Potentiation of transforming growth factor (TGF-β1) by natural coral and fibrin in a rabbit cranioplasty model

The association of a biodegradable material and a growth factor could be of clinical value for treating bone defects. We therefore tested the association of transforming growth factor (TGF-1) in fibrin glue and coral granules to heal skull defects in rabbits. Adult rabbits underwent a double trepanation symmetrically in both parietal bones. Using histomorphometry, we compared bone repair after 1 month in control animals (n=5) and in animals treated with either TGF-1 as a single injection of 1 g in methylcellulose (n=5) or in fibrin glue (n=5), or with coral granules in fibrin glue (n=4) or with coral granules and TGF-1 1 g in fibrin glue (n=5). We measured the diameter of the remaining defect and the surface of the bone growth. TGF-1 without coral in either methyl cellulose or fibrin induced a partial closure of the defect as assessed by a significant decrease in the defect diameter, compared with the control group. However, the association of TGF-1 in fibrin and coral induced an area of the bone growth higher than in any other groups (P<0.05). Two months after surgery, this triple association induced a better healing of the defect than coral alone or control group. In each group treated with TGF-1, the mineralization rate was increased not only at the treated side but also in the contralateral defect which was untreated, suggesting a diffusion of the growth factor. Indeed, when pooled together, the diameter of the defect at the contralateral side of 14 animals that had received TGF-1 was reduced compared with the control group. Significant coral granules resorption occurred between month 1 and 2 and was unchanged by the addition of TGF-1. In conclusion, the triple association of coral granules and TGF-1 in fibrin could be of interest for treating bone defects.     

Management of severe burned-hand deformities at Huê Central Hospital

During the years 1998–2002 there was collaboration between surgeons at Huê Central Hospital and Belgian plastic surgeons coming each year to teach at the Huê Medical School and to work at the Hospital. Of 150 hands deformed after burns admitted to Huê Central Hospital from 1998 to 2003, 52 patients presented with severe hand deformities. The classification of deformities was as follows: dorsal hand contractures—21 hands, palmar hand contractures—9 hands, and wrist contractures—22 hands. The management of these deformities is a combination of surgical treatment, postoperative splinting and physical exercise in order to regain the function of the hand as much as possible. The strategy of surgical procedures is based on the lesions of the individual patient. After releasing the contractures, the raw area is covered by skin grafts and local flaps. There were also 50 osteo-articular procedures. Long-term results: Good 33% (17 hands), Mild 13% (7 hands), Moderate 50% (26 hands) and Poor: 4% (2 hands).     

Serum levels of alpha-1 microglobulin and beta-2 microglobulin in bone marrow transplant recipients treated with cyclosporin A

The levels of alpha-1 microglobulin ( ₁m) and beta-2 microglobulin ( ₂m) in serum were estimated in 77 bone marrow transplant recipients. In comparison to pretransplant levels, the highest levels of ₁m and ₂m were found during impairment of renal function, i.e., during cyclosporin-induced nephrotoxicity and during treatment with other nephrotoxic drugs (P<0.001). The ₁m levels were less elevated during infections and acute graft-versus-host disease (P<0.01), while ₂m levels were markedly elevated during the same conditions (P<0.001). The linear correlations between serum creatinine and ₁m and creatinine and ₂m were r=0.7 and 0.8, respectively (P<0.001). The overall correlation between ₁m and ₂m was 0.4 (P<0.001). It is concluded that ₁m might be a complement to serum creatinine levels in monitoring renal function after bone marrow transplantation.     

Absorptiometry and “osteoporosis”: problems

connecting the dots between diverse clinical and other matters and an updated bone physiology reveals relationships that could modify some ideas about the roles and uses of absorptiometry in osteoporosis work. Herein, absorptiometry means that part of clinical densitometry that depends on X-ray absorption by bone and other tissues, thus excluding ultrasound methods and magnetic resonance imaging. The modifications concern, in part, some limitations of bone mineral density data, the kinds of physiological information that absorptiometry can and cannot provide, the relative importance of bone mass and whole-bone strength, how to define and study bone health and osteoporosis, and two kinds of osteoporotic fractures. As those modifications concern important national health care issues, they deserve answers based on hard evidence. Identifying those modifications might help others to evaluate them.     

