Two cases of BRAF-mutated, bulbar conjunctival melanoma, and review of the published literature.

We describe two patients with BRAF-mutated melanoma of the epithelioid cell type arising from primary acquired melanosis with severe atypia of the right bulbar conjunctiva. Patient 1 was a 71-year-old Japanese man. After adjuvant cryotherapy and enucleation of the right eyeball, therapy with vemurafenib was administered for a distant metastasis to a lumbar vertebra, accompanied by erythema multiforme and two keratinous tumours. The patient died due to metastases to the liver and multiple vertebrae, despite therapy with nivolumab and combination therapy with dabrafenib plus trametinib. Patient 2 was a 72-year-old Japanese man. After adjuvant cryotherapy, periodic mitomycin C eye drops, and excision of the superficial portion of the right parotid gland and the dissection of cervical lymph nodes, he was treated with adjuvant combination therapy with dabrafenib plus trametinib. Dermatologists should be familiar with BRAF-mutated conjunctival melanoma, which is usually located on the bulbar conjunctiva and associated with more frequent distant metastasis.

Self-awareness of fast eating and its impact on diagnostic components of metabolic syndrome among middle-aged Japanese males and females.

OBJECTIVE: The aim of the present study was to examine the association between subjects with self-awareness of fast eating and diagnostic components of metabolic syndrome in Japanese middle-aged male and female. PATIENTS AND METHODS: Subjects consisted of 3208 males (average age 50.6 years) and 2055 females (average age 50.0 years). Associations between subjects with self-awareness of fast eating and multiple components of metabolic syndrome (waist circumference, body mass index [BMI], blood pressure, and related blood sample tests) were evaluated. RESULTS: Significantly more males (57.7%) acknowledged themselves as "fast eater" than females (46.5%). Self-reported fast eaters showed significantly elevated body weight, BMI, and waist circumference in both genders. However, only male self-reported fast eaters showed high levels of blood pressure, fasting blood glucose, uric acid, and low-density lipoprotein (LDL)-cholesterol. CONCLUSION: Fast eating is associated with diagnostic components of metabolic syndrome. The effect of acknowledging themselves as fast eater presents a higher impact on males than on females in the middle-aged Japanese population. The present study indicates that finding subjects with self-awareness of fast eating may lead to the prevention of developing metabolic syndrome.

Insulin-like growth factor-1 and lipoprotein profile in cord blood of preterm small for gestational age infants.

Low birth weight was associated with cardiometabolic diseases in adult age. Insulin-like growth factor-1 (IGF-1) has a crucial role in fetal growth and also associates with cardiometabolic risks in adults. Therefore, we elucidated the association between IGF-1 level and serum lipids in cord blood of preterm infants. The subjects were 41 consecutive, healthy preterm neonates (27 male, 14 female) born at <37-week gestational age, including 10 small for gestational age (SGA) infants (<10th percentile). IGF-1 levels and serum lipids were measured in cord blood, and high-density lipoprotein cholesterol (HDLC), low-density lipoprotein cholesterol (LDLC) and very low-density lipoprotein triglyceride (VLDLTG) levels were determined by HPLC method. SGA infants had lower IGF-1 (13.1 ± 5.3 ng/ml), total cholesterol (TC) (55.0 ± 14.8), LDLC (21.6 ± 8.3) and HDLC (26.3 ± 11.3) levels, and higher VLDLTG levels (19.0 ± 12.7 mg/dl) than in appropriate for gestational age (AGA) infants (53.6 ± 25.6, 83.4 ± 18.9, 36.6 ± 11.1, 38.5 ± 11.6, 8.1 ± 7.0, respectively). In simple regression analyses, log IGF-1 correlated positively with birth weight (r = 0.721, P < 0.001), TC (r = 0.636, P < 0.001), LDLC (r = 0.453, P = 0.006), and HDLC levels (r = 0.648, P < 0.001), and negatively with log TG (r = -0.484, P = 0.002) and log VLDL-TG (r = -0.393, P = 0.018). Multiple regression analyses demonstrated that IGF-1 was an independent predictor of TC, HDLC and TG levels after the gestational age and birth weight were taken into account. In preterm SGA infants, cord blood lipids profile altered with the concomitant decrease in IGF-1 level.

