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[The results of long-term permixon treatment in patients with symptoms of lower urinary tracts dysfunction due to benign prostatic hyperplasia].

The trial enrolled 155 patients (mean age 65 years) with documented benign prostatic hyperplasia and lower urinary tracts symptoms (LUTS) (IPSS > 6). All the patients received permixon in a dose 160 mg twice a day for 2 years. The data on 130 patients eligible for assessment were processed statistically by dynamics of IPSS, quality of life (QOL), index of sexual function (MSF-4), size of the prostate, urodynamic and biological parameters which were estimated in 6 (V6), 12 (V12), 18 (V18) and 24 months (V24). Clinical examination with registration of all side effects was made each 3 months. Permixon was found to noticeably reduce IPSS and QOL and increase maximal urine flow speed. The size of the prostate diminished insignificantly. Sexual function remained unchanged for 1 year and improved markedly within the second year (p = 0.001). Permixon had no effect on the level of prostate-specific antigen. Plasma hormones (testosterone, DHT, estradiol, LH, androstendion) did not change. Nine patients developed 10 side effects but they were unrelated to the treatment.

5-alpha Reductase Inhibitors↗

Racial differences in cellular composition of benign prostatic hyperplasia.

BACKGROUND: The present study was designed to compare the cellular composition of benign prostatic hyperplasia (BPH) in Caucasian-American (CA), African-American (AA), and Japanese (JP) men. METHODS: Biopsy specimens of the prostate were obtained from 15 men of each racial group with a prostate-specific antigen (PSA) of 4.1-10.0 ng/mL. The stained cores were quantitatively analyzed for the percentage of the area with different cellular composition (stroma (S), epithelium (E), epithelial lumen (L), and glandular component (E + L = G)), using computer-assisted color imaging. RESULTS: The mean percent area density of S, E, and L in the prostate of CA men was 84.2, 12.1, and 3.8%, respectively; for AA, 84.4, 12.4, and 3.2%; for JP, 77.4, 15.2, and 7.5%. The S/E ratio is significantly lower in JP than in CA men. The S/G ratio is significantly lower in JP than in CA and AA men. Overall, JP contained more glandular lumen and less stromal component than that of CA and AA. CA and AA showed no significant difference in cellular composition. CONCLUSIONS: The present study demonstrated the differences in cellular composition of BPH among the three races. This cellular composition divergence may account for previously observed racial differences in PSA, PSA density, and the incidence of clinical BPH.

Aged↗

Symptom-specific quality of life in patients with benign prostatic hyperplasia.

BACKGROUND: We investigated which factors are most bothersome to preoperative patients with benign prostatic hyperplasia (BPH). METHODS: A total of 423 newly diagnosed patients and 388 preoperative patients with symptomatic BPH were evaluated. International prostate symptom score (IPSS) and IPSS quality-of-life (QOL) assessment score were used for assessment of symptoms and symptom-specific QOL of the patients with BPH. Uroflow variables were measured in all patients. Other objective variables such as prostate volume, transition zone volume, Schaefer's obstruction grade, and detrusor pressure at maximal urinary flow were evaluated in 209 preoperative patients. We analyzed the relationships between symptom-specific QOL and other variables. Statistical analyses were performed using Spearman's correlation coefficient and a stepwise linear regression model. RESULTS: Symptom-specific QOL scores had moderate to good correlation with IPSS (P < 0.0001; r = 0.525-0.560). Filling symptom subscore had a slightly greater impact on symptom-specific QOL than voiding subscore in both groups of patients. Weak stream, feeling of incomplete emptying, and nocturia significantly decreased symptom-specific QOL in both groups of patients. While newly diagnosed patients suffered from frequency as well, urgency had the strongest impact on symptom-specific QOL of preoperative patients. Objectively measurable variables had no association with symptom-specific QOL. CONCLUSION: Japanese patients with BPH generally suffer from weak stream, feeling of incomplete emptying, and nocturia in all disease phases. Frequency is problematic for newly diagnosed patients and urgency is problematic for preoperative patients as well. Symptom-specific QOL of BPH patients cannot be estimated by physically measurable variables.

Adult↗

Diet and benign prostatic hyperplasia: a study in Greece.

