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Biomedical subjects

F S Kaplan

Publications and source records attributed to F S Kaplan.

At least 55 records · Page 3Linked to original sources
PubMed1996

Submandibular swelling in patients with fibrodysplasia ossificans progressiva.

Fibrodysplasia ossifcans progressive (FOP) is a rare genetic disorder characterized by congenital malformation of the great toes and by progressive heterotopic ossification of soft tissues. Although ankylosis of the temporomandibular joint occurs commonly in the late stages of the disease, only one well-documented case of submandibular heterotopic ossification in a patient who had FOP exists. Twelve (11 %) of our 107 patients who have FOP had submandibular heterotopic ossification that was mistaken initially in seven of the patients for mumps, angioneurotic edema, abscess, mononucleosis, or neoplasm. Two male patients and 40 female patients ranging in age from 6 to 47 years (mean, 21 years) were studied. Ten patients survived following assiduous precautionary measures. One patient who required emergency tracheostomy and ventilatory support also survived. Another patient died of inanition from chronic swallowing difficulty. An effective treatment program includes early identification of the submandibular flare-up, nutritional support, and glucocorticoid therapy. Submandibular swelling in patients who have FOP can be a medical emergency and requires intensive precautionary measures to avoid catastrophic clinical deterioration. These measures include avoidance of lesional manipulation, airway monitoring, and aspiration precautions. Submandibular swelling should be recognized as a variable feature of FOP.

Adolescent↗
PubMed1996

Severe restriction in jaw movement after routine injection of local anesthetic in patients who have fibrodysplasia ossificans progressiva.

OBJECTIVE: To determine the relationship of dental procedures to immediate ossification and ankylosis of the jaw in patients who have fibrodysplasia ossificans progressiva. STUDY DESIGN: A mail survey was conducted of the 60 patient-members of the International Fibrodysplasia Ossificans Progressiva Association. All 41 patients (18 males, 23 females) who responded were examined. Instantaneous exact hazard rates for ossification of the jaw were calculated by the Weibull model. RESULTS: Thirty-six patients had dental procedures performed. Twenty-one (58%) patients had received an injection of local anesthetic. Five (24%) patients had an immediate flare-up of fibrodysplasia ossificans progressiva with ossification and permanent ankylosis of the jaw (expected occurrence, 0.031; p < 0.0001). None of the 12 patients who had comparable dental work without injections developed heterotopic ossification (expected occurrence, 0.019; not significant). CONCLUSION: Injections of local anesthetic during dental procedures pose serious and immediate risk for inciting heterotopic ossification and ankylosis of the jaw in patients who have fibrodysplasia ossificans progressiva and should be assiduously avoided.

Adolescent↗
PubMed1996

Bone morphogenetic proteins and C-FOS: early signals in endochondral bone formation.

The earliest events in endochondral ossification, whether in the formation of the skeleton during embryogenesis or in the regeneration of a bone during fracture healing, involve the establishment of a tissue-specific plan of gene expression arising from pluripotent mesenchymal cells. Recent data from studies of vertebrate limb bud development implicate gradients of diffusable morphogens that specify complex patterns of position-specific gene expression. Diffusable signaling molecules involved at the earliest stages of tissue development include fibroblast growth factors, platelet derived growth factors, bone morphogenetic proteins, transforming growth factor beta, and sonic hedgehog; there are undoubtedly others. An equally elaborate array of trans-membrane receptors in the tyrosine kinase and serine-threonine kinase signaling pathways are responsible for transducing these morphogenetic signals and for establishing boundaries of gene expression. Nuclear signals for transcriptional activation, such as the fos-jun proto-oncogene family and homeobox genes, are also involved in the specification and modification of morphogenetic plans. While much has been learned recently about the presence and interaction of these growth factors and transcription factors in the development of the vertebrate limb bud, very little is known about their presence and interaction in the earliest stages of post-natal bone formation at a fracture site or in heterotopic osteogenesis. Fibrodysplasia ossificans progressiva (FOP) a rare genetic disorder of heterotopic ossification, provides a unique opportunity to study the role of these morphogens and proto-oncogenes in the earliest events of endochondral bone formation.

Animals↗
PubMed1996

Skeletal response to immobilization in Paget's disease of bone: a case report.

