Effects of chlorpromazine as a systemic vasodilator during cardiopulmonary bypass in neonates

OBJECTIVES: Vasodilator use during cardiopulmonary bypass is important in pediatric cardiac surgery, but the full range of their effects on hemodynamics remains to be clarified. We studied the effects of chlorpromazine, a potent alpha-blocking agent, in neonates. METHODS: Subjects were 60 neonates undergoing arterial switch operations for complete transposition of the great arteries with an intact ventricular septum. Of these, 37 received 2.1 to 6.5 mg/kg of chlorpromazine during cardiopulmonary bypass (CPZ group) and 23 received no vasodilator (control group). We then compared hemodynamic parameters between groups during and early after surgery. RESULTS: The systemic vascular resistance index and mean arterial pressure during cardiopulmonary bypass were significantly lower in the CPZ group (p < 0.05), but systolic pressure 15 minutes after cessation of cardiopulmonary bypass did not differ between groups. The rise in peripheral temperature during rewarming after hypothermia was significantly higher and the acid-base status 40 minutes after cardiopulmonary bypass less acidotic in the CPZ group. Urine output during cardiopulmonary bypass was higher in the CPZ group. CONCLUSIONS: Chlorpromazine effectively counteracts systemic vasoconstriction induced by cardiopulmonary bypass without serious side effects in neonatal cardiac surgery.     

Posttraumatic volar tendon subluxation out of the first extensor compartment: a case report

Symptomatic volar subluxation of the abductor pollicis longus and the extensor pollicis brevis tendons developed in a 29-year-old man after a sprain that occurred with the wrist in flexion and ulnar deviation. The extensor retinaculum, which forms the extensor compartment, was partially avulsed from its insertion on the radius. Palmar abduction and extension of the thumb with the wrist flexed produced subluxation of the tendons over the volar side of the radius ridge where the retinaculum forming the first extensor compartment attached. Nonoperative treatment including steroid injection and splinting was ineffective. Surgery was performed to reconstruct a new tendon restraint with part of the extensor retinaculum.     

Introducing the clusterin gene into human renal cell carcinoma cells enhances their metastatic potential

PURPOSE: We recently reported a protective role of clusterin expression against apoptosis induced by a wide variety of stimuli in several human cancer models. In the current study we tested the hypothesis that clusterin over expression confers a benefit for the metastasis of renal cell carcinoma through the inhibition of apoptosis induced by the various obstacles the cancer cells may confront after detachment from their primary origin. MATERIALS AND METHODS: We introduced clusterin complementary DNA into human renal cell carcinoma ACHN cells, which do not express detectable level of clusterin expression, and generated the clusterin over expressing cell line ACHN/CL and the control vector only transfected cell line ACHN/C. In vitro anti-cell death activity under anchorage independent conditions among ACHN sublines was examined by limiting dilution assay and cell survival assay in suspension. To investigate the in vivo effects of clusterin over expression on metastatic potentials each cell line was injected into the tail vein or renal subcapsule of nonobese diabetic, severe combined immunodeficient mice and the metastatic features in all abdominal and thoracic organs were evaluated. RESULTS: ACHN/CL showed significantly enhanced growth in limiting dilution cultures compared with ACHN/C. The analysis of cell survival in the floating assay also revealed that ACHN/CL had a powerful survival advantage in suspension compared with ACHN/C. Furthermore, ACHN/CL formed more than 5-fold as many metastatic nodules in the lung after intravenous injection than ACHN/C. Similarly more marked lung metastasis was observed after implanting ACHN/CL cells into the renal subcapsule than after implanting ACHN/C cells. In contrast, there were no significant differences among ACHN sublines in the growth rates in vitro and in vivo, cell motility or invasive ability. CONCLUSIONS: These findings suggest that, if clusterin is over expressed, it prolongs cell survival under unfavorable conditions in the metastatic process, resulting in the enhanced metastatic potential of renal cell carcinoma.     

Gene expression profile of renal proximal tubules regulated by proteinuria

BACKGROUND: Proximal tubules activated by reabsorption of protein are thought to play significant roles in the progression of kidney diseases. Thus, identification of genes related to proteinuria should provide insights into the pathological process of tubulointerstitial fibrosis. METHOD: Gene expression profiles were constructed by means of direct sequencing procedures to identify genes induced in the mouse kidney proximal tubules (PT) exposed to proteinuria. RESULTS: By comparing the gene expression of control PT to that of disease model PT, the abundantly expressed genes in control PT were down-regulated presumably because of potentially toxic effects of proteinuria. From the more than 1000 up-regulated genes, an immunity related gene, thymic shared antigen-1 (TSA-1), and a novel gene, GS188, were selected for further characterization. The increased expression of TSA-1, a member of the Ly-6 family, and of GS188 in response to proteinuria was confirmed by Northern analysis, immunohistochemistry, in situ hybridization and laser microdissection along with real-time PCR analysis. Full length cloning of GS188 identified it as a family member of LR8 that was reported to express predominantly in fibroblasts. CONCLUSIONS: The gene expression profiles showed that the expression patterns in PT were changed dramatically by proteinuria. The profiles include novel genes that should be further characterized to aid the understanding of the pathophysiology of progressive kidney diseases.     