Methylated β-cyclodextrins are able to improve the nasal absorption of salmon calcitonin

The absorption enhancing effect of methylated -cyclodextrins on the nasal absorption of salmon calcitonin (sCT) was studied in rats and rabbits. The nasal absorption of sCT following administration without additives was low in both species. The absorption in rats could be largely improved by coadministration of cyclodextrins as apparent from the effect on serum calcium concentrations. Trimethyl--cyclodextrin (TMCD), at a concentration of 5% (w/v), was the least potent enhancer. Randomly methylated--cyclodextrin (RMCD) and dimethyl--cyclodextrin (DMCD), all at a concentration of 5% (w/v), were almost equally effective in decreasing serum calcium levels, and the hypocalcemic responses were similar to those of i.v. and s.c. injected sCT. Absorption enhancement was already achieved with 1% DMCD added to the nasal formulations. In rabbits, only the effect of DMCD on the nasal sCT absorption was investigated. A total serum calcium decrement in 4 hours of 9.4±3.9% (mean±SD) was observed following nasal administration of 12.6 IU/kg sCT with 5% DMCD, comparable to that of i.v.-injected sCT. In conclusion, the methylated cyclodextrins DMCD and RMCD are suitable absorption enhancers for nasal sCT administration, which is expected to have a clinical impact on the therapy with calcitonin.     

219. Ursachen und Behandlungsprobleme der syminetrischen Unterschenkelfraktur

Zusammenfassung Als Ursache der symmetrischen Unterschenkelfrakturengibt es direkte Trauma durch Kantensturz, Fahrzeugkollision oder Stoßstangenanprall. Gehäuft treten die zweizeitigen Kombinationsverletzungen Beine, Kopf, Becken auf. Lokal überwiegen die offenen Trümmerbrüche verschiedener Höhe. Gefäß-Nerven-Verletzung ist relativ selten. Therapeutisch erfordert die Mehrfachverletzung individuelle Indikationsstellung nach vitaler Dringlichkeit. Daher Osteosynthese praktisch nur verzögert primär möglich, und dann eventuell mit zwei Operationsgruppen. Vorbeugend sind verbesserte Sicherheitssysteme zur Unfallverhütung zu fordern.     

Changes in amino-acid composition of developing rat incisor enamel

Summary The amino-acid composition and total protein content of enamel particles dissected serially from the developing enamel of rat incisors have been determined. Changes in protein content and amino-acid composition occurred throughout all stages of development. The most obvious alterations occurred in the vicinity of a white opaque band. Here, protein was lost most rapidly and considerable changes in amino-acid composition occurred.     

“Kissing” bilateral large carotid-ophthalmic aneurysms

A case of unruptured bilateral large carotid-ophthalmic aneurysms, which appear to be adjoining and kissing each other when visualized by three-dimensional computed tomographic angiography (3-D CTA), is reported. Although bilateral carotid-ophthalmic aneurysms are not rare, bilateral large ones are quite rare, and direct imaging of kissing aneurysms of this portion has not been reported. Since 3-D CTA is becoming a useful tool for the diagnosis of cerebral aneurysms, we propose that these and similar bilateral large carotid-ophthalmic aneurysms are good candidates for the term kissing aneurysms.     

Study of the microstructure of renal stones: Uric acid and calcium oxalate

This paper represents the results of experimental study on the microstructure of uric acid and calcium oxalate crystallites in renal stones. The size distribution parameters and morphological characteristics of the microcrystals forming the stone were determined using SEM and image analysing system. Information on the fabric of the renal stones examined indicates that the mean volume diameter is 15.5 m for uric acid and 32 m for calcium oxalate stones. The polydispersity index , the shape factor , and the distribution of particle shape show close similarity. Quantitative studies on stone microstructure could furnish valuable information on stone genesis.This work was supported by the Kidney Foundation and by the Medical Research Council of Canada.     

Polymeric pyelotomy

A non-toxic, soluble polymeric preparation MAG with controlled period of gelation was synthetized for the extraction of stones from the pyelocalyceal system during surgery for urolithiasis.With respect to toughness the preparation proved superior to the fibrinogenthrombin mixture, used in the so-called fibrin pyelotomy according to Dees. Its biologic testing in animals (rabbits, dogs and pigs) yielded excellent results.By analogy with fibrin pyelotomy we took the liberty to propose the term polymeric pyelotomy.     

