EFFICACY AND SAFETY OF CONTINUOUS MORPHINE INFUSION FOR POSTOPERATIVE ANALGESIA IN THE PAEDlATRlC SURGICAL WARD

This study determines the efficacy and safety of continuous infusion of morphine following major surgery in non-ventilated children being nursed in general paediatric surgical wards. Pain and analgesia were assessed by a linear analogue scale. Assessment of pain by nursing staff was similar to that made by the patient and parent. Continuous infusions were easy to institute, well accepted by staff and patients alike and resulted in few side effects. The safety and efficacy of morphine infusions allow for wider adoption as a routine method of analgesia for children following major surgery.     

INCREASING THE THERMAL DOSE IN TRANSURETHRAL MICROWAVE THERMOTHERAPY PRODUCES NO IMPROVEMENT IN THERAPEUTIC EFFICACY

Background:
Transurethral microwave thermotherapy (TUMT) is a minimally invasive treatment for benign prostatic hyperplasia (BPH). It has been reported that increased thermal dose and higher intraprostatic temperatures resulted in improved clinical response. Recently we treated BPH patients with the prostatron device using a new version of software (Prostasoft 2.5), which was intended to increase thermal delivery by allowing maximum power up to 70W. The safety and clinical results were compared between the patients treated with Prostasoft 2.5 and those treated with the currently available software (Prostasoft 2; maximum power up to 50W).
Methods:
A total of 105 patients were treated successively with two treatment protocols. Sixty-three patients were treated with Prostasoft 2 between September 1992 and July 1993. while 42 were treated with Prostasoft 2.5 between August 1993 and April 1994. Therefore, this investigation was a retrospective nonrandomized study. There was no significant difference in the baseline patient characteristics between the two groups.
Results:
Total thermal dose delivered to the prostate was significantly higher in the Prostasoft 2.5 group than that in the Prostasoft 2 group (137 kJ versus 116 kJ, P < 0.05). No serious complications were encountered in either group. Six months after TUMT, in both the Prostasoft 2.5 and Prostasoft 2 groups there was an improvement in patient condition as measured by the mean I-PSS, OOL, and peak How rate values, as well as the overall therapeutic efficacy. The two groups differed in the amount of posttreatment improvement from between 8% and 22%, but this difference was not statistically significant.
Conclusions:
Our study suggests that higher thermal dose attained by Prostasoft 2.5 does not necessarily result in more pronounced clinical improvement, although clinical response to TUMT has often been reported to be dependent upon thermal dose.     

PROPOFOL AND ALFENTANIL IN CHILDREN: INFUSION TECHNIQUE AND DOSE REQUIREMENT FOR TOTAL I.V. ANAESTHESIA

We estimated the dose of propofol (initial dose followed bya stepped infusion) when given with two different infusion ratesof alfentanil for total i. v. anaesthesia in 59 children aged3–12 yr. Patients in series 1 (four groups) received analfentanil loading dose of 85g kg^–1 and an infusion of65 g kg^–1 h^–1. Patients in series 2 (groups 5 and6) received an alfentanil loading dose of 65 g kg^–1 andinfusion of 50 g kg^–1 h^–1. Parents gave their informedconsent. Premedication comprised temazepam 0.3 mg kg^–1.Glycopyrronium 5 g kg^–1 was administered and anaesthesiainduced and maintained with alfentanil (loading dose and infusion)followed by propofol (loading dose and three-stage manual infusionscheme). Suxa-methonium 1 mg kg^–1 was used to facilitatetracheal intubation and the lungs were ventilated artificiallyto normocapnia with 30% oxygen in air. Probit analysis was usedto determine the dose requirement of propofol. In series 1.the ED₅₀ was 6.0 mg kg^–1 h^–1 (95% confidence limits5.5-6.2 mg kg^–1 h^–1) and ED₉₅ 8.6 (6.8-7.8) mg kg^–1h^–1. Corresponding values for series 2 were ED₅₀ 7.5 (8.0-9.8)mg kg^–1 h^–1 and ED₉₅ 10.5 (9.6^–13.1) mg kg^–1h^–1. ^*Department of Anaesthesia, University of Newcastle upon Tyne,Royal Victoria Infirmary, Newcastle upon Tyne NE1 4LP.      

