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Feng Luo and Richard Stong introduced the average edge order μ0(K) of a triangulationK and showed in particular that for closed 3-manifolds μ0(K) being less than 4.5 implies that K is on S3. In this paper, we establish similar results for 3-manifolds with non-empty boundary; in particular it is shown that μ0(K) being less than 4 implies that K is on the 3-ball.

A 78-year-old man sustained right knee dislocation in a fall. His pain was diminished on account of his past history of tabes dorsalis due to neurosyphilis, resulting in delayed hospital attendance for a week. The injury was posterolateral rotatory dislocation of the knee. Since closed reduction was not possible, open reduction was performed. Most cases of knee joint dislocation are easy to reduce. However, it is difficult to conduct closed reduction in this type of dislocation, because the joint capsule and medial collateral ligaments are torn by the medial femoral condyle. It is important to recognize that some types of dislocation of the knee are difficult to reduce.

The effect on intraosseous bone formation of a single local injection of recombinant human basic fibroblast growth factor into the distal femur was examined in normal and ovariectomized rabbits. In normal rabbits, basic fibroblast growth factor increased bone mineral density around the injected site in a dose-dependent manner at 4 weeks, with significant effects at concentrations of 400 micrograms and greater. Doses of 400 and 1,600 micrograms of basic fibroblast growth factor increased bone mineral density by 8 and 9%, respectively, compared with the opposite control femur. Histological examination showed that basic fibroblast growth factor (400 micrograms) induced the proliferation or recruitment of undifferentiated mesenchymal cells around the existing trabeculae at 3 days after the injection. For the first 2 weeks, osteoid formation was strongly stimulated, and this was followed by mineral apposition for another 2 weeks, at which time the femurs were harvested. Consequently, basic fibroblast growth factor stimulated intraosseous bone formation at 4 weeks. We speculate that the direct action of basic fibroblast growth factor on bone formation may be to stimulate proliferation or recruitment of minimally differentiated mesenchymal cells and to initiate the cascade of events in later stages of bone formation. In ovariectomized rabbits, basic fibroblast growth factor (400 micrograms) also increased bone mineral density, histomorphometrical bone formation markers, and trabecular connectivity to levels similar to those in rabbits who had received sham operations.

We have established a method for obtaining an enriched preparation of functionally active osteoclast-like multinucleated cells (enriched OCLs) from co-cultures of mouse primary osteoblasts and bone marrow cells. Using these enriched OCLs, the effect of osteoblastic cells on osteoclast function was examined in two assays: a pit formation assay and an assay for actin ring formation. The enriched OCLs cultured for 24 h on dentine slices formed only a few resorption pits. When various numbers of primary osteoblasts were added to the enriched OCLs, the areas of the resorption pits increased proportionally to the number of osteoblasts added. Like primary osteoblasts, the established cell lines of osteoblastic cells (MC3T3-E1 and KS-4) and bone marrow-derived stromal cells (MC3T3-G2/PA6 and ST2) potentiated the pit formation caused by enriched OCLs. In contrast, the fibroblastic cell lines NIH3T3 and C3H10T1/2) and the myoblastic cell line (C2C12) failed to activate OCL function. When cell-to-cell contact between MC3T3-E1 cells and enriched OCLs was prevented, only a few resorption pits were formed. Pit formation by enriched rat osteoclasts placed on dentine slices was also stimulated by adding MC3T3-E1 cells. Actin ring formation and pit forming activity were well correlated in either culture of enriched mouse OCLs or authentic rat osteoclasts on dentine slices. These results indicate that osteoclast function is activated by osteoblastic cells through a mechanism involving cell-to-cell and/or cell-to matrix contact.

We discuss a problem posed by Gersten: Is every automatic group which does not contain Z+Z subgroup, hyperbolic? To study this question, we define the notion of "n-tracks of length n", which is a structure like Z+Z, and prove its existence in the non-hyperbolic automatic groups with mild conditions. As an application, we show that if a group acts effectively, cellularly, properly discontinuously and cocompactly on a CAT(0) cube complex and its quotient is "weakly special", then the above question is answered affirmatively., Comment: 15 pages, 5 figures

We observed the occurrence of abnormal electrocardiogram (ECG) findings during the procedure of peripheral blood stem cell collection (PBSCC) in a 9-year-old child treated with chemotherapy for advanced rhabdomyosarcoma. Holter-electrocardiogram (Holter-ECG) recording over 23hrs at 7 weeks after PBSCC showed episodes of premature ventricular complexes (PVC). ECG findings were normal at the time of patient discharge.These findings indicate that the observation of ECG is necessary before and during PBSCC, and that the clinician is required during PBSCC.