Effects of Cilostazol on Human Venous Smooth Muscle

In this study, we evaluated the effect of therapeutic doses of cilostazol on human venous smooth muscle. Saphenous vein rings (two to four per patient sample) were suspended in tissue baths for isometric tension recordings. At the beginning of the experiment, optimal tension for isometric contraction was achieved for each ring in a stepwise fashion in the presence of norepinephrine (10^–2 M). Norepinepherine was then added cumulatively in half-molar increments and isometric tension developed by the rings was measured, thereby obtaining a dose-response curve. Following washout and reequilibration, the rings were precontracted with a 30-50% submaximal dose of norepinepherine determined from the dose-response curve and allowed to contract until a stable plateau was reached. Cilostazol was then added in a cumulative manner (680-2,720 g/L), and the tension generated was recorded. A total of 76 venous rings were tested, and all relaxed in the presence of cilostazol. The amount of relaxation increased as the concentration of cilostazol increased. Relaxation of 15±1.9% (mean±SEM) at low cilostazol doses (680 g/L) to 37±3% at high cilostazol doses (2,720 g/L) was demonstrated. A second finding of this study was demonstrated when the patient samples were divided according to the presence or absence of risk factors for arteriosclerosis. The specific risk factors examined included diabetes mellitus, smoking, hypercholesterolemia, and hypertension. The presence or absence of hypertension (n=52) or hypercholesterolemia (n=18) did not affect the amount of relaxation of the venous rings. Smokers (n=46) had less relaxation 16±2.4% (680 g/L) to 41±3.6% (2,720 g/L) compared to nonsmokers (n=53) who relaxed 22±3.5% (680 g/L) to 48±5.7% (2720 g/L). This did not reach statistical significance at any concentration cilostazol (p=0.11-0.18). Diabetics (n=53) did have statistically significantly less relaxation at every concentration of cilostazol compared to nondiabetics (n=11, p < 0.05). All venous rings relaxed in the presence of cilostazol. Veins of nondiabetics relaxed statistically significantly more than those of diabetics. Smokers had less relaxation than non-smokers, but this was not statistically significant. We are the first to demonstrate that human venous smooth muscle cells undergo relaxation when exposed to therapeutic concentrations of cilostazol.     

Distended glands or overreplacement of ampullary mucosa at the papilla of Vater

Background/Purpose The role of the ampullary mucosa, especially its distended glands at the papilla of Vater, has not been fully explored.Methods Twenty-nine pancreatoduodenectomized specimens from pancreatobiliary diseases and 44 autopsied cases, as controls, were studied histopathologically and immunohistochemically.Results In 12 out of the 29 pancreatoduodenectomized cases the ampullary mucosa was in contact with the duodenal mucosa just at the outlet of the ampulla. In the remaining 17 cases, the ampullary mucosa overgrew beyond the ostium, replacing a portion of the surrounding duodenal mucosa, termed distended glands, which measured an average of 1532µm in length. The muscularis mucosae of the duodenum and the Oddis sphincter muscle merged in an end-to-end, sharp-angled manner at the ostium in the former, whereas this occurred in an end-to-side, less sharp, rather right-angled manner in the latter. Immunohistochemically, the distended glands in some cases showed negative/weakly positive staining for anti-carbohydrate antigen (CA) 19-9 and a high proliferation index evaluated using Ki67. In the autopsied materials, distended glands were found in 24 out of the 44 cases.Conclusions Distended glands of the ampullary mucosa were frequently found and only grew on the Oddis sphincter muscle extension. They may represent not only malignant change but also an adaptive phenomenon for bile and pancreatic juice flow.     

Intracranial meningiomas: Analysis of recurrence after surgical treatment

Summary Recurrence of intracranial meningiomas after surgery has long been recognized, but there is still no consensus about factors responsible for recurrence. To better understand such factors, we analysed data on 276 patients with meningiomas who were treated at our institution from 1976 to 1990 (mean follow-up=5.1 years). Effects of sex, tumour histology, tumour site, and radiotherapy on recurrence were closely studied. Using World Health Organization criteria to define malignancy, 254 of the tumours were benign and 22 were atypical or malignant. For data analysis, distinction was made between recurrence (i.e., reappearance of tumour after total resection) and regrowth (i.e., tumour enlargement after subtotal removal). Recurrence was seen in 2 of 183 benign meningiomas and in 10 of 16 malignant meningiomas. Recurrence and regrowth rates for malignant meningiomas far exceeded those for benign meningiomas (p=0.001). Neither sex nor tumour site was associated with subsequent recurrences in patients whose tumours had been completely resected.The influence of radiotherapy was studied in terms of its effects on benign versus malignant meningiomas, whether given after complete or incomplete resection, and whether given after primary resection or on reoperation. We found that radiotherapy did not decrease recurrence or regrowth regardless of when administered, either at first resection or on recurrence. This was true for benign as well as malignant meningiomas. However, due to the small number in our series, we cannot conclude that radiotherapy has no beneficial role in the treatment of meningiomas.We do believe that the rate of recurrence for benign meningiomas is far lower than has been reported and that the majority of recurrences are in fact regrowths representing continuous tumour growth after incomplete removal. In fact, whenever recurrence is seen after complete surgical removal, chances are that tumour was atypical or malignant.     

