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Biomedical subjects

R Baron

Publications and source records attributed to R Baron.

At least 253 records · Page 14Linked to original sources

Ileocecal endometriosis presenting with abdominal pain and gastrointestinal bleeding.

A 26-year-old woman with enteric endometriosis presenting with cecocolic intussusception, a cecal mass on barium enema, and gastrointestinal hemorrhage is described. Laparotomy revealed cecocolic intussusception, ileocecal endometrial implants, and cecal mucosal ulceration presumed secondary to ischemia of the intussuscepted bowel. Histopathology showed serosal and subserosal endometrial implants without mucosal invasion. A review of the literature of endometrial bowel disease is presented.

Abdomen↗

Effect of spaceflight on the non-weight-bearing bones of rat skeleton.

Male Wistar rats prelabeled with tetracycline to mark surfaces of bone and tooth formation-mineralization were placed into orbit for 18.5 days aboard the Soviet COSMOS-1129 Biosatellite. They were injected with tetracycline for a second and third time on the 6th and 27th days, respectively, after recovery of the Biosatellite. Spaceflight did not alter the rate of periosteal bone formation in the non-weight-bearing ribs and regions of the mandibles, which were covered by masticatory muscles. Bone formation-calcification rates were impaired at those sites in the jaw that had no contiguous muscle (molar region). The remodeling activity on the alveolar bone around the buccal roots of the molar teeth was significantly reduced but without creating a negative balance between formative and resorptive activities. Total Ca, P, and hydroxyproline concentrations in the jaws, incisors, and ribs were normal after spaceflight, but gravity density fractionation studies indicated that in the jaws alone, O-G conditions caused a delay in the maturation of bone mineral and matrix. A 29-day postflight recovery period at earth's gravity was sufficient to fully correct these anomalies. Relative to tooth formation, relatively normal circadian and infradian biorhythmic periodicities of Ca and P in dentin and enamel were maintained during spaceflight. We conclude that most of the non-weight-bearing bones of the rat skeleton are at risk to the effects of hypogravity.

Animals↗

Increased bone turnover with decreased bone formation by osteoblasts in children with osteogenesis imperfecta tarda.

Iliac crest bone biopsies from nine children (6-15 yrs old) with osteogenesis imperfecta tarda (OI) have been studied by bone histomorphometry after double fluorescent labeling with tetracycline and compared to five unlabeled biopsies from normal children in the same age group. The results indicate that children with OI have a low trabecular bone volume associated with an increased bone turnover rate. Bone formation is increased at the tissue level despite a decrease in the activity of individual osteoblasts. The original defects in OI seems, therefore, to be in the rate of matrix synthesis by osteoblasts. It is, however, compensated by an increase in the number of these cells. These results suggest that these children were not losing bone at the time of the biopsy, which fits with the clinical stability of OI with age. Our study therefore suggests that the osteopenia observed in OI is most likely due to an inability to accumulate bone during growth, as normal children do, rather than to a progressive net loss of bone.

Adolescent↗

A detailed evaluation of oral phosphate therapy in selected patients with primary hyperparathyroidism.

Recent studies have emphasized the pathophysiological importance of circulating 1,25-dihydroxyvitamin D ((1,25-(OH)2D] in the pathogenesis of hypercalciuria and renal stone formation in primary hyperparathyroidism. Reasoning that phosphate administration might be capable of reducing the plasma concentration of 1,25-(OH)2D in patients with a prominent 1,25-(OH)2D-mediated absorptive component to their disease, 10 carefully selected patients were treated with oral phosphate (1500 mg elemental phosphorus daily) for 1 yr. Phosphate treatment significantly reduced circulating 1,25-(OH)2D levels (84 to 56 pg/ml), the calciuric response to an oral calcium tolerance test (0.30 to 0.21 delta mg calcium/dl GF), and calcium excretion on an unrestricted calcium diet (438-269 mg/day), in essence reversing the absorptive pattern of abnormalities observed before treatment. This response, however, was accompanied by an increase in biochemical hyperparathyroidism, as assessed by circulating immunoreactive PTH and nephrogenous cAMP excretion. In patients with biochemical evidence of an increase in bone resorption before therapy, histomorphometric, radiographic, and biochemical data revealed a trend toward a reduction in bone turnover during phosphorus therapy, with an apparent maintenance of coupled bone resorption and bone formation. This trend, however, was of marginal statistical significance in the patient group as a whole. It is concluded 1) that phosphate therapy represents a viable medical alternative in selected patients with primary hyperparathyroidism, 2) that the net response in treated patients is multifaceted and complex, and 3) that the efficacy of phosphate therapy will ultimately depend upon its long term effects on skeletal homeostasis.

