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Biomedical subjects

D D Lee

Publications and source records attributed to D D Lee.

At least 37 records · Page 2Linked to original sources

alpha-BSM: a biomimetic bone substitute and drug delivery vehicle.

alpha-BSM is a biomimetic endothermically setting apatitic calcium phosphate bone substitute material. Its injectability and ability to harden at body temperature in the presence of physiologic saline, and other buffering agents, makes it an attractive clinical bone substitute and delivery vehicle for therapeutic agents in orthopaedic and dental applications. In osseous tissue, alpha-BSM alone remodels into bone and promotes bone healing. alpha-BSM treatment has been shown in several animal models to be effective in promoting healing of surgically created critical size defects and restoring bone biomechanical strength to values equal to or greater than values achieved with autograft controls. In vitro studies with alpha-BSM containing gentamicin show that antibiotics can be incorporated stably into alpha-BSM and that the release kinetics can be controlled with the appropriate formulation and preparative procedures. Growth factors and enzymes also are compatible with the alpha-BSM setting reaction. The incorporation of recombinant human bone morphogenetic protein-2 with alpha-BSM was shown to be effective in stimulating bone formation and accelerating restoration of the differentiated phenotype in an osteotomy model. Clinical trial investigators in Europe currently are using alpha-BSM implantations for treatment of fractures and other indications.

Animals↗

Resorbable calcium phosphate bone substitute.

The in vitro and in vivo properties of a novel, fully resorbable, apatitic calcium phosphate bone substitute (ABS) are described. The ABS was prepared from calcium phosphate precursors that were hydrated to form an injectable paste that hardens endothermically at 37 degrees C to form a poorly crystalline apatitic calcium phosphate (PCA). The PCA reaction product is stable in vivo as determined by FTIR and XRD analysis of rabbit intramuscular implants of ABS retrieved 4, 7, and 14 days postimplantation. Bone formation and resorption characteristics of the ABS material were characterized in a canine femoral slot defect model. Femoral slot defects in dogs were filled with either autologous bone implants or the ABS material. Sections of femoral bone defect site from animals sacrificed at 3, 4, 12, 26, and 52 weeks demonstrated that new bone formation proceeded similarly in both autograft and ABS filled slots. Defects receiving either material were filled with trabecular bone in the first 3 to 4 weeks after implantation; lamellar or cortical bone formation was well established by week 12. New bone formation in ABS filled defects followed a time course comparable to autologous bone graft filled defects. Histomorphometric evaluation of ABS resorption and new bone formation indicated that the ABS material was greater than 99% resorbed within 26 weeks; residual ABS occupied 0.36+/-0.36% (SEM, n = 4) of the original defect area at 26 weeks. Quantitatively and qualitatively, the autograft and ABS were associated with similar new bone growth and defect filling characteristics.

Animals↗

Dermatopathologic findings in 20 cases of systemic amyloidosis.

The clinical findings of systemic amyloidosis are often variable and nonspecific. The early recognition of this disorder relies upon clinical suspicion, and definite diagnosis requires the confirmation of amyloid deposits in tissue. We reviewed 31 skin biopsy specimens from 20 patients, including 17 with amyloid light chain (AL) protein amyloidosis and 3 with serum amyloid A (AA) protein amyloidosis. Histologically, amyloid can be present in the papillary dermis, reticular dermis, subcutis, around the appendages, and in or around blood vessels. In our series, all 20 patients had at least one positive skin biopsy. Amyloid was found in 30 of 31 specimens (97%), a higher rate than in most series. Skin biopsy is a simple, safe procedure with high yield and may be used to obtain a firm diagnosis of systemic amyloidosis.

Aged↗

General principles of anesthesia and sedation in food animals.

Minimal-risk anesthesia practice demands that fundamental physiologic and pharmacologic principles be applied to the specific medical and surgical needs of individual patients. In developing an anesthesia plan for a patient, health status must be assessed and considered along with other extrinsic factors such as the physical setting in which the anesthetic procedure will be performed, the availability of equipment and supplies, and the academic and technical training and abilities of participating personnel. This article reviews considerations for developing anesthesia protocols for ruminant and swine species.

Anesthesia↗

Genetic heterogeneity of familial primary cutaneous amyloidosis: lack of evidence for linkage with the chromosome 10 pericentromeric region in Chinese families.