Upon irradiation of a stable cyclotrisilene, 1,3,3-tris(tert-butyldimethylsilyl)-2-[tris(tert-butyldimethylsilyl)silyl]cyclotrisilene (5), in toluene with a low-pressure mercury-arc lamp, the isome...

I群抗不整脈薬 (プロカインアミド) とIII群抗不整脈薬 (アミオダロン, E-4031およびMS-551) のリエントリー性心室頻拍 (VT) への作用を定量的に評価した.VT周期長, VTを停止させる最長の頻回刺激周期 (Block周期) , およびその差としてのエントレーンメント帯を抗不整脈薬投与前後で比較し, エントレーンメント帯を興奮間隙の大きさの指標とした.VT周期はプロカインアミドで308±63msecから410±77msecと延長し (p

動悸を主訴とする58歳の男性に電気生理学的検査を施行した.イソプロテレノール (以下lSP) 単独時およびISP下のプロカインアミド投与後, 左室からの2連早期刺激により右脚ブロック様ORS波形の心室頻拍 (以下VT) が誘発され, VT周期はおのおの235msecと310msecであった.メキシレチン内服下で薬効判定を行なったが, 右室からの2連早期刺激で同一QRS波形の非持続性VTが誘発された.しかしISP負荷後は逆にVTは誘発されなくなった.VTの機序にはリエントリーが考えられた.リエントリーが成立するのはVT周期が235msecから310msecに相当するリエントリー回路内の伝導速度のときで, メキシレチン投与下に誘発されたVTがISPにより誘発されなくなったのは, ISPがリエントリー回路内の伝導速度を亢進させて, リエントリーの成立を妨げたためと推定された.

催不整脈性右室異形成による心室頻拍 (VT) を認めた59歳の男性に対し頻拍起源を切除し, 5年間発作を認めなかった.今回めまいが出現しVTの再発の有無を検討するため電気生理検査を行なった.VTはプログラム刺激で誘発されなかった.心電図上QRS波の後半に遅れて認めた波形に一致する緩徐伝導部位を心内膜マッピングにより右室自由壁下方に同定した.この遅延電位は術前に認められず, 手術操作により形成されたと考えられた.緩徐伝導部位の伝導様式は急速反応型を示し, プロカインアミド (PA) により刺激からこの電位まで, およびこの部位からの刺激の延長は, 正常心筋における伝導時間に比し有意に大であった (p

Cholesterol ester (ChE) and triacylglycerol (TG) hydroperoxides in human plasma were determined by high-performance liquid chromatography with postcolumn detection with diphenyl-1-pyrenylphosphine. Human plasma was extracted once with n-hexane. 2,6-Di-tert.-butyl-4-methylphenol and N-stearylcinnamide were added to human plasma before extraction as an antioxidation agent and an internal standard, respectively. The detection limits of both ChE and TG hydroperoxides were 1 pmol. The sample size was minimized to 250 microliters for each run. The recoveries of ChE and TG hydroperoxides from fresh plasma were ca. 90 and 80%, respectively. The relative standard deviations (n = 8) of their values in frozen human plasma were 5.4% (ChE hydroperoxides, 298 nM) and 5.7% (TG hydroperoxides, 267 nM). No TG hydroperoxides and 24.5 +/- 9.6 nM (n = 15) ChE hydroperoxides were detected in fresh human plasma. The relative standard deviation (n = 8) of ChE hydroperoxides values in fresh plasma was 5.8% (27.1 nM).

We describe a case in which the guide wire penetrated through the left anterior descending artery into the left ventricular cavity during percutaneous transluminal coronary angioplasty. This complication of coronary angioplasty which had not been previously reported was suspected because of the characteristic motion of the guide wire on the X-ray image and was confirmed by echocardiography.