OBJECTIVES: To evaluate the nutritional etiology of benign prostatic hyperplasia (BPH) by conducting a case-control study in Athens, Greece. Despite the high morbidity and substantial human suffering produced by BPH, little research has been undertaken concerning the nutritional etiology of this disease. METHODS: The study sample consisted of 184 patients with histologically confirmed BPH and 246 control patients without clinical evidence of prostate disease. All patients and controls were permanent residents of the greater Athens area. The data were modeled through unconditional logistic regression. RESULTS: Among the food groups, fruits were inversely related to BPH risk, with a logistic regression-derived odds ratio of 0.79 per quintile increase and 95% confidence interval 0.67 to 0.93. Increased consumption of both butter and margarine was positively associated with BPH risk, and a marginally significant positive association was also evident for seed oils. No overall association was found with respect to consumption of olive oil. In analyses evaluating the role of nutrients rather than foods, zinc, an element selectively concentrated in the prostate gland, was significantly positively associated with BPH risk. CONCLUSIONS: Our study provides evidence that, among added lipids, butter and margarine may increase the risk of BPH, and fruit intake may reduce this risk. Dietary zinc may play an important role in the etiology of BPH.

Case-Control Studies↗

Differential effect of finasteride on the tissue androgen concentrations in benign prostatic hyperplasia.

OBJECTIVE: The 5 alpha-reductase inhibitor, finasteride, provides a logical medical treatment for benign prostatic hyperplasia (BPH). However, the effects of chronic finasteride treatment on prostatic androgen levels, 5 alpha-reductase activity and tissue prostatic specific antigen (PSA) have not been studied. We have examined prostate tissue androgen concentrations and 5 alpha-reductase activity of the gland in men with BPH treated with the drug for 3 months. DESIGN AND PATIENTS: Twenty-eight patients with clinically diagnosed BPH, awaiting transurethral resection of the prostate, were entered in a double-blind placebo controlled study. Nineteen patients were randomly allocated to treatment with finasteride (5 mg daily) and 9 received placebo for 3 months. MEASUREMENTS: Prostate specimens were collected immediately following surgery and analysed for testosterone, dihydrotestosterone (DHT), androstenedione, 5 alpha-reductase activity and PSA. Blood specimens obtained before the start and immediately following treatment were also tested for steroid hormone concentrations and PSA levels. RESULTS: There was no significant difference in the median levels of intraprostatic testosterone (P = 0.77), DHT (P = 0.46) and androstenedione (P = 0.09) between the finasteride and placebo groups. However, the 5 alpha-reductase activity of the placebo group (237.9 pmol DHT/g tissue/30 min) was approximately 10 times that of the finasteride group (21.5 pmol DHT/g tissue/30 min; P = 0.0008). Although we were unable to detect any differences in the PSA concentrations of the prostate glands, there was a significant difference (P = 0.0002) in the median percentage change of serum PSA concentrations for the two patient groups. Serum DHT levels were also depleted (P = 0.038) whilst serum testosterone was increased (P = 0.054) in the finasteride patients when compared to the placebo group. Furthermore our study demonstrated no correlation between the in vitro 5 alpha-reductase activity of the gland and tissue DHT concentrations. CONCLUSIONS: Whilst finasteride treatment induced a reduction in serum dihydrotestosterone and prostatic specific antigen levels with a concomittant increase in blood testosterone concentrations, the impact of the drug on tissue androgen concentrations varied considerably from one patient to another. The differential effect of the drug on tissue androgen concentrations suggests that in the human prostate there are possibly more than one isoform of 5 alpha-reductase responsible for the accumulation of DHT in the gland.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗

[Laser treatment of benign prostatic hyperplasia].

This review article describes the different methods of laser treatment of benign prostatic hyperplasia and their development. Published treatment results are compared with our own results obtained with different procedures. The aim of therapy is to reduce the volume of the gland by coagulation, with subsequent secondary ablation or primary vaporization. Due to the desired volume effects Nd:-YAG lasers are used almost exclusively. The technique most frequently used is transurethral laser coagulation of the prostate. Radiation is done in the non-contact mode with beam-detecting applicators, with either direct vision (VLAP) or ultrasound guidance (TULIP). In interstitial laser coagulation of the prostate (ILC) laser energy is applied by light guides inserted into the tissue either transurethrally or transperineally. Contact lasers are used for incision of the prostate or superficial ablation.