Primary cutaneous amyloidosis is a relatively common skin disease in Southeast Asia, South America, and the Republic of China. Although most cases are sporadic, some patients have a family history, suggesting that genetic factors may play a role in its pathogenesis. Some patients with multiple endocrine neoplasia type 2A also have a clinical picture of primary cutaneous amyloidosis. It is thus suggested that the gene of familial primary cutaneous amyloidosis is linked to the pericentromeric region of chromosome 10, the location of the RET proto-oncogene. We have carried out linkage analysis in seven families with cutaneous amyloidosis using four dinucleotide repeat markers from the RET region. Negative lod scores at all recombination frequencies were obtained. We thus conclude that there is no evidence for linkage between Chinese families with primary cutaneous amyloidosis and the pericentromeric region of chromosome 10. The distinct genetic basis, plus their apparent phenotypic differences in sex ratio, age of onset, and sites of cutaneous lesions, suggests that familial primary cutaneous amyloidosis includes clinical subtypes attributable to genetic heterogeneity.

Adolescent↗

Systemic amyloidosis with initial polyneuropathy.

We report a case of systemic amyloidosis with the initial sign of polyneuropathy. The patient eventually developed heart failure, macroglossia, and ecchymoses 6 years later. Biopsies from the sural nerve and normal-looking skin both proved the existence of amyloid.

Aged↗

Increased blood pressure and neural tone in the silent ischemia of hypertension: disparate effects of immediate release nifedipine.

OBJECTIVES: The aims of this study were 1) to evaluate the role of blood pressure and associated neural tonicity in ambient ischemia of a group of hypertensive patients with stable angina, and 2) to determine the efficacy of immediate release nifedipine therapy in controlling the total ischemic burden in both office-measured and ambulatory blood pressure. BACKGROUND: Low heart rate ischemia, as detected by Holter ambulatory electrocardiographic monitoring, suggests that reduced coronary flow is the major factor leading to ischemia. We previously found that 91% of the ischemic episodes in our hypertensive patients with stable angina were silent. METHODS: We measured plasma norepinephrine content during ischemic events from blood obtained from automatic pump withdrawal with the assistance of a real-time ST segment depression monitor. We then related the norepinephrine content to ischemic episodes assessed by 48-h Holter recording, blood pressure reading by ambulatory blood pressure monitoring and patients' diaries. Measurements were taken during the placebo period and immediate-release nifedipine therapy in 30 hypertensive patients (20 with and 10 without stable angina). RESULTS: More than half of the patients had ischemic episodes; 95% of these were silent. Ischemic episodes peaked in the early morning, and 55% occurred during routine sedentary activities. There was a 10% to 15% increase in heart rate at the onset of ischemia associated with a 30% higher plasma norepinephrine level. Seventy-five percent of patients had increased norepinephrine after nifedipine therapy. Nifedipine therapy controlled measured blood pressure but not 24-h ambulatory blood pressure. Ischemic episodes were reduced only in patients whose ambulatory blood pressure was controlled. CONCLUSIONS: The results suggest that increased neural tone at the time of the ischemic event may play a role in reducing coronary perfusion leading to silent ischemia. Nifedipine therapy (immediate release) was effective in control of ischemia only when both ambulatory and office-measured blood pressure were controlled.

Activities of Daily Living↗

KONCPA: a new method for diagnosing tinea unguium.

Tinea unguium (TU) is very common in tropical and subtropical regions. An inexpensive, quick and sensitive test is essential for screening the nail specimens. We investigated if a test using potassium hydroxide (KOH)-treated nail clippings, which were then crushed and stained with periodic acid-Schiff (PAS), could be useful for diagnosing TU. The new method (abbreviated as KONCPA) was proved to be more fruitful to identify fungal hyphae in comparison with conventional KOH nail scraping preparation, histopathologic examination and fungal culture. The positive rates of each method were 77, 44, 60 and 16%, respectively. All 10 KONCPA-negative nails failed to show fungus by the other three methods. The KONCPA slides can be permanently stored as records. In addition, we also found that treatment of nail specimens in 20% KOH at 56 degrees C for 10 min prior to histopathologic processing is a simple method to soften the nail plate.

Humans↗

Altered sympathetic tone in hypertensives with angina and lowered threshold for pacing ischemia.