Adynamic bone disease with negative aluminium staining in predialysis patients: prevalence and evolution after maintenance dialysis

Aplastic bone disease (ABD) is a common form of renal osteodystrophyand is characterized by a defect in bone matrix formation andmineralization without an increase in osteoid thickness. Theprevalence and pathogenesis of ABD in predialysis patients islargely unknown. We prospectively studied 92 unselected predialysispatients with a creatinine clearance <10 ml/min/1.73 m² anda mean age of 45±2 years (61 M, 31 F). None of the studypatients had received any form of vitamin D therapy, and CaCO₃was the primary phosphate binder. Aplastic bone disease wasobserved in 30 (32%) patients. Stainable bone aluminium surfacewas <3% in all ABD patients. Patients with ABD were older(52±3 versus 42±2 years; P<0.01) and had reducedserum intact PTH compared to non-ABD patients (199±25versus 561 ±87 pg/ml; P<0.001). Patients with diabetesmellitus showed lower PTH values (179±31 versus 432±62pg/ml; P<0.001) and a lower incidence of advanced by chperparathyroidismbone lesions (16% versus 46%; P<0.05) than non-diabetic patients.However, diabetes was not clearly associated with low bone turnoverdisease (56% in diabetics versus 41% in non-diabetics; P=0.1). A second bone biopsy was obtained in eleven ABD patients aftera period of 16.6±2.2 months on maintenance dialysis witha dialysate calcium of 7 mg/dl. Bone histology was unchangedin 10 patients, and one evolved to mild hyperparathyroidism.Trabecular bone volume did not change (22.7± 1.7 versus20.7±1.7%), and the stainable bone aluminium surfaceremained <3%. In summary, ABD not associated with positive histological stainingfor aluminium is a common finding in asymptomatic end-stagerenal failure patients in the Canary Islands. Older age andrelatively low PTH values are associated with this form of bonedisease. After a period of 12–36 months of dialysis, progressiveosteopenia and other clinical problems do not occur.     

EFFICACY AND SAFETY OF FLUOXETINE, SERTRALINE AND CLOMIPRAMINE IN PATIENTS WITH PREMATURE EJACULATION: A DOUBLE-BLIND, PLACEBO CONTROLLED STUDY

Purpose

We compared the efficacy and safety of fluoxetine, sertraline, clomipramine and placebo for the oral pharmacotherapy of premature ejaculation.

Materials and Methods

The study included 36 men (mean age 44 years) who had intravaginal ejaculation latency of less than 2 minutes. Patients took each of 3 drugs and the placebo consecutively during a 4-week period per each agent. Efficacy and side effects data were obtained by a self-reported patient questionnaire that rated intravaginal ejaculation latency, sexual satisfaction of patient and partner, and possible side effects.

Results

After 4 weeks of treatment with placebo, fluoxetine, sertraline and clomipramine the mean intravaginal ejaculation latency time was significantly increased from 46 seconds to 2.27 minutes, 2.30 minutes, 4.27 minutes and 5.75 minutes, respectively (all p <0.01). However, treatment with clomipramine or sertraline caused a greater increase in mean intravaginal ejaculation latency time than fluoxetine or placebo (p <0.01). Patient sexual satisfaction rate after treatment with clomipramine was significantly higher (p <0.05) than with sertraline, fluoxetine or placebo. Partner sexual satisfaction rate was also higher with clomipramine than with sertraline or fluoxetine but no statistical difference was found. The incidence of side effects with clomipramine was significantly higher (p <0.05) compared to that of fluoxetine, sertraline and placebo, while no significant difference among sertraline, fluoxetine and placebo was noted.

Conclusions

In men with premature ejaculation clomipramine was the most useful drug in terms of efficacy. Treatment with sertraline was nearly as effective and had a lower incidence of side effects.     

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.     

