Experience of Quatro-Therapy With Everolimus to Minimize Calcineurin Inhibitor for Kidney Transplant Recipients.

BACKGROUND: This study was divided into three phases, on the occasion of the introduction of everolimus (EVR) in our hospital. METHODS: In the first phase, a study group of six maintenance patients (three living related donors, three deceased donors) who had a history of malignant disease with less than 500 mg/day of proteinuria were enrolled; a high serum creatinine and upper limit of duration after kidney transplant operation was not considered. EVR was discontinued in four of the six patients because of side effects or worsening renal function. The second phase comprised a study group of 12 maintenance patients (12 living related donors) who were more than 5 years after kidney transplant operation with serum creatinine <3 ng/mL and proteinuria <500 mg/day. In two patients, EVR was discontinued because of a skin rash or general fatigue, but EVR was continued in 10 cases. Calcineurin inhibitor (CNI) dosage was reduced and renal function improved, and mean estimated glomerular filtration rate recovered from 42.3 mL/min to 44.8 mL/min, with no rejections occurring. In the third phase, a study group of eight de novo transplant patients who were 2 to 3 weeks after transplant operation were examined. In one case, EVR was discontinued because of proteinuria but was restarted with a stepwise increasing method after 4 months and was continued without any side effects. RESULTS: Our study indicates that EVR was a useful drug for the maintenance of kidney transplant recipients for the optimal patients. CONCLUSIONS: In de novo cases, EVR plus a high dose of mizoribine and low CNI protocol was a useful regimen without serious adverse effects.

Lower thigh muscle mass is associated with all-cause and cardiovascular mortality in elderly hemodialysis patients.

BACKGROUND/OBJECTIVES: Higher body mass index appears protective in hemodialysis patients, although it remains to be determined which component of muscle or fat mass is primarily associated with this survival advantage. SUBJECTS/METHODS: Eighty-one hemodialysis patients in our institution were prospectively followed from July 2011 to August 2015. Muscle and fat mass were evaluated by measuring the cross-sectional areas of the thigh and abdomen using computed tomography. The relationship between muscle and fat mass, and all-cause and cardiovascular mortality was studied using the Kaplan-Meier analyses and multivariate Cox proportional hazard models. RESULTS: During more than 4 years of follow-up, 26 patients (32%) died. In the Kaplan-Meier curve analyses, lower thigh muscle mass was significantly associated with all-cause and cardiovascular mortality (log-rank test, P<0.01 and P<0.001, respectively), but there was no such association with thigh fat, abdominal muscle and fat mass levels. In multivariate Cox proportional hazard models, each 0.1 cm2/kg increase in the thigh muscle area adjusted by dry weight was associated with an estimated 22% lower risk of all-cause mortality (95% confidence interval (95% CI), 0.64-0.95, P<0.05) and a 30% lower risk of cardiovascular mortality (95% CI, 0.54-0.90, P<0.01). CONCLUSIONS: Lower thigh muscle mass is significantly associated with all-cause and cardiovascular mortality in hemodialysis patients. Our findings indicate the importance of focusing on the muscle mass of lower extremities to predict the clinical outcomes of hemodialysis patients.

Orgasm is preserved regardless of ejaculatory dysfunction with selective alpha1A-blocker administration.

We evaluated whether ejaculatory dysfunction induced with a selective alpha1A-blocker influenced orgasm. Fifteen healthy male volunteers took silodosin or a placebo in a randomized, double-blind crossover design. We investigated the ejaculatory volume before and after administration of the agents. After each ejaculation, participants self-reported the answers to an original questionnaire, which was about discomfort on ejaculation, orgasm and satisfaction with the discomforting ejaculation. All participants on silodosin had a complete lack of seminal emission and expulsion. All participants felt orgasm in spite of a complete lack of seminal emission. Of the 15, 12 (80%) who had a somewhat uncomfortable feeling during orgasm were dissatisfied with this feeling, although 9 of the 12 reported that its degree was mild. Orgasm is preserved regardless of the loss of seminal emission with silodosin administration. Although most participants reported mild discomfort during orgasm, they were greatly dissatisfied with the loss of seminal emission.

