Biomedical subjects

S C Marks

Publications and source records attributed to S C Marks.

246 records · Page 14Linked to original sources

PubMedDate not supplied

Ultrastructural investigations of bone resorptive cells in two types of autosomal dominant osteopetrosis.

In order to investigate the ultrastructure of bone resorptive cells in the two types of adult benign human osteopetrosis, iliac crest biopsies were obtained from 11 patients and 10 normal males, who served as a control group. Six patients had the radiological type I (4 women, 2 men, aged 23-58 years, mean = 36.5 years), and 5 type II disease (5 men, aged 20-48 years, mean = 29.8 years). The normal controls (aged 23-48 years, mean 34.1 years) were recruited from the medical staff. The biopsies were immediately divided. From each patients, half was embedded in paraffin for histochemistry and light microscopy, and half in epon for transmission electron microscopy. The osteoclasts were markedly reduced in number and size in Type I disease (0.2 +/- .7 cells vs. 2.9 +/- 1.0 cells per 2.7 mm2 of bone area, p < 0.01) compared to controls, and stained only weakly for tartrate-resistant acid phosphatase (TRAP). At the ultrastructural level, no signs of active bone resorption were identified, whereas numerous mononuclear cells were observed at the bone surfaces. In type II disease, the osteoclasts were large and highly multi-nucleated, with an increased number (8.3 +/- 2.3 cells vs. 2.9 +/- 1.0. cells per 2.7 mm2 of bone area, p < 0.01) compared to controls. In all patients with this type, but never in type I or in the controls, a smooth, TRAP-positive substance was seen between the osteoclasts and the bone surface. Ultrastructurally, this substance was amorphous, with a condensation along the cell membrane.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMedDate not supplied

Interdependence of skeletal sclerosis and elevated circulating levels of 1,25-dihydroxyvitamin D in osteopetrotic (op and tl) rats.

Osteopetrosis describes a heterogeneous group of inherited, metabolic bone disorders characterized by reduced bone resorption which coexists with elevated circulating levels of 1,25-dihydroxyvitamin D [1,25(OH)2D]. To determine whether or not skeletal sclerosis and high concentrations of 1,25(OH)2D are interdependent, this study used two distinct, nonallelic osteopetrotic mutations in the rat, osteopetrosis (op) and toothless (tl). The op rat is a mutation in which skeletal sclerosis can be cured (mutant) or induced (normal) following the transfer of normal or mutant osteoclast progenitors, respectively. Although these procedures are ineffective in rats of tl stock, infusions of pharmacological doses of macrophage colony-stimulating factor (CSF-1) can stimulate bone resorption and eliminate most of the excess skeletal matrix in tl mutants. This study examined the effects of cure/induction in neonatal mutant/normal rats of op stock and CSF-1 infusions in mutant rats of tl stock on skeletal (bone resorption) and serum [1,25(OH)2D] parameters as a function of time after treatment. Osteopetrotic mutants transplanted (cured) with normal spleen cells demonstrated cellular changes in osteoclast phenotype within 2-3 days followed by histologic and radiographic evidence for increased bone resorption that culminated in a normal appearance of the skeleton by 4 weeks. The markedly elevated serum levels of 1,25(OH)2D observed in untreated mutants fell significantly in transplanted mutants by the end of the first week and were similar to those in normal littermates at 3 and 4 weeks. Normal littermates transplanted (induced) with mutant spleen cells showed a progressive increase in skeletal sclerosis paralleled by significant increases in circulating levels of 1,25(OH)2D.(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of Variance↗

PubMedDate not supplied

Neonatal reductions in osteoclast number and function account for the transient nature of osteopetrosis in the rat mutation microphthalmia blanc (mib).

We have examined the general and skeletal manifestations of osteopetrosis in a new, mild osteopetrotic mutation in the rat, microphalmia blanc (mib). Newborn mutant (mib) rats exhibit the typical skeletal deformities and sclerosis of osteopetrosis at birth, which are reduced significantly during the first postnatal month but don't disappear entirely up to 8 months later. Osteoclast numbers, staining for TRAP and TraATPase, and bone resorption are reduced in mutants during the first 2 postnatal weeks but improve by 1 month. In mutants, serum concentrations of calcium and phosphorus are normal, but 1,25(OH)2 D levels are higher at 1 week than those in normal littermates. Neonatally, mutants exhibit extramedullary hemopoiesis in the spleen. These results are interpreted to mean that the transient perinatal skeletal sclerosis in mib rats is caused by reduced production and function of osteoclasts in this period. The recent description of transient, perinatal osteopetrosis in a child suggests that analyses of the early differences between mild and severe animal mutations might distinguish those children with osteopetrosis who need treatment from those who do not.