C REACTIVE PROTEIN IN PATIENTS WITH CHRONIC RENAL DISEASES

Base-line serum levels of plasma C-reactive protein (CRP) are predictive of future myocardial infarction and sudden cardiac death in apparently healthy subjects, suggesting the hypothesis that chronic inflammation might be important in the pathogenesis of atherothrombosis. CRP production is mediated by several inflammatory mediators: interleukin 6 (IL-6) is currently felt to be the major cytokine influencing the acute phase response. CRP and other acute phase proteins are elevated in dialysis patients and cardiovascular diseases represent the single largest cause of mortality in chronic renal failure patients. Little information is available, however regarding CRP and IL-6 plasma levels in pre-dialysis renal failure. Plasma CRP was determined by a modification of the laser nephelometry technique; IL-6 by immunoassay (RD System); and fibrinogen, serum albumin, cholesterol, triglycerides, hematocrit, white blood cell count, erythrocytic sedimentation rate (ESR) and urinary protein levels by standard laboratory techniques. Results were obtained in 102 chronic pre-dialysis patients whose mean age was 53 ± 5.8 years with a mean creatinine clearance (C_Cr) of 52 ± 37 mL/min). CRP was greater than 5 mg/L in 25% of the global population. CRP and IL-6 were 4.0 ± 4.6 mg/L and 5.8 ± 5.6 pg/mL, respectively and were not significantly correlated (r = 0.11, p = n.s.). CRP and IL-6 were however related with renal function (CRP versus C_Cr r = ?0.40 p < 0.001; IL-6 versus C_Cr r = ?0.45; p < 0.001). When patients were divided in two groups according to renal function, CRP resulted 7.4 ± 6.3 mg/L in the group of patients with a C_Cr lower than 20 mL/min (n = 32) and 2.76 ± 4.35 in the group of patients with a C_Cr higher than 20mL/min (n = 70) (p < 0.0001). CRP and IL-6 were positively related with ESR (r = 0.32 and 0.46 respectively). Serum albumin levels were not significantly different in the two groups of patients (3.2 ± 0.4 versus 3.0 ± 0.5 g/dL). CRP and serum albumin were not significantly related (r = 0.17). CRP and IL-6 correlated positively with ESR (r = 0.32 and 0.46 respectively). In pre-dialysis patients we have demonstrated an increase in both CRP and IL-6 that occurs as renal function decreases. These data provided evidence of the activation – even in the predialysis phase of renal failure – of mechanisms known to contribute to the enhanced cardiovascular morbidity and mortality of the uremic syndrome.     

Annual change in bone mineral density in predialysis patients with chronic renal failure: significance of a decrease in serum 1,25-dihydroxy-vitamin D

Bone disease occurs in the predialysis phase of chronic renal failure (CRF). The aim of this study was to examine how a decrease in renal function affects annual bone mineral density (BMD) changes in predialysis CRF patients and to examine the factors that affect BMD. The BMD of the distal radius in 53 predialysis CRF patients (age, 61.3 ± 10.8 years; serum creatinine 2.7 ± 1.2 mg/dl) was measured by peripheral quantitative computed tomography (pQCT) twice with a 1-year interval. The total BMD of the radius significantly decreased over a year (P < 0.001), and both trabecular and cortical BMD showed a significant decrease. Significant positive correlations with BMD changes were found for estimated creatinine clearance (r = 0.375, P < 0.01) and baseline serum 1,25(OH)₂D (r = 0.434, P < 0.005), indicating that BMD decreased to a greater extent with larger reductions in creatinine clearance and serum 1,25(OH)₂D. Of several bone metabolic markers examined, baseline serum osteocalcin was significantly positively correlated with annual BMD changes (r = −0.276, P < 0.05). Multiple regression analysis showed that baseline serum 1,25(OH)₂D (β = 0.434) was a significant predictor of decreases in total and trabecular BMD (R ² = 0.188, P < 0.01; and R ² = 0.207, P < 0.01), independent of other confounding factors. These results indicate that BMD decreases as renal function deteriorates in predialysis CRF patients, and that osteocalcin is a clinically useful marker associated with the decrease in BMD. The serum 1,25(OH)₂D level is the principal factor affecting BMD of the radius, suggesting that supplementation with an active form of vitamin D is of importance for predialysis CRF patients.     