CHINUSHI, M., et al.: Frequency and Output-Dependent Change in Conduction Over Slow Pathways in a Patient with Sustained Ventricular Tachycardia Unrelated to Coronary Artery Disease. In a patient with sustained ventricular tachycardia, we obtained two different paced QRS morphologies from a single pacing site. In one QRS morphology the stimulus to the QRS complex was long, 150 msec, and in the other it was 100 msec. At the paced cycle Iength of 600 msec and the stimulus output of 4 V, one QRS morphology with the stimulus to the onset of QRS activation (St-QRS) interval of 150 msec was observed. At the paced cycle length of 400 msec, the other QRS morphology with a St-QRS interval of 100 msec was observed alternately with the former. At the paced cycle length of 353 msec or 316 msec, the latter with a shorter St-QRS interval was exclusively observed. When the stimulus output was increased from 4 to 10 V, keeping with the paced cycle length at 400 msec, the St-QRS interval was shortened from 100 to 80 msec. For the two QRS morphologies with two St-QRS intervals, two slowly conducting pathways would be responsible. The site of the block in the faster pathway must be located at the proximity of the pacing site and the conduction at a shorter paced cycle length would be explained by “supernormal conduction.”

An electrophysiologic study was performed on a patient with ischemic sustained ventricular tachycardia (VT). During pacing at the right ventricular apex, ventricular double potential was recorded at the left ventricular apex. Sustained VT was induced by double extra stimuli from the right ventricular apex. Three types of VTs with different QRS morphologies were observed, and each VT was changeable to other types. The interval between one of the two potentials and the surface QRS was constant during all VTs, but the other potential showed dissociation from the surface QRS. During this dissociation, an intrinsic rhythm of the potential was sometimes shorter than the cycle length of the VT. The mechanism of a block between the VT and a bystander could hardly explain these electrophysiologic findings. Concealed double ventricular tachycardia was considered to be the likely mechanism. (Internal Medicine 31 : 227-231, 1992)

頻回刺激による持続型心室頻拍 (VT) の停止の機序が, リエントリー回路での川頁行伝導途絶による可能性が示唆された2症例を提示する.2例とも自然発作と同一波形のVTが誘発され, 頻拍周期より短い周期のペーシングで, constant fusionとProgressive fusionが確認され, さらに短い周期でVTは停止した.VT停止時には以下の所見が観察された. (1) リエントリー回路の出口において, 各々の刺激に対応する局所電位が欠如し, 電位出現間隔が延長した. (2) その後の刺激で同部位の局所電位の形態が変化し, (3) 体表面QRS波形もoonstant fusionの波形から洞調律時のペーシング波形に変化した.これらの所見はVTを停止させる周期のペーシング中に, リエントリー回路を経て回路外で融合波を形成していた興奮が途絶し, そこにペーシング部位からの逆行性興奮が伝導したための現象と考えられた.これらの所見が確認された症例の頻拍停止は, リエントリー回路内緩徐伝導路での順行伝導途絶が一次的な原因と考えられた.

Pleistocene corals have been successfully dated by the electron spin resonance (ESR) method among various geologic materials, however, this method even for corals has not been established yet. The ESR dating is controlled by following factors : pretreatment of samples, dose rates of artificial gamma irradiation, uranium concentrations in the samples, regression methods of total doses, and methods for calculating ESR dates from total doses. These methods are discussed in this paper.The present study shows that the total dose of a fossil coral generated at the higher dose rate of artificial gamma irradiation is larger than at the lower one. The total dose at a dose rate of 10 kR/hr was about 4 times as large as the one at 1 kR/hr for the last interglacial corals. The gamma doses-ESR intensities data produced by the so-called additive dose method are regressed into a saturation curve or a straight line using the program made by M. Koba. This can choose the most adequate curve by the iteration method. ESR ages are calculated using the program of M. Ikeya revised by M. Koba which does not presume radioactive equilibria in the processes of decay.Two raised atolls, Kita-Daito and Minami-Daito Islands, are situated nearly at lat. 26°N and long. 131°E in the Philippine Sea. They are almost entirely composed of the Daito Dolostone originated from coral reefs, and have small raised fissure deposits and reefs of the late Pleistocene time at a few places. Both allochthonous and autochthonous corals were dated by the ESR, the 230Th/234U (Omura et al., this issue) and the 226Ra/238U methods (Kawana et al., this issue).238U concentrations of the common coral samples were obtained by the radioactivation analysis which the present authors used, the alpha spectrometry (Omura et al., this issue), and the gamma non-destructive spectrometry (Kawana et al., this issue). The 12 paired results of the former two methods demonstrate a correlation of 0.831. The 8 paired data by the radioactivation analysis and the gamma non-destructive spectrometry show a correlation of 0.211. The ESR and 230Th/234U methods for the six powdered coral samples give us the concordant dates almost within one standard deviation. The average dates of ESR and 230Th/234U are 119, 700 and 115, 500 yr B. P., respectively.11 corals were collected at a small (2 × 3 m2) outcrop of late Pleistocene limestone in the eastern coast of Kita-Daito Island, checking carefully their stratigraphic relations. The stratigraphically upper samples show the younger ESR dates comparing with the lower. The shoreline of the last interglacial time is estimated to have been situated at 11 m above sea level here. Finely recrystallized 100 % dolomitic corals were collected from the top surface, 45 m above sea level, of the atoll ring of Kita-Daito Island. Their corals are dated ca. 4.6 million years ago by the ESR method. The uplift rate of Kita-Daito Island since 4.6 million years ago was estimated less than 0.01 m/kyr assuming that the present sea level did not move.Although every calcitic coral converted from an aragonitic coral shows dull ESR spectra on a warping base level, these dolomitic corals showed clear ESR spectra on a straight base level. ESR spectra of a dolomitic coral resemble the ones of an aragonitic coral. It was introduced that signal C, whose g value was identical with one of an aragonitic coral, could be used for the dating of the dolomitic corals. The dip-depth of signal C from the base level, so-called signal C/2, was used as an ESR intensity for the dating of dolomitic corals, because it was found that signal C/2 was more difficult to saturate than signal C. Their uranium concentrations were very low owing to leaching, therefore the lower limit of the ESR method was extended considerably.

