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Biomedical subjects

D A Martinez

Publications and source records attributed to D A Martinez.

At least 19 recordsLinked to original sources
PubMed2000

Elastic and physicochemical relationships within cortical bone.

The purpose of this study was to examine the relationships that exist between the elastic properties and the physicochemical properties of cortical bone in two groups of experimental animals. The animal model was the immature mutant dwarf rat, and the groups consisted of rats treated and not treated with recombinant human growth hormone (rhGH). The objective was to establish and broaden the quantifiable link between the three-dimensional form and function of bone beyond the typical unidirectional measures. This study was based on previously reported work that refined the ultrasonic elasticity technique for use with small specimens (<1.0 mm) and determined that the administration of rhGH can counter the degenerative effects produced by hormone-suppressed downregulation on the elastic and physicochemical characteristics of cortical bone. Ultrasonic wave propagation and density measurements were used previously to determine the three-dimensional (orthotropic) material properties of rat femoral cortical bone. X-ray powder diffraction, microscopic, morphometric, and biochemical analysis techniques have been used to describe physicochemical properties, including mineral crystal size, cortical porosity, mineral and nonmineral content, and microstructural characteristics. In this study, mathematical relationships between the local physicochemical (independent variable) and elastic (dependent variable) properties were formulated via linear and nonlinear regression analyses. In general, apparent density was found to have the highest level of correlation with most of the longitudinal and shear moduli (R(2) = 0.300 to 0.800). Concomitantly, mineral crystal width and cortical porosity offered the best correlations with the Poisson's ratios (R(2) up to 0.600). Wilcoxon t tests verified a significant decrease in the elastic properties in dwarf rat cortical bone after rhGH treatments (p < 0.05). Physicochemical measures of bone quality (density, crystal size) generally decreased while measures of bone quantity (cortical area, moments of inertia) generally increased (p < 0.05) after rhGH treatments. Some mineral and nonmineral properties were unchanged. This study presents a quantifiable link between cortical bone elasticity and its composite construction as measured across two dramatically different experimental groups.

Animals↗
PubMed1998

Cortical bone responses to 2G hypergravity in growing rats.

BACKGROUND: Rat cortical bone adaptation to chronic hypergravity (2G) was studied using young growing male Wistar rats (60 d). METHODS: Animals (10 rats) were subjected to chronic hypergravity (14 d) in order to understand the plastic nature of bone under a constant hypergravity stress using a special rodent habitat that was attached to a 12-ft. radius centrifuge. Also, an equal number of stationary controls were housed in a rodent vivarium containing identical cages that were used for centrifugation. After 14 d of centrifugation, femur bones were excised and prepared for morphological and biochemical measurements. RESULTS: Results showed that 2G had significantly shortened the femurs (3%) and reduced the cortical bone area (13%). In particular, hypergravity induced significant reductions in the thicknesses of cortical bone at the anterior (13%) and medial regions (15%) of the mid-diaphysis. However, femoral bone density, collagen and calcium concentrations were unaltered. The content of mature, stable bone collagen cross-links hydroxylysylpyridinoline (HP), lysylpyridinoline (LP), were significantly greater in bones from centrifuged animals. CONCLUSION: Our findings suggest that short term exposure to 2G does not enhance bone formation or induce changes in cortical bone composition, or alter specific gravity. These data also suggest that bone maturation as reflected by collagen cross-linking is upregulated. However, it is undetermined at this time whether the enhanced content of mature bone collagen in the centrifuged rats is a result of either an increased rate of cross-linking or reduction in the degradation of "older collagen."

Adaptation, Physiological↗
PubMed1997

Assessment of disseminated pancreatic cancer: a comparison of traditional exploratory laparotomy and radioimmunoguided surgery.

