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Biomedical subjects

J M Harrelson

Publications and source records attributed to J M Harrelson.

At least 55 records · Page 3Linked to original sources

Pyomyositis in a temperate climate. Presentation, diagnosis, and treatment.

The cases of eighteen patients who were treated for pyomyositis between 1970 and 1988 were evaluated. The diagnosis was often delayed because other primary diagnoses were considered, including muscle strain, synovitis, thrombophlebitis, and neoplasm, and because the symptoms were vague and prolonged (maximum duration, one year). The muscles around the hip and thigh were most commonly involved (twelve patients), and Staphylococcus aureus most commonly grew on culture (twelve patients). Computed tomography aided in the accurate diagnosis of the infection and of the extent of involvement. Incision, drainage, and antibiotic therapy eradicated the infection in all patients, and they had no residual functional limitations and minimum residual symptoms.

Adolescent↗

Tumor temperature distributions predict hyperthermia effect.

Review of clinical hyperthermia (HT) trial results shows that there previously has not been a robust model relating efficacy of HT treatments to characteristics of the temperature distribution. Lack of a model has been an impediment in Phase II trials; these trials must include defining the prescription for HT treatment, optimizing the schedule of HT treatments, and defining quality assurance procedures. We propose a model that is based upon noting that the majority of a tumor volume is contained in the outermost "shell" of a solid tumor, across which shell the radial temperature distribution is assumed to be linear. Any linear distribution can be defined by coordinates of a point and a slope, and we choose the temperature at the radiographically defined edge of a tumor and the slope (dT/dr) across the outer shell as these determinants of the linear radial temperature distribution. A discriminant analysis of success or failure of treatment can then be based upon these two descriptors (Tedge, dT/dr). We have tested this model using data from patients with soft tissue sarcoma (Stage IIB or greater) that have entered an ongoing prospective trial of conventional preoperative radiotherapy (5000 cGy/25 Fx/5 wk) together with HT, the latter randomized to be given once or twice weekly during the 5 week course. Wide local excision of the primary tumor is done 1 month after completion of radiotherapy, and the extent of histologic change in the resected specimen is scored. Our model has an 86% predictive value for lack of complete or nearly complete necrosis in the resected specimen according to whether the time-averaged Tedge and slope during each HT treatment satisfy the equation Tedge + 1.2 (slope in degree C/cm) less than or equal to 40.6 degrees C in all but one treatment at most. Conversely, in 85% of cases with complete or nearly complete tumor necrosis, temperature distributions satisfied Tedge + 1.2 (slope in degree C/cm) greater than 40.6 degrees C during at least one HT treatment. Requiring greater than or equal to one third of treatments of a patient to satisfy the preceeding discriminant equation resulted in 80% of patients being correctly classified as a responder or nonresponder, with only one false positive prediction (patient incorrectly classified as a responder). The model can reveal systematic changes in the edge temperature distribution during the treatment course that are consistent with tumor perfusion changes inferred and measured by independent means.(ABSTRACT TRUNCATED AT 400 WORDS)

Body Temperature↗

Management of the diabetic foot.

Treatment of diabetic foot pathology requires an accurate assessment of the etiologic factors involved. Dysvascular deterioration may be amenable to vascular reconstruction. When the vascular status cannot be improved, however, amputation is preferable to continued conservative care. Neuropathic ulceration is the product of decreased sensation, deformity, and increased pressure at the site of the ulcer. Pressure relief by conservative or surgical means is required for healing. Neuroarthropathy is increasing in frequency and results primarily from autonomic denervation. Protection from weight bearing and orthotic control usually minimize deformity and ultimately restore the patient to an ambulatory status. Surgical intervention in neuroarthropathy may be effective when conservative means fail. All efforts at treatment may be undermined by poor compliance. Patient education, reinforced at each clinic visit, makes the patient a part of the treatment team.

Arthropathy, Neurogenic↗

Evaluation in cats of a new material for cranioplasty: a composite of plaster of Paris and hydroxylapatite.