Pseudohyperkalemia occurring in a patient with chronic renal failure and polycythemia vera without severe leukocytosis or thrombocytosis.

Pseudohyperkalemia is defined as a serum potassium concentration 0.4 mEq/l greater than the plasma concentration. The basis of this phenomenon is the release of intracellular potassium from platelets, leukocytes, or erythrocytes, commonly in the setting of extreme leukocytosis (> 10 x 10(4)/microl) or thrombocytosis (> 60 x 10(4)/microl). We report a case of pseudohyperkalemia in a patient with chronic renal failure and polycythemia vera without the finding of severe leukocytosis or thrombocytosis (white blood cell count 1.88 x 10(4)/microl and platelet count 37.9 x 10(4)/microl, respectively). The serum potassium concentration was 8.2 mEq/l, while the plasma potassium level was 6.4 mEq/l in a sample obtained simultaneously. The concentrations of platelet factor IV and beta-thromboglobulin, known to be markers of platelet activation, were greater than 100 ng/ml and 200 ng/ml, respectively, indicating that platelet activation may have been related to the development of pseudohyperkalemia in this patient. These findings suggest that pseudohyperkalemia should be considered when hyperkalemia is seen in a patient with chronic renal failure and myeloproliferative disorders.

Hypercalcemia in a patient with B-cell acute lymphoblastic leukemia: a role of proinflammatory cytokine.

The complication of hypercalcemia is reported to occur only in 2.5-4.8% of patients with acute lymphoblastic leukemia (ALL). We herein report a 53-year-old female patient with early B-cell ALL, complicated with extreme hypercalcemia (15.2 mg/dL). Bone X-ray revealed osteolytic changes in many locations. Serum 1,25(OH)2vitaminD3 and parathyroid hormone (PTH) levels were suppressed below normal ranges on admission. The circulating parathyroid hormone-related protein (PTHrP) value was within a normal range (< 1.1 pmol/L). Serum concentrations of tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, and soluble IL-2 receptor were increased to 72 pg/ml, 25.3 pg/ml, and 1469 U/ml, respectively. Following the induction chemotherapy, the serum calcium level was promptly normalized accompanied with decreases in serum TNF-alpha, IL-6 and soluble IL-2 receptor values to 34 pg/ml, 6.35 pg/ml, and 737 U/ml, respectively. Serum PTHrP values remained within detectable levels. To our knowledge, this is the first case of B-cell ALL in a patient who developed hypercalcemia with elevated concentrations of TNF-alpha, IL-6, and soluble IL-2 receptor, but not related to PTHrP. High circulating proinflammatory cytokines may have contributed to development of ALL-induced osteolysis and hypercalcemia in the present case.

The dipeptide, gamma-glutamylcysteine, is recognized by the anti-glutathione antibody single chain Fv fragment 20C9.

The anti-glutathione antibody scFv 20C9, which we previously isolated from a human synthetic phage antibody scFv library [Hirose, M., Hayano, T., Shirai, H., Nakamura, H., and Kikuchi, M. (1998) Protein Eng. 11, 243-248], was expressed in the E. coli pET system and purified by sequential chromatography on Ni and glutathione-conjugated affinity resins. The purified scFv 20C9 antibody was characterized for its binding affinity for several glutathione derivatives by the BIACORE system. Although GSH, GSSG, and gamma-Glu-Cys could bind to the immobilized antibody, this was not the case for Cys-Gly, l-Glu, l-Cys, l-Gly, or several other glutathione derivatives such as gamma-Glu-Ser-Gly. The results suggest that a gamma-glutamic acid and sulfur atom are important for scFv 20C9 antibody recognition of glutathione. This is the first report to indicate that an scFv antibody can recognize a region as small as a dipeptide.