Effect of manipulating serum phosphorus with phosphate binder on circulating PTH and FGF23 in renal failure rats.

Phosphorus directly controls parathyroid hormone (PTH) synthesis and secretion. Serum levels of the novel phosphate-regulating hormone, fibroblast growth factor 23 (FGF23), are positively correlated with hyperphosphatemia in patients with chronic renal insufficiency (CRI). We proposed that changes in serum PTH and FGF23 levels might be associated with changes in serum phosphorus levels caused by the phosphate binder sevelamer hydrochloride (sevelamer, i.e. crosslinked poly[allylamine hydrochloride]). Rats were fed a diet containing adenine for 4 weeks to establish CRI. Animals were then offered either a normal diet or a diet containing 1 or 3% sevelamer for 8 weeks continuously, or intermittently with sevelamer diet or a normal diet offered for alternating 2-week periods. Changes in the serum levels of phosphorus, calcium, PTH, FGF23, and 1alpha,25-dihydroxyvitamin D(3) (1,25(OH)(2)D(3)) were monitored over time. Adenine-treated rats developed severe CRI, with markedly elevated serum levels of phosphorus, PTH and FGF23, and reduced levels of serum 1,25(OH)(2)D(3). Continuous treatment with sevelamer suppressed these increases throughout the study period. Serum phosphorus, PTH, and FGF23 levels decreased rapidly when sevelamer treatments commenced and recovered rapidly once they were discontinued. However, the changes in serum FGF23 levels began after the onset of changes in serum phosphorus and PTH levels. In conclusion, circulating PTH, and FGF23 levels can be promptly manipulated through the control of serum phosphorus levels. Moreover, phosphate-binder treatment can effectively inhibit the elevation of serum FGF23 levels, as well as PTH levels, under conditions of CRI.

Design and application of a novel brain slice system that permits independent electrophysiological recordings from multiple slices.

We describe a novel brain slice system 'SliceMaster' that allows electrophysiological recordings from eight brain slices independently. The system consists of two autonomous units each supporting four modular brain slice chambers enabling high signal-to-noise ratio recordings, each chamber has one stimulation electrode, one recording electrode, a twin camera system and a solution application system. The positioning of both electrodes and cameras are controlled from a remote user console. The software both acquires and performs on-line analysis of the data. We have demonstrated utility of this system in obtaining recordings of spontaneous firing activity and evoked synaptic activity from mouse hippocampal slices, with reduced variability within and between experiments. Furthermore, we show recordings of population spikes from the perirhinal cortex, indicating applicability of this system for further brain regions. In addition, stable recordings could be maintained until recording was terminated after 3 h, permitting investigation of the induction and maintenance of synaptic plasticity. Recordings of spontaneous and synaptic activity, and effects of pharmacological and electrophysiological manipulation, were consistent with reports using conventional methods. However, the described system permits concurrent and independent recordings from eight brain slices, thus improving throughput, statistical design, and reducing animal use.

Augmented cytoplasmic Smad4 induces acceleration of TGF-beta1 signaling in renal tubulointerstitial cells of hereditary nephrotic ICGN mice with chronic renal fibrosis; possible role for myofibroblastic differentiation.