The authors discuss a case of Paget's disease of the forearm in which the Pagetic radius and non-Pagetic ulna responded differently to immobilization. The high turnover state of Pagetic bone is more sensitive to physical unloading than normal bone, and thus more rapidly develops osteopenia of immobilization. The different responses to immobilization between Pagetic bone and site controlled normal bone illustrate how physical and metabolic factors interact at a skeletal site to regulate bone remodeling and bone mass.

Bone Remodeling↗
PubMed1996

Skin and bones.

Through the examples above, we can begin to see how rare diseases may shed light not only on more common conditions but also on each other. Disorders such as FOP, POH, MAS, and AHO provide a fertile molecular neighborhood for investigating a disease such as POH. Will POH be linked to the G proteins, c-fos, the BMPs, the BMP receptors, or perhaps an as yet undiscovered gene? For the moment, there are few answers, but there are at least some tantalizing questions to ponder and investigate. We all look forward to the day when our knowledge of, and treatment for, diseases like POH will be more than just skin and bones.

Bone Morphogenetic Proteins↗
PubMed1995

Severe osteoporosis in men.

OBJECTIVE: To evaluate men with severe osteoporosis for pathogenetic factors and to review the reported features of primary osteoporosis in men. DESIGN: Case series and clinical review. PATIENTS: 47 men consecutively referred to a metabolic bone center because of atraumatic (or minimally traumatic) fractures (91%) or radiographic osteopenia (9%). MEASUREMENTS: Clinical assessment, radiographs, chemical analyses of serum and urine, hormone assays, skeletal densitometry, and histomorphometry of iliac crest biopsy specimens. RESULTS: 27 of the 47 men (57%) had vertebral fractures, and 16 (34%) had appendicular fractures. Causal factors identified in 30 men (64%) included glucocorticosteroid treatment (8 men); hypogonadism (7 men); excessive alcohol consumption (7 men); and anticonvulsant use, osteomalacia, severe hyperthyroidism, or bone marrow neoplasia (8 men). Seventeen men (36%) had no medical conditions or known risk factors associated with bone disease. Spinal mineral density was well below the mean value for healthy young men in 94% of the patients with primary osteoporosis tested. Examination of biopsy specimens from 13 of 17 men with primary osteoporosis showed reduced trabecular bone volumes, normal bone formation rates, and slightly increased resorption surfaces. Fasting hypercalciuria was seen in some men (41%). In the primary osteoporosis group, eight men were followed serially (range of follow-up, 6 months to 9 years) while they were receiving a nonpharmacologic regimen (diet and activity); the mean axial bone mineral density of these men increased slightly. CONCLUSIONS: A thorough evaluation for identifiable causes of severe osteoporosis in men is warranted because definable pathogenetic factors are seen in many cases. A few men with severe osteoporosis have primary or idiopathic osteoporosis. Primary osteoporosis in men is probably caused by many factors because heterogeneous clinical, laboratory, and histologic features were seen in our series and in those of others. Further studies of primary osteoporosis are needed to define the course of the disease, to identify pathogenetic mechanisms, and to develop therapeutic interventions.

Adult↗
PubMed1995

Topographic changes in a heterochromatic chromosome block in humans (15P) during formation of the nucleolus.

Fluorescence in situ hybridization and multispectral confocal laser scanning microscopy revealed a highly dynamic nucleolar-associated chromosome 15 satellite III heterochromatin cluster in humans. This nucleolar-associated DNA was highly decondensed at the metaphase plate compared with its topography at interphase and appeared to act as a centre for the post-mitotic reorganization of the nucleolus. Our data showed unexpected trans-mitotic changes in the topography of this nucleolar-associated satellite III DNA that suggest that this locus-specific heterochromatin superstructure may be involved in nucleolar organization.

Cell Nucleolus↗
PubMed1995

Diabetes-like renal glomerular disease in Fanconi-Bickel syndrome.