Acute effects of ovariectomy on wound healing of alveolar bone after maxillary molar extraction in aged rats.

Acute effects of ovariectomy on the bone wound healing processes after maxillary molar extraction in aged rats were examined by means of quantitative scanning electron microscopy (SEM), backscattered electron image (BSE) analysis and energy-dispersive X-ray (EDX) microanalysis. Six-month-old female rats underwent either sham operation or bilateral ovariectomy, and 7 days postoperatively, the maxillary first molars were extracted. On post-extraction days 7, 30 and 60, the dissected maxillary bone surfaces were examined by SEM to reveal the bone formative and resorptive areas around the extracted alveolar sockets. In addition, the resin-embedded maxillae were micromilled in the transverse direction through the extracted alveolar sockets, and the newly-formed bone mass on the buccal bone surfaces and within the extracted sockets was examined by BSE analysis. Compared with sham-operated controls, the extent of newly-formed bone mass on the buccal bone surfaces in OVX rats was significantly decreased, due to increased bone resorption. On the other hand, new bone formation within the extracted sockets was similar in the experimental groups. In EDX microanalysis of these newly-formed bone matrices, both Ca and P weight % and Ca/P molar ratio were similar in the experimental groups. Our results suggest that 1) acute estrogen deficiency induced by ovariectomy stimulates sustained bone resorption, but has less effect on bone formation, and 2) bone wound healing after maxillary molar extraction within extracted alveolar sockets is not significantly delayed by ovariectomy, but bony support by newly-formed bone mass on the maxillary bone surfaces at the buccal side of the extracted sockets is significantly decreased, due to increased bone resorption.

Bone wound healing after maxillary molar extraction in ovariectomized aged rats: quantitative backscattered electron image analysis.

The processes of bone wound healing after maxillary molar extraction in ovariectomized aged rats were examined by means of quantitative backscattered electron image analysis and energy-dispersive X-ray microanalysis. Six-month-old female rats were either sham-operated or underwent bilateral ovariectomy (OVX), and 60 days postoperatively, the maxillary first molars were extracted. On post-extraction days 7, 30, and 60, the dissected and resin-embedded maxillae were micromilled in the transverse direction through the extracted alveolar sockets, and new bone formation on the buccal maxillary bone surface and within the extracted alveolar sockets was examined. In both sham-operated control and OVX rats, new bone formation was recognized on the buccal bone surface, as well as within the extracted sockets, and increased daily through to day 60. In comparison to sham-operated controls, new bone formation in OVX rats was significantly decreased both on the buccal bone surface and within the extracted sockets. Our results suggest that bone wound healing by new bone formation after maxillary molar extraction is significantly decreased in OVX-induced osteoporosis.

Stimulation of the locus coeruleus suppresses trigeminal sensorimotor function in the rat.

The nucleus locus coeruleus (LC) has been implicated in the modulation of the spinal sensorimotor function. The aim of the present study was to examine the effect of electrical stimulation of the LC on sensorimotor function in the trigeminal system. The following two cases of sensorimotor behaviors mediated by the trigeminal brainstem sensory nuclear complex were examined: (1) the activity of the masseter muscle evoked by pressure on the region of the temporomandibular joint (TMJ); and (2) the activity of the digastric muscle evoked by electrical stimulation of the tooth pulp, resulting in the jaw-opening reflex. In the first case, LC stimulation at 10, 30 and 50 microA resulted in a 70%, 68% and 55% reduction in the magnitude of electromyogram (EMG) activity of the masseter muscle compared with the control (without LC stimulation), respectively. The threshold intensity for the onset of masseter EMG activity increaced to 106%, 111% and 121% of the control with 10, 30 and 50 microA LC stimulation, respectively. In the second case, EMG magnitude in response to the digastric muscle decreased to 42% of the control when 30 microA of LC stimulation was delivered. These results suggest that descending influences from the LC can act in suppression of the trigeminal sensorimotor function.