BACKGROUND: After curative resection for pancreatic cancer, only 10% of patients survive disease for 5 years. These dismal results suggest the presence of occult tumor at the time of initial operation. This phase I/II study was conducted to compare traditional exploratory laparotomy with radioimmunoguided surgery (RIGS) in the assessment of disseminated pancreatic cancer. METHODS: Ten patients with the diagnosis of adenocarcinoma of the pancreas were injected intravenously with 1 mg CC49 monoclonal antibody radiolabeled with 2 mCi iodine 125. All patients were evaluated by a standard abdominal exploration followed by RIGS. Tumor identified by each technique was documented and categorized as neoplasm disseminated to viscera or lymphatics. RESULTS: There were 25 visceral sites of disease that were traditionally discovered at the time of exploration including pancreas, omentum, small bowel, pelvis, liver, and other. All 25 sites of disease were positive by RIGS plus an additional four sites of visceral tumor for a total of 29 RIGS positive sites of disease. Six lymphatic sites of disease were discovered by traditional examination; however, 44 sites of lymphatic sites were documented by RIGS (p < 0.001). In addition, nine traditionally and pathologically negative/RIGS positive nodes were subjected to cytokeratin and MOC 31 immunohistochemistry. Six of nine nodes were positive by cytokeratin immunohistochemistry, and five of the six cytokeratin positive nodes were MOC 31 positive. CONCLUSIONS: These data suggest that the RIGS technique detected significantly more foci of visceral spread of tumor than traditional exploratory laparotomy and significantly more sites of lymphatic dissemination were identified by RIGS than by standard exploration.

Adenocarcinoma↗
PubMed1996

Disseminated neuroblastoma in the nude rat. A xenograft model of human malignancy.

BACKGROUND: The overall survival of children with neuroblastoma remains less than 30% due to disease dissemination at the time of diagnosis. An animal model of neuroblastoma, with characteristics similar to those observed clinically in children, would be beneficial to investigations into the diverse biology of this tumor. The purpose of this study was (1) to develop a model of disseminated neuroblastoma in the nude rat by intracardiac injection of neuroblastoma cells derived from cell lines with different N-myc copy numbers; (2) to investigate the effect of age on tumor growth and dissemination; and (3) to assess progression of disease radiologically and correlate with autopsy findings. METHODS: Nude rats (n = 38), 5-13 weeks of age, underwent intracardiac injection of the human neuroblastoma cell lines IMR-32 with amplified N-myc oncogene and SKNSH with 1 N-myc copy. The animals were observed for at least six weeks for the development of tumor. Twelve rodents injected with IMR-32 cells underwent imaging studies including magnetic resonance imaging (MRI), skeletal radiographs, and indium-111(IN-111)-diethylenetriamine penta-acetic acid-D-Phe1-octreotide scintigraphy. Autopsies with standardized microscopic examinations were performed on all animals. RESULTS: Most of the nude rats (95%) developed neuroblastoma following intracardiac injection of neoplastic cells. Disseminated tumor was evident in 66% of animals. Anatomic sites of neuroblastoma growth were similar to those observed clinically in children, including adrenal glands, paraspinal ganglia, bone, bone marrow, and skin, but no tumor was identified in the liver. Disseminated disease occurred in more animals injected with IMR-32 (78% of animals) than with SKNSH cells (34% of animals) (P < 0.05). Tumor spread appeared to be age dependent; only rodents 5-8 weeks old at the time of injection developed disseminated disease when compared with animals 9 weeks of age or older (P < 0.0001). Radioreceptor scintigraphy demonstrated only pericardial tumor; MRI identified pericardial, adrenal gland, and subcutaneous neoplasms; only skeletal radiographs detected neuroblastoma in cortical bone. CONCLUSIONS: (1) Following intracardiac injection of human neuroblastoma cell lines into nude rats, a xenograft model of disseminated disease develops that closely parallels the malignant process in children. (2) Tumor dissemination is associated with the cell line that demonstrates N-myc amplification and with young age of the recipient at the time of injection. (3) Tumor growth and dissemination may be assessed radiologically. (4) This model of human malignancy may offer an opportunity to investigate the pathophysiologic mechanisms underlying tumor development and dissemination in advanced stage neuroblastoma.

Age Factors↗
PubMed1996

Cortical bone growth and maturational changes in dwarf rats induced by recombinant human growth hormone.