The materials ordinarily used to reconstruct bone defects in the calvaria and facial bones either are difficult to shape, are partially resorbed by the body, or are likely to become infected if used near a contaminated area such as the frontal sinus. Calcium sulfate hemihydrate (plaster of Paris) has been known for years to have excellent reparative qualities in bone defects, but ordinarily it is quickly resorbed. Consequently, a new material, a composite of a dense form of plaster of Paris and hydroxylapatite, was devised to provide nonabsorbable hydroxylapatite particles for bone to form around and within during the phase of plaster absorption. Two types of this material were evaluated in cranial defects in cats. Each of the plaster of Paris/hydroxylapatite mixtures was placed into a surgically unroofed frontal sinus and into a contralateral parietal trephine hole in a group of 32 cats. Two cats in each group succumbed to anesthesia, leaving two sets of 30 cats. During the entire follow-up period there was only one other death, with no evidence of wound infection, wound dehiscence, implant rejection, or cerebral dysfunction among the survivors. The cats in each group were sacrificed at 1, 2, 3, 5, 7, 8, 9, 10, or 12 months after operation. Following sacrifice, both the frontal and parietal defects were exposed and examined visually, histologically, and with histomorphometric analysis for new bone formation. New bone formation was present as early as 1 month after operation and continued to increase during the 12 months of the study. Based upon these osteogenic qualities, the ease of shaping the composite, and the lack of infection in the frontal sinus region, it is concluded that this substance could be a valuable new material for human cranioplasty.

Animals↗

Fractures of the polyethylene bearing insert in Bateman bipolar hip prostheses.

Six cases of fractures of the polyethylene bearing insert of Bateman bipolar hip prostheses were observed in three patients at four to eight years after implantation. Three fractured prostheses were salvaged by replacement with new bearing inserts. In three patients, excessive acetabular cartilage wear was the indication for revision to total hip arthroplasty. Although dislocation and component disassembly have been reported as complications of the Bateman and other bipolar prostheses, fractures of the polyethylene bearing insert seems not to have been previously reported. The presumed mechanism of failure is cyclic loading of a femoral cup that is tipped into varus alignment. This concentrates stress on the weakest part of the polyethylene insert--the deep circumferential groove that joins the leaflets to the main body of the insert. Obesity and overuse were associated factors in this rare complication.

Adult↗

Calcification of entheses associated with X-linked hypophosphatemic osteomalacia.

We undertook a retrospective analysis of 26 patients with X-linked hypophosphatemic osteomalacia (or rickets), whose ages ranged from 1 to 62 years and who were from 11 different kindreds, to determine the prevalence and clinical characteristics of a unique disorder of the entheses (tendons, ligaments, and joint capsules). We found a generalized involvement of the entheses, with exuberant calcification of tendon and ligament insertions and of joint capsules, in 69 per cent of the subjects. The prevalence and extent of disease increased with age but were not correlated with sex. Commonly affected sites included the hand and sacroiliac joints. Histologic evaluation in a selected patient revealed intratendinous lamellar bone but no inflammatory cells. Our observations indicate that this disorder is an integral part of X-linked hypophosphatemic osteomalacia and exhibits clinical, radiographic, and histologic characteristics that differentiate it from degenerative disorders of these tissues and seronegative spondyloarthropathies.

Adolescent↗

Aluminum deposition at the osteoid-bone interface. An epiphenomenon of the osteomalacic state in vitamin D-deficient dogs.

Although aluminum excess is an apparent pathogenetic factor underlying osteomalacia in dialysis-treated patients with chronic renal failure, the mechanism by which aluminum impairs bone mineralization is unclear. However, the observation that aluminum is present at osteoid-bone interfaces in bone biopsies of affected patients suggests that its presence at calcification fronts disturbs the cellular and/or physiochemical processes underlying normal mineralization. Alternatively, aluminum at osteoid-bone interfaces may reflect deposition in preexistent osteomalacic bone without direct effects on the mineralization process. We investigated whether aluminum accumulates preferentially in osteomalacic bone and, if so, whether deposition of aluminum occurs at calcification fronts and specifically inhibits mineralization. Aluminum chloride (1 mg/kg) was administered intravenously three times per week for 3 wk to five normal and five vitamin D-deficient osteomalacic dogs. Before administration of aluminum the vitamin D-deficient dogs had biochemical and bone biopsy evidence of osteomalacia. Bone aluminum content in the osteomalacic dogs (15.1 +/- 2.2 micrograms/g) and the plasma aluminum concentration (10.4 +/- 2.1 micrograms/liter) were no different than those of normal dogs (10.5 +/- 3.5 micrograms/g and 11.9 +/- 1.2 microgram/liter, respectively). After the 3 wk of aluminum administration the plasma phosphorus, parathyroid hormone, and 25-hydroxyvitamin D concentrations were unchanged in normal and vitamin D-deficient dogs. Similarly, no alteration in bone histology occurred in either group. In contrast, bone aluminum content increased to a greater extent in the vitamin D-deficient dogs (390.3 +/- 24.3 micrograms/g) than in the normal dogs (73.6 +/- 10.6 micrograms/g). Moreover, aluminum localized at the osteoid-bone interfaces of the osteomalacic bone in the vitamin D-deficient dogs, covering 42.9 +/- 9.2% of the osteoid-bone surface. Further, in spite of continued aluminum chloride administration (1 mg/kg two times per week), vitamin D repletion of the vitamin D-deficient dogs for 11 wk resulted in normalization of their biochemistries. In addition, while normal dogs maintained normal bone histology during the period of continued aluminum administration, vitamin D repletion of the vitamin D-deficient dogs induced healing of their bones. Indeed, the appearance of aluminum in the cement lines of the healed bones indicated that mineralization had occurred at sites of prior aluminum deposition. These observations illustrate that aluminum deposition in osteomalacic bone may be a secondary event that does not influence bone mineralization. Thus, although aluminum may cause osteomalacia in chronic renal failure, its presence at mineralization fronts may not be the mechanism underlying this derangement.