The Institute of Cancer Research (ICR)-derived glomerulonephritis (ICGN) mouse is a hereditary model animal for nephrotic syndrome with chronic renal tubulointerstitial fibrosis. In most fibrotic diseases, myofibroblastic differentiation is considered to play crucial roles in pathogenesis of fibrosis and is dominantly regulated by the transforming growth factor (TGF)-beta1 signaling system. To reveal the pathogenic mechanism of chronic renal fibrosis in ICGN mice, we examined the expression and localization of TGF-beta1 signal transducer proteins (TGF-beta receptor-I and -II, Smad2/3 and Smad4) in kidney sections and in primarily cultured tubulointerstitial fibroblasts (TIFs). In kidneys of ICGN mice, many tubulointerstitial cells were differentiated to myofibroblastic cells and were alpha-smooth muscle actin (alphaSMA)-positive. The numbers of alphaSMA-positive TIFs prepared from kidneys of ICGN mice (ICGN-TIFs), but not those of ICR control mice (ICR-TIFs), increased during cell culture. No significant differences in production or activation of TGF-beta1 between ICGN-TIFs and ICR-TIFs were seen by enzyme-linked immunosorbent assay. In vitro transcriptional reporter assay for TGF-beta1 and Western immunoblotting for TGF-beta1 signal transducers showed no notable differences in the expression levels of TGF-beta receptor-I or -II or Smad2/3 between these TIFs. However, augmented cytoplasmic Smad4 protein in ICGN-TIFs, but not ICR-TIFs, seemed to cause hypersensitivity against TGF-beta1, and the eventual nuclear localization of Smad2/3-Smad4 complex was increased in ICGN-TIFs. Thus, the abnormal cytoplasmic augmentation of Smad4 induces acceleration of TGF-beta1 signaling in the renal tubulointerstitial cells of ICGN mice.

Neurological phenotype and synaptic function in mice lacking the CaV1.3 alpha subunit of neuronal L-type voltage-dependent Ca2+ channels.

Neuronal L-type calcium channels have been implicated in pain perception and neuronal synaptic plasticity. To investigate this we have examined the effect of disrupting the gene encoding the CaV1.3 (alpha 1D) alpha subunit of L-type Ca2+ channels on neurological function, acute nociceptive behavior, and hippocampal synaptic function in mice. CaV1.3 alpha 1 subunit knockout (CaV1.3 alpha 1(-/-)) mice had relatively normal neurological function with the exception of reduced auditory evoked behavioral responses and lower body weight. Baseline thermal and mechanical thresholds were unaltered in these animals. CaV1.3 alpha 1(-/-) mice were also examined for differences in N-methyl-D-aspartate (NMDA) receptor-dependent (100 Hz tetanization for 1 s) and NMDA receptor-independent (200 Hz in 100 microM DL-2-amino-5-phosphopentanoic acid) long-term potentiation within the CA1 region of the hippocampus. Both NMDA receptor-dependent and NMDA receptor-independent forms of long-term potentiation were expressed normally. Radioligand binding studies revealed that the density of (+)[3H]isradipine binding sites in brain homogenates was reduced by 20-25% in CaV1.3 alpha 1(-/-) mice, without any detectable change in CaV1.2 (alpha 1C) protein levels as detected using Western blot analysis. Taken together these data indicate that following loss of CaV1.3 alpha 1 subunit expression there is sufficient residual activity of other Ca2+ channel subtypes to support NMDA receptor-independent long-term potentiation and some forms of sensory behavior/function.

The (betaalpha)(8) glycosidases: sequence and structure analyses suggest distant evolutionary relationships.

There are currently at least nine distinct glycosidase sequence families which are all known to adopt a TIM barrel fold [Henrissat,B. and Davies,G. (1997) CURR: Opin. Struct. Biol., 7, 637-644]. To explore the relationships between these enzymes and their evolution, comprehensive sequence and structure comparisons were performed, generating four distinct clusters. The first cluster, S1, comprises the alpha-amylase related enzymes, all with the retention mechanism (axial-->axial). The second cluster, S2, included two functional subgroups, one composed of various kinds of glucosidases all with the retention mechanism (equatorial-->equatorial) (the so-called 4/7 superfamily), and the other subgroup including the beta-amylases with the inversion mechanism (axial--> equatorial). The third cluster, S3, with the retention mechanism (equatorial-->equatorial), could be subdivided, based on the catalytic residues and mechanisms, into two functional subgroups: the chitinase group, catalysed by two acidic residues on the C-termini of beta-4 and beta-6, and the hevamine group, using two acidic residues on the C-termini of beta-4 for catalysis. The fourth cluster, S4, is composed of chitobiase with the retention mechanism (equatorial--> equatorial). These clusters are compared with the sequence families derived by Henrissat and coworkers. PSI-BLAST profiles and multiple-alignments of tertiary structures suggest that S1 and S2 are distantly related, as are S3 and S4, which have N-acetylated substrates. This work highlights the difficulties of untangling distant evolutionary relationships in ubiquitous folds such as the TIM barrel.