Aging↗

PubMedDate not supplied

One stage carotid artery resection: reconstruction in radiated head and neck carcinoma.

PURPOSE: Management of the carotid artery involved with metastatic squamous cell carcinoma continues to be a topic of much discussion. Early reports, for the most part, focused on the sequel of ligation and the development of various tests to predict patient tolerance for the procedure. More recent alternatives have described resection reconstruction in multistage procedures. By using immediate reconstruction with autogenous arterial grafting, carotid artery resection can be accomplished in patients with radiation failure in a single stage. This technique can be used without the addition of myocutaneous flaps, controlled fistulas, or intracranial surgery advocated for usage with alternative techniques. PATIENTS AND METHODS: Immediate reconstruction after resection of the carotid artery with superficial femoral arterial graft is described. RESULTS: In a series of 18 high-risk patients with radiation failure, the artery was successfully resected and reconstructed in 1 stage without any neurologic or vascular complications. The technique has been associated with prolonged survival in selected patients. CONCLUSION: Carotid artery resection and immediate reconstruction can be performed in high-risk radiation failure patients with acceptable complications, and is associated with prolonged survival in selected cases.

Carcinoma, Squamous Cell↗

PubMedDate not supplied

Dense incisors (din): a new mouse mutation on chromosome 16 affecting tooth eruption and body size.

Dense incisors (din) is a new autosomal recessive mutation in the mouse that interferes with complete eruption of the incisors. The initial eruption of incisors through the gingiva does not differ in mutants and normal littermates, but subsequent further eruption of incisors is arrested in mutants. Radiographic examinations show that, because the incisors do not erupt, continued dentin formation gradually occludes the pulp chambers of these teeth creating as dense incisor. The arrested eruption of the incisor results in an anterior open bite. The pleiotropic phenotype of din/din mutant mice also includes small body size, reduced ear pinna size, and coat color dilution. The din mutation was mapped to Chr 16 near the pituitary transcription factor gene Pit1, but din is not a mutation in Pit1.

Animals↗

PubMedDate not supplied

Osteopetrosis, a new recessive skeletal mutation on chromosome 12 of the mouse.

Osteopetrosis (op/op) is a new mutation in the mouse that is transmitted as an autosomal recessive linked with variant waddler (Va) on chromosome 12. Compared with normal littermates, young op/op mice have excessive accumulations of bone without marrow cavities, increases in bone matrix formation and concentrations of parafollicular cells of the thyroid, and are hypophosphatemic. Osteoclasts from op/op mice are small, few in number and have an abnormal cytoplasmic distribution of the lysosomal enzyme acid phosphatase. In contrast to the three other mutations that transmit osteopetrosis in mice, the skeletal signs of the disease slowly disappear in op/op animals after bone matrix formation declines about 6 weeks after birth from 145 percent to 20 percent of that in normal siblings. The main skeletal defect in op/op mice appears to be a severe restriction in bone remodeling that is capable of slowly removing the excessive skeletal mass characteristic of the disease only after bone formation has declined to one-fifth that of normal littermates.

Animals↗

PubMedDate not supplied

Osteosclerosis, a recessive skeletal mutation on chromosome 19 in the mouse.

Osteosclerosis (oc) is an osteopetrotic mutation in the mouse inherited as an autosomal recessive on chromosome 19. Affected animals (oc/oc) exhibit the characteristic radiologic and histologic hallmarks of osteopetrosis including a generalized increase in skeletal density and absence of marrow cavities. Most die within three weeks after birth. Osteoclasts are cytologically abnormal by light microscopy in that they do not have cytoplasmic vacuoles. Presumptive evidence of rickets in this mutation includes thick cartilagenous growth plates and excessive osteoid. Extensive extramedullary hemopoiesis occurs in the liver and spleen of mutants. This unique constellation of features suggests that the oc mutation is a valuable model in which to investigate the pathogenesis of osteopetrosis.

Animals↗

PubMedDate not supplied

Management of sinusitis in adult cystic fibrosis.

