Efficacy and safety of holmium laser enucleation of the prostate for elderly patients: surgical outcomes and King’s Health Questionnaire

BackgroundHolmium laser enucleation of the prostate (HoLEP) has been a widely utilized minimally invasive surgical procedure for benign prostate hyperplasia. The current study aimed to compare surgical outcomes and King’s Health Questionnaire (KHQ) assessment scores following HoLEP between younger men and those aged ≥75 years.MethodsThis prospective single-center study compared perioperative complications, postoperative urinary conditions, and KHQ scores (nine categories) between men aged ≥75 years (group A) and men aged <75 years (group B) before and 1, 3, and 6 months after surgery.ResultsA total of 100 patients were included for analysis (group A, n=38 and group B, n=62). No differences in patient backgrounds, perioperative complications, such as perioperative decrease in hemoglobin, postoperative fever, postoperative indwelling catheterization duration, or postoperative hospitalization duration, and KHQ were observed between both groups. Both groups showed significantly better International Prostate Symptom Scores, quality of life, maximum urinary flow rate, and postvoid residual volume 1, 3, and 6 months after HoLEP compared to their respective preoperative levels (P<0.01). Regarding KHQ categories, both groups showed significantly better general health perceptions, impact on life, emotions, and sleep/energy 1 month after HoLEP; role limitations, physical limitations, and social limitations 3 months after HoLEP; and personal relationships and incontinence severity measures 6 months after HoLEP compared to their respective preoperative levels (P<0.05).ConclusionsHoLEP could be safe and effective even for men aged ≥75 years, comparing complications, urinary condition, and KHQ scores.     

Wnt signaling plays an essential role in neuronal specification of the dorsal spinal cord

In the developing spinal cord, signals from the roof plate are required for the development of three classes of dorsal interneuron: D1, D2, and D3, listed from dorsal to ventral. Here, we demonstrate that absence of Wnt1 and Wnt3a, normally expressed in the roof plate, leads to diminished development of D1 and D2 neurons and a compensatory increase in D3 neuron populations. This occurs without significantly altered expression of BMP and related genes in the roof plate. Moreover, Wnt3a protein induces expression of D1 and D2 markers in the isolated medial region of the chick neural plate, and Noggin does not interfere with this induction. Thus, Wnt signaling plays a critical role in the specification of cell types for dorsal interneurons.     

Combined treatment of pelvic exenterative surgery and intra-operative pelvic hyperthermochemotherapy for locally advanced rectosigmoid cancer: Report of a case

A huge rectosigmoidal cancer which extended into the urinary bladder in a 64-year-old man is herein described. The tumor occupied the pelvic and lower abdominal cavities, while the rectosigmoid was totally obstructed. No hepatic or pulmonary metastasis was evident. The ventral and flank sides of the peritoneum in the right lower abdomen, right common iliac vessels, bilateral ureters, terminal ileum, cecum, ascending colon, and urinary bladder were all directly invaded by the tumor, but the aorta, sacrum, and lower rectum were free of cancer. Consequently, an anterior pelvic exenteration was carried out along with an ileal conduit and a right hemicolectomy. Immediately after the exenteration, intra-pelvic hyperthermochemotherapy was performed using a 46–47°C perfusate containing 40 g/ml of mitomycin C (MMC) and 200 g/ml of cisplatin (CDDP), for 90 min, in an attempt to prevent any further local recurrence. A right hemicolectomy and a permanent colostomy were done simultaneously with the hyperthermia treatment. After an uneventful postoperative course, the patient was prescribed adjuvant chemotherapy, i.e., two administrations of 17 mg/m² and 21 mg/m² of MMC, and ten doses of 710 mg/m² of 5-fluorouracil (5-FU) followed by five doses of 535 mg/m² of 5-FU. At the time of this writing, the patient is still alive without recurrence at 21 months after surgery.     