他剤無効性の持続型心室頻拍に対するアミオダロン (以下AMD) の抗不整脈効果を電気生理検査 (以下EPS) により検討した.対象は持続型心室頻拍12例と心室細動1例で, 4例に失神の既往があった.全例コントロール状態のEPSで頻拍が誘発され, プロカインアミドやジソピラマイドなどの単独および併用投与で予防効果は認めなかった.AMDの投与量は11例で400mg/日を1週間, その後200mg/日を1週間投与し, 1例で400mg/日を2週間投与し, 1例で800mg/日をプロカインアミド1.5g/日と2週間併用投与した.副作用による投与中止例はなかった.2例で投与期間中にVT発作が頻発した.残り11例でEPSを施行し, 4例でVTは誘発不能となった.自然再発VTを含め予防効果を認めない9例中7例で15～120msecのVT周期の延長を, 2例で55～105msecのVT周期の短縮を認め, AMDは必ずしもVTレートを低下させないと考えられた.投与中再発を認めず, EPSでも誘発されない例を有効と判定すると, AMDのVTに対する予防効果は13例中4例, 31%に認めた.

Dendritic morphogenesis is an essential process for the establishment of proper neural circuitry. In the epileptic hippocampus, mature dentate granule cells (GCs) possess basal dendrites (BDs), which is abnormal and is assumed to contribute to seizure progression. However, there is a lack of direct time-lapse evidence showing that neuronal hyperactivity regulates the dendritic development of GCs. In the present study, we carried out time-lapse confocal analysis of the dendritic morphogenesis of GCs in hippocampal slice cultures that were prepared from postnatal 6-day-old (P6) rats. By electroporating membrane-targeted green fluorescent protein at 5 days in vitro (DIV), we found that most of the Prox1-positive and calbindin-negative immature GCs possessed several BDs and filopodia-rich apical dendrites at 7 DIV. BDs were gradually eliminated from 7 to 9 DIV, and they completely vanished at 14 DIV in all the GCs examined. However, most BDs failed to retract from 7 to 9 DIV, when the GABA(A) receptor antagonist picrotoxin was chronically applied to induce epileptic conditions in the cultures. These effects were blocked by coapplying tetrodotoxin, a sodium channel blocker, thus convincing us that neuronal hyperactivity contributes to the maintenance of BDs. Further, in the picrotoxin-treated cultures, most of the GCs persistently exhibited several BDs even after 14 DIV. In contrast, neither the progressive pruning of the filopodia nor the branch dynamics of the apical dendrites during the culture periods was affected by picrotoxin. These results, for the first time, provide us with direct evidence that neuronal hyperactivity contributes to the stability of pre-existing BDs.