Until recently, cystic fibrosis was frequently fatal during childhood. However, with current medical management, many patients are living into adulthood. This has created a new population of patients with chronic sinusitis and severe medical problems. In this report, experience with 22 patients, eight of whom have undergone sinus surgery, is presented, and recommendations for management are proposed. Presenting symptoms are typical of sinusitis, but in a few patients, severe debilitating headaches predominate. Oral antibiotics are often of little use due to the numerous courses of high dose intravenous antibiotics used for resistant pulmonary infections. Topical nasal steroids and mucolytics have been of some benefit. Fourteen operative procedures were performed on eight patients. These procedures included 12 endoscopic sphenoethmoidectomies, four Caldwell-Luc procedures, two frontal sinus obliterations, and one transseptal sphenoidotomy (many of these were in combination.) Results from this experience indicate 1) Failure of endoscopic surgery to control frontal and maxillary sinus disease; 2) Delayed healing of the ethmoid cavity with persistent crusting; and 3) Significant, albeit short term, symptomatic relief following surgical intervention. Based on this limited series, we conclude that surgery should be delayed until absolutely necessary and that an aggressive approach should be adopted when surgery is performed. In our hands this included initial endoscopic sphenoethmoidectomy with open surgical techniques used for removal of trapped inspissated secretions. We recommend long term intravenous antibiotics postoperatively and frequent cleaning of the ethmoid cavity after surgery, continuing indefinitely, to optimize the benefit of surgery.

Administration, Intranasal↗

PubMedDate not supplied

Evaluation of prognostic factors in endoscopic sinus surgery.

A retrospective analysis of 115 consecutive patients who underwent endoscopic sinus surgery for chronic sinusitis was conducted to evaluate the effect on outcome of variables including previous sinus surgery, allergy, asthma, and computed tomography stage of disease. Outcome was assessed in each patient by a survey in which the patient rated the benefit of surgery in terms of percent improvement in different symptoms compared with symptoms before surgery. Outcome was also assessed by the need for revision surgery and the presence of endoscopic criteria for failure. The results indicate that allergy and previous sinus surgery are associated with lower individual symptom scores, but no variable was associated with overall symptomatic failure. Previous sinus surgery was strongly associated with the need for subsequent revision surgery. The computed tomography stage was strongly associated with endoscopic evidence of failure. In conclusion, both history of previous sinus surgery and computed tomography stage of disease are correlated to poor outcomes after endoscopic sinus surgery.

Chronic Disease↗

PubMedDate not supplied

Middle turbinate graft for repair of cerebral spinal fluid leaks.

Endoscopic management of CSF leaks has been reported as highly successful by several authors. Various techniques are used for site preparation, graft selection, and graft stabilization. In this report the middle turbinate as a donor site for repair is described. Guidelines for harvest, preparation, and application are presented. The middle turbinate graft can be used as a free mucosal graft for linear cracks or small defects, as a composite bone/mucosal graft for moderate sized defects, or as a donor site for separate bone and mucosal grafts for large defects or encephaloceles when intracranial bone placement is desirable. Experience with 18 patients is presented with 100% initial graft take, and 17/18 (94%) with long term success. The middle turbinate is an excellent source of donor material for repair of almost any endoscopically repairable CSF leak.

Adult↗

PubMedDate not supplied

Bone remodeling as an expression of altered phenotype: studies of fracture healing in untreated and cured osteopetrotic rats.

The healing of tibial fractures was studied in 3 groups of young littermate rats; untreated osteopetrotic (ia/ia), normal littermates (ia/+) and osteopetrotic (ia/ia) cured of the disease 3 days earlier by transplanted normal spleen cells. The fracture site was completely remodeled in 4 weeks in normal rats, 6 weeks in transplanted (cured) osteopetrotic rats and 9 weeks in untreated osteopetrotic rats. The delayed healing in untreated osteopetrotic rats resulted from reduced resorption present in this mutation. Increased resorption brought about by transplantation of normal spleen cells accelerated healing in the transplanted osteopetrotic rats. Fracture repair took longer in the latter group than in normal littermates presumably because tibial fracture occurred before the 2 week interval required for skeletal transformation from osteopetrotic to normal phenotype following transplantation of normal spleen cells. These data show that alteration of the phenotype of osteopetrotic rats is reflected in fracture healing.

Animals↗

PubMedDate not supplied

Metaphyseal extensions of hypertrophied chondrocytes in abused infants indicate healing fractures.

We examined histologically 40 bones from 11 infants aged < 1 year who died with evidence of infant abuse. Twenty-three bones had fractures, and 15 of these contained conspicuous metaphyseal extensions of hypertrophied chondrocytes (EHC) which were highly associated with healing fracture sites. These data indicate that such lesions are common in fractures related to child abuse, are easily identified, and are indicative of healing fractures. The presence of this lesion has significant implications for those who assess skeletal injury in abused infants because the determination of infant abuse often relies on establishing a pattern of skeletal trauma. Quantitation of the growth rate of individual physes in this age group may eventually permit assessment of the minimum age of these skeletal injuries.

Bone and Bones↗