Effects of ovariectomy on bone morphology in maxillae of mature rats.

Postmenopausal oestrogen deficiency results in bone loss (osteoporosis) in humans and experimental animals. The loss of trabecular bone in the ovariectomized (OVX) rat provides a useful experimental model of post-menopausal osteoporosis. At 5 months after ovariectomy of 3-month-old female rats, the mid and distal femurs and maxillae were dissected and processed for quantitative backscattered electron microscopic examinations. Histomorphometric analysis of femurs in OVX rats showed significant loss in metaphyseal trabecular bone areas compared with sham-operated controls; no significant bone loss was observed in the cortical bone areas of mid-diaphyses in OVX rats. Net bone areas in the maxillae of OVX rats was similar to that of sham-operated controls. Bone structure of maxillae in OVX rats was also similar to that in controls. Our results suggest that, in this animal model of osteoporosis, prominent bone loss occurs mainly in the bone areas formed by endochondral ossification such as distal femurs, but those areas formed by intramembranous ossification such as mid-femurs and maxillae sustained less effects by OVX.

Altered abdominal fat distribution and its association with the serum lipid profile in non-diabetic haemodialysis patients.

BACKGROUND: Disturbances of lipid and carbohydrate metabolism may be associated with the distribution of abdominal adiposity. However, little is known about the alteration of abdominal adiposity and its association with the serum lipid profile in haemodialysis patients. METHODS: We evaluated the distribution of abdominal adiposity by using computed tomography and examined its relationship with the serum lipid profile in 92 non-diabetic haemodialysis patients and 80 control subjects with normal renal function. Since the mean body mass index (BMI) and total body fat mass were significantly lower in the haemodialysis patients than in the control subjects, the subcutaneous abdominal fat area and the visceral fat area were standardized by body mass index and compared between the haemodialysis patients and the control subjects. RESULTS: Mean subcutaneous fat area/body mass index (SFA/BMI) was significantly lower, and mean visceral fat area/body mass index (VFA/BMI) was significantly higher in the haemodialysis patients (SFA/BMI, 2.40+/-0.12; VFA/BMI, 2.28+/-0.15) than in the control subjects (SFA/BMI, 3.75+/-0.21, P<0.01; VFA/BMI, 1.65+/-0.15, P<0.01). Consequently, visceral fat area/ subcutaneous fat area ratio was significantly higher in the haemodialysis patients (1.05+/-0.07) than in the control subjects (0.46+/-0.04, P<0.01). A scattered plot of visceral fat area relative to BMI revealed that visceral fat area was higher in the haemodialysis patients than in the control subjects at any BMI level. A simple regression analysis showed that BMI, total body fat mass, subcutaneous fat area and visceral fat area were all associated with serum triglycerides and the atherogenic index, (total cholesterol-HDL cholesterol)/HDL cholesterol. Furthermore, a multiple regression analysis indicated that the visceral fat area was the best predictor for either the atherogenic index or triglycerides among these fat components. CONCLUSIONS: These data indicate that haemodialysis patients exhibited a visceral fat accumulation irrespective of BMI, and this shift of abdominal adiposity might be associated with disturbance of the serum lipid profile in non-diabetic haemodialysis patients.

Comparison of the effects of convulsant and depressant barbiturate stereoisomers on AMPA-type glutamate receptors.