Bone and Bones↗

Cellular kinetics of the bone remodeling sequence in the rat.

The kinetics of the bone remodeling sequence in the rat has been studied using a system in which well-synchronized remodeling units were induced along the periosteum of rat mandibles. Remodeling of the periosteal surface of the mandibles was induced according to Tran Van (1979) by extraction of the opposing row of teeth; namely, the right maxillary molars were extracted under light ether anesthesia, therefore allowing the right mandibular molars to egress; this, in turn, induced a wave of remodeling activity on the buccal side of the periosteal surface of the alveolar bone. The quantification of the different cellular activities involved in bone remodeling has been performed up to 16 days after induction. This allowed us to demonstrate the sequential activity of the different cell types involved in bone remodeling, to study the cellular kinetics of this sequence of events, and to directly measure the duration of each phase of the bone remodeling sequence. A single wave of osteoclasts appeared 3 days after induction, reached a peak of 4-5 days, and then decreased sharply. This was followed by a single wave of mononuclear cells (Baron et al., 1980) within remodeling sites during the reversal phase; they appeared 4 days after induction, reached a peak by day 7, and then decreased sharply. This reversal activity was then followed by osteoblasts forming new bone on top of a reversal cement line in the remodeling sites, starting 6 days after induction and increasing until the end of the experiment. In addition, the synchronization of the system used in this study allowed direct measurement of the duration of the successive steps of the remodeling sequence. The directly measured values have then been compared to previous data calculated from other systems.

Animals↗

Histomorphometry and autoradiography of cultured fetal rat long bones.

The behavior of fetal rat long bones cultured in vitro according to Raisz's technique (1969) was studied by histomorphometry and autoradiography for a period of four days. The changes were recorded daily both on the trabecular and cortical bone by measuring the bone volume, the number of osteoclasts, and the number of nuclei per osteoclast. Radioactive calcium release was measured and compared to the changes in bone volume and in the number of osteoclasts. An autoradiographic study, using 3H-proline and 3H-thymidine in flash labeling in the medium and 3H-thymidine in follow-up labeling after one injection in vivo was performed to evaluate the bone formation, the cellular proliferation rate and cell differentiation. After four days in culture, an increase in total calcified bone volume was observed which correlated with changes in the trabecular bone. No significant changes were recorded in the cortical bone. The results showed a good maintenance of the resorption and formation phenomena through an active process of cellular multiplication and differentiation. Undifferentiated cells were labeled in flash label and osteoblast, osteocyte and some osteoclast nuclei were labeled in follow-up studies.

Animals↗

An electron-microscopic study of the bone-remodeling sequence in the rat.

A detailed chronological electron-microscopic study of the bone remodeling sequence has been performed in the rat based on a previously described model (Tran Van et al. 1982) in which the remodeling activity is synchronized. This allowed the observation of the cellular and extracellular events during the bone remodeling process, including the activation of the sequential process and the reversal phase, intermediate between osteoclastic resorption and osteoblastic formation. Most important is the fact that throughout the whole process cells with the morphological characteristics of mononuclear phagocytes have been observed in proximity or in contact with the bone surface and/or the various bone cells. Coated pits (receptor-mediated endocytosis) are frequently observed in close apposition ot bone spicules and gap junctions are frequent between the cells. These observations suggest that, besides being likely candidates as osteoclast precursors, mononuclear phagocytes may play an important role in bone remodeling.

Animals↗

25-hydroxyvitamin D3 (calcifediol) therapy of juvenile renal osteodystrophy: beneficial effect on linear growth velocity.

A prospective study of renal osteodystrophy in moderate renal insufficiency was undertaken to assess the effects of 25(OH)D3 (Calcifediol) on healing of bone lesions and improvement of linear growth. One year after entering the study, the mean group growth velocity increased into the normal range and remained there in the next two therapy years. A significant correlation existed between pretherapy and one-year therapy values of growth velocity and serum 25(OH)D3 concentration. Qualitative bone histology obtained by transilial bone biopsy was also evaluated during the course of study. Catch-up growth was not seen, but potential for such growth may exist in later years in our patients.

Child↗

Quantitative bone histomorphometry in humoral hypercalcemia of malignancy: uncoupling of bone cell activity.