The growth hormone (GH)-deficient dwarf rat was used to investigate recombinant human (rh) GH-induced bone formation and to determine whether rhGH facilitates simultaneous increases in bone formation and bone maturation during rapid growth. Twenty dwarf rats, 37 days of age, were randomly assigned to dwarf plus rhGH (GH; n = 10) and dwarf plus vehicle (n = 10) groups. The GH group received 1.25 mg rhGH/kg body wt two times daily for 14 days. Biochemical, morphological, and X-ray diffraction measurements were performed on the femur middiaphysis. rhGH stimulated new bone growth in the GH group, as demonstrated by significant increases (P < 0.05) in longitudinal bone length (6%), middiaphyseal cross-sectional area (20%), and the amount of newly accreted bone collagen (28%) in the total pool of middiaphyseal bone collagen. Cortical bone density, mean hydroxyapatite crystal size, and the calcium and collagen contents (microgram/mm3) were significantly smaller in the GH group (P < 0.05). Our findings suggest that the processes regulating new collagen accretion, bone collagen maturation, and mean hydroxyapatite crystal size may be independently regulated during rapid growth.

Animals↗
PubMed1995

Identification of functional insulin-like growth factor-II/mannose-6-phosphate receptors in isolated bone cells.

The role of the IGF-II/cation independent mannose-6-phosphate (IGF-II/M6P) receptor in the transduction of cellular effects evoked by IGF-II has been extensively debated in the literature. Many reports suggest that IGF-II transduces its effects through the IGF-I receptor, while others show that IGF-II utilizes the type II receptor to affect cellular activity. This study 1) verifies the presence of the IGF-II/M6P receptor in rat calvarial osteoblasts, and 2) evaluates the ability of the receptor to initiate intracellular signals. Using conventional receptor binding assays, it was found that osteoblasts bind IGF-II with high affinity. Scatchard analyses indicated that there are 5.08 x 10(4) IGF-II/M6P receptors per osteoblast with a Kd near 2.0 nM). The receptor protein was further identified by cross-linking with 125I-IGF-II. Northern analysis was used to identify an mRNA transcript for the IGF-II/M6P receptor protein. To examine if the IGF-II/M6P receptor can initiate second messenger signals, the ability of IGF-II to evoke Ca2+ transients was evaluated. Osteoblasts pretreated with IGF-I did not lose their ability to respond to IGF-II. Further, a polyclonal antibody against the rat IGF-II/M6P receptor (R-II-PAB1) 1) was able to evoke its own Ca2+ response, and 2) was able to block the generation of Ca2+ transients caused by IGF-II. The data in this report show that the osteoblastic Ca2+ response to IGF-II appears to be caused by an intracellular release of Ca2+ which is mediated by the IGF-II/M6P receptor making it possible to envision how the receptor may be an important modulator of osteoblast mediated osteogenesis.

Animals↗
PubMed1995

Intraoperative detection and resection of occult neuroblastoma: a technique exploiting somatostatin receptor expression.

Tumor cell expression of specific high-affinity somatostatin receptors has been associated with a favorable prognosis in children with neuroblastoma. The purpose of this study was (1) to document intraoperatively the in vivo binding of the somatostatin analogue 125I-tyr3-octreotide to high-affinity somatostatin receptors expressed on human neuroblastoma, using a hand-held gamma detector; (2) to determine whether gamma-probe detection of radioligand binding to tumor receptors could identify occult malignancy; and (3) to determine the safety and biodistribution of 125I-tyr3-octreotide in children. Six children with stage III or IV neuroblastoma received an intravenous injection of 125I-tyr3-octreotide and underwent operative exploration using gamma-probe detection of radioligand binding to tumor somatostatin receptors. Tissue that demonstrated in vivo binding of 125I-tyr3-octreotide, or that was suspicious for tumor, was extirpated and analyzed by histopathology, immunohistochemistry, and microautoradiography. The biodistribution of 125I-tyr3-octreotide was recorded intraoperatively over time. Tumor tissue from each child also was assayed in vitro for somatostatin receptor expression by competitive binding studies using 125I-tyr3-octreotide. In vivo binding of 125I-tyr3-octreotide to malignant tissue was documented in the five children with a known tumor burden. Seventeen sites of radioreceptor binding were amenable to resection. Histopathological analysis confirmed neuroblastoma in 15 of these specimens. Four of the 15 proven tumor foci were occult malignancies. Every site of histologically proven neuroblastoma demonstrated in vivo binding of 125I-tyr3-octreotide. Five of seven sites histologically negative for neuroblastoma also were negative for in vivo radioreceptor binding. Microautoradiography confirmed in vivo binding of 125I-tyr3-octreotide to tumor cells. Uptake of 125I-tyr3-octreotide in abdominal organs occurred within 15 minutes of injection, was highest in the liver and gallbladder, and decreased over 24 hours. The conclusions were as follows. (1) 125I-tyr3-octreotide binds, in vivo, to somatostatin receptors on neuroblastoma, with 100% sensitivity and 71% specificity. (2) Occult neuroblastoma is found through gamma-probe detection of radioligand binding to receptors. (2) The biodistribution of 125I-tyr3-octreotide reflects the hepatobiliary clearance of this radionuclide. (4) Radioreceptor-guided surgery may safely provide more complete operative staging and cytoreduction of neuroblastoma.