BACKGROUND: Alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA)-type glutamate receptors mediate fast excitatory synaptic transmission in the central nervous system. Although barbiturates have been shown to suppress the AMPA receptor-mediated responses, it is unclear whether this effect contributes to the anesthetic action of barbiturates. The authors compared the effects of depressant [R(-)] and convulsant [S(+)] stereoisomers of 1-methyl-5-phenyl-5-propyl barbituric acid (MPPB) on the AMPA and gamma-aminobutyric acid type A (GABA(A)) receptor-mediated currents to determine if the inhibitory effects on AMPA receptors correlate to the in vivo effects of the isomers. METHOD: The authors measured whole-cell currents in the rat cultured cortical neuron at holding potential of -60 mV. Kainate 500 microM was applied as the agonist for AMPA receptors. Thiopental (3-300 microM), R(-)-MPPB or S(+)-MPPB (100-1,000 microM) was coapplied with kainate under the condition in which the GABA(A) receptor-mediated current was blocked. Effects of MPPB isomers on the current elicited by GABA 1 microM were studied in the separate experiments. RESULTS: Thiopental inhibited the kainate-induced current reversibly and in a dose-dependent manner, with a concentration for 50% inhibition of 49.3 microM. Both R(-)-MPPB and S(+)-MPPB inhibited the kainate-induced current with a little stereoselectivity. R(-)-MPPB was slightly but significantly more potent than S(+)-MPPB. In contrast, R(-)-MPPB enhanced but S(+)-MPPB reduced the GABA-induced current. CONCLUSIONS: Both convulsant and depressant stereoisomers of the barbiturate inhibited the AMPA receptor-mediated current despite of their opposite effects on the central nervous system in vivo. Although thiopental exhibited a considerable inhibition of AMPA receptors, the results suggest that the inhibition of AMPA receptors contributes little to the hypnotic action of the barbiturates.

Depressant and convulsant barbiturates both inhibit neuronal nicotinic acetylcholine receptors.

UNLABELLED: Neuronal nicotinic acetylcholine receptors (neuronal nAchRs) are sensitive to many anesthetics, including barbiturates, which suggests that these receptors are potential sites for anesthetic action. Subtle changes in molecular structures of the anesthetic barbiturates can produce compounds with potent convulsant activity. Whereas R(-) isomer of 1-methyl-5-phenyl-5-propyl barbituric acid (MPPB) exerts anesthetic action, S(+)MPPB exhibits pure excitatory effects, including convulsion. 5-(2-cyclohexilidene-ethyl)-5-ethyl barbituric acid is another example of a convulsant barbiturate. We compared the effects of depressant and convulsant barbiturates on the neuronal nAchR-mediated current to determine whether inhibition of neuronal nAchRs contributes to the anesthetic action of barbiturates. Whole cell nicotine-induced currents were recorded in PC12 derived from rat pheochromocytoma, using the conventional whole cell patch clamp technique in the presence and absence of barbiturates. Both depressant and convulsant barbiturates inhibited the nicotine-induced inward current reversibly and in a dose-dependent manner when co-applied with nicotine. All barbiturates accelerated the current decay. There was no significant difference between the concentrations for 50% inhibition for MPPB isomers. There was no correlation between inhibition of ganglionic nAchRs and anesthetic effects of the barbiturates. These results strongly oppose the idea that inhibition of neuronal nAchRs contributes to the anesthetic action of barbiturates. IMPLICATIONS: We found that both convulsant and depressant barbiturates inhibit the current mediated through ganglionic nicotinic acetylcholine receptors in PC12 cells. This finding suggests that the inhibition of neuronal nicotinic acetylcholine receptors does not contribute to the anesthetic action of barbiturates.

Association of the serum leptin concentration with weight loss in chronic hemodialysis patients.