Aging↗

Healing of bone disease in X-linked hypophosphatemic rickets/osteomalacia. Induction and maintenance with phosphorus and calcitriol.

Although conventional therapy (pharmacologic doses of vitamin D and phosphorus supplementation) is usually successful in healing the rachitic bone lesion in patients with X-linked hypophosphatemic rickets, it does not heal the coexistent osteomalacia. Because serum 1,25-dihydroxyvitamin D levels are inappropriately low in these patients and high calcitriol concentrations may be required to heal the osteomalacia, we chose to treat five affected subjects with high doses of calcitriol (68.2 +/- 10.0 ng/kg total body weight/d) and supplemental phosphorus (1-2 g/d) performing metabolic studies and bone biopsies before and after 5-8 mo of this therapy in each individual. Of these five patients, three (aged 13, 13, and 19 yr) were receiving conventional treatment at the inception of the study and therefore showed base-line serum phosphorus concentrations within the normal range. The remaining two untreated patients (aged 2 and 37 yr) displayed characteristic hypophosphatemia before calcitriol therapy. All five patients demonstrated serum calcitriol levels in the low normal range (22.5 +/- 3.2 pg/ml), impaired renal phosphorus conservation (tubular maximum for the reabsorption of phosphate per deciliter of glomerular filtrate, 2.13 +/- 0.20 mg/dl), and osteomalacia on bone biopsy (relative osteoid volume, 14.4 +/- 1.7%; mean osteoid seam width, 27.7 +/- 3.7 micron; mineral apposition rate, 0.46 +/- 0.12 micron/d). On high doses of calcitriol, serum 1,25-dihydroxyvitamin D levels rose into the supraphysiologic range (74.1 +/- 3.8 pg/ml) with an associated increment in the serum phosphorus concentration (2.82 +/- 0.19 to 3.78 +/- 0.32 mg/dl) and improvement of the renal tubular maximum for phosphate reabsorption (3.17 +/- 0.22 mg/dl). The serum calcium rose in each patient while the immunoactive parathyroid hormone concentration measured by three different assays remained within the normal range. Most importantly, repeat bone biopsies showed that high doses of calcitriol and phosphorus supplements had reversed the mineralization defect in all patients (mineral apposition rate, 0.88 +/- 0.04 micron/d) and consequently reduced parameters of bone osteoid content to normal (relative osteoid volume, 4.1 +/- 0.7%; mean osteoid seam width, 11.0 +/- 1.0 micron). Complications (hypercalcemia and hypercalciuria) ensued in four of these five patients within 1-17 mo of documented bone healing, necessitating reduction of calcitriol doses to a mean of 1.6 +/- 0.2 micrograms/d (28 +/- 4 ng/kg ideal body weight per day). At follow-up bone biopsy, these four subjects continued to manifest normal bone mineralization dynamics (mineral apposition rate, 0.88 +/-0.10 micrometer/d) on reduced doses of 1.25-dihydroxyvitamin D with phosphorus supplements (2 g/d) for a mean of 21.3 +/- 1.3 mo after bone healing was first documented. Static histomorphometric parameters also remained normal (relative osteoid volume, 1.5 +/- 0.4%; mean osteoid seam width, 13.5 +/- 0.8 micrometer). These data indicate that administration of supraphysiologic amounts of calcitriol, in conjunction with oral phosphorus, results in complete healing of vitamin D resistant osteomalacia in patients with X-linked hypophosphatemic rickets. Although complications predictably require calcitriol dose reductions once healing is achieved, continued bone healing can be maintained for up to 1 yr with lower doses of 1,25-dihydroxyvitamin D and continued phosphorus supplementation.