Biomarkers, Tumor↗
PubMed1995

Intraoperative identification of parathyroid gland pathology: a new approach.

Technetium 99m-sestamibi, a radiopharmaceutical used for the diagnostic imaging of abnormal parathyroid tissue, and the Neoprobe 1000, a hand-held, gamma-detecting probe, were used concurrently, during surgical exploration, in three children with hyperparathyroidism. This novel combination assisted with the identification of an ectopic mediastinal parathyroid adenoma and with the localization of multiple hyperplastic parathyroid glands. 99mTc-sestamibi combined with the Neoprobe 1000 may prove to be a useful adjunctive technique for the intraoperative localization of abnormal parathyroid tissue in selected patients.

Adenoma↗
PubMed1995

Changes in diaphragm muscle collagen gene expression after acute unilateral denervation.

The purpose of the present study was to examine the effects of acute (3 days) unilateral diaphragm denervation (DNV) on 1) levels of alpha 1(I) and alpha 1(III) procollagen mRNA; 2) collagen concentration [hydroxyproline (HYP)]; 3) amount of the nonreducible collagen cross-link hydroxylysylpyridinoline (HP); and 4) the passive force-length relationship of the muscle. The levels of alpha 1(I) and alpha 1(III) procollagen mRNA, HYP concentration, and amount of HP were measured in muscle segments from the midcostal region of DNV and intact (INT) hemidiaphragms of adult male Fischer 344 rats (250-300 g). The in vitro passive force-length relationship of DNV and INT hemidiaphragm was determined by lengthening and shortening the diaphragm muscle segments from 85 to 115% of optimal length at a constant velocity (0.6 optimal length/s). Three days after DNV, the level of alpha 1(I) procollagen mRNA was increased over 15-fold in the DNV hemidiaphragm compared with INT (P < 0.05), whereas the level of alpha 1(III) procollagen mRNA was increased by approximately sixfold in the DNV hemidiaphragm compared with INT (P < 0.05). Collagen (HYP) concentration did not differ between groups, averaging 8.7 and 8.9 micrograms/mg dry wt for the DNV and INT hemidiaphragms, respectively. In addition, there was no difference in the amount of the mature nonreducible collagen cross-link HP between the DNV and INT hemidiaphragms (0.66 vs. 0.76 mole HP/mole collagen, respectively). The amount of passive force developed during lengthening did not differ between DNV and INT hemidiaphragms. These data indicate that acute DNV of the hemidiaphragm is associated with an increase in the mRNA level of the two principal fibrillar collagen phenotypes in skeletal muscle. However, despite extensive muscle remodeling, the passive force-length relationship of the DNV hemidiaphragm is unaffected compared with the INT muscle.

Amino Acids↗
PubMed1994

Passive length-force properties of senescent diaphragm: relationship with collagen characteristics.

The purpose of this study was to examine the effect of aging on collagen concentration and extent of nonreducible collagen cross-linking as well as with the passive length-force relationship of the diaphragm muscle. Midcostal diaphragm muscle strips from young (6 mo) and senescent (24 mo) Fischer 344 rats were perfused in a tissue bath containing mammalian Ringers solution (25 degrees C) aerated with 95% O2-5% CO2. The segments were lengthened and shortened from 85 to 115% of optimal length (L(o)) at a constant velocity (0.6 L(o)/s), and the passive force was measured. Hydroxyproline (HYP) and the mature nonreducible collagen cross-link, hydroxylysylpyridinoline (HP), were measured by high-pressure liquid chromatography. The resting force at Lo did not differ between young and senescent diaphragm muscles. However, the senescent diaphragm exhibited greater passive force compared with the young (P < 0.05) at lengths > 110% of L(o). High-pressure liquid chromatography analysis revealed a higher concentration of HYP in the senescent compared with the young diaphragm (9.32 +/- 0.83 and 6.59 +/- 0.78 g HYP/mg dry wt, respectively; P < 0.05). Additionally, the content of HP was greater in the senescent compared with the young diaphragm (1.16 +/- 0.05 and 0.91 +/- 0.05 mol HP/mol collagen, respectively; P < 0.05). These results suggest that diaphragm collagen metabolism, maturation, and the passive length-force characteristics of the muscle are altered with senescence.