The Fanconi-Bickel syndrome is a rare inherited disorder of metabolism characterized by hepatic glyconeogenesis, galactose intolerance, renal Fanconi syndrome with nephromegaly, and glycogen accumulation in proximal renal tubular cells. An 8-year-old patient with this disease and severe rickets due to medically resistant hypophosphatemia was found to have the previously unrecognized complication of renal glomerular hyperfiltration, microalbuminuria, and diffuse glomerular mesangial expansion. Similar to patients with glucose-6-phosphatase deficiency, the glomerular disease in this patient resembles incipient diabetic nephropathy. The Fanconi syndrome may be due to the defective transport of glucose at the proximal tubular basolateral membrane, which results in accumulation of glucose and secondarily glycogen within tubular cells. Since the metabolic defect, as evidenced by glycogen accumulation, selectively involves proximal renal tubular cells in the kidney of patients with Fanconi-Bickel syndrome and glucose-6-phosphatase deficiency, the abnormalities in renal glomerular hemodynamics and mesangial construct in these rare diseases are likely due to renal tubular factors, if the mechanism originates in the kidney. A delineation of these phenomena may further our understanding of the pathogenesis of diabetic nephropathy.

Albuminuria↗
PubMed1995

Permanent heterotopic ossification at the injection site after diphtheria-tetanus-pertussis immunizations in children who have fibrodysplasia ossificans progressiva.

In patients who have fibrodysplasia ossificans progressiva, routine childhood diphtheria-tetanus-pertussis immunizations administered by intramuscular injection caused a significant risk of permanent heterotopic ossification at the site of injection (p < 10(-8)), whereas measles-mumps-rubella immunizations administered by subcutaneous injection posed no significant risk. Intramuscular injections should be avoided, if possible, once a diagnosis of fibrodysplasia ossificans progressiva has been established.

Adolescent↗
PubMed1995

Tutorial. Molecular biology for the clinician. Part II. Tools of molecular biology.

This is the second of a series of tutorials on molecular biology for the clinician. Part I introduced general principles of nucleic acid and gene structure. This tutorial will build on those general principles and describe some of the commonly used techniques employed in research and diagnosis to examine genes and gene function. The tools of molecular biology include recombinant DNA techniques that have revolutionized the study of DNA and genetic information. Recombinant DNA technology allows the isolation of specific regions of chromosomal DNA and the recovery of unlimited quantities of that DNA for analyses, including determination of the nucleotide sequence of genes, examination of the mechanisms of gene regulation, and the identification of gene products (RNA and protein).

Animals↗
PubMed1995

BMP-1 sublocalization on human chromosome 8. Molecular anatomy and orthopaedic implications.

Bone morphogenetic proteins are capable of inducing mesenchymal tissue to form mature bone. Bone morphogenetic protein 1 (BMP-1) has a structure unique from the other bone morphogenetic proteins and may be involved in activation of other bone morphogenetic proteins. Localization of the human BMP-1 gene to chromosome 8 led to its consideration as a candidate gene for Langer-Giedion syndrome. Individuals with Langer-Giedion syndrome (also known as trichorhinophalangeal syndrome Type II) exhibit several skeletal abnormalities, including multiple exostoses and cone-shaped epiphyses of the hands and feet. The genetic locus responsible for this disease has been localized to the long arm of human chromosome 8 at 8q24.1. Somatic-cell hybrid and molecular biology techniques were used to sublocalize the BMP-1 gene to the short arm of chromosome 8 within the 8p22-cen region. Although this locus falls outside the Langer-Giedion syndrome region, and therefore excludes BMP-1 as a candidate gene for this disorder, BMP-1 gene sublocalization establishes a chromosomal landmark for evaluating other possible disease associations with BMP-1.

Animals↗
PubMed1995

Severe symptomatic osteopenia in a man with pigmented micronodular adrenal hyperplasia.

The authors describe the unusual case of a 52-year-old man with Cushing's syndrome caused by bilateral pigmented micronodular adrenal hyperplasia. The only features of hypercortisolism were hypertension and severe symptomatic osteopenia with vertebral, rib, and scapular fractures. Four years after bilateral adrenalectomy, the bone density had increased slightly, but the patient remained osteopenic and continued to have vertebral compression fractures. This case report emphasizes the importance of an indepth search for secondary causes of osteoporosis, including evaluation of adrenal function in patients who have unexplained osteoporosis. Early diagnosis and treatment is imperative to prevent severe bone loss and associated skeletal morbidity.