Circulating leptin, which is partly cleared by the kidney, has been reported to increase with chronic renal failure and thus may play a role in the weight loss of patients with chronic renal failure. We investigated the association of body weight loss with the serum leptin concentration in Japanese hemodialysis patients. The relationship between serum leptin and the body mass index (BMI) or body fat mass was compared among 181 patients undergoing hemodialysis and 185 control subjects. There was no difference in the serum leptin concentration between the hemodialysis patients (HD) and controls (C) for either the men (3.9 +/- 0.2 ng/mL for HD, n=117; 3.9 +/- 0.3 ng/mL for C, n=89; NS) or women (8.9 +/- 1.2 ng/mL for HD, n=64; 7.4 +/- 0.5 ng/mL for C, n=96; NS), whereas BMI of the hemodialysis patients was significantly lower than that of the controls for both the men (20.1 +/- 0.2 kg/m2 for HD, 22.4 +/- 0.3 kg/m2 for C, P < 0.001) and women (19.2 +/- 0.3 kg/m2 for HD, 22.0 +/- 0.4 kg/m2 for C, P < 0.001). The serum leptin/body fat mass ratio was significantly correlated with the weight change of the patients during a follow-up evaluation period of 17 months (r = -0.37, P < 0.05 for men, n=27 and r = -0.53, P < 0.005 for women, n=28), indicating the possibility that a relatively high level of serum leptin had induced weight loss in the hemodialysis patients. The serum leptin/body fat mass ratio also showed a significant inverse correlation with the duration of hemodialysis (r = -0.31, P < 0.05 for men and r = -0.49, P < 0.05 for women). A multiple regression analysis indicated that the body fat mass was significantly correlated with serum leptin concentration, whereas the fat distribution did not have any relationship with leptin. These data indicate that a high level of serum leptin relative to the body fat mass might be associated with weight loss in long-term hemodialysis patients. The serum leptin level relative to the body fat mass also seems to have been affected by the duration of hemodialysis.

The effects of ketamine and propofol on neuronal nicotinic acetylcholine receptors and P2x purinoceptors in PC12 cells.

UNLABELLED: We studied the effects of ketamine and propofol on two ligand-gated ion channels mediating fast synaptic transmission through sympathetic ganglia, neuronal nicotinic acetylcholine receptors (nAchRs), and P2X purinoceptors in a rat pheochromocytoma cell line PC12 using whole cell voltage clamp recording. Ketamine and propofol similarly inhibited the nicotine-induced inward current reversibly and dose-dependently at the membrane potential of -60 mV but had no effects on the adenosine triphosphate-induced current. Both anesthetics accelerated the current decay during agonist application, resulting in greater inhibition on the steady current than the peak current. The 50% inhibition concentration values for the steady current were lower than the clinically relevant concentrations for ketamine (2.8+/-0.6 microM) and higher than those for propofol (5.4+/-0.6 microM). Both anesthetics induced an addition of the fast component to the decay phase and an acceleration of the slow component, which suggests an open channel blockade or an enhancement of desensitization as a mechanism. The effects on closed channels seemed to be small because preincubation with the anesthetics did not significantly augment the block. Inhibition was voltage-independent at membrane potentials between -20 and -70 mV and was consistent with a noncompetitive block. Inhibition of the neuronal nAchR-mediated current may lead to the suppression of synaptic transmission in sympathetic ganglia by ketamine, but not by propofol, at the clinically relevant concentrations. However, these results are not consistent with changes in sympathetic nerve activities reported for animals or humans anesthetized with ketamine or propofol, which suggests effects from other systems, such as the central nervous system in vivo. IMPLICATIONS: Ketamine (at smaller than clinically relevant concentrations) and propofol (at larger than clinically relevant concentrations) inhibited neuronal nicotinic acetylcholine receptor-mediated current in PC12 cells, which possess the receptors that resemble those in postganglionic sympathetic neurons. These findings are not consistent with in vivo experiments, which suggests that effects from other systems, such as the central nervous system, are of importance.

Impaired water excretion in a hyponatremic patient following thyroidectomy: causal role of glucocorticoid deficiency.