Renal mineral handling in normal rats treated with sevelamer hydrochloride (Renagel), a noncalcemic phosphate binder.

The effects of sevelamer hydrochloride (Renagel); hereafter referred to as sevelamer), a noncalcemic phosphate binder, on renal mineral handling were examined in rats. Normal rats were fed a diet containing 0.3, 1, 3, and 5% sevelamer for 8 days, and serum, urine, and the immunohistochemical localization of the type II Na/Pi cotransporter protein in the kidney were analyzed. Rats treated with 3 or 5% sevelamer showed significant decreases in serum phosphorus (P) and parathyroid hormone (PTH) levels, with no changes in serum calcium (Ca), magnesium (Mg), or 1,25(OH)2D3 levels. Increases were observed in urinary excretions of Ca and Mg associated with a reduction in the PTH level in rats treated with 3 or 5% sevelamer. Rats treated with 1% or higher concentrations of sevelamer showed significant dose-dependent and marked reductions of the urinary P excretion, and the tubular reabsorption of P was maximized to almost 100% in the 5% sevelamer group. The hypophosphaturia in rats treated with 3 or 5% sevelamer was accounted for by the reductions in serum PTH and P per se, and immunohistochemical analysis showed that the expression of type II Na/Pi cotransporter protein was markedly increased at the brush border membranes of the deep and superficial nephrons in rats treated with 5% sevelamer as compared with rats given a normal diet. In conclusion, sevelamer rapidly lowered serum P and PTH levels in normal rats. Sevelamer treatment also produced a marked hypophosphaturia associated with translocation of type II Na/Pi cotransporter protein and increased urinary Ca and Mg excretions by the reduction of PTH.

Coronary artery bypass grafting for patients with non-dialysis-dependent renal dysfunction (serum creatinine > or =2.0 mg/dl).

INTRODUCTION: Patients with renal dysfunction carry a risk of coronary atherosclerosis. The purpose of this study was to evaluate the outcome after coronary artery bypass grafting (CABG) in patients with decreased renal function (serum creatinine > or =2.0 mg/dl). METHODS: We retrospectively analyzed consecutive patients who had undergone isolated CABG at Shin-Tokyo Hospital between May 1, 1991 and April 31, 2000. Preoperative, perioperative, and follow-up data of the non-dialysis-dependent patients with preoperative serum creatinine equal to or more than 2.0mg/dl (group R, n=59) were collected, and compared with those of the control patients (serum creatinine < 2.0, group C, n=1666). Group R was further divided into the off-pump and on-pump CABG group and their perioperative results were compared. RESULTS: Group R included 51 males and eight females with a mean age of 66.4. The mean number of anastomoses was not significantly different between groups; however, clump time and pump time were longer in group R. Postoperative recovery was longer in group R than in group C, which is associated with a more frequent occurrence of major complications (28.8% in group R and 10.7% in group C, P<0.0001) and mortalities (6.8% in group R and 0.5% in group C, P<0.0005). The patients who underwent off-pump CABG experienced relatively faster recovery than those who underwent on-pump CABG, despite decreased renal function. At the mean follow-up of 2.4 years, the actuarial 3-year survival rate of groups R and C were 75.3 and 96.9%, respectively (P<0.0001), excluding hospital mortality. The actuarial 3-year cardiac event-free rate was 76.7% in group R and 87.3% in group C (P<0.05). CONCLUSIONS: Patients with decreased renal function carry significant operative risks and require prolonged hospital care. Even after adequate surgical revascularization was completed, the long-term cardiac event-free and survival rates in the patients with renal dysfunction were inferior to the patients with normal renal function.

Sevelamer hydrochloride (Renagel), a non-calcaemic phosphate binder, arrests parathyroid gland hyperplasia in rats with progressive chronic renal insufficiency.