Aging↗
PubMed1993

The presence of lysylpyridinoline in the hypertrophic cartilage of newly hatched chicks.

The presence of lysylpyridinoline (LP) as a nonreducible cross-link in appreciable quantities has primarily been limited to the mineralized tissues, bone and dentin. However, the results reported here show that LP is not only present in the hypertrophic cartilage of the tibiotarsus isolated from newly hatched broiler chicks, but it is approx. 4-fold as concentrated as hydroxylysylpyridinoline (HP). Bone and articular cartilage surrounding the hypertrophic cartilage do not contain measurable quantities of LP. Purified LP has a fluorescent scan similar to purified HP and literature values, confirming that we indeed were measuring LP. Also, the cartilage lesion produced by immature chondrocytes from birds with tibial dyschondroplasia had LP but the HP:LP ratio was > 1. Thus, the low HP:LP ratio could be a marker for hypertrophic cartilage in avians.

Amino Acids↗
PubMed1993

Interstitial space and collagen alterations of the developing rat diaphragm.

The effect of growth on the relative interstitial space [%total cross-sectional area (CSA)] and collagen content of the rat diaphragm muscle was examined at postnatal ages of 0, 7, 14, and 21 days as well as in adult males. The proportion of interstitial space relative to total muscle CSA was determined by computerized image analysis of lectin-stained cross sections of diaphragm muscle. To assess collagen content and extent of collagen maturation (i.e., cross-linking), high-pressure liquid chromatography analysis was used to measure hydroxyproline concentration and the nonreducible collagen cross-link hydroxylysylpyridinoline (HP), respectively. At birth, interstitial space accounted for approximately 47% of total diaphragm muscle CSA. During postnatal growth, the relative contribution of interstitial space decreased such that by adulthood the interstitial space accounted for approximately 18% of total muscle CSA. The change in relative interstitial space occurred without a concomitant change in hydroxyproline concentration. However, the concentration of HP markedly increased with age such that the adult diaphragm contained approximately 17 times more HP than at birth. These results indicate that during development the relative CSA occupied by interstitial space decreases as muscle fiber size increases. However, the reduction in relative interstitial space is not associated with a change in collagen concentration. Thus collagen density in the interstitial space may increase with age. It is possible that the observed changes in relative interstitial space and collagen influence the passive length-force properties of the diaphragm.

Animals↗
PubMed1992

Reversible achalasia-like motor pattern of esophageal body secondary to postoperative stricture of gastroesophageal junction.

Two cases are presented of benign stenosis of the cardia secondary to fibrosis following antireflux surgery in which the patients developed a motor alteration in the esophageal body similar to that of achalasia of the cardia. There was a complete absence of contractions in one patient, which had developed over a long period of time, and a vigorous pattern in the other patient, which had evolved over a short period. In both cases, after surgical treatment of the stenosis, normal motility in the esophageal body returned.

Adult↗
PubMed1992

Sequelae of antireflux surgery in profoundly disabled children.

Between 1976 and 1989 an antireflux operation (193 Nissen; 5 Thal) was performed in 198 children with profound neurological impairment (NI). Etiology of the NI was a syndrome in 24%, congenital in 30%, and acquired in 46%. The most frequent symptoms of gastroesophageal reflux (GER), vomiting and pneumonia, were significantly reduced (P less than .05) after the antireflux operation. Postoperatively, 141 children (71%) developed return of one or more symptoms that had been preoperatively associated with GER, whereas 57 patients (29%) remained asymptomatic. Of the children with symptoms, 86 (61%) underwent diagnostic testing to exclude recurrent GER and 55 (39%) had no diagnostic evaluation. Recurrent GER was documented in 31 patients and a mechanical problem with the fundoplication in 18 children, an operative failure rate of 25%. The symptom-free interval following the antireflux operation averaged 11 months postoperatively; return of symptoms showed no statistical relationship to the etiology of NI, presence of seizures, or degree of muscle tone. The majority of children required multiple outpatient or emergency department visits for evaluation of these symptoms or assessment of gastrostomy tube problems. Survival of all children was 71% at an average postoperative follow-up of 3.5 years.