Adrenal Glands↗
PubMed1995

Progressive osseous heteroplasia in male patients. Two new case reports.

Progressive osseous heteroplasia is a rare developmental disorder of mesenchymal differentiation characterized by cutaneous osteomas in infancy and by progressive heterotopic intramembranous ossification of skin and deep connective tissue. To date, typical features of the disorder have been reported only in 8 female patients. This report documents progressive osseous heteroplasia in 2 boys and has important implications for the clinical detection and pathogenetic understanding of this rare disorder.

Child↗
PubMed1995

Prevention and management of osteoporosis.

The importance of osteoporosis as a health problem in the United States was underscored by the enthusiastic reception given to the two previous Clinical Symposia (1983 and 1987) written by Frederick S. Kaplan, MD. Along with discussions of the physiology of bone remodeling and pathophysiology of bone loss, this extensive revision clarifies the roles of estrogen, other hormones, and cytokines in bone maintenance and resorption. The author outlines the latest therapeutic guidelines, emphasizing the life-long preventive measures and medical interventions that can help halt the development of this preventable disorder.

Adolescent↗
PubMed1995

Mild expression of fibrodysplasia ossificans progressiva: a report of 3 cases.

We describe 3 unusually mild cases of fibrodysplasia ossificans progressiva (FOP) in an 80-year-old man, a 44-year-old woman, and a 17-year-old woman. The man, whose daughter had classic features of FOP, lacked malformation of the great toes and experienced unusually slow progression of the disease. Both women displayed late onset heterotopic ossification. The older women displayed an unusually slow progression of the disease. All 3 patients remained ambulatory at the time of examination. Recognition of a mild form of FOP will influence diagnosis, counselling, and research in this rare condition.

Adolescent↗
PubMed1994

Paget's disease of bone: orthopedic complications.

Orthopedic complications of Paget's disease are among the most common indications for treatment of Paget's disease. These complications include severe bone pain, joint pain, skeletal deformity, pathological fracture, and rarely malignant degeneration. The use of effective pharmacological modalities has transformed the treatment of Paget's disease in the past four decades. Although few patients with Paget's disease ever require surgical therapy, successful surgical management of severe orthopedic complications has improved the quality of life for many sufferers. Selected modalities with promising results include total hip replacement for intractable pagetic arthritis of the hip, proximal tibial osteotomy for painful malalignment of the knees, total knee replacement for intractable arthritis of the knee, and internal fixation for pathological fracture. Common surgical complications of joint replacement include infection, hemorrhage, heterotopic ossification, and aseptic loosening. The medical, surgical, and rehabilitation modalities available in managing primary and secondary orthopedic complications of Paget's disease provide a wide array of options that must be carefully considered in each patient.

Arthroplasty↗
PubMed1994

Spinal deformity in patients who have fibrodysplasia ossificans progressiva.

We reviewed roentgenograms and clinical records in order to characterize the spinal deformity in forty patients who had an established diagnosis of fibrodysplasia ossificans progressiva. Twenty-six (65 per cent) of the patients had scoliosis, which, according to the clinical records and the recollection of the patients, had been present during childhood. Twenty-three (88 per cent) of the twenty-six curves were unbalanced c-shaped curves, while the remaining three (12 per cent) were balanced s-shaped curves. Twenty-one (91 per cent) of the twenty-three c-shaped curves involved the thoraco-lumbar or lumbar spine. The c-shaped curves ranged in magnitude from 15 to more than 80 degrees. Curves became rigid by early adulthood and many resulted in severe pelvic obliquity with impaired sitting or standing balance. An osseous bridge developed between the posterolateral aspect of the iliac crest and the posterolateral aspect of the rib cage in twenty-two (55 per cent) of the forty patients. Nineteen (86 per cent) of these twenty-two patients had scoliosis; there was a significant association between the development of scoliosis and the presence of the osseous bridge (p < 0.005). Ossification of the paravertebral muscles and fascia during the first decade of life limited the development of a normal thoracic kyphosis in ten (42 per cent) of twenty-four patients for whom lateral roentgenograms of the spine were available. A spinal orthosis was used to treat the scoliosis in two patients, but this method resulted in breakdown of the skin and failed to halt progression of the curve.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