BACKGROUND: It has been demonstrated that dietary phosphate restriction suppresses parathyroid hormone (PTH) secretion and parathyroid cell proliferation in experimental animals with chronic renal insufficiency (CRI) independently of serum calcium and 1,25(OH)(2)D3 levels. This study was conducted to examine whether sevelamer hydrochloride (Renagel); hereafter referred to as sevelamer), a non-calcaemic phosphate binder could inhibit the parathyroid gland (PTG) hyperplasia in rats with progressive CRI. METHODS: Male Sprague-Dawley rats were injected twice with low doses of adriamycin (ADR). Two weeks after the last injection of ADR, rats were fed a diet containing 1 or 3% sevelamer for 84 days. Time course changes of serum levels of calcium, phosphorus, and PTH were measured. At the end of study, serum 1,25(OH)(2)D3 levels were measured and the maximal two-dimension area of the PTG in paraffin section was calculated using an imaging analyser. RESULTS: Dietary sevelamer treatment inhibited the elevations of serum phosphorus, calciumxphosphorus product, and PTH levels that occurred as the study progressed. Sevelamer also suppressed maximal PTG area and there existed positive strong correlation between maximal PTG area and serum PTH levels at the end of the study. Serum phosphorus levels positively correlated well with serum PTH levels and maximal PTG area. In contrast, serum calcium or 1,25(OH)(2)D3 levels did not show any correlation with serum PTH levels and maximal PTG area. CONCLUSIONS: Sevelamer treatment arrested hyperphosphataemia and PTG hyperplasia accompanied by the elevation of serum PTH levels. The correlation analysis suggests that reduced serum phosphorus levels contributed to the suppression of PTG hyperplasia and resulted in the reduction of PTH levels in this animal model after the sevelamer treatment. The management of phosphorus control started from early stage of CRI could prevent PTG hyperplasia and facilitate later management of secondary hyperparathyroidism.

Cloning of rodent megsin revealed its up-regulation in mesangioproliferative nephritis.

BACKGROUND: We recently cloned a new human mesangium-predominant gene, megsin. Megsin is a novel member of the serine protease inhibitor (serpin) superfamily. To elucidate functional roles of this gene, we cloned megsin in rodents and investigated its role in a rat nephritis model. METHODS: Megsin homologues were cloned from cultured rat and mouse mesangial cDNAs utilizing polymerase chain reaction (PCR) with degenerative primers. Expression of megsin in three different types of resident glomerular cells was investigated by PCR. Levels of megsin mRNA expression at various time points in the anti-Thy1 rat nephritis model were studied by semiquantitative PCR and Northern blotting analysis. In order to investigate megsin protein expression in anti-Thy1 nephritis rats, we raised antibody against rat megsin-specific synthetic peptide, with which immunohistochemical studies were performed. RESULTS: Rat and mouse megsins were composed of 380 amino acids, which revealed 75.3 and 73.9% identity, respectively, with human megsin at the amino acid level. Characteristic features as an inhibitory serpin were conserved in both rat and megsin megsins. PCR analysis revealed expression of megsin in cultured mesangial cells but not in glomerular epithelial or endothelial cells. In anti-Thy1 nephritis rats, semiquantitative PCR and Northern blotting showed that expression of megsin mRNA was up-regulated in glomeruli at day 8. Immunohistochemical studies demonstrated the prominent accumulation of megsin in glomeruli at the same time point. Megsin was mainly localized in mesangial area. The megsin expression level returned to the basal level at day 28. CONCLUSION: Sequences of megsin were well conserved among different species. Rat megsin was also predominantly expressed in mesangial cells. Expression of megsin was up-regulated at the peak of hypercellularity and matrix accumulation in the mesangioproliferative glomerulonephritis model, suggesting that megsin may participate in the process of glomerulosclerosis by modulating extracellular matrix deposition or cell survival.

Local Ca(2+) transients and distribution of BK channels and ryanodine receptors in smooth muscle cells of guinea-pig vas deferens and urinary bladder.