Effect of Ventilatory Settings on Accuracy of Cardiac Output Measurement Using Partial CO2 Rebreathing

Background: Recently, a new device has been developed to measure cardiac output noninvasively using partial carbon dioxide (CO2) rebreathing. Because this technique uses CO2 rebreathing, the authors suspected that ventilatory settings, such as tidal volume and ventilatory mode, would affect its accuracy: they conducted this study to investigate which parameters affect the accuracy of the measurement.

Methods: The authors enrolled 25 pharmacologically paralyzed adult post-cardiac surgery patients. They applied six ventilatory settings in random order: (1) volume-controlled ventilation with inspired tidal volume (VT) of 12 ml/kg; (2) volume-controlled ventilation with VT of 6 ml/kg; (3) pressure-controlled ventilation with VT of 12 ml/kg; (4) pressure-controlled ventilation with VT of 6 ml/kg; (5) inspired oxygen fraction of 1.0; and (6) high positive end-expiratory pressure. Then, they changed the maximum or minimum length of rebreathing loop with VT set at 12 ml/kg. After establishing steady-state conditions (15 min), they measured cardiac output using CO2 rebreathing and thermodilution via a pulmonary artery catheter. Finally, they repeated the measurements during pressure support ventilation, when the patients had restored spontaneous breathing. The correlation between two methods was evaluated with linear regression and Bland-Altman analysis.

Results: When VT was set at 12 ml/kg, cardiac output with the CO2 rebreathing technique correlated moderately with that measured by thermodilution (y = 1.02x, R = 0.63; bias, 0.28 l/min; limits of agreement, -1.78 to +2.34 l/min), regardless of ventilatory mode, oxygen concentration, or positive end-expiratory pressure. However, at a lower VT of 6 ml/kg, the CO2 rebreathing technique underestimated cardiac out-put compared with thermodilution (y = 0.70x; R = 0.70; bias, -1.66 l/min; limits of agreement, -3.90 to +0.58 l/min). When the loop was fully retracted, the CO2 rebreathing technique overestimated cardiac output.     

Clinical features and outcomes in children with antineutrophil cytoplasmic autoantibody-positive glomerulonephritis associated with propylthiouracil treatment.

A retrospective investigation was conducted by members of the Japanese Society for Pediatric Nephrology from 1990 to 1997 to define the clinical features and outcomes in children with antineutrophil cytoplasmic autoantibody (ANCA)-positive glomerulonephritis associated with propylthiouracil treatment. Seven Japanese pediatric patients who had myeloperoxidase-specific ANCA-positive biopsy-proven pauci-immune necrotizing crescentic glomerulonephritis associated with propylthiouracil administration were entered in the study. Three patients had nephritis alone, and four had nephritis and extrarenal organ system vasculitis. Females predominated, and the mean age at onset was 14 yr. Propylthiouracil was reduced or discontinued in all patients and was switched to methimazole in three patients. For the treatment of nephritis, five patients received corticosteroids; three had pulse methylprednisolone, one had plasma exchange, and one had plasma exchange and pulse methylprednisolone before initiating oral prednisolone. The remaining two patients received cyclophosphamide and corticosteroids, one of whom had pulse methylprednisolone before initiating oral prednisolone and cyclophosphamide. All patients achieved remission. In general, ANCA titers correlated with the response to treatment and disease activity, with some exceptions. No patient progressed to end-stage renal disease, renal dysfunction, or death during the follow-up period (58 +/- 25 mo; range, 32 to 108 mo). All but one patient remained euthyroid. In conclusion, this experience suggests that the clinical disease spectrum of ANCA-positive disease associated with propylthiouracil treatment is similar in pediatric and adult patients and that the overall prognosis may be better than that in the non-drug-induced ANCA-positive disease.     