Follow-Up Studies↗

Managing benign prostatic hyperplasia in primary care. Patient-centred approach.

PROBLEM ADDRESSED: Management of benign prostatic hyperplasia (BPH) is changing from a surgical approach to a medical approach, and the role of primary care physicians is expanding. OBJECTIVE OF PROGRAM: To introduce a patient-centred approach to managing BPH in primary care through a continuing medical education (CME) program. MAIN COMPONENTS OF PROGRAM: A practice-based, small group, peer-led CME program focused on application of the International Prostate Symptom Score and Quality of Life Assessment in four case studies on prostatism, including BPH. At 86 workshops held across Canada, 658 physicians participated in discussions with case materials that included videos and a handbook. A before-after practice behaviour questionnaire was administered at each workshop to evaluate "intent to change." CONCLUSIONS: Participating physicians showed willingness to learn new skills for patient-centred management of BPH. These results suggest that peer-led, small group CME can successfully encourage use of new practice guidelines in primary are and teach physicians practical steps for developing therapeutic alliances with their patients.

Aged↗

A prospective study of the safety and efficacy of suprapubic transvesical prostatectomy in patients with benign prostatic hyperplasia.

PURPOSE: We investigate the safety and efficacy of suprapubic transvesical prostatectomy, and the change in bladder wall thickness after surgery. MATERIALS AND METHODS: We conducted a prospective 1 center study of 32 consecutive patients who underwent transvesical prostatectomy from December 1996 to March 1997 for benign prostatic hyperplasia with large prostate volume, who were followed for 1 year. Pressure flow study and transrectal sonography were performed at baseline and repeated at 6 months. Bladder wall thickness was measured at baseline and regular intervals postoperatively. A morbidity questionnaire was completed during the first 6 weeks after surgery. RESULTS: An average of 63 gm. prostate adenoma were enucleated at surgery. An indwelling catheter was required for an average plus or minus standard deviation of 5.4 +/- 2.6 days after treatment. The International Prostate Symptom Score decreased from 19.9 +/- 4.4 to 1.5 +/- 2.7 and the quality of life score decreased from 4.9 +/- 1.0 to 0.2 +/- 0.4 at year 1, respectively. Maximum flow rate improved from 9.1 +/- 5.3 to 29.0 +/- 8.9 ml. per second. Residual urine decreased from 128 +/- 113 to 8 +/- 18 ml. Before surgery 30 patients had obstruction and 2 were in the equivocal zone of the International Continence Society nomogram. At 6 months after prostatectomy 30 patients did not have obstruction, and 2 who were subsequently operated on for bladder neck sclerosis were equivocal and had obstruction, respectively. No patient had significant postoperative bleeding and no heterologous blood transfusions were required. There were 4 men who had urinary tract infection and 1 who had wound infection. A slight decrease in erectile function was observed 6 weeks postoperatively, and no change in patient libido and quality of sex life was reported. The total complication rate was 31.3%. The bladder was unstable in 7 men before and 3 after surgery. A significant decrease in bladder wall thickness was observed from 5.2 +/- 0.7 at baseline to 2.9 +/- 0.9 mm. at year 1 postoperatively. CONCLUSIONS: Our study confirms the excellent clinical outcome of transvesical prostatectomy, and rapid improvement of most subjective and objective parameters during the 4 weeks after surgery. Bladder hypertrophy appears to be significantly reduced after prostate surgery. The urodynamic results in patients who underwent open surgery probably represent the maximum obtainable relief of obstruction and should be considered the reference standard to which all other treatments, including transurethral resection, should aspire.

Aged↗

Benign prostatic hyperplasia: now we can begin to tailor treatment.

Our treatment strategies for benign prostatic hyperplasia (BPH) have changed, with new insights into the pathophysiology of the disease, new clinical trials, and surgical advances. We present an update on treatment options and a diagnostic and treatment algorithm for this condition.

Humans↗

Variations of transition zone volume and transition zone index after transurethral needle ablation for symptomatic benign prostatic hyperplasia.