Adolescent↗
PubMed1992

Recognition of recurrent gastroesophageal reflux following antireflux surgery in the neurologically disabled child: high index of suspicion and definitive evaluation.

Multiple symptoms suggestive of gastroesophageal reflux (GER) developed in 181 of 240 children (75%) with profound neurological impairment (NI) following operative management of GER. Diagnostic testing was performed in 102 children, 56% of patients with symptoms. Recurrent GER was evident on one or more diagnostic studies in 46% of children evaluated. Significant differences (P less than .05) were found in the testing protocols of children with studies positive for GER and those individuals with negative tests. Children with study-documented recurrent GER: (1) had testing conducted at a more remote time postoperatively; (2) received a greater number of total tests; (3) were evaluated by more than one type of diagnostic test; and (4) underwent upper endoscopy and pH monitoring more frequently. No single clinical symptom was predictive of study-documented recurrent GER. These results suggest that recognition of recurrent GER after an antireflux operation in a child with profound NI requires a high index of suspicion. Definitive evaluation of children with postoperative symptoms demands repeated testing over time and the use of more than one type of diagnostic test. A contrast study should be used to evaluate the mechanical properties of the fundoplication and esophagoscopy and/or esophageal pH monitoring to assess the physiological control of GER.

Child↗
PubMed1992

Resection of the primary tumor is appropriate for children with stage IV-S neuroblastoma: an analysis of 37 patients.

Current recommendations for treatment of children with IV-S neuroblastoma (NB) indicate that "supportive care is the cornerstone of therapy" and resection of the primary tumor is not mandated. The presentation and clinical management of 37 IV-S NB patients from three pediatric oncology centers were retrospectively reviewed. The 22 boys and 15 girls presented at an average age of 107 days (range, 4 to 616 days). Primary tumor sites were identified in the adrenal gland in 19 children, the thorax in 5, the retroperitoneum in 4, and 1 each in the pelvis and kidney. At the time of presentation, metastatic disease was documented in the liver (27), bone marrow (19), skin (7), and regional lymph nodes (7). Massive hepatomegaly (below the umbilicus) was demonstrated in 18 patients. Twenty-eight children (76%) have survived on average 90 months following diagnosis. Eight patients (22%) died; six of disease and two of complications of therapy (mean, 9.6 months). One child was lost to follow-up. Only 3 of the 37 patients (8%) were managed solely by supportive care and all are alive. Extirpation of the primary tumor was accomplished in 24 individuals (65%). Twenty patients underwent excision at diagnosis and four had delayed resection with few postoperative complications and no deaths related to resection. One death resulted from progression of disease in a child who had tumor removal. Chemotherapy as a single treatment or in combination with radiation was used in 10 children with three children surviving (30%).(ABSTRACT TRUNCATED AT 250 WORDS)

Female↗
PubMed1992

Adaptations of young adult rat cortical bone to 14 days of spaceflight.

To determine whether mature humeral cortical bone would be modified significantly by an acute exposure to weightlessness, adult rats (110 days old) were subjected to 14 days of microgravity on the COSMOS 2044 biosatellite. There were no significant changes in peak force, stiffness, energy to failure, and displacement at failure in the flight rats compared with ground-based controls. Concentrations and contents of hydroxyproline, calcium, and mature stable hydroxylysylpyridinoline and lysylpyridinoline collagen cross-links remained unchanged after spaceflight. Bone lengths, cortical and endosteal areas, and regional thicknesses showed no significant differences between flight animals and ground controls. Our findings suggest that responsiveness of cortical bone to microgravity is less pronounced in adult rats than in previous spaceflight experiments in which young growing animals were used. We hypothesize that 14 days of spaceflight may not be sufficient to impact the biochemical and biomechanical properties of cortical bone in the mature rat skeleton.

Adaptation, Physiological↗