Humoral hypercalcemia of malignancy (HHM) results from elaboration by tumors of a circulating bone-resorbing factor(s). THe specific mechanism responsible for this bone resorption is poorly understood, and no comprehensive study employing quantitative histomorphometric analyses of bone biopsies obtained from living patients with HHM has been reported. We describe bone histology and quantitative bone histomorphometry in bone biopsies obtained from seven patients defined biochemically (elevated nephrogenous cAMP excretion) and histologically (no tumor in biopsy sample) as having HHM. These biopsies are compared to biopsies from nine patients with primary hyperparathyroidism (HPT). Compared to patients with HPT, those with HHM displayed (mean +/- SD) greater osteoclastic activity (osteoclast surface, 8.6 +/- 6.1% vs. 2.7 +/- 1.5%; P less than 0.001) and more frequent empty lacunae (9.2 +/- 4.0% vs. 5.8 +/- 3.0%; P less than 0.01), but markedly reduced osteoblastic surface (2.5 +/- 3.1% vs. 13.8 +/- 7.0%; P less than 0.001), osteoid surface (12.9 +/- 11.9% vs. 42.0 +/- 15.0%; P less than 0.001), and osteoid volume (0.3 +/- 0.3% vs. 1.3 +/- 1.0%; P less than 0.01). These findings directly confirm the presence of humorally mediated bone resorption and indicate a striking uncoupling of osteoclast and osteoblast activities in bone from patients with HHM. These findings are in sharp contrast to those in HPT patients, where osteoclast and osteoblast activities are tightly coupled, and net skeletal calcium loss is minimal. This uncoupling provides a mechanism for the marked skeletal calcium losses observed in patients with HHM.

Adult↗

Waterskier's enema.

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Athletic Injuries↗

Dynamic histomorphometry of alveolar bone remodeling in the adult rat.

Alveolar bone normally undergoes remodeling on one side of the socket and modeling on the opposite side as the tooth migrates at a rate of 6.7 micrometer per day. Periodontal ligament width, however, remains constant. Because of this very high turnover rate, this bone is a good model to study bone modeling and remodeling activities. This study was undertaken in order to measure the different cellular events occurring during tooth migration along the alveolar bone of the rat. The histomorphometric measurements performed on this model permitted us to calculate the duration of each phase of the remodeling cycle, i.e., resorption lasts about 1.5 days and reversal about 3.5 days. Since the duration of the forming phase is about 1 day (Guyomard and Baron, '74), the total duration of each remodeling cycle is about 6 days. This time is very short compared to 60--120 days in adult human trabecular bone. Additionally, in this model each osteoclast resorbs 2--4 times its own volume of bone per day. Based on this knowledge, it will be possible to measure accurately the effects of experimental conditions on bone cells and bone remodeling in this rat alveolar bone model.

Alveolar Process↗

1,25(OH)2D3 is not the only D metabolite involved in the pathogenesis of osteomalacia.

Three patients are described in whom there was no simple correlation between plasma 1,25(OH)2D3 concentration and the occurrence of osteomalacia. One patient had severe osteomalacia with high plasma 1,25(OH)2D3 and normal mineral ion product; the second had a normal mineral ion product and no evidence of osteomalacia even though plasma 1,25(OH)2D3 was undetectable; and the third had osteomalacia, low plasma 1,25(OH)2D3 and a reduced mineral ion product. In considering these data in the light of presently available information, it is concluded that osteomalacia can occur as a consequence of a lack of a vitamin D metabolite other than 1,25(OH)2D3, or a consequence of a reduced mineral ion product, but not as a consequence of 1,25(OH)2D3 lack if the mineral ion product is normally maintained and other D metabolites are present. However, a deficiency of 1,25(OH)2D3 normally leads to a reduction in the mineral ion product hence 1,25(OH)2D3 deficiency may play a role in the development of certain forms of osteomalacia.

Adult↗

Early diagnosis of juvenile renal osteodystrophy.

Renal osteodystrophy has assumed growing importance as a major and frequently disabling complication of chronic renal failure in children since the advent of successful hemodialysis and renal transplantation programs. The frequency and severity of renal osteodystrophy appears greatest in younger children with congenital diseases of the kidney and urinary tract, who experience long intervals of chronic renal failure prior to reaching end-stage. Twenty-nine children with varying degrees of chronic renal failure were studied to learn: (1) how early renal osteodystrophy can be diagnosed; and (2) how the various clinical, biochemical, and hormonal abnormalities correlate with abnormal bone histomorphometry as determined from percutaneous transilial bone biopsies. Results showed: (1) marked-to-moderate reductions in GFR (mean = 35 ml/minute/1.73 m2; range 11 to 65 ml/minute/1.73 m2); (2) elevations of serum PTH concentrations in all patients with a GFR < 45 ml/minute/1.73 m2; (3) abnormal bone histomorphometry in all patients with elevated PTH concentrations; (4) "early" renal osteodystrophy (elevated PTH concentrations and abnormal bone histomorphometry but normal serum chemistry values and radiographs) in one quarter of the patients; (5) poor correlations of serum chemistry values and radiographs with bone histomorphometry; and (6) a wide range of histologic abnormalities including predominant osteomalacia (n = 7), predominant hyperparathyroidism (n = 6), or a mixed picture (n = 11).