To determine the role of the sympathetic nervous system in myocardial ischemia with essential hypertension, plasma norepinephrine, heart rate (HR), blood pressure (BP), and the HR.BP double product at the time of silent ischemia during pacing and exercise treadmill test (ETT) were compared with basal values in 20 patients with sustained essential hypertension and stable angina, 3 to 60 days (12.6 +/- 11.6) after discontinuation of all antihypertensive and coronary vasodilator therapy. Group I (N = 6) had silent ischemia with a higher HR.BP product at ETT than at pacing (ratio = 157 +/- 10.4% [+/- SD] v a value in group II [N = 5] of 102 +/- 18.8 [P less than .01]. Group III (N = 9) had no silent ischemia at ETT or pacing. Group I v group II plasma norepinephrine levels at rest and with pacing silent ischemia were 76 +/- 37 v 138 +/- 36 pg/mL, P less than .02, and 101 +/- 50 v 230 +/- 43 pg/mL, P less than .01, respectively. In groups I and II plasma norepinephrine levels were significantly lower than those of group III. Eleven of 20 patients had ischemia on pacing or ETT. Left ventricular myocardial mass were greater (224 +/- 49 v 180 +/- 28 g, p less than .05), HR (67 +/- 13 v 76 +/- 11 beats/min, P = NS) and plasma norepinephrine levels at rest (104 +/- 47 v 241 +/- 99 pg/mL, P less than .01), pacing (160 +/- 81 v 338 +/- 94 pg/mL, P less than .01), and ETT (758 +/- 268 v 1203 +/- 611 pg/mL, P less than .05), were lower in patients with ischemia (N = 11, group II) than in patients without ischemia (N = 9, group III) on pacing or ETT. Eight patients were on reserpine prestudy; reserpine prestudy was associated with lower basal HR (63 +/- 9 v 76 +/- 12 beats/min, P less than .05) and plasma norepinephrine (106 +/- 48 v 169 +/- pg/mL, P less than .07) and greater ratio of HR.BP double product on ETT/pacing, (141 +/- 33 v 111 +/- 19, P less than .02). The sympathetic nervous tone of group I was low at baseline but there may have been raised alpha/beta-receptor responsiveness to laboratory stresses with concomitant micro/macrovascular constriction at higher oxygen demand.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗

Three-dimensional spatial relationship between the collagen fibrils and the inorganic calcium phosphate crystals of pickerel (Americanus americanus) and herring (Clupea harengus) bone.

High-voltage (1.0 MV) electron microscopy and stereomicroscopy, electron probe microanalysis, electron diffraction and three-dimensional computer reconstruction, have been used to examine the spatial relationship between the inorganic crystals of calcium phosphate and the collagen fibrils of pickerel and herring bone. High-voltage stereo electron-micrographs were obtained of cross-sections of the cylinder-shaped intramuscular bones in uncalcified regions, in regions where only one or only several crystals had been deposited in some of the fibrils, and in successive sections containing progressively more mineral crystals until the stage of full mineralization was reached. High-resolution electron probe microanalysis confirmed that the electron-dense particles contained calcium and phosphorus. In the earliest stages of mineralization and progressing throughout the mineralization process, the crystals are located only within the collagen fibrils; crystals are not observed free in the extracellular spaces between collagen fibrils. The progressive increase in the mass of mineral deposited in the bone tissue with time occurs, essentially, completely within the collagen fibrils including the stage of full mineralization. At this stage, cross-sectional profiles of collagen fibrils are completely obliterated by mineral. A small number of crystals that are located on or close to the surface of the fibrils appear to extend a very short distance into the spaces between the fibrils. These ultrastructural observations of the very onset of calcification in which nucleation of the calcium phosphate crystals is clearly shown to begin within specific volumes of collagen fibrils, and of the subsequent temporal and spatial sequences of this phenomenon, which shows that calcification continues wholly within the collagen fibrils until maximum calcification is achieved, add important information on the basic physical chemical mechanism of the calcification and the structural elements that are involved. The spatial and temporal independence of the sites where mineralization is initiated establishes that such ultrastructural locations within individual collagen fibrils represent independent, physical chemical nucleation loci. The findings are totally inconsistent with the proposal that crystals must first be deposited in matrix vesicles, or other components such as mitochondria, and subsequently released and propagated in the interfibrillar space, until they eventually reach and impregnate the hole zone regions of the collagen fibrils. Three-dimensional computer reconstruction of serial transverse and longitudinal sections demonstrates periodic swellings along the collagen fibrils, corresponding to the hole zone region of their axial period as mineralization proceeds.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Blood pressure reactivity and sympathetic hyperactivity. Predictors of hypertension.

Raised sympathetic nerve activity appears to be a predictor and factor in primary hypertension. Sympathetic activation alone does not appear to be a sufficient cause of sustained hypertension, however. Over the past two decades we have studied several populations of primary hypertensive patients and found neural hyperactivity in 25 to 30% of them. Metaanalyses of other studies have supported these findings.