Adolescent↗

The concurrence of hypoparathyroidism provides new insights to the pathophysiology of X-linked hypophosphatemic rickets.

Controversy exists over the role that PTH and extracellular fluid calcium concentration may play in modulation of the renal phosphate transport defect in X-linked hypophosphatemic rickets. In previous studies, administration of PTH to affected subjects resulted in an increase or no effect on renal phosphate excretion, while calcium infusion increased renal tubular phosphate transport. In contrast, patients with X-linked hypophosphatemic rickets and hyperparathyroidism have no change in their renal phosphate wasting after parathyroidectomy. However, none of these were permanently hypoparathyroid postoperatively. We describe a patient with idiopathic hypoparathyroidism in whom we proved the coexistence of X-linked hypophosphatemic rickets using family history and dental abnormalities. Initially, the patient had a mean serum calcium level of 5.6 +/- 0.07 (+/- SE) mg/dl and a renal tubular maximum for reabsorption of phosphate per liter glomerular filtrate (TmP/GFR) of 6.5 +/- 0.46 mg/dl. Hypoparathyroidism was confirmed, and therapy with vitamin D (50,000 U/day) and calcium (1,000 mg/day) was begun. On this regimen, serum calcium rose to 8.1 +/- 0.2 mg/dl, and TmP/GFR declined to 2.59 +/- 0.12 mg/dl. Bone biopsy revealed the persistence of osteomalacia. Subsequently, therapy with 1,25-dihydroxyvitamin D3 (1.0 microgram/day) was initiated, and serum calcium rose to 9.6 +/- 0.07 mg/dl, and TmP/GFR declined to 1.79 +/- 0.16 mg/dl. The prevailing serum calcium level correlated inversely with the TmP/GFR (r2 = 0.91; P less than 0.001). These data indicate that calcium and/or PTH are involved in modulation of the renal phosphate transport defect in X-linked hypophosphatemic rickets.

Adult↗

Computed tomography of axial skeletal osteoid osteomas.

Five cases of axial skeletal osteoid osteomas were viewed with particular attention to the role of computed tomography (CT) as a key diagnostic tool in the evaluation of osteoid osteoma. The complex anatomy of the axial skeleton can make the diagnosis of osteoid osteoma extremely difficult on routine films or tomograms, and the lesion often is well delineated only on CT scans. As complete surgical excision of this benign bony tumor is curative, precise anatomic localization is essential to the surgeon. The unique cross-sectional display of CT of the axial skeleton provides the surgeon with the exact location and extent of the lesion, which may allow a more limited surgical resection of the involved bone by defining the optimal surgical approach or procedure. Conventional radiographs were normal in all patients. Bone scans were positive when obtained and were useful in localizing the lesion and directing CT to the appropriate level. In all five cases CT was of proven value in accurately demonstrating the location, nidus, and other characteristic diagnostic radiographic features of osteoid osteoma.

Adolescent↗

Postparathyroidectomy hypocalcemia as an accurate indicator of preparathyroidectomy bone histology in the uremic patient.

19 chronic renal failure patients underwent iliac crest bone biopsy prior to total parathyroidectomy with autotransplantation. The preoperative serum calcium concentration did not correlate with the number of osteoclasts/mm2 present on the preparathyroidectomy iliac biopsy. However, the postparathyroidectomy decrement in serum calcium (mg/dl and percent change) and the osteoclasts/mm2 were strongly correlated (p less than 0.001). In addition, the postoperative fall in serum calcium also correlated with the postoperative change in serum alkaline phosphatase (p less than 0.001). The nadir in postparathyroidectomy serum calcium was attained in a mean of 4.4 +/- 2.7 days. Our results indicate that the preoperative serum calcium concentration does not necessarily reflect active bone resorption, but the postoperative decrement in serum calcium provides an accurate index of preoperative histologic activity. The available data do not provide information with respect to the mechanism of postparathyroidectomy hypocalcemia since either the cessation of bone resorption, continued bone deposition, or a combination of both may be operative.

Adult↗

Hormonal and metabolic regulation of human chondrosarcoma in vitro.