Heart failure (HF), which can be caused by left ventricular systolic dysfunction (LVSD), is a growing problem in developed countries with a large aging population. The aim of the present study was to characterize outpatients with LVSD in the adult population (45-84 years) in an urban Japanese community (Niigata City), and delineate their characteristics in comparison with those in a rural one (Sado).Over a 5-year period, 1,297 patients (67% males) with LVSD (defined as ejection fractionor =50%) were extracted from 87,953 echocardiography records available in 15 hospitals in Niigata City. The proportion of LVSD increased progressively with age (p-for-trend0.0001), reaching 1-2% in those agedor =75 years. The prevalence of comorbidities was noticeable (47% had hypertension, 41% myocardial ischemia, 34% atrial fibrillation, 33% previous hospitalization because of congestive HF, 27% cerebral stroke). In comparison with Sado, Niigata patients were younger, with a higher prevalence of comorbidities (hypertension, diabetes, dyslipidemia, and cerebral stroke).As the proportion of LVSD cases increases progressively with age, it is expected to simulate a future epidemic. The differences between patients' characteristics and disease patterns in urban and rural communities may favor individually tailoring preventive strategies for HF in these areas.

A case of sustained ventricular tachycardia (VT) with two possible exits from one re-entrant circuit is described in this paper. The patient was a 27-year-old female who had undergone corrective surgery for tetralogy of Fallot at the age of 8, and developed VT of distinctly different QRS configurations. The exit of one VT was at the right ventricular (RV) outflow tract and the other at the RV apex as determined by endocardial and pace-mapping. Continuous and split activities were observed at the RV outflow tract during both types of VT. One VT was entrained by rapid pacings, and the causal mechanism was thought to be re-entry and common re-entrant circuit was established for two QRS configurations of VTs. A discrepancy was observed between the site of the earliest activation and the site of the pace-mapping which resulted in QRS configuration of VT of the RV apex origin. The findings in this paper should be considered when contemplating aggressive therapy such as electrical ablation.

Hippocampal mossy fibers, which are the axons of dentate granule cells, are continuously generated owing to adult neurogenesis of granule cells. They extend exclusively into the stratum lucidum, a proximal layer of the CA3 pyramidal cells. We visualized the mossy fiber tracts by Timm histochemical staining and DiI labeling in the cultured hippocampal slices from newborn rats. The fibers were abnormally expanded when the slices were cultured in the presence of K252a, an inhibitor of the neurotrophin receptor Trk. Similar defasciculation was observed with an inhibitor of MEK, which is one of the signaling molecules downstream of Trk. This study suggests for the first time that Trk and the MEK pathway are required for mossy fiber pathfinding.

Gold alloys with Cu contents of 10 mass%, 20%, and 30% were used for morphological observation of porous surface structures after heating at 800 degrees C in air followed by pickling with acid solution. With increasing Cu content in the gold alloy, the internal oxidation zone became well-developed in the alloy matrix. The mechanism by which a porous structure was formed on the surface of a gold alloy containing only Cu as a base metal was thought to be as follows: Cu2O which formed along the grain boundaries acted as a diffusion path, permitting the penetration of O2- into the inner alloy matrix, and thereby resulting in internal oxidation occurring predominantly along the grain boundaries.

It is important for a hospital to have a well organized blood transfusion service.Our hospital adopted the maximum surgical blood order schedule (MSBOS) and type and screen (TS) systems in April 1999 and opened a division of transfusion therapy, thus introducing an integrated control system for blood transfusion.In the year (2002), the crossmatch-to-transfusion (C/T) ratio has dropped from 3.94 to 2.01, and the volume of blood transported outside the central operating room and that of waste blood have decreased.The new systems are instrumental in saving preoperatively prepared blood and exercising its qualitative control. From now on, our task is to improve measures to cope with cases of transfusion in excess of MSBOS and reevaluate MSBOS on a regular basis.

The aim of this study was to determine priorities for specific intractable disease from the viewpoint of countermeasures.A significance evaluation to provide a priority framework for intractable disease was performed with a questionnaire distributed to the staff of preventive medicine and public health departments of medical schools in Japan. To determine the actual conditions of these intractable diseases question were directed at the chairmen of individual clinical study groups. The priority to be assigned countermeasures for such diseases was obtained from the two questionnaires.When the 4 factors "rare nature of diseases," "level of clarity of causes and pathology," "unestablished curative treatment", and "influence on daily life" were evaluated using 100 point as a full score, the mean scores were 14.5, 27.1, 28.5 and 29.9 points, respectively. In attaching importance to the various items, regarding the "rare nature of disease" the elements of "few patients nationwide" and "few specialist doctors nationwide" proved important; for the "level of clarity of causes and pathology," this was the case for the elements of "unclear triggering mechanism" and "diagnostic criteria not established." With the "unestablished curative treatment," the "no efficacious treatment available" and "low 5-year survival rate elements were important; and with the factor of "influence on daily life," the two most significant were "high proportion of patients needing assistance in daily life" and "high percentage of patients impeded from attending school or obtaining a job (playing a role in society)".When the priority among the 118 intractable diseases was evaluated by combining the overall results of the questionnaire survey with preventive medicine and public health staffs, and actual condition data from survey investigation of the intractable diseases among chairmen of clinical study groups, it was suggested that some intractable diseases whose medical expenses are covered by the medical aid program have a low ranking.

