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Biomedical subjects

M P Whyte

Publications and source records attributed to M P Whyte.

At least 145 records · Page 8Linked to original sources
PubMed1982

Adult hypophosphatasia with chondrocalcinosis and arthropathy. Variable penetrance of hypophosphatasemia in a large Oklahoma kindred.

Three sisters, each with chondrocalcinosis/arthropathy, are described who have the clinical, laboratory and pathologic findings characteristic of the adult form of hypophosphatasia. Premature loss of adult teeth, arthralgias and pain from bilateral femoral pseudo-fractures were associated with subnormal circulating alkaline phosphatase levels, phosphoethanolaminuria and osteomalacia diagnosed by iliac crest biopsy. Assay of alkaline phosphatase activity in the blood of kindred members revealed hypophosphatasemia in one of two younger brothers. Several subjects in subsequent generations also had suspiciously low alkaline phosphatase activity, but did not have histories of significant dental, bone or joint disease. Review of the medical records of the sisters' parents, aunts and uncles revealed normal alkaline phosphatase levels in their father and five of his siblings, but consistently low levels in their mother and two of her siblings. Despite hypophosphatasemia, the sisters' mother and her siblings lived to old age without clinical or radiographic evidence of bone disease. Our findings suggest that although adult hypophosphatasia can be transmitted as a dominant trait in some kindreds, there is considerable variation in the clinical expression of the biochemical defect. One person, generation or family may manifest clinical bone disease and arthropathy whereas the biochemical defect may be present but remain asymptomatic in others. Furthermore, in some cases, the adult form of hypophosphatasia may represent a developmental disorder with hypophosphatasemia appearing during adulthood.

Adolescent↗
PubMed1982

Postmenopausal osteoporosis. A heterogeneous disorder as assessed by histomorphometric analysis of Iliac crest bone from untreated patients.

Twenty-six women with untreated postmenopausal osteoporosis underwent iliac crest biopsy following tetracycline-labeling and mineral metabolism studies. Histomorphometric assessment of their bone remodeling rates, including formation determined by the tetracycline-labeling technique, revealed considerable variation. Eight women had no evidence of active bone formation (inactive remodeling osteoporosis), whereas the others showed a spectrum of bone formation rates (active remodeling osteoporosis). Clinical and biochemical studies failed to predict the histomorphometric findings. Postmenopausal osteoporosis is a histologically heterogeneous disorder with morphologic expression in bone that cannot be predicted by single or combined routine clinical and laboratory parameters. Bone biopsy, necessary to identify the histologic lesion and assess skeletal dynamics, may prove to be important for optimal therapy of osteoporosis, as a variety of agents--with different effects on bone remodeling--are available.

Aged↗
PubMed1982

Infantile hypophosphatasia: enzyme replacement therapy by intravenous infusion of alkaline phosphatase-rich plasma from patients with Paget bone disease.

Enzyme replacement therapy for a severely affected 6-month-old girl with hypophosphatasia was attempted by repeated intravenous infusions of alkaline phosphatase-rich plasma, obtained by plasmapheresis, from two men with Paget bone disease. Circulating Paget AP activity was found to have a half-life (two days) similar to that reported in adults, which did not change during a five-week period of six AP infusions. Normalization of the patient's serum AP activity was followed by better control of her hypercalcemia and hypercalciuria. Sequential radiographic studies revealed arrest of worsening rickets with slight remineralization of metaphyses, although urinary excretion of the AP substrates phosphoethanolamine and inorganic pyrophosphate was unaltered by therapy. Our findings suggest that the infantile form of hypophosphatasia results from defective production of AP rather than from accelerated destruction of circulating enzyme, and that hydrolysis of AP substrates like PEA and PPi occurs primarily in tissue rather than blood. Study of additional cases of hypophosphatasia will be necessary to assess the clinical efficacy of this form of enzyme replacement therapy.

Alkaline Phosphatase↗
PubMed1982

Normal cortical bone mass in patients after long term coumadin therapy.

Clinical delineation of the warfarin embryopathy and the recent discovery of osteocalcin (a vitamin K-dependent bone protein) suggest that coumadin therapy could adversely affect the skeleton. Using bone densitometry and metacarpal cortical width measurement, we found normal cortical bone mass in 17 adults receiving long term coumadin therapy.

Adult↗
PubMed1982

Circulating vitamin D metabolite levels in hypophosphatasia.