We evaluated the causal role of glucocorticoid deficiency in the hyponatremia that developed in a 57-year-old Japanese man with hypothyroidism following the performance of a total thyroidectomy for laryngeal cancer. The plasma concentration of vasopressin (1.78 pg/ml) was not suppressed in the presence of hyponatremia (125 mEq/l). The urinary excretion of sodium was increased, and the plasma renin activity and plasma aldosterone concentration were suppressed. The infusion of hypertonic saline increased the plasma osmolality, but not the plasma concentration of vasopressin. An oral water load (20 ml/kg of body weight) did not suppress the plasma vasopressin level or induce diuresis. Pretreatment with hydrocortisone normalized the response of plasma vasopressin to the water load was well as the diuretic response during the hypothyroid state. The urinary excretion of 17-hydroxycorticosteroids was below normal in the hypothyroid state in the face of normal serum cortisol concentration. The correction of the hypothyroidism returned these abnormalities to normal. A disturbed metabolism of glucocorticoid may have been responsible for the hyponatremia and disturbance in plasma vasopressin regulation observed in this hypothyroid patient.

The proliferation and differentiation of neonatal epidermal melanocytes in F1 hairless mice of HR-1 x HR/De in serum-free culture.

To investigate the characteristics of the proliferation and differentiation of epidermal melanocytes in F1 hairless mice of HR-1 x HR/De parents in vitro, cell suspensions of the neonatal epidermis were cultured in a serum-free medium supplemented with dibutyryl adenosine 3',5'-cyclic monophosphate (DBcAMP) and/or basic fibroblast growth factor (bFGF). The differentiation of melanocytes was induced by treatment with DBcAMP. In contrast, the sustained proliferation of melanoblasts was induced by combined treatment with DBcAMP and bFGF. The melanoblasts could be subcultured in serum-free medium supplemented with the two factors in the presence of keratinocytes, but not in their absence. This is the first report of successful culture of melanoblasts and melanocytes from hairless mice; it is expected to be useful in understanding the mechanism of the development of pigmented spots in the epidermis of (HR-1 x HR/De)F1 mice, which are reported to be induced by repeated exposure to ultraviolet light B.

A patient with thrombotic microangiopathy accompanied by glomerular subendothelial electron dense deposits.

A 50-year-old woman presented with thrombocytopenia, microangiopathic hemolytic anemia, and nephrotic syndrome. Although a high level of circulating immune complexes, mild hypocomplementemia, and the antinuclear antibody also were present, the criteria for collagen disease were not fulfilled. Renal biopsy demonstrated a typical thrombotic microangiopathy (TMA) involving glomeruli. There also were electron-dense deposits located just beneath the original glomerular basement membrane in the dilated subendothelial space, thought to be immune complexes following positive IgG, C1q and C3 staining on an immunofluorescent study. Corticosteroid therapy rapidly ameliorated her hematologic abnormalities and proteinuria and normalized the immunologic data. These findings strongly suggest that the TMA in this patient was induced by immune complex-associated mechanisms.

Bone wound healing after maxillary molar extraction in ovariectomized aged rats.

We studied bone wound healing processes after maxillary molar extraction in ovariectomized (OVX) aged rats, as an experimental model of postmenopausal osteoporosis, by means of scanning electron microscopy. Six-month-old female rats were either sham-operated or bilaterally OVX; and at 60 days postoperatively, the maxillary first molars were extracted. On postextraction days 4, 7, 30 and 60, the dissected maxillae were fixed and the alveolar bone surfaces around the extracted alveolar sockets were examined. In sham-operated controls, new bone formation was recognized on the buccal-side bone surfaces on day 4 and then increased in extent daily through day 60 mainly on the buccal and mesial sides. On day 60, the extracted sockets were filled with new bone mass and the surrounding alveolar bone surfaces had become smooth, indicating decreased bone metabolism. Bone resorption was prominent throughout the bone surfaces around and within the extracted sockets, increased in extent through day 7, but had decreased by day 60. In comparison to sham-operated controls, new bone formation in OVX rats was slightly increased in the early phase but subsequently showed a marked decrease. Bone resorption in OVX rats was greatly stimulated and was comparatively long-lasting. These results suggest that, under the present experimental conditions, in bone wound healing after maxillary molar extraction, (i) ovariectomy stimulates sustained bone resorption and (ii) bone formation and resorption both take place at specific sites on alveolar bone surfaces.