Cellular proliferation during compensatory renal growth in neonatal rats using flow cytometry

BACKGROUND: Compensatory renal growth consists of cellular enlargement and a small but consistent increase in DNA content. It has been assumed that the increase in the total renal DNA content was due to new cell formation. METHODS: To test the hypothesis of whether cellular hyperplasia is the cause of the compensatory renal growth after the loss of the renal parenchyma and the timing of the DNA increase in neonatal rats, we performed cell cycle analysis using flow cytometry. RESULTS: Following unilateral nephrectomy, the maximum increases of neonatal cortical cells entering the S phase occurred at 72 and 120 h (9.4 and 9.6% compared to 7.0 and 6.1% of the sham-operated group). Peak increases of neonatal kidney cortical cells entering the G2M phase occurred at 48 and 72 h (4.3 and 4.6% compared to 3.3 and 3.9% of the sham-operated group). CONCLUSION: DNA synthesis and replication occurs during compensatory renal growth following unilateral nephrectomy in neonatal rats as evidenced by an increase in cells entering both the S and G2M phases. In neonatal rats these events appear to be completed within 48-120 h after nephrectomy.     

Association of the Ser9Gly polymorphism in the dopamine D3 receptor gene with tardive dyskinesia in Korean schizophrenics

Tardive dyskinesia (TD) is usually regarded as one of the most serious side-effects of the long-term usage of neuroleptics due to its high prevalence and potentially irreversible nature. Previously, several genetic polymorphisms were investigated for an association with TD in various ethnic populations. Among them, the Ser9Gly variant in the MscI restriction site of the dopamine D3 receptor gene was reported to be associated with TD. We have investigated the association of Ser9Gly polymorphism of the dopamine D3 receptor gene with TD in Korean schizophrenics. The frequencies of the genotypes of Ser/Ser, Ser/Gly and Gly/Gly in 54 schizophrenic patients without TD were 21 (38.9%), 33 (61.1%) and 0 (0%), while the corresponding frequencies in 59 schizophrenic patients with TD were 25 (42.4%), 28 (47.5%) and 6 (10.1%). We have found a significant genotypic association of the Gly/Gly genotype with TD in Korean schizophrenics (P = 0.028, two-tailed Fisher's exact test). However, there was no significant allelic association of the Ser9Gly allele with TD (chi2 = 0.288, d.f. = 1, P = 0.591) and there was no significant difference in the Abnormal Involuntary Movement Scale score between the three genotypic groups (P = 0.071, anova). In conclusion, we suggest that Gly/Gly homozygotes in the MscI polymorphic site of the dopamine D3 receptor gene may cause some change in the function of the dopamine D3 receptor and may be involved the pathogenesis of TD.     

Microarray-based Analysis of Anti-angiogenic Activity of Demethoxycurcumin on Human Umbilical Vein Endothelial Cells: Crucial Involvement of the Down-regulation of Matrix Metalloproteinase

cDNA microarray-based gene expression analysis has been successfully employed to explore the action mechanism and to validate the targets of several drugs. In the present study, we evaluated anti-angiogenic activity of demethoxycurcumin (DC), a structural analog of curcumin, isolated from Curcuma aromatica , and investigated the effect of DC on genetic reprogramming in cultured human umbilical vein endothelial cells (HUVECs) using cDNA microarray analysis. Of 1024 human cancer-focused genes arrayed, 187 genes were up-regulated and 72 genes were down-regulated at least 2-fold by DC. Interestingly, 9 angiogenesis-related genes were down-regulated over 5-fold in response to DC, suggesting that the genetic reprogramming was crucially involved in anti-angiogenesis by the compound. To verify the results obtained from cDNA microarray analysis, matrix metalloproteinase-9 (MMP-9), the product of one of the angiogenesis-related genes down-regulated over 5-fold by DC, was investigated using gelatin zymography. DC potently inhibited the expression of MMP-9, yet showed no direct effect on its activity. These data show that gene expressional change of MMP-9 is a major mediator for angiogenesis inhibition by DC. All genes identified and microarray data are available on the web at http://dasan.sejong.ac.kr/bioprobe/ .     