25OHD, 1,25,-(OH))2D, and 24,25-(OH)2D were assayed in the serum of 16 patients with the infantile, childhood, or adult form of hypophosphatasia. Except for diminished 1,25-(OH)2D and elevated 24,25-(OH)2D levels in 2 infants (which could be attributed to nonparathyroid hormone-mediated hypercalcemia), the mean circulating level of each vitamin D metabolite was normal in the 3 patient groups. Abnormalities in vitamin D metabolism do not appear to contribute to the pathogenesis of this rare hereditary form of rickets or osteomalacia, which occurs despite normal circulating calcium, inorganic phosphate, and vitamin D metabolite levels.

25-Hydroxyvitamin D 2↗
PubMed1981

Mixed-sclerosing-bone-dystrophy: report of a case and review of the literature.

We present clinical, laboratory, radiologic, genetic, and pathologic findings in a 49-year-old man with mixed-sclerosing-bone-dystrophy (MSBD), review the six cases previously reported as "MSBD", and examine the nosology of this rare bone dysplasia. Our asymptomatic patient showed radiographic changes consistent with osteopoikilosis, osteopathia striata, and melorheostosis and had widespread osteosclerosis of the axial skeleton. Several previous reports of combined osteosclerotic disorders suggest the latter finding represents osteopetrosis, however, histologic examination of our patient's iliac crest excluded that diagnosis. Limited radiographic surveys of his eight children were unremarkable except for isolated bone islands in two sons. Literature review revealed that "MSBD" has actually been used generically to describe the association of a variety of osteosclerotic bone dysplasias when they occur together in a single patient.

Bone Diseases↗
PubMed1981

Axial osteomalacia. Clinical, laboratory and genetic investigation of an affected mother and son.

Axial osteomalacia--a rare osteosclerotic bone disorder characterized by axial skeleton pain, coarsening of the trabecular bone pattern on radiographs of the axial but not appendicular skeleton, and osteomalacia on biopsy of a rib or iliac crest--has been reported in 10 apparently sporadic cases, all of which were in middle-aged or elderly Caucasian men. The etiology is unknown but has been postulated to be a bone cell defect. We describe the clinical, laboratory, pathologic and family study of a black mother and son with axial osteomalacia associated with polycystic liver and kidney disease. Investigation of the son suggested that radiographic osteosclerosis can be detected in early adulthood. Limited skeletal survey of his three children revealed no abnormalities. Examination of undecalcified iliac crest bone after in vivo tetracycline labeling revealed severe osteomalacia in the son despite normal circulating calcium, inorganic phosphate and vitamin D metabolite levels and persistently elevated alkaline phosphatase activity. Although osteoblasts appeared flat and inactive, histochemical studies showed intense alkaline phosphatase activity in the osteoblasts along most trabecular bone surfaces. Electron microscopy revealed intact matrix vesicles within unmineralized osteoid. The presence also of unexplained myopathy in the son--characterized by proximal muscle weakness, persistently elevated circulating creatine phosphokinase levels and pathogenic changes of myopathy on biopsy of quadriceps muscle--together with impaired bone mineralization, suggests that a disorder of vitamin D action may be involved in the pathogenesis of this unusual condition. Axial osteomalacia affects blacks as well as Caucasians, women as well as men, may be familial, and may perhaps be a developmental abnormality inherited in association with polycystic kidney and liver disease.

Adolescent↗
PubMed1981

Systemic mastocytosis associated with generalized osteopenia. Histopathological characterization of the skeletal lesion using undecalcified bone from two patients.

Although mast cell proliferation in the bone marrow frequently occurs in systemic mastocytosis and is often associated with radiographically detectable bone lesions, the pathologic correlates of the skeletal abnormalities are poorly characterized. We therefore examined three nondecalcified transiliac crest biopsy specimens from two patients with systemic mastocytosis and diffuse osteopenia with vertebral crush fractures. Marrow involvement included unusual mast cell aggregates, as revealed by metachromatic staining, that mimicked granulomas. Histomorphometric analysis or trabecular bone revealed accelerated bone remodeling or "turn over" characterized by osteoidosis, peritrabecular fibrosis, increased numbers of osteoblasts and osteoclasts, and an increase in osteoclastic resorbing surfaces. Our observations and review of the literature suggest that with the recent development of techniques for assessing undecalcified bone biopsy specimens, mastocytosis will probably be shown to be a more common etiology in "osteoporosis" than previously recognized. Metachromatic staining of the biopsy specimen should be a routine procedure in the investigation of any patient who undergoes diagnostic bone biopsy.