33. Der „kalte” Schilddrüsenknoten

Zusammenfassung Der kalte Schilddrüsenknoten gilt als typischer Verdachtsbefund für ein Schilddrüsencarcinom. Seine tatsächliche Dignität ist mit klinischen Mitteln sowie Szintigraphie und Sonographie letztlich nicht zu klären. Das beste abgrenzende Selektionskriterium ist die Feinnadel-Punktionscytologie, wodurch mit Gültigkeit für das Kropfendemiegebiet etwa die Hälfte als suspekte Befunde von dem anderen Teil hochwahrscheinlich gutartiger Veränderungen getrennt und für die Operationsindikation reserviert werden kann.     

An interpretation of acute changes in plasma45Ca following parathyroid hormone administration to thyroparathyroidectomized rats

Acute changes in plasma calcium and⁴⁵Ca were studied in young adult male thyroparathyroidectomized (TPTX) rats injected with moderate doses of parathyroid hormone (PTH). For plasma calcium changes, comparison was made between rats fasted or fed prior to PTH injection. For plasma⁴⁵Ca changes, the effect of the time of administration of the radionuclide was also studied; this included rats injected with PTH 1 h after radionuclide (1 h⁴⁵Ca), 18 h later (18 h⁴⁵Ca) and more than 6 days later (6 day⁴⁵Ca). The results can be summarized as follows: (1) Plasma calcium changes were greater when PTH was injected into fed rather than into fasted rats. (2) PTH always produced a relative increase (compared to controls tested concurrently) in plasma⁴⁵Ca concentrations. This increase was the same in the 1 h⁴⁵Ca and the 18 h⁴⁵Ca groups. (3) Plasma⁴⁵Ca rose at least temporarily following PTH injection in the 18 h⁴⁵Ca group. (4) The⁴⁵Ca rise following PTH was always greater in fed than in fasted groups. (5) Plasma⁴⁵Ca specific activities (S.A.) tended to rise in the 6 day⁴⁵Ca group and to fall in the 18 h⁴⁵Ca group, following PTH injection. However, the⁴⁵Ca S.A. was always higher in fed than fasted groups. (6) In a few experiments in which³²P was injected with⁴⁵Ca, specific activity changes in plasma⁴⁵Ca following PTH injection werenot accompanied by similar changes in³²P specific activity.These results could not be adequately explained by PTH effects on bone resorption, but the data supported the postulate that PTH controls plasma calcium concentrations by increasing transport of calcium through the osteocyte-lining cell (osteoblast) bone cell complex from the bone fluid compartment to the ECF.     

Wear of ultra-high-molecular-weight polyethylene cup articulating with 22.225 mm zirconia diameter head in cemented total hip arthroplasty

A number of studies have highlighted the increasing incidence of aseptic cup loosening with increasing depth of cup penetration by the metal head. We present our experience with a 22.225mm diameter zirconia head on a 9–10 taper articulating with an ultra-high-molecular-weight polyethylene (UHMWPE) cup in cemented total hip arthroplasties. We prospectively studied the wear of the UHMWPE cup articulating with a 22.225mm diameter zirconia head in cemented total hip arthroplasties. A total of 339 patients (153 men, 186 women, 373 hips) were included. The patients mean age at surgery was 52 years (17–76 years), with 41% age 50 years or younger. Their mean weight was 72.4kg (24–125kg). At a mean follow-up of 4.3 years (0–8 years) the mean penetration rate of the cup was 0.03mm/year (0–0.51mm/year). Altogether, 289 (77.5%) showed no measurable wear, 38 (10.2%) had a penetration rate of 0.11mm/year or less, 33 (8.9%) had a rate of 0.12–0.2mm/year, and in 13 (3.5%) the rate was more than 0.2mm/year. Ceramic–UHMWPE is the next stage in the evolution of total hip arthroplasty for addressing wear and any possible related issues.     