Adolescent↗

Assessment of bone mass in the radius by computed tomography.

A reproducible method for quantitative analysis of computed tomographic cross-sections of the distal radius of patients with various metabolic bone diseases is described. A statistically significant correlation between the CT measurements in the radius and quantitative histomorphometric measurement of the trabecular bone volume of corresponding transilial bone biopsies is demonstrated. Selected longitudinal studies are presented to demonstrate the possible clinical applications of this type of CT analysis.

Adult↗

The inverse relationship between cost and survival in the critically ill cancer patient.

The enormous cost of intensive multiple organ system support is apparent from patient or third party charges of $1500--$2000 per day exclusive of physician fees sampled during a retrospective review of 700 consecutive recent admissions to the Critical Care Facility of Memorial Cancer Center. Mortality rates of 49% for general medical, 54% for lymphoma or leukemia, and 20% for surgery patients suggest the need for a selective admission and discharge policy which concentrates financial and personnel resources on those for whom there remains a reasonable chance of worthwhile palliation, if not cure, of their malignancy. An informal policy of this kind may have contributed to a 10% increase in hospital discharges and a reduction of in-unit mortality from 22--18% when compared to 1035 earlier unselected admissions. A modified version of the classification suggested by the Critical Care Committee of the Massachusetts General Hospital has been adopted for use at this institution. A similar approach by other cancer centers is urged so that predictive indices based on prognosis of the underlying disease as well as physiological status may be developed. Otherwise, cost-benefit analysis by third party payers or government will become an unavoidable, and less satisfactory, alternative.

Adult↗

Effects of parathyroid hormone on the osteoclastic pool, bone resorption and formation in rat alveolar bone.

The osteoclast number and its relation to parathyroid hormone have been studied in rat alveolar bone by quantitative histology and fluorescent labeling. The osteoclast number decreases 60 h after parathyroidectomy and remains constant for the next 132 h. Parathyroid hormone administration to parathyroidectomized animals 96 h after the operation induces an increase in osteoclast number within 12 h to somewhat above those of control animals. The elevated osteoclast counts remain constant for 60 h then rapidly fall over the next 24 h to the level seen in untreated parathyroidectomized animals. As determined by fluorescent labeling, normal alveolar bone resorption and formation were disturbed by parathyroidectomy, such that significant bone formation occurred for only 6 days after surgery, after which a quiescent state followed.

Alveolar Process↗

Sleep patterns in the intensive care unit and on the ward after acute myocardial infarction.

Twelve patients aged 33--70 years (mean 49.5) underwent nightly recordings in the ICU and subsequently on the ward following acute myocardial infarction. Sleep patterns were analyzed according to night after infarct and ICU versus ward environment. Significant differences in nocturnal sleep patterns from matched controls initially after infarction included greater wakefulness, low REM sleep per cent, long REM latency, fewer REM periods, more awakenings, more stage shifts and decreased sleep efficiency. The usual circadian variation in HR was absent, and there was an estimated 8--10 h of unrecorded daytime sleep, which together suggested a quite generalized disruption of biological rhythms. With time, there was loss of daytime sleep, lowered nocturnal wakefulness and increased REM sleep. Slow-wave sleep (sometimes with very long duration delta waves) increased above normal over post-infarction nights 3--9, and sleep was otherwise renormalized by post-infarction night 9. No sudden sleep changes occurred with transfer from ICU to ward. The altered sleep patterns appeared mainly attributable to infarction itself. Twelve nocturnal anginal attacks occurred. Ten began in NREM sleep and two in REM periods without particularly intense phasic activity. Post-infarction nocturnal angina therefore appears to differ in pathogenesis from angina outside this period, which usually occurs in REM sleep. ECG changes could occur during sleep before awakening with pain, and overall decrease in ECG amplitude sometimes accompanied angina. Most attacks (10 of 12) occurred on post-infarction nights 4 and 5, indicating that undetermined that undetermined factors produce a secondary period of heightened risk at that time.

Adult↗