Mucinous cystic tumors of the pancreas

Purpose: This study was conducted to clarify the clinicopathologic characteristics relevant to the specific diagnosis of mucinous cystic tumors of the pancreas. Methods: We retrospectively reviewed the clinical features and histopathologic findings of five patients who underwent curative resection for mucinous cystic tumors of the pancreas at our hospital between 1975 and 2000. Results: All five patients were women, ranging in age from 36 to 69 years, and the tumors were located in the pancreatic body and tail. Histopathologically, three tumors were mucinous cystadenomas and two were mucinous cystadenocarcinomas. All five tumors had ovarian-type stroma, and stromal luteinization was found in the three adenomas. These tumors were classified into two groups according to whether the epithelial lining was endocervical or intestinal. All tumors were spherical and multilocular with a fibrous pseudocapsule. On T1-weighted magnetic resonance images, mucinous cystadenomas with watery mucin showed low signal intensity, but mucinous cystadenocarcinomas with gelatinous mucin or hemorrhagic contents demonstrated high signal intensity. Conclusions: Signal intensity on T1-weighted magnetic resonance images provides highly useful diagnostic information on mucinous cystic tumors of the pancreas. Furthermore, tumors may be classified into two groups according to the type of epithelial lining. Received: December 19, 2001 / Accepted: May 7, 2002 Reprint requests to: T. Hara     

Superdrainage of the ileocolic vein to the internal jugular vein interposed by an inferior mesenteric vein graft in replacing the esophagus with the right hemicolon

The fear of serious complications, such as a necrotic conduit caused by an impaired blood circulation can arise when replacing the esophagus with an intestinal conduit. The aim of this paper is to present effective superdrainage of an intestinal conduit using an inferior mesenteric vein (IMV) interposition graft. In 2008, we performed superdrainage of the ileocolic vein to the internal jugular vein interposed by an IMV graft in replacing the esophagus with the right hemicolon for advanced thoracic esophageal cancer in three patients with a synchronous gastric cancer or a previous gastrectomy. No leakage at the enteric anastomoses occurred. Neither ischemic lesions in these intestinal conduits nor complications caused by harvesting an IMV graft were observed. Superdrainage of the ileocolic vein to the internal jugular vein interposed by an IMV graft effectively improves the blood circulation in intestinal conduits brought up to the neck as an esophageal replacement.     

Regulation of ER molecular chaperone prevents bone loss in a murine model for osteoporosis

Endoplasmic reticulum (ER) stress response is important for protein maturation in the ER. Some murine models for bone diseases have provided significant insight into the possibility that pathogenesis of osteoporosis is related to ER stress response of osteoblasts. We examined a possible correlation between osteoporosis and ER stress response. Bone specimens from 8 osteoporosis patients and 8 disease-controls were used for immunohistochemical analysis. We found that ER molecular chaperones, such as BiP (immunoglobulin heavy-chain binding protein) and PDI (protein-disulfide isomerase) are down-regulated in osteoblasts from osteoporosis patients. Based on this result, we hypothesized that up-regulation of ER molecular chaperones in osteoblasts could restore decreased bone formation in osteoporosis. Therefore, we investigated whether treatment of murine model for osteoporosis with BIX (BiP inducer X), selective inducer BiP, could prevent bone loss. We found that oral administration of BIX effectively improves decline in bone formation through the activation of folding and secretion of bone matrix proteins. Considering these results together, BIX may be a potential therapeutic agent for the prevention of bone loss in osteoporosis patients.     

Expression of potential molecular markers in prostate cancer: correlation with clinicopathological outcomes in patients undergoing radical prostatectomy

The objective of this study was to evaluate the expression levels of multiple potential molecular markers in prostate cancer to clarify the significance of these markers as prognostic indicators in patients undergoing radical prostatectomy (RP). This study included a total of 193 patients with clinically organ-confined prostate cancer who underwent RP without any neoadjuvant therapies. Expression levels of 12 proteins, including Ki-67, p53, androgen receptor (AR), matrix metalloproteinase (MMP)-2, MMP-9, vascular endothelial growth factor, Aurora-A, Bcl-2, clusterin, heat shock protein 27 (HSP27), HSP70, and HSP90, in RP specimens obtained from these 193 patients were measured by immunohistochemical staining. Of the 12 molecules, Ki-67, p53, AR, MMP-2, MMP-9, and HSP27 expression were significantly associated with several conventional prognostic factors. Univariate analysis identified these 6 markers as significant predictors for biochemical recurrence as well, while prostate-specific antigen, Gleason score, seminal vesicle invasion (SVI), surgical margin status (SMS), lymph node metastasis, and tumor volume were also significant. Of these significant factors, Ki-67 expression, SVI, and SMS appeared to be independently related to biochemical recurrence by multivariate analysis. Furthermore, there were significant differences in biochemical recurrence-free survival according to positive numbers of these three independent risk factors. These findings suggest that consideration of expression levels of potential molecular markers in RP specimens, in addition to conventional prognostic parameters, would contribute to accurate prediction of biochemical recurrence following RP in patients with clinically localized prostate cancer, and that combined evaluation of Ki-67 expression, SVI, and SMS would be particularly useful for further refinement of the system in predicting biochemical outcome.