is selectively toxic to cartilage from immature rabbits with a greater effect on growth plate than articular cartilage. The selective toxicity observed appears to be the consequence of ATP depletion. These results support the hypothesis that the chondro-osseous dysplasia observed in patients with ADA deficiency is caused by the disordered metabolism that results from the enzyme deficiency.

Adenosine Deaminase↗

PubMed1986

Ecto-nucleoside triphosphate pyrophosphohydrolase activity and calcium pyrophosphate dihydrate crystal deposition disease.

Articular cartilage contains any ectoenzyme activity, NTP-PPH, which is capable of generating PPi from NTP substrates. The PPi generated is from the cleavage of the alpha-beta pyrophosphate bond of NTP and does not result from the effects of NTP catabolites. NTP-PPH activity is expressed on human skin fibroblasts in culture and is significantly increased in subjects with CPPD deposition. In addition, cultured fibroblasts from subjects with CPPD disease have higher intracellular PPi concentrations compared to cells from normals and patients with OA. These results support the hypothesis that alterations in PPi metabolism provide the metabolic basis for CPPD deposition.

Adenine Nucleotides↗

PubMed1986

Pyrophosphohydrolase activity and inorganic pyrophosphate content of cultured human skin fibroblasts. Elevated levels in some patients with calcium pyrophosphate dihydrate deposition disease.

In calcium pyrophosphate dihydrate (CPPD) crystal deposition disease, metabolic abnormalities favoring extracellular inorganic pyrophosphate (PPi) accumulation have been suspected. Elevations of intracellular PPi in cultured skin fibroblasts from a single French kindred with familial CPPD deposition (19) and elevated nucleoside triphosphate pyrophosphohydrolase activity (NTPPPH), which generates PPi in extracts of CPPD crystal-containing cartilages (14) favor this suspicion. To determine whether NTPPPH activity or PPi content of cells might be a disease marker expressed in extraarticular cells, human skin-derived fibroblasts were obtained from control donors and patients affected with the sporadic and familial varieties of CPPD (CPPD-S and CPPD-F) deposition. Intracellular PPi was elevated in both CPPD-S (P less than 0.05) and CPPD-F (P less than 0.01) fibroblasts compared with control fibroblasts. Ecto-NTPPPH activity was elevated in CPPD-S (P less than 0.01) but not CPPD-F. Intracellular PPi correlated with ecto-NTPPPH (P less than 0.01). Elevated PPi levels in skin fibroblasts may serve as a biochemical marker for patients with familial or sporadic CPPD crystal deposition disease; ecto-NTPPPH activity further separates the sporadic and familial disease types. Expression of these biochemical abnormalities in nonarticular cells implies a generalized metabolic abnormality.

Calcium Pyrophosphate↗

PubMed1986

Myositis ossificans simulating acute monoarticular arthritis.

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Acute Disease↗

PubMed1985

Cartilage nucleoside triphosphate pyrophosphohydrolase. II. Role in extracellular pyrophosphate generation and nucleotide metabolism.

Extracellular generation of inorganic pyrophosphate (PPi) in cartilage organ culture is markedly augmented by ATP.ATP, not an ATP metabolite (ADP, AMP, adenosine) is necessary for this augmentation. Excess PPi production is effectively blocked by known inhibitors of nucleoside triphosphate (NTP) pyrophosphohydrolase (EDTA, EGTA, dithiothreitol). Excess 32P-PPi is generated directly from gamma 32P-ATP by cartilage, as substrate and product have similar specific activities. These findings strongly favor ecto-NTP pyrophosphohydrolase as the source of extracellular PPi generation in the presence of NTP. Additionally, active nucleotide and nucleoside catabolism is demonstrated in these cartilage organ cultures.

Adenosine Triphosphate↗

PubMed1985

Antihyperuricemic properties of amflutizole in gout.

The antihyperuricemic properties of amflutizole were investigated in studies designed to determine its efficacy and mechanisms of action in individuals with gout and hyperuricemia. In a randomized double blind, multiple dose, crossover study of 29 patients, amflutizole caused a significant dose dependent reduction in serum urate concentrations. Mean serum urate concentrations decreased significantly from 9.6 +/- 1.5 mg/dl to 7.2 +/- 1.3 mg/dl with the 500 mg dosage (p less than 0.01). Detailed studies in 5 patients demonstrated evidence for modest xanthine oxidase inhibition. However, the majority of the antihyperuricemic effect was derived from an enhanced renal clearance of uric acid. Although the drug has significant antihyperuricemic properties, these were inadequate to achieve adequate control of the serum urate concentration in hyperuricemia and gout at the doses utilized.