1. The relationship between Ca(2+) sparks spontaneously occurring at rest and local Ca(2+) transients elicited by depolarization was analysed using two-dimensional confocal Ca(2+) images of single smooth muscle cells isolated from guinea-pig vas deferens and urinary bladder. The current activation by these Ca(2+) events was also recorded simultaneously under whole-cell voltage clamp. 2. Spontaneous transient outward currents (STOCs) and Ca(2+) sparks were simultaneously detected at -40 mV in approximately 50 % of myocytes of either type. Ca(2+) sparks and corresponding STOCs occurred repetitively in several discrete sites in the subplasmalemmal area. Large conductance Ca(2+)-dependent K(+) (BK) channel density in the plasmalemma near the Ca(2+) spark sites generating STOCs was calculated to be 21 channels microm(-2). 3. When myocytes were depolarized from -60 to 0 mV, several local Ca(2+) transients were elicited within 20 ms in exactly the same peripheral sites where sparks occurred at rest. The local Ca(2+) transients often lasted over 300 ms and spread into other areas. The appearance of local Ca(2+) transients occurred synchronously with the activation of Ca(2+)-dependent K(+) current (I(K,Ca)). 4. Immunofluorescence staining of the BK channel alpha-subunit (BKalpha) revealed a spot-like pattern on the plasmalemma, in contrast to the uniform staining of voltage-dependent Ca(2+) channel alpha1C subunits along the plasmalemma. Ryanodine receptor (RyR) immunostaining also suggested punctate localization predominantly in the periphery. Double staining of BKalpha and RyRs revealed spot-like co-localization on/beneath the plasmalemma. 5. Using pipettes of relatively low resistance, inside-out patches that included both clustered BK channels at a density of over 20 channels microm(-2) and functional Ca(2+) storage sites were obtained at a low probability of approximately 5%. The averaged BK channel density was 3-4 channels microm(-2) in both types of myocyte. 6. These results support the idea that a limited number of discrete sarcoplasmic reticulum (SR) fragments in the subplasmalemmal area play key roles in the control of BK channel activity in two ways: (i) by generating Ca(2+) sparks at rest to activate STOCs and (ii) by generating Ca(2+) transients presumably triggered by sparks during an action potential to activate a large I(K,Ca) and also induce a contraction. BK channels and RyRs may co-localize densely at the junctional areas of plasmalemma and SR fragments, where Ca(2+) sparks occur to elicit STOCs.

Coronary artery bypass grafting using the radial artery: midterm results in a Japanese institute.

BACKGROUND: To avoid remote cardiac events associated with graft occlusions, arterial conduits are being increasingly utilized in coronary artery bypass grafting (CABG). The development of antispasmic agents has enabled the use of the radial artery as a graft conduit in CABG. METHODS: Between December 1995 and December 1998, 920 consecutive isolated CABG operations were performed at Shin-Tokyo Hospital. The radial artery was used for graft conduits in 475 of these patients, and their data were analyzed in this study. The patients were followed to determine midterm graft patency, cardiac events, and survival. All data are given as mean +/- standard deviation. The end points were patient death or occurrence of cardiac events. RESULTS: The radial artery was used in 475 patients (366 males and 109 females, with a mean age of 64.5+/-8.5 years). The left internal mammary artery was used in 94.9% of patients, the right internal mammary artery in 17.5%, the gastroepiploic artery in 50.9%, the inferior epigastric artery in 0.2%, and the saphenous vein in 39.2%. The in-hospital morbidity and mortality rates of the studied group were 12.8% and 0.6%, respectively. A major complication related to radial artery harvesting, compartment syndrome of the arm due to postoperative bleeding, was observed in 1 patient. No postoperative myocardial infarction attributable to radial artery bypass was observed. During the late follow-up period of 3.5+/-0.9 years, cardiac events were observed in 63 patients, giving actuarial 2- and 3-year event-free rates of 92.8% and 89.6%, respectively. A total of 24 late deaths were noted, including seven cardiac deaths, giving actuarial 2- and 3-year survival rates of 98.1% and 97.2%, respectively. Postoperative angiography was performed in selected patients. The cumulative graft patency rate of the radial artery was 93.0% during the mean angiographical follow-up period of 1.5+/-1.1 years. CONCLUSIONS: No adverse effects were noted after CABG using a radial artery graft in this short- and midterm follow-up period.

Coronary artery bypass grafting for hemodialysis-dependent patients.