BACKGROUND: Transurethral needle ablation (TUNA) is less invasive than other therapies for benign prostatic hyperplasia (BPH) and produces coagulative necrosis within selected adenoma lesions. The action mechanism of TUNA is still obscure, even though many early studies have demonstrated good clinical results of TUNA. It is of interest and importance to know how TUNA influences the volume of the intraprostatic region responsible for bladder outlet obstruction in order to elucidate the anatomical action mechanism of TUNA. METHODS: We retrospectively investigated postoperative variations in volumetric parameters of whole prostate volume (PV), transition zone volume (TZV) and transition zone index (TZI = TZV/PV) in 41 patients with symptomatic BPH who were treated with TUNA. The data were analyzed statistically in relation to the preoperative overall severity and postoperative therapeutic efficacy. RESULTS: Both PV and TZV showed a significant decrease at 3 months after TUNA (P < 0.01) as did the symptom score, quality of life (QOL) score and functional variables, and a decreased level of PV and TZV was sustained until 12 months of follow-up when compared to the baseline (P < 0.01 at 6 months, not significant at 12 months). TZI also showed a similar pattern with a significantly decreased level until the postoperative 6th month (P < 0.05 at 6 months, not significant at 12 months). In 'moderate' cases, TZI achieved the minimum value (0.44 +/- 0.13, P < 0.05 compared to the baseline) at 3 months of follow-up, but the level immediately increased, while in 'severe' cases, TZI gradually decreased and achieved the minimum value (0.44 +/- 0.08, P < 0.05 compared to the baseline) at 12 months of follow-up. In the evaluation by postoperative therapeutic efficacy, there were no significant differences in PV, TZV and TZI between 'excellent and good' cases (E/G group) and 'fair and poor/worse' cases (F/P group) at the baseline or 3 months of follow-up. Both of the efficacy groups showed a significant decrease in PV, TZV and TZI at 3 months when compared to the baseline (P < 0.05). The mean decrease in TZI was significantly larger in the E/G group than in the F/P group (0.064 +/- 0.13 vs 0.027 +/- 0.12, P < 0.05). CONCLUSION: Therapeutic efficacy of TUNA did not depend on the baseline value of PV, TZV and TZI, but on variation of a decrease in TZI during follow-up. Moreover, a slow and lasting decrease in TZI seemed to influence durability of the therapeutic efficacy of TUNA, which was clearly observed in 'severe' cases with a larger prostatic volume than in 'moderate' cases.

Aged↗

[Tamsulosin with or without Serenoa repens in benign prostatic hyperplasia: the OCOS trial].

OBJECTIVE: In the treatment of the symptoms of benign prostatic hyperplasia (BPH), a French guideline opposes the use of drugs in conjunction, in the absence of proven utility. The OCOS trial therefore compared one of the possible drug combinations (tamsulosin and Serenoa repens) with tamsulosin alone, to see if there was any difference in effectiveness and to evaluate the clinical tolerance of each in patients with symptoms of BPH. MATERIAL AND METHODS: In this double-blind, randomised trial, patients had to have an IPSS (International Prostate Symptom Score) > or = 13 and a Qmax between 7 and 15 mL/s. Tamsulosin (0.4 mg) was to be administered once a day for 52 weeks, with, twice daily, a placebo (TAM) or Serenoa repens 160 mg (TAM + SR). RESULTS: 352 patients were recruited by 47 centres; 329 (average age 65) were randomised: 161 into the TAM group and 168 into the TAM + SR group. No statistically significant difference was found between the two groups, neither for the major end-point [change in total IPSS between the baseline value and the final evaluation (TAM: -5.2; TAM + SR: -6.0; p = 0.286)], nor for the secondary end-points [changes in the voiding scores (p = 0.239) and in filling scores (p = 0.475) of the IPSS, Qmax (p = 0.564), percentage of respondents according to the IPSS (p = 0.361), improvement in quality of life (IPSS-QoL: p = 0.091; UROLIFE BPH QoL: p = 0.442), safety]. CONCLUSION: The addition of Serenoa repens to tamsulosin did not provide any significant benefit to the patients: the OCOS trial does not cast doubt on the guideline applicable to the treatment of BPH.

Adrenergic alpha-Antagonists↗

Metabolic syndrome and lower urinary tract symptoms secondary to benign prostatic hyperplasia.