Adult↗

PubMed1984

Cartilage nucleoside triphosphate (NTP) pyrophosphohydrolase. I. Identification as an ecto-enzyme.

When 1 mM ATP was added to ambient media of canine cartilage in organ culture or canine chondrocytes in monolayer culture, PPi was generated linearly over 4 hours. The appearance of PPi was related to an ectoenzyme based upon its ability to act upon extracellular substrate, to generate extracellular products, failure to detect enzyme activity in supernatant media, failure to increase activity by cell disruption, and susceptibility to digestion by extracellular trypsin. The enzyme responsible for PPi generation is nucleoside triphosphate (NTP) pyrophosphohydrolase, which acts upon a number of purine and pyrimidine nucleoside triphosphates. This enzyme may play a role in generation of extracellular PPi which participates in calcium pyrophosphate dihydrate crystal formation.

Adenosine Triphosphate↗

PubMed1984

Tophaceous gout: a clinical and radiographic assessment.

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Age Factors↗

PubMed1984

Gouty arthritis: a prospective radiographic evaluation of sixty patients.

A prospective analysis of 60 patients with gout was undertaken to evaluate the radiographic spectrum of gouty arthritis in patients treated in the era of hypouricemic therapy. Twenty-two of these patients were clinically tophaceous; 36 were considered to have radiographic findings diagnostic of gouty arthritis by strict radiographic criteria. Up to 24% of the patients denied symptoms in joints with radiographic changes of gout; 42% with no evidence of tophi on clinical examination had radiographic changes characteristic of gout. Radiographic assessment can be extremely helpful in the management of gout by documenting the degree and extent of bony involvement, particularly in patients with limited symptoms or without clinical tophi.

Ankle Joint↗

PubMed1983

Biological variation of rabbit chondrocyte 5'nucleotidase.

The activity of 5'nucleotidase was investigated in rabbit chondrocytes. Studies of chondrocytes in organ culture and intact cells revealed that ecto-5'nucleotidase activity varies with the age of the animal. Specific activities of 0.29, 0.62, 1.97, and 1.39 mumole/hr/10(6) cells were observed in intact cells from 3-week-, 3-month-, 6-month-, and 2-year-old animals. Specific activities of 15.5, 33.1, 80.3, and 39.5 mumole/hr/mg protein, respectively, were observed when the enzyme protein was solubilized from disrupted cells with the detergent octyl-beta-D-glucopyranoside. Membrane-bound nonspecific neutral phosphatase activity did not vary with age. Activity of 5'nucleotidase was observed on all chondrocytes using a histochemical staining technique. Kinetic properties of the enzyme from animals of different ages were investigated. No differences were noted in apparent Km value for AMP (23 microM), pH optima (7.3), substrate competition studies, and effects of MgCl2 or CaCl2. These data demonstrate a biological variation in rabbit chondrocyte 5'nucleotidase activity with age. The variation of activity represents an apparent increase in the amount of enzyme protein rather than an alteration in kinetic properties.

5'-Nucleotidase↗

PubMed1982

The chief medical residency: a description and recommendations.

Individuals occupying the position of chief medical resident have the opportunity to influence significantly the quality and tenor of medical education and medical practice. To assess the status of the position, the authors surveyed chief medical residents completing their tenure in 1980. These residents distributed their time among administrative (41 percent), teaching (35 percent), patient care (21 percent), and research (3 percent) activities. They reported that their experience was quite positive. However, overall satisfaction was significantly negatively correlated with percentage of time spent performing administrative tasks. The percentage of time chief medical residents allocate to administration has increased during the past decade, while time spent teaching and delivering patient care has decreased. Based upon this survey, recommendations for improved utilization of the time and talents of these individuals are presented.

Education, Medical↗

PubMed1982

Computerized house officer schedules at the University of Michigan.

An economical, computerized system was developed for producing the annual schedule of monthly assignments for medical house officers. This program can generate schedules that conform to the individual preferences of the house officers while meeting the requirements of the residency program. As a result, more individual requests of the house officers are granted than under the previous manual system. Besides providing these direct benefits, the system ensures that house officers are assigned to each rotation according to their appropriate level of skill.

Appointments and Schedules↗