Patients with end-stage renal disease carry a risk of coronary atherosclerosis. This study was performed to evaluate the perioperative and remote data of coronary artery bypass grafting (CABG) in hemodialysis dependent patients. We retrospectively analyzed the results of isolated CABG performed at Shin-Tokyo Hospital between June 1, 1993 and May 31, 2000. Preoperative, perioperative, and follow-up data of the patients on hemodialysis (Group HD, n = 37) were collected and compared with those of control patients (Group C, n = 1,639). Group HD consisted of 26 males and 11 females with a mean age of 59.9 +/- 8.1 years, and the mean number of bypasses was 2.5 +/- 1.1. Group HD had a longer postoperative intubation time, ICU stay, and hospital stay than Group C. The postoperative major complication rate in Group HD (18.9%) was not significantly different from that in Group C (11.3%). However, the inhospital mortality rate in Group HD (5.4%) was higher than Group C (0.6%). At the mean follow-up of 2.4 years, the actuarial 3-year survival of Groups HD and C were 90.6% and 97.6%, respectively (p < 0.001), excluding hospital mortality. The actuarial 3-year cardiac event-free rates were 84.3% in Group HD and 88.8% in Group C, showing no difference. Patients on chronic hemodialysis carry a significant risk of prolonged inhospital care and hospital death. Once successful surgical revascularization was completed, their long-term cardiac events could be controlled as effectively. The increased distant death rates was probably associated with the nature of renal disease.

A previous mastectomy does not increase sternal complications after coronary artery bypass grafting regardless of whether an internal mammary artery is used.

A mastectomy for breast cancer may alter the selection of grafts or the postoperative outcomes after coronary artery bypass grafting (CABG). To clarify these points, a retrospective analysis of patients who underwent CABG after a mastectomy was undertaken. A total of 19 mastectomy patients (13 left, 6 right, and 1 bilateral mastectomy) were identified prior to CABG, and their perioperative data as well as late outcomes were examined. The studied group consisted of all females with a mean age of 68.8 +/- 6.2 years. The internal mammary artery (IMA) was used in 14 (73.7%) patients; however, there were no patients in whom bilateral IMAs were harvested. Among these 14 patients, an ipsilateral IMA was harvested in 6 and a contralateral IMA in 8. Alternative grafts were selected in 6 patients. A contralateral IMA or other graft conduits were utilized instead of an ipsilateral IMA. There were no in-hospital deaths or sternal wound complications. With a mean follow-up of 2.6 years, 3 patients died (1 cardiac death and 2 noncardiac deaths) and 1 patient developed angina due to de-novo coronary artery stenosis. In patients who have undergone a previous mastectomy, CABG using a single IMA is considered to be safe. If the IMA has good pulsation and if IMA harvesting is not difficult, even after a mastectomy, it can be used as a graft conduit without increasing the risk of sternal wound complications.

[New subjects for exceeding conventional on-pump CABG].

Coronary artery bypass grafting (CABG) used to be performed under cardiac arrest and cardiopulmonary bypass (CPB). During the last decade, efforts were made to minimize CPB-related complications. The technique of off-pump CABG (OPCAB) has been established during the last 5 years. Elimination of CPB and OPCAB has successfully reduced a number of perioperative complications and has provided early patient recovery. A compression type of coronary stabilizer was used early phase of OPCAB. Off-pump revascularization using the compression device was limited to the anterior wall of the heart. Bypass to the posterior wall under a beating heart was not popular until the suction type of stabilizer had become available. A suction device assisted by the Lima's pericardial suture allowed us to perform bypass grafting any aspects of the heart. Recently, we are skeltonizing the arterial grafts using the Harmonic scalpel. Applying skeltonizing technique to the radial artery or internal thoracic artery, we can successfully perform sequential grafting in selected cases. The number of distal anastomoses has been gradually increased as the device and technique were advanced (2.1 distal anastomoses with a compression device, 2.9 with a suction device, and 3.2 with the skeltonization technique). The frequency of the complete revascularization also increased. On the other hand, the complications associated with the procedure were comparable among these three off-pump methods, but were significantly fewer than on-pump CABG. Currently performed OPCAB can provide almost same number of distal anastomoses as on-pump CABG, with less frequency of postoperative mortality and morbidity, and with early patient recovery. These favorable results were attributed to the progress of the device and technique.