Increasing evidence recently has pointed toward a relationship between lower urinary tract symptoms (LUTS) and the presence of metabolic syndrome. This relationship has been supported by recent epidemiologic findings. Possible pathophysiologic links also have been proposed to explain the relationship between these two syndromes. The increasing prevalence of obesity in the United States makes this an increasingly relevant problem. Animal studies support a link between autonomic nervous system (ANS) overactivity and the development of urinary symptoms, low bladder compliance, compensatory prostatic hyperplasia, and blockage of the same using alpha-blockade. There appears to be a significant link between ANS overactivity as part of the metabolic syndrome and LUTS secondary to benign prostatic hyperplasia (BPH). However, it is unlikely that ANS overactivity could be responsible for the development of LUTS. Rather, ANS overactivity plays a key role in increasing the severity of LUTS above an intrinsic basal intensity that is determined by the genitourinary anatomic/pathophysiologic characteristics of each BPH patient. This paper defines metabolic syndrome as a collection of abnormalities, including being overweight (visceral abdominal fat distribution), dyslipidemia, hypertension, impaired glucose metabolism, elevated C-reactive protein (chronic inflammation), and autonomic-sympathetic overactivity, with insulin resistance as the hypothesized underlying pathogenic mechanisms.

Animals↗

How frequent are invasive therapies required in patients receiving tamsulosin for benign prostatic hyperplasia? A retrospective long-term study.

Three hundred Japanese patients with benign prostatic hyperplasia (BPH) who started an alpha1-adrenoceptor blocker, tamsulosin, between 1993 and 1996 were followed for 3.0+/-3.3 years (mean+/-SD) to determine whether an association existed between the disease severities measured prior to the tamsulosin treatment and the timing at which the invasive therapy was implemented. Patients with a lower quality of life (QOL) index or maximum urinary flow rate (Qmax) were transferred for invasive therapy earlier than those with less severe BPH. The International Prostate Symptom Score (I-PSS) was also associated, but apparently to a lesser extent, with the timing of the invasive therapy. Finally, the overall severity evaluated using all of the above three indices, I-PSS, QOL index, and Qmax, in accordance with the 'Severity Criteria for BPH' issued by the Japanese Urological Association, was found to be a good measure for predicting the prognosis of patients with BPH treated with tamsulosin.

Adrenergic alpha-Antagonists↗

Current and future trends in interventional therapy for benign prostatic hyperplasia in Japan.

PURPOSE: Procedures of Japanese urologists of interventional therapy for benign prostatic hyperplasia (BPH) should be defined for resource economy and policy establishment. MATERIALS AND METHODS: A questionnaire was mailed to the urology departments of 80 medical schools in Japan for clarification of surgical procedures presently in use for treating bladder outlet obstruction due to BPH. Prospects for the next 5 years (year 2002) were also requested. RESULTS: We received 76 questionnaire responses from medical school urology facilities (95%) by the end of January 1997. Standard transurethral resection of the prostate gland is and will continue to be the most common surgical procedure. Open adenectomy is the first choice for large glands but may be replaced by other interventional procedures. Laser prostatectomy and transurethral electrovaporization will be used more often for treating all severities of BPH. CONCLUSIONS: Even with increasing interest in new techniques, transurethral resection of the prostate will continue to serve as the standard therapy for BPH during the next 5 years. Transurethral electrovaporization may become established in the near future.

Humans↗

Morphometry of benign prostatic hyperplasia during androgen suppressive therapy. Relationships among epithelial content, PSA density, and clinical outcome.

We performed light microscopic morphometry on prostate biopsies of 41 patients who underwent androgen suppressive therapy for 24 weeks with the luteinizing hormone releasing hormone (LHRH) agonist leuprolide depot for symptomatic benign prostatic hyperplasia (BPH). Before treatment started, the prostates consisted of 88.4% stroma, 9.0% epithelium and 2.6% glandular lumen. After completion of therapy, the percentages were 94.7, 3.0 and 2.3, respectively. The absolute reductions of volume were 27% for stroma, 77% for epithelium and 40% for lumen. Correlations between pretreatment parameters (epithelial content, stromal epithelial ratio and prostate specific antigen density (PSAD)) and the clinical outcome parameters (prostate volume reduction, improvement in maximum flow rate, reduction of symptom score and reduction in outflow resistance) were not statistically significant, indicating that the histological composition of BPH tissue or PSAD are poor parameters to predict differences in response for individual patients during hormonal therapy for BPH. By comparing morphometry results of the core biopsies with morphometry performed on corresponding TURP tissue, it appeared that the lumen content of the biopsies was somewhat underestimated.