Prostaglandin A1 has a profound inhibitory effect on uridine incorporation into RNA of normal cartilage whereas N6-monobutyryladenosine 3',5'-cyclic monophosphate is either stimulatory or without an effect. Sera from intact and growth hormone-treated hypophysectomized rats stimulate RNA synthesis but serum from untreated hypophysectomized rats does not. The present study investigated the in vitro regulation of [3H]uridine incorporation into RNA of six human chondrosarcomas to determine if malignant human chondrocytes are under similar metabolic and hormonal regulation. Prostaglandin A1 (25 micrograms/ml) markedly inhibited uridine incorporation in all six tumors (56 to 80%). N6-Monobutyryladenosine 3',5'-cyclic monophosphate (1 mM) inhibited uridine incorporation in five tumors (20 to 50%). Uridine incorporation was stimulated by growth hormone-dependent serum factors in one tumor and by growth hormone-independent serum factors in two tumors. Two tumors were more responsive to serum from growth hormone-treated hypophysectomized rats than to serum from intact rats, and one tumor was unresponsive to serum stimulation. The data indicate that: (a) prostaglandin A1 is a very potent inhibitor of RNA synthesis in human chondrosarcomas; (b) N6-monobutyryladenosine 3',5'-cyclic monophosphate affects human chondrosarcomas differently than it does normal cartilage; and (c) responses of human chondrosarcomas to serum growth factors vary among individual tumors.

Bucladesine↗

A quantitative histomorphometric comparison of 40 micron thick Paragon sections with 5 micron thick Goldner sections in the study of undecalcified bone.

The value of quantitative histomorphometric analysis of undecalcified stained sections of bone is widely recognized. Five micron thick sections have been regarded as essential to carry out this analysis, but their production requires expensive equipment. Our laboratory was equipped initially only for the production of Paragon-stained 40 micron thick sections. These thicker sections have been used traditionally to guide the planimetric analysis of microradiographs. However, we found that they could be used for the simpler eyepiece graticule histomorphometric analysis in the same way that 5 micron sections have been examined. Sequential sections from iliac bone biopsy of 12 different patients with renal osteodystrophy were examined using each method. For 7 histologic features, the analysis of the thick sections compared very well with that of the Goldner-stained thin sections. The correlation coefficients varied from 0.88 for osteoid volume to 0.99 for osteoid surface. Other features compared included active and inactive osteoclastic surface activity. Further evidence of the usefulness of these thicker sections come from three other analyses. The expected close coupling of osteoblastic and osteoclastic activity was demonstrated (N = 56, r = 0.87, P less than 0.001). For 19 additional patients, two forms of histologic evidence of the degree of hyperparathyroidism correlated very well with the measured immunoreactive PTH (r = 0.93 and 0.93). Finally, normal values obtained with our method compare favorably with published normal values.

Benzopyrans↗

Osteomalacia in chronic renal failure: a syndrome previously reported only with maintenance dialysis.

Osteomalacia without marked elevations of parathyroid hormone (PTH) has been described in maintenance dialysis patients. The proposed etiology has centered upon the transfer of an environmental agent (aluminum) from the dialysis water system. The present report describes an azotemic patient, who, prior to the initiation of dialytic therapy, presented with severe osteomalacia and low PTH concentrations for the severity of renal failure. The osteomalacia was documented by bone histology on two occasions 1 year apart, and aluminum deposits at the osteoidmineralized bone interface were demonstrated with histologic techniques. PTH concentrations were within the normal range (less than 0.1 ng/ml) on three widely spaced intervals. No definite statement can be made regarding the etiology of the osteomalacic syndrome in this patient, but maintenance dialysis does not appear to be necessary for its expression.

Aged↗

Osteomalacia after parathyroidectomy in patients with uremia.

Five patients on maintenance dialysis had symptoms of osteomalacia, proven by biopsy, after parathyroidectomy. In all five patients clinical and radiographic manifestations of secondary hyperparathyroidism were present before surgery, and in two patients preoperative biopsy of bone confirmed the existence of osteitis fibrosa. Like previously described patients with osteomalacia all five had multiple fractures and normal or high serum calcium concentrations that rose to abnormally high values on treatment with vitamin D or dihydrotachysterol. Quantitative histomorphometry of biopsy after parathyroidectomy showed no residual parathyroid hormone effect and nearly complete cessation of mineralization. Four patients had forearm autografts of parathyroid tissue that appeared to be functioning at very low rates according to paired venous sampling, and all five patients had relatively low circulating concentrations of parathyroid hormone. This and earlier experiences reported by others suggest that secondary hyperparathyroidism may have an important facilitative role in the mineralization of bone in uremic patients.

Adult↗