Different uptake of 99mTc-ECD adn 99mTc-HMPAO in the same brains: analysis by statistical parametric mapping

The purpose of this study was to investigate the differences between technetium-99m ethyl cysteinate dimer (99mTc-ECD) and technetium-99m hexamethylpropylene amine oxime (99mTc-HMPAO) uptake in the same brains by means of statistical parametric mapping (SPM) analysis. We examined 20 patients (9 male, 11 female, mean age 62+/-12 years) using 99mTc-ECD and 99mTc-HMPAO single-photon emission tomography (SPET) and magnetic resonance imaging (MRI) of the brain less than 7 days after onset of stroke. MRI showed no cortical infarctions. Infarctions in the pons (6 patients) and medulla (1), ischaemic periventricular white matter lesions (13) and lacunar infarction (7) were found on MRI. Split-dose and sequential SPET techniques were used for 99mTc-ECD and 99mTc-HMPAO brain SPET, without repositioning of the patient. All of the SPET images were spatially transformed to standard space, smoothed and globally normalized. The differences between the 99mTc-ECD and 99mTc-HMPAO SPET images were statistically analysed using statistical parametric mapping (SPM) 96 software. The difference between two groups was considered significant at a threshold of uncorrected P values less than 0.01. Visual analysis showed no hypoperfused areas on either 99mTc-ECD or 99mTc-HMPAO SPET images. SPM analysis revealed significantly different uptake of 99mTc-ECD and 99mTc-HMPAO in the same brains. On the 99mTc-ECD SPET images, relatively higher uptake was observed in the frontal, parietal and occipital lobes, in the left superior temporal lobe and in the superior region of the cerebellum. On the 99mTc-HMPAO SPET images, relatively higher uptake was observed in the medial temporal lobes, thalami, periventricular white matter and brain stem. These differences in uptake of the two tracers in the same brains on SPM analysis suggest that interpretation of cerebral perfusion is possible using SPET with 99mTc-ECD and 99mTc-HMPAO.     

Impact of continued hospitalization in patients pre-treated with clopidogrel prior to coronary angiography and undergoing coronary artery bypass grafting

Pre-treatment of patients with clopidogrel prior to coronary angiography (CAG) and possible percutaneous coronary intervention (PCI) is a standard practice. Candidates for coronary artery bypass surgery (CABG) are discharged or remain in the hospital until CABG after clopidogrel is discontinued. We investigated whether any differences exist in the rates of surgical complications and outcomes between these two groups of patients. We conclude that continued hospitalization of clopidogrel pre-treated patients does not confer any safety benefit with regard to post-operative complications and 30-day mortality. Discharging these patients after CAG may reduce hospitalization costs.     

CT and MRI findings of cystadenofibromas of the ovary

The aim of this study was to assess imaging findings on CT or MR images of histologically proven ovarian cystadenofibromas. In the period 1995–2001, 32 histologically proven ovarian cystadenofibromas were identified in 28 women. Of the 32 ovarian cystadenofibromas, 16 tumors were purely cystic and the remaining 16 were complex cystic on CT or MR images. Solid components of 16 complex cystic tumors were seen as nodular (n=8) or trabecular (n=9) solid areas. One tumor had both nodular and trabecular solid components. Among 16 complex cystic tumors, 14 had thick or irregular septa; thus, half of ovarian cystadenofibromas had morphological imaging features of malignancy on CT or MR images. On histology, solid components in the cystic tumors were correlated with fibrous stromas that occasionally made a false-positive result for malignancy on imaging.     

Necessity of ureteral catheter during laparoscopic partial nephrectomy

PURPOSE: Laparoscopic partial nephrectomy (LPN) is a relatively recently introduced method of treating renal tumors and, as such, surgical technique is evolving. In open series urinary fistula formation represents a common postoperative complication. In the laparoscopic approach investigators have advocated the placement of a ureteral catheter with retrograde dye injection to visualize caliceal entry to aid in closure. In this study we assessed the necessity of ureteral catheter placement during LPN in decreasing urinary leakage. MATERIALS AND METHODS: From February 1998 until November 2002 laparoscopic partial nephrectomy was performed in 103 patients with renal tumors. The patients were assessed retrospectively and divided into 2 groups according to placement (group 1) or no placement (group 2) of an external ureteral catheter. Group 1 included 54 patients (mean age +/- SD 57.4 +/- 13.4 years) and group 2 included 49 patients (mean age +/- SD 57.5 +/- 10.9). Intraoperative and postoperative parameters including blood loss, operative time, ischemia time, mass size, complications and hospital stay were reviewed and compared between the 2 groups. RESULTS: There were no differences between the 2 groups in mean estimated blood loss (group 1, 394.7 cc vs group 2, 291.5 cc, p = 0.07), postoperative serum creatinine (group 1, 0.95 mg/dl vs group 2, 0.89 mg/dl, p = 0.12), requirement for pain medication (group 1, 8.9 mg vs group 2, 4.9 mg morphine equivalents, p = 0.12), hospital stay (group 1, 3.1 vs group 2, 2.9, p = 0.29) and warm ischemia time (group 1, 28 minutes vs group 2, 26.5 minutes, p = 0.18). Mean total operative time was significantly longer for group 1 compared to group 2 (191.1 vs 149.4 minutes, respectively, p = 0.001). Postoperative urinary leakage requiring prolonged drainage occurred in 1 patient in group 1 and 1 in group 2. In both cases caliceal entry was identified and sutured. CONCLUSIONS: With experience caliceal entry can be identified without the need for a ureteral catheter in patients undergoing LPN for a tumor less than 4.5 cm. Urinary fistula may occur despite caliceal entry and repair. A ureteral catheter may not decrease urinary fistula in patients undergoing LPN.     