Prediction of ACNU plasma concentration-time profiles in humans by animal scale-up

Summary Plasma concentration-time profiles of nimustine hydrochloride, 1-[(4-amino-2-methyl-5-pyrimidinyl)methyl]-3-(2-chloroethyl)-3-nitrosourea hydrochloride (ACNU), in the mouse, rat, rabbit, and dog were determined by high-performance liquid chromatographic analysis. The pharmacokinetic parameters for these four animal species and previously reported clinical data were analyzed for investigation of interspecies correlation. Loglog plots of body weight (W; kg) vs total plasma clearance (CLtot, p; ml/min) and steady-state distribution volume (Vd, ss; 1) for the four animal species were linear, with high correlation coefficients (r 0.996 for both parameters), despite the fact that the nonrenal clearance was >97% in these species. Linear regression on the plots excluding human data yielded allometric equations (CL_tot,p=50.6 W^0.957; Bd, ss=1.29 W^1.03) that were extrapolated to predict ACNU pharmacokinetic parameters in humans. For both parameters, however, there were 3-fold differences between the predicted and observed parametric values. To investigate these discrepancies, we measured serum protein binding of ACNU in these animal species and in humans. The values of CLtot,p and Vd,ss were converted into those of CL^u _tot,p and Vd,^u _ss, which correspond to the parameters for unbound ACNU. In this case, correlation coefficients of the log-log plots excluding human data (CL^u _tot,p=71.7 W^0.891; Bd,^u _ss=1.82 W^0.966) were also high (r0.991). The extrapolated values vs those observed in a 70-kg human were the following: CL^u _tot,p, 3,160 vs 2,290 ml/min; Vd,^u _ss, 110 vs 1061. Thus, the animal data were successfully extrapolated to yield better predictions of human pharmacokinetic parameters if the analysis was based on the unbound plasma concentration of ACNU. In addition, the predicted plasma concentration-time profile for humans also showed good agreement with the observed ones. These results suggest the importance of measuring unbound fractions of drugs for more accurate prediction of human pharmacokinetic parameters by extrapolation of animal data to the human situation.     

Risk estimation for hypertension based on follow-up health examination data in a small village in Kumamoto prefecture, Japan

The estimation of risk for incidence of hypertension was carried out by follow-up study in a small village in Kumamoto Prefecture, Japan (N=750, 48.2±15.2months). The most significant risk in both sexes was blood pressure at entry. As for other risks, age, total cholesterol, and BMI in females were significant risks for systolic and diastolic blood pressure changes to greater than the borderline level. These factors in males were not significant. From the results of analysis using Cox's proportional hazards model, drinking in males was shown to be a significant risk for diastolic change, and in females for systolic change. It was concluded that excessive drinking in both sexes and obesity in females led to important health problems associated with hypertension among the subjects of the study.     

The effect of glibenclamide on the production of interstitial adenosine by inhibiting ecto-5′-nucleotidase in rat hearts

1. Adenosine exerts cardioprotective effects on the ischaemic myocardium. The production of adenosine in the ischaemic myocardium is attributed primarily to the enzymatic dephosphorylation of adenosine 5′-monophosphate (AMP) by 5′-nucleotidase. We determined the activity of 5′-nucleotidase in rat hearts. The objective of the study was to determine the effects of ATP-sensitive K⁺ (K_ATP) channel antagonists (glibenclamide and 5-hydroxydecanoate) on the production of adenosine, by use of a flexibly mounted microdialysis technique.
2. Rats were anaesthetized and the microdialysis probe was implanted in the left ventricular myocardium, followed by perfusion with Tyrode solution. The baseline level of dialysate adenosine was 0.51±0.09 μM (n=16). Introduction of AMP (100 μM) through the probe increased the dialysate adenosine markedly to 9.79±0.43 μM (n=12, P<0.001 vs baseline), and this increase was inhibited by the ecto-5′-nucleotidase inhibitor, α,β-methyleneadenosine 5′-diphosphate (100 μM), to 0.76±0.12 μM (n=8). Thus, the dialysate adenosine noted during the perfusion of AMP originated from dephosphorylation of AMP by ecto-5′-nucleotidase, and the dialysate level of adenosine attained reflects the ecto-5′-nucleotidase activity in the tissue in situ.
3. Glibenclamide (0.1–100 μM) decreased the adenosine concentration measured during the perfusion of AMP (100 μM) in a concentration-dependent manner (IC₅₀=10.5 μM). In contrast, 5-hydroxydecanoate (10–100 μM) did not affect the concentrations of dialysate adenosine, measured in the presence of AMP (100 μM). These results suggest that glibenclamide inhibits the activity of endogenous ecto-5′-nucleotidase and decreases the concentration of adenosine in the interstitial space of rat ventricular muscles in situ.