Aged↗

Assessment of sextant biopsy of the prostate for detecting cancer prior to therapy in patients clinically diagnosed as benign prostatic hyperplasia.

Pathological results and perioperative morbidity were compared in 199 patients who had undergone prostatectomy and/or biopsy in order to determine the extent to which systematic biopsy is effective for detecting prostate cancer prior to therapy in patients clinically diagnosed as having benign prostatic hyperplasia. Seventeen (8.5%) cancers were detected in 199 patients following surgery and/or biopsy. Digitally-guided biopsy as a means of detecting prostate cancer was found to be just as effective as ultrasound-guided biopsy. Seven (12.5%) cancers were detected in 56 patients who had undergone biopsy and transurethral resection. Preprostatectomy biopsy detected only two of three patients with stage T1b disease. All four stage T1a and one stage T1b failed to be diagnosed. Of 90 patients who had biopsy prior to surgery other than TURP, seven (7.8%) cancers were found. Four of these were advanced. The incidence of postoperative fever > 38.0 degrees C and duration of postoperative pyuria did not differ significantly between groups with or without biopsy. Preoperative biopsy did not contribute to perioperative morbidity. Tumors detected by systematic biopsy are usually large and clinically significant. Positive biopsy results are often diagnostic, but the pathological features of a tumor together with clinical parameters should be considered to reduce the chance of overdiagnosing an insignificant tumor. Sextant biopsy would be most applicable to patients scheduled for any type of therapy other than TURP especially in those with markedly elevated serum PSA levels. This procedure may be beneficial particularly for younger patients with long life expectancy who will benefit from definitive therapy.

Aged↗

Effects of the aromatase inhibitor testolactone on human benign prostatic hyperplasia.

UNLABELLED: The aromatase inhibitor testolactone was used for endocrine treatment of benign prostatic hyperplasia (BPH). Thirteen patients (mean age 79 years) with complete urinary retention (BPH stage IV) without improvement after 4 weeks of bladder drainage by suprapubic catheter were treated with testolactone 100 mg, b.i.d., for 6 months. Nine men (mean age 80 years) with identical conditions who did not receive hormonal therapy served as controls. Results, treatment group: In 7 patients spontaneous micturation reoccurred after an average treatment period of 8 weeks (group A); 6 patients continued to need the catheter (group B). Prostatic volume decreased in all patients, and an average volume reduction of 26% was found in group A, whereas in group B the decrease averaged 15%. Finally, the testosterone/estradiol ratio significantly increased in all patients during treatment. CONTROL GROUP: Prostatic volume did not change nor did spontaneous micturation occur during the whole observation period.

Aged↗

[Benign prostatic hyperplasia and growth factors: mechanisms and hypotheses].

The aetiology and pathogenesis of benign prostate hyperplasia (BPH) are still unresolved questions, although a number of hypotheses have been developed, most of which have still not been confirmed by experimentation. BPH has been regarded as a kind of adenoma, as a stromal disease, as the result of either hormonal imbalance (altered oestrogen/testosterone ratio) or testosterone or dihydrotestosterone stimulation, and finally as the result of oestrogen stimulation, perinatally or involutionally. More recently, scientific interest has focused on the presence and possible function of growth factors and their receptors in the human prostate and their autocrine or paracrine stimulatory effects in BPH development. Hypotheses on their hormonal regulation as well as their interplay during epithelial-stromal interaction have been developed. The intact human prostate produces epithelial (EGF) and basic fibroblast (bFGF) growth factors. Normally, they do not appear to have autocrine or paracrine effects. In androgen deficiency, however, as shown experimentally in castrated rats, the stromal cells express increased amounts of TGF beta, of TGF beta receptor, and of bFGF. Platelet-derived growth factor (PDGF), but not the corresponding receptor, has been shown in prostate. The growth factor receptor-associated tyrosine protein kinase is present in the human prostate in two different forms, but its functional significance in BPH development has not yet been elucidated. A more significant role may be attributed to the recently described growth factors in cultured human stromal cells, which exert multifarious mitogenic and non-mitogenic effects on prostatic epithelium as well as neuronal and non-neuronal cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Cell Division↗