Comparative study of nonbridging and bridging external fixators for unstable distal radius fractures

The purpose of this study was to compare nonbridging external fixators (group NB) with bridging external fixators (group B) in the treatment for unstable distal radius fractures. The subjects consisted of 84 patients, 42 in each group. Mean patient age was 64.0 years in group NB and 59.6 years in group B. According to Saitos classification, most fractures were of the comminuted Colles type. No bone graft was made in group NB. Patients of group B showed serious reflex sympathetic dystrophy (RSD). On Saitos evaluation criteria, the proportion of patients evaluated as good or better was 100% in group NB and 95.6% in group B. This finding can be taken as evidence that group NB patients showed better results.     

In comparison: 1.064 μm-1.318 μm Nd-YAG continuous wave lasers. In vitro and in vivo experiments for endoscopic tumour therapy in the gastrointestinal tract

In in vitro and animal experiments the tissue effects of the 1.318m Nd-YAG laser were compared to those of the standard 1.064m Nd-YAG laser in order to evaluate the advantages of the new wavelength with a ten times higher absorption in water for gastroenterological tumour treatment. Under irradiation parameters related to clinical endoscopic practice, the laser of the wavelength 1.318m needs for both vaporization and coagulation significantly less energy than the 1.064m laser. Since vaporization at 1.318m is always accompanied by a higher coagulation effect compared to 1.064m the risk of late necrosis and resulting perforation appears to be increased.     

Chronic intramedullary infusion of interleukin-1α increases bone mineral content in rats

Interleukin-1 (IL-1) is known to have a potent bone-resorbing activity in vitro, however, results from in vivo studies are conflicting. We performed experiments with the continuous infusion of recombinant IL-1 directly into the femoral bone marrow of rats for 2 weeks and examined its effects on bone by soft X-ray photographs, bone mineral assessment, and histological examination. Infusion of IL-1 at doses greater than 1 g/ml (0.6 ng/hour) caused sclerosis around the infusion site on soft X-ray photographs, and the bone mineral content of IL-1 infused femora was increased significantly. Histologically, extensive periosteal bone formation was observed around the infusion site and small mononuclear cells replaced the normal fat tissue. Infusion of prostaglandin E₂ alone produced intramedullary bone formation more extensively. Simultaneous infusion of IL-1 and indomethacin (10^-3 M; 179 ng/hour) inhibited the increase of bone mineral content (BMC) induced by IL-1. Thus, the chronic intramedullary administration of IL-1 stimulates bone formation, especially in the periosteum, and increases BMC in intact rats.     

Hypoxia and HIF-1α in osteoarthritis

We have previously shown that functional inactivation of hypoxia-inducible factor-1 (HIF-1) in growth-plate chondrocytes will dramatically inhibit anaerobic energy generation and matrix synthesis. Using immunohistochemistry, we have now analyzed the spatial distribution of HIF-1 and its target genes in normal cartilage and in cartilage from knee joints with osteoarthritis. We detected HIF-1 and its target genes in both types of cartilage. In cartilage from joints with osteoarthritis, the number of HIF-1-, Glut-1-, and PGK-1-stained chondrocytes increased with the severity of osteoarthritis. Activated matrix synthesis and strongly decreased oxygen levels are hallmarks of osteoarthritic cartilage. Thus, we assume that chondrocytes are depending on the adaptive functions of HIF-1 in order to maintain ATP levels and thereby matrix synthesis during the course of osteoarthritis.

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Résumé Nous avons montré précédemment que linactivation du facteur de lhypoxie 1- (HIF-1) dans les chondrocytes du cartilage de conjugaison inhibe très nettement la génération dénergie anaérobie et la synthèse de la matrice. Utilisant limmuno-histochimie nous avons analysé la distribution spatiale de HIF-1, et ses gène- cibles dans le cartilage normal et dans le cartilage darticulations avec arthrose. Nous avons détecté des HIF-1 et ses gène-cibles dans les deux types de cartilage. Dans le cartilage arthrosique le nombre de chondrocytes marqués HIF-1, Glut-1 et PGK-1 a augmenté avec la sévérité de larthrose. La synthèse de la matrice activée et le niveau doxygène fortement diminué sont des caractéristiques du cartilage arthrosique. Donc nous supposons que les chondrocytes dépendent de la fonction adaptative de HIF-1 pour maintenir le niveau dATP et de cette façon la synthèse de la matrice pendant lévolution de larthrose.