Adult↗
PubMed1981

Biochemical and ultrastructural demonstration of elastin accumulation in the skin lesions of the Buschke-Ollendorff syndrome.

The Buschke-Ollendorff syndrome is an association of cutaneous lesions, dermatofibrosis lenticularis disseminata, with osteopoikilosis. This condition is inherited in an autosomal dominant pattern. In order to clarify the biochemical nature of the skin lesions, we have examined 12 patients with the Buschke-Ollendorf syndrome, representing 2 unrelated kindreds. Histologically, the lesions were characterized by excessive amounts of unusually broad, interlacing elastic fibers in the dermis. Digestion of skin secretions with pancreatic elastase completely removed these fibers. Electron microscopy of the dermis further revealed markedly branched elastic fibers without fragmentation. The accumulation of elastin in the skin was also demonstrated by measurements of desmosine employing a radioimmunoassay. The desmosine content of the skin lesions increased 3- to 7-fold when compared to the skin either from healthy controls or from uninvolved skin adjacent to a lesion. The results indicate that the skin lesions of the Buschke-Ollendorff syndrome are connective tissue nevi of the elastin type. Cell cultures from these patients may provide a convenient model to study the control mechanisms involved in elastin metabolism.

Desmosine↗
PubMed1981

Progressive diaphyseal dysplasia (Engelmann disease(: scintigraphic-radiographic-clinical correlations.

Four patients (2 males, 2 females; ages 15-47 yrs.) with variable clinical, radiographic, and scintigraphic manifestations of progressive diaphyseal dysplasia (PDD) or Engelmann disease were studied with 99mTc methylene diphosphonate bone imaging and radiographic skeletal surveys. Comparison of the results of the two imaging procedures showed that some affected bones were scintigraphically normal but radiographically abnormal and vice versa. These findings suggest that the lesions of PDD may mature, causing a significant decrease in disease activity, and that abnormally increased radiopharmaceutical accumulation during bone scintigraphy appears to be a sensitive indicator of disease activity.

Adolescent↗
PubMed1981

Heterogeneity of adult hypophosphatasia. Report of severe and mild cases.

Two cases of women with adult hypophosphatasia illustrate the clinical spectrum and potential difficulties in the diagnosis of this condition. Both patients had subnormal serum alkaline phosphatase activity, absence of leukocyte alkaline phosphatase, increased amounts of urinary phosphoethanolamine, and normal levels of immunoreactive calcitonin and parathyroid hormone. In undecalcified bone biopsy specimens, the number of osteoblasts and the tetracycline-labeled calcification front were similar in the two patients, although the percentage of unmineralized bone matrix and the extent of osteoid-covered bone surface were different. Twenty years of bone pain, severe skeletal deformities, and a generalized increase of osteoid in one patient contrasted with an 18-month history of bone pain and patchy osteoid in the other. These cases suggest that adult hypophosphatasia is a heterogeneous disorder and may be more common than previously realized.

Alkaline Phosphatase↗
PubMed1980

Osteopathia striata associated with familial dermopathy and white forelock: evidence for postnatal development of osteopathia striata.

Osteopathia striata and a macular, hyperpigmented dermopathy were found in a Caucasian woman and her two daughters. Sequential radiographs in one daughter showed that the bone lesions were not present during infancy but developed during early childhood. The skin lesions were not those most often associated with osteopathia striata, but appeared tgo be a unique dermatosis, which also included a hypopigmented forelock. A son had neither osseous nor ectodermal lesions. These abnormalities appear to represent a new syndrome, which is inherited with X-linked or autosomal dominant transmission.

Adult↗
PubMed1980

Osteopetrosis, renal tubular acidosis and basal ganglia calcification in three sisters.

Three adult sisters with osteopetrosis in infancy had spontaneous resolution of bone modeling defects and osteosclerosis. During adolescence, basal ganglia calcification developed in two. Renal tubular acidosis (type I) was diagnosed in each during early adulthood. The disorder was transmitted apparently as a recessive trait--the same mode of inheritance as for the "malignant" form of osteopetrosis which is usually fatal during childhood. Electron microscopy of bone suggested that osteoclasts failed to form "ruffled membranes" characteristic of active bone resorbing cells. Chronic systemic acidosis may have ameliorated the skeletal manifestations of this new syndrome.

Acidosis, Renal Tubular↗