     

Fertilization and early embryology: Autocrine/paracrine function of transforming growth factor-{beta}1 in porcine granulosa cells

The present study was undertaken to investigate the effectsof transforming growth factor (TGF)-1 on ovarian steroidogenesisin immature or moderately mature porcine granulosa cells invitro. TGF-1 (0.01–10 ng/ml) significantly attenuatedprogesterone release from the basal and follicle stimulatinghormone-stimulated porcine granulosa cells, and significantlyincreased DNA synthesis. TGF-1 also significantly increasedthe extracellular accumulation of cyclic AMP, but did not changethe production of inositol phosphate or the intracellular calciumconcentration in these cells. Thus, TGF-1 appears to have adirect effect on porcine granulosa cell function, regulatingthe differential synthesis of progesterone mainly via the intracellularsignal transduction of the cyclic AMP—protein kinase Apathway. This growth factor may play a physiologically significantrole in controlling differentiation of immature and moderatelymature porcine granulosa cells via an autocrine/paracrine mechanism.     

Anaesthetic management of a neonate with prenatally diagnosed cervical tumour and upper airway obstruction

We report the anaesthetic management of a mother, and airway management of a neonate with a prenatal diagnosis of cervical cystic hygroma causing upper airway obstruction. The mortality of such neonates due to upper airway obstruction is reported to exceed 20% following deliveries. Elective Caesarean section was performed under general anaesthesia, and in utero tracheal intubation of the neonate was accomplished under uninterrupted maternal-fetal circulation. By utilizing isoflurane and ritodrine, the heart rate of the neonate remained between 120 to 150 bpm for four minutes following uterine incision. We believe that it is important that a multidisciplinary approach be initiated for planning of airway management of the neonate soon after the diagnosis is made. Laryngoscopy blades larger than normal for neonates, and a portable Doppler to monitor the viability of the neonate were found to be useful in the management of the neonate during in utero tracheal intubation. Although estimated blood loss was not increased, nor did uterine atony occur postoperatively despite the use of ritodrine during Caesarean section, the efficacy and safety of ritodrine to delay placental detachment have not been proved.     

Pathophysiology of dogs after 84% hepatectomy with emphasis on prostaglandin metabolites and the effect of a thromboxane A2 synthesis inhibitor and a prostaglandin I2 analog

The pathophysiological conditions following 84% hepatectomy were examined in terms of the changes in thromboxane A₂ (TxA₂) and prostaglandin I₂ (PGI₂) in canine model. OKY-046, TxA₂ inhibitor, and OP-2507, a PGI₂ analog, were administered to evaluate the possibility of extending hepatic resection. The 2-week survival rate following 84% hepatectomy significantly improved after the administration of OKY-046 and OP-2507, from 12.5% to 58.3% and 75.0%, respectively. Furthermore, OP-2507 significantly improved impaired hepatocyte and sinusoidal endothelial cell function after 84% hepatectomy, resulting in a satisfactory recovery to the preoperative levels. Within 24 h after 84% hepatectomy, the plasma levels of thromboxane B₂ (TxB₂) increased significantly, and the 6-keto-prostaglandin F_l (6-KF) levels became slightly elevated. OKY-046 and OP-2507 decreased TxB₂ and increased 6-KF in the plasma, resulting in the maintenance of sufficient blood flow in the portal vein and hepatic tissue and the mitigation of microcirculatory disorders. Moreover, the cytoprotective effects of the two drugs inhibited functional impairment of the residual liver. In conclusion, abnormal prostaglandin metabolites were produced after 84% hepatectomy, being involved in residual liver disorders. However, the administration of either an inhibitor of TxA₂ synthesis or PGI₂ analog ameliorated the functional impairment of the residual liver, which suggests their potential value for extending the resectability of the liver from what is presently feasible.An abstract of this study was presented at the 92nd Annual Meeting of the Japan Surgical Society held in 1992.