Correlation between urodynamic test results, perineal ultrasound and degree of stress urinary incontinence

OBJECTIVE: To evaluate whether the results of urodynamic tests and the perineal ultrasound were different between grade 1 and 2 stress urinary incontinence. STUDY DESIGN: Forty premenopausal women with a diagnosis of stress urinary incontinence according to urodynamic tests were enrolled in this study. Stress urinary incontinence was defined as urine leakage during stress without detrusor contraction. Twenty patients had grade 1 and 20 had grade 2 stress urinary incontinence. We compared the parameters of uroflowmetry, filling cystometry, urethral pressure profile, dynamic urethral function test, perineal ultrasound and stress urethral axis between grade 1 and 2 levels of stress urinary incontinence. RESULTS: There were no significant differences in age, parity or body mass index between the grade 1 and 2 patients. Uroflowmetry results showed that there were no significant differences in maximal flow rate, average flow rate, voided volume or residual urine between grade 1 and 2. As to cystometry results, only the first desire to void was significantly increased in grade 2 over 1 (304 +/- 113.65 vs. 194 +/- 48.24 [mL], P = .04). There were no significant differences in any of the urethral pressure profile parameters. In the dynamic test, the Valsalva leak point pressure and cough leak point pressure were not significantly different between the 2 groups. There were no significant differences in perineal ultrasound parameters or the stress urethral axis. CONCLUSION: Most stress urinary incontinence-related parameters showed no difference between the grade 1 and 2, and no urodynamic or ultrasonographic evidence for a difference between the grade 1 and 2 was demonstrated.     

SS-penogram: a new diagnostic test for erectile dysfunction

The clinical reports on Sildenafil sulfate (Viagra) are mainly based on individual observations. However, there is a paucity of objective studies in the literature. In order to objectively examine the effect of Sildenafil, a SS (Sexual Stimulation)-Penogram that is a non-invasive, simple and physiologic method was developed using a radioisotope (RI). One hundred and four SS-penograms were performed on patients who had a documented erectile dysfunction (ED) lasting for more than 6 months. After an intravenous injection of 99mTc-RBC (15 mCi), the first penogram was taken immediately after sexual stimulation, which was done by 30 minutes of erotic videotape viewing. Forty minutes after administering 25 to 100 mg of Sildenafil, a second penogram was taken. The characteristics of each penogram were analyzed according to a previously reported method. The results were graded as follows; Type I(normal function; 5 min or more of peak erectile response with an induction period of 1 to 6 min), Type II-A (impossible function type; i.e., showing less than 2 times the basal radioactivity level), Type II-B (the unstable type; showing less than 5 min of peak erectile response), and Type II-C (the delayed type; which showed a delay of more than 15 min after the start of sexual stimulation). The patients were grouped according to their response after Sildenafil administration, and the effect of Sildenafil was assessed by comparing the radioactivity from between 7 to 22 minutes and the changes in the characteristics of the penogram. The mean age of the patients was 44.9 +/- 10.2 (23 - 68) years. In the first penogram, Type I was found in 12 patients, and Type II-A in 14, Type II-B in 73, Type II-C in 1 and a mixed (II-B + C) type was found in 4 patients. A second penogram after Sildenafil administration, showed Type I in 46 patients, and Type II-A in 10, Type II-B in 46 and a mixed type was found in 2 patients. The responses after Sildenafil were categorized as follows: 1) An excellent response group (consisting of 56 patients-53.9%); Those who showed greater than 50% increase in the RI area after Sildenafil treatment. 2) A good response group consisting of (23 patients-22.1%); i.e., those who showed a less than 50% but greater than a 20% increase in the RI area after Sildenafil administration. 3) A borderline group (consisting of 15 patients-14.4%); showing less than a 20% change in the RI area after Sildenafil treatment. 4) non-response group (consisting of 10 patients-9.6%). The therapeutic efficacy of Sildenafil, as determined by the SS-penograms, revealed that there was an augmentation in the erectile capabilities in 76% of men (79/104) but a non-response was observed in 9.6% (10/104). The efficacy of Sildenafil on the SS-penogram did not correlate with the patient's age (p=0.198). It is believed that the SS-penogram can be used to accurately evaluate the natural erectile status in sexual and pharmacological stimulation, and provides the most objective erectile response in any therapeutic trial. Consequently, the primary challenge for any erectile dysfunction remedy is to be able to demonstrate its efficacy. A further evaluation is warranted in the non-response group, which was not based on any severe organic dysfunction.