Blood Pressure↗

Noradrenergic activity and silent ischaemia in hypertensive patients with stable angina: effect of metoprolol.

30 patients (10 normotensive, 20 hypertensive) with stable angina and positive treadmill exercise tests entered a double-blind, placebo-controlled crossover trial of metoprolol, 100 mg twice daily. At the end of each treatment phase, blood pressure was monitored for 24 h and Holter and real-time electrocardiographic (ECG) monitoring were carried out and an activity diary kept for 48 h. Blood samples for catecholamine measurement were taken after 30 min supine, 60 min standing, and at the first silent ischaemic event, triggered by the real-time ECG monitor, by means of an ambulatory blood withdrawal pump. Metoprolol lowered blood pressure and heart rate in both normotensive and hypertensive subjects, and reduced the frequency and duration of silent ischaemic episodes in hypertensive subjects. Plasma noradrenaline measured during silent ischaemia while the patients were resting was significantly higher than the control supine level without ischaemia. These findings suggest that noradrenergic hyperactivity may have a role in coronary vasoconstriction and that treatment which neutralizes sympathetic tone may be especially beneficial in treatment of silent ischaemia in hypertensive patients.

Angina Pectoris↗

Plasma norepinephrine in Chagas' cardioneuromyopathy: a marker of progressive dysautonomia.

Chronic Chagas' disease produces pathologic changes of the cardiovascular, digestive, and autonomic nervous systems. In an attempt to elucidate the nature of the dysautonomia in patients with Chagas' disease, we measured plasma norepinephrine levels, blood pressure, and heart rate, both supine and standing in 26 patients, and compared these values of patients classified according to three clinical subsets of cardiovascular manifestations with the values of nine normal volunteers and 16 patients with nonchagasic heart failure. Results suggested (1) progressive blockade of the alpha receptor in patients with Chagas' disease who have minimal clinical symptoms (group I) and in those who have ECG alterations without congestive symptoms (group II), as reflected by normal or raised plasma norepinephrine levels without change of diastolic blood pressure during standing, which indicates absent postural reflexes; and (2) blockade associated with partial denervation in patients with Chagas' disease who have class III or IV heart failure (group III), as suggested by a lower supine plasma norepinephrine level and a fall in diastolic blood pressure in the upright position. The findings of reduced plasma norepinephrine levels are in contrast to the elevated plasma norepinephrine levels in patients without Chagas' disease with class III and IV heart failure who have sympathetic hyperactivity.

Adult↗

The effect of substrate composition and condition on resorption by isolated osteoclasts.

Osteoclasts isolated from 10-day-old rabbits were studied in a cell culture system to obtain further insight into the possible mechanisms involved in the process of bone resorption. Osteoclasts were cultured on the surfaces of devitalized mammalian bones, a composite of polycrystalline synthetic hydroxyapatite and geological single crystal hydroxyapatite. The structural interaction of osteoclasts with these various substrates was morphologically characterized by using a scanning electron microscope. Viable osteoclasts were observed to adhere and extend pseudopodia and filopodia for all cases of calcium-phosphate surfaces. However, actual resorbing process was only observed in devitalized bone surfaces. Resorption pits of various sizes were found in multiple series and showed a preference for mineral-exposed area over collagen-exposed area. The difference observed between resorption of those areas of bone surface and the failure of osteoclasts to resorb non-tissue substrates are discussed in relation to current theories of the mechanisms of mineral dissolution and resorption in mammalian calcified tissues.

Animals↗

Lattice fringe studies of (100) defects in enamel crystallites.

Lattice imperfections in the structure of shark (Nataprion brevirostrais) enamel crystallites have been studied by means of lattice-imaging in a high-resolution transmission electron microscope. Line defects exhibiting various lengths (100-2500 A) and widths (10-30 A) and demonstrating phase behaviour different from that of the host crystal were observed along the fringes representing (100) lattice planes. When defect sites were subjected to an electron beam, an annealing process was observed in which the difference in phase contrast eventually disappeared and the defect itself became an intricate part of the (100)-type lattice planes. A through-focal series of the defects show a reversal in phase contrast. By examining the contrast behaviour under certain focal conditions and by adopting the Fresnel diffraction mode, the refractive index of the defect regions was determined to be lower than that of the apatite crystal. Present findings suggest that the interlayering structure along the (100) planes is responsible for the line defects observed in enamel apatites.

Animals↗