In contrast to carbon, silicon does not readily form double bonds, and compounds containing silicon-silicon double bonds can usually be stabilized only by protection with bulky substituents. We have isolated a silicon analog of spiropentadiene 1 , a carbon double-ring compound that has not been isolated to date. In the crystal structure of tetrakis[tri( t -butyldimethylsilyl)silyl]spiropentasiladiene 2 , a substantial deviation from the perpendicular arrangement of the two rings is observed, and the silicon-silicon double bonds are shown to be distorted. Spectroscopic data indicate pronounced interaction between two remote silicon-silicon double bonds in the molecule. Silicon-silicon bonds may be more accessible to synthesis than previously assumed.

The compressive properties of Fe-25Al-10Ti intermetallic alloy were studied as a function of temperature and strain rate. Optical microscopy and transmission electron microscopy (TEM) were used to examine the deformation microstructure. The alloy exhibited strong tendency of strain hardening at low temperatures. A positive temperature dependence of strength was observed in the 673 – 873 K range. The mechanical behavior was interpreted in terms of dislocation structures. Based on the analysis of the stress-strain response, strain rate sensitivity and deformation microstructure, possible hot working range was proposed.

Five children with neuroblastoma (NB) stage IV and five children with rhabdomyosarcoma (RMS) stage III were treated with myeloablative chemotherapy and autologous peripheral blood stem cell transplantation (MCT/PBSCT) in the state of complete remission (CR) achieved by conventional therapy. PBSCs were collected in CR status using a cell separator with blood access through a double-lumen central venous catheter. PBSCs with 1.9+/-0.8x10(5) of CFU-GM per patient weights (kg) were infused following MCT after a period of conventional therapy for 11.1+/-2.1 or 9.7+/-0.9 months in NB or RMS patients, respectively. Regimen-related toxicity of MCT was tolerable and peripheral white blood cell count recovered beyond 1.0x10(3)/microl 10-12 days after infusion of PBSCs in all patients. All of RMS patients and three of five NB patients survived for an average of 31.6 months (ranged 10.8-58.1). The survival rate of these patients was improved as compared with our historical controls, and presumably, with that of conventional chemotherapy previously reported. Despite a limited number of patients, it appears that MCT/PBSCT may be effective in improving survival by preventing relapse which may occur thereafter if treated with conventional therapy alone. Furthermore, MCT/PBSCT reduced the duration of treatment, as compared with that of conventional chemo-therapy. Therefore, this study may suggest the feasibility and promise of the therapy including MCT/PBSCT for children with advanced stages of NB and RMS.

The objective of this study is to enhance the bone induction activity of basic fibroblast growth factor (bFGF) for reconstruction of skull bone defects which has been clinically recognized as almost impossible. For this purpose, we prepared biodegradable hydrogels from gelatin with an isoelectric point of 4.9 which is capable of polyionic complexing with basic bFGF. When implanted in rabbit skull defects of 6 mm in diameter (6 defects per experimental group), the gelatin hydrogels incorporating 100 microg of bFGF promoted bone regeneration at the defect in marked contrast to free bFGF of the same dose, finally closing the bone defects after 12 weeks of implantation as is apparent from histological examination. In dual energy X-ray absorptometry analysis, the bone mineral density at the skull defects enhanced by the hydrogels was significantly higher than that by free bFGF at doses ranging from 2 to 200 microg/defect (P < 0.05). The extent of bone regeneration induced by gelatin hydrogels incorporating 100 microg of bFGF increased with a decrease in their water content. Histological examination indicated that more slowly degrading hydrogels of lower water content prolonged the retention period of osteoblasts in the bone defects. This led to enhanced bone regeneration compared with faster degrading hydrogels of higher water content. It was concluded that this biodegradable hydrogel system was a promising surgical tool to assist self-reconstruction of the skull bone.