Changes in quantitative profile of extracellular matrix components in the kidneys of rats with adriamycin-induced nephropathy.

Extracellular matrix components (ECMs) in histological sections of the kidney cortex from the rats with adriamycin (ADR)-induced nephropathy (5 mg/kg, i.v.) were quantified by an immunohistochemical micromethod. Changes in kidney histopathology and urine and blood biochemistry were investigated. Enlarged kidneys were granular on the surface and pale in color in ADR-treated rats, and these rats had kidneys with glomeruli with expanded mesangial area and with capillary aneurysm. Severe albuminuria, hypoalbuminemia, hypercholesterolemia and disorders in other nephrotic parameters were observed in ADR-treated rats. Type I and IV collagens, fibronectin and laminin contents in the renal cortex of ADR-treated rats at 10 weeks were 329, 317, 263 and 295%, respectively, higher than in each vehicle control, and those at 28 weeks were 1,211, 930, 1,057 and 1,012%, respectively. The glomerular sclerotic abnormalities progressed in a time-dependent manner. Moreover, there was a strong correlation between the ECM levels and serum creatinine and blood urea nitrogen levels. In conclusion, microquantification provided useful information for accurate diagnosis and prognosis of nephrotic lesions and is a good tool to assess the advancement of renal disorders in patients with nephropathy.

Off-pump coronary artery bypass. Mid-term results.

OBJECTIVES: Off-pump coronary artery bypass grafting (CABG) on the beating heart has become popular procedure in cardiac surgery and its initial results appeared favorable. We report our early and mid-term results of off-pump CABG performed at Shin-Tokyo Hospital. METHODS: Medical records of patients undergoing off-pump or conventional on-pump CABG from September 1, 1996, to August 31, 1999 were retrospectively reviewed. Patients underwent off-pump CABG were further classified into 2 groups; MIDCAB (Off-pump CABG for single vessel revascularization via a small skin incision) and OPCAB (off-pump CABG mainly approached via midline sternotomy) group. Their preoperative, perioperative, and follow-up data were collected and analyzed. RESULTS: Among a total of 995 cases of CABG, 194 cases were off-pump CABG (male/female 142/52, mean age 66.9). The mean number of distal anastomoses in off-pump CABG was 1.9 +/- 0.9 (1.0 +/- 0.0 in MIDCAB and 2.3 +/- 0.7 in OPCAB), which was significantly fewer than in on-pump CABG (3.6 +/- 1.1), with p < 0.0001. Intubation time (5.3 +/- 5.7 hours in off-pump CABG vs 13.1 +/- 24.2 hours in on-pump CABG), ICU stay (1.7 +/- 1.1 vs 3.2 +/- 3.0 days), and postoperative hospital stay (14.0 +/- 7.9 vs 18.1 +/- 12.1 days) in off-pump CABG were significantly shorter than in on-pump CABG (p < 0.0001). In the off-pump CABG group, there were no in-hospital deaths and 14 major complications, fewer than in on-pump CABG (8 hospital deaths and 114 major complications). Postoperative angiography before hospital discharge was conducted in 80 patients (41.2%) and showed 2 occlusions, giving a graft patency rate of 98.6% in the off-pump group. During follow-up (0.9 +/- 0.6 year) period, there were 5 non-cardiac deaths and 20 cardiac events in the off-pump group. The actuarial survival rate at 36 months was 94.6% for off-pump CABG, showing no significant difference from the rate for conventional CABG patients (95.2% at 36 month, p = NS) The event-free rate was 84.0% at 36 months in off-pump CABG patients; however, which was less favorable than on-pump CABG patients (88.0% at 36 months, p < 0.05). CONCLUSIONS: Both in-hospital and mid-term results for off-pump CABG patients were acceptable. Isolated CABG can thus be safely performed without cardiopulmonary bypass. Advances in coronary stabilization have contributed to these improved results. The observed long-term cardiac events may be related to incomplete revascularization.