Heart and iron deficiency anaemia in rats with renal insufficiency: the role of hepcidin

Aim: Anaemia is prevalent in chronic kidney disease (CKD) and induces significant changes in heart and kidney. In this study, we evaluated the relationship between iron metabolism, hepcidin and inflammation focusing on left ventricular (LV) function, in a remnant kidney rat model. Methods: Rats with 5/6 subtotal nephrectomy (STNx) and sham operation. Haemoglobin (Hb), serum iron (SI), fractional shortening (FS%) by echocardiograms were evaluated. Six months after STNx, the heart and kidney were processed by immunohistochemistry with antibodies against hypoxia-inducible factors (HIF)-1α, erythropoietin (EPO), pro-hepcidin, caspase-3, tumour necrosis factor (TNF)-α and interleukin (IL)-6. Results: Hb (g/dL) STNx: 10.8 ± 0.8, sham: 14.7 ± 0.6 (P < 0.01); SI (µg/dL) STNx: 154.5 ± 24.5, sham: 287.5 ± 32.1 (P < 0.01); heart weight (g) STNx: 2.21 ± 0.15, sham: 1.12 ± 0.12 (P < 0.01); FS% STNx: 28.4 ± 2.5, sham: 45.1 ± 4.1 (P < 0.01). There was a correlation between Hb and FS% (r = 0.95; P < 0.01) and between SI and FS% (r = 0.86; P < 0.01) in the STNx group. Tissue ferritin was reduced in heart and in kidney in the STNx group (P < 0.01). HIF-1α was expressed in cardiomyocytes (positive cells/area) STNx: 32 ± 5, sham: 4 ± 1; and tubular cells in STNx group: 70 ± 16, sham: 10 ± 3, P < 0.01. Hepcidin (% staining/area) in heart STNx: 6.6 ± 0.8, sham: 0.8 ± 0.1; in kidney STNx: 9.7 ± 2.6, sham: 3.7 ± 0.9, P < 0.01. EPO (% staining/area) in heart STNx: 2.6 ± 0.4, sham: 0.8 ± 0.2; in kidney STNx: 10.2 ± 1.4, sham: 1.2 ± 0.6; P < 0.01. In STNx group positive caspase-3, TNF-α and IL-6 were detected in heart and renal cells. Conclusion: Low LV performance is associated with iron deficiency anaemia in rats with CKD. Furthermore, overproduction of HIF-1α and the activation of caspase-3 seem to be associated with iron deficiency and with inflammatory markers. Hepcidin seems to plays a key role in this mechanism.     

THE IMPACT OF CHRONIC RENAL FAILURE ON NITRIC OXIDE SYNTHASE ISOFORMS GENE EXPRESSION IN THE PENIS AND PELVIC GANGLIA OF RATS

PURPOSE: Patients with chronic renal failure experience a variety of physical and metabolic alterations. Uremia is often accompanied by erectile dysfunction (ED). Little information is available concerning the underlying pathophysiological mechanisms by which chronic renal failure can lead to erectile dysfunction. In this study, chronic renal failure was induced by 5/6 nephrectomy in a rat model. Cavernous nerve stimulation was used to measure the intracavernous pressure (ICP) rise. MATERIALS AND METHODS: Adult male Sprague-Dawley rats, aged between 10-12 weeks and weighing 200-250 gm. were divided into two groups. The first group (n = 20) served as a control (sham-operated) and underwent laparotomy with dissection of the perirenal fat around both kidneys. The second group (n = 40) were subjected to an excisional 5/6 nephrectomy (unilateral nephrectomy and contralateral upper and lower polar nephrectomy). Serum creatinine was measured 3 days post-operatively and at the end of the 12th week. Development of renal failure was considered if the animal had serum creatinine more than 120 microM/l. After 12 weeks, 10 animals per group were subjected to electric field stimulation (EFS) of the cavernous nerve with simultaneous recording of ICP-rise and systemic blood pressure. Northern and western blot analyses were used to determine the mRNA expression and protein contents of NOS isoforms (neuronal and endothelial) in the penile tissues and MPG. RESULTS: This remnant kidney model resulted in renal failure in 20 of 40 animals. The ICP-rise after cavernous nerve stimulation in the renal failure group was significantly impaired, 7.7+/-2.9 cm. H2O, as compared to control rats, 55.5+/-1.2 cm. H2O (p<0.001). The latency period after cavernous nerve stimulation was significantly increased in renal failure rats (6.9+/-0.95 sec.) in comparison to controls (2.4+/-0.25 sec.). Six of ten uremic animals had significantly lower testosterone (<1 nmol./l.) levels compared to non-uremic rats (3.6 nmol./l.) (p<0.005). Northern blot analysis revealed that renal failure rats had significantly higher levels of nNOS mRNA in the MPG and penile tissues than controls. There was no change in eNOS mRNA in either group. Western blot analysis demonstrated that eNOS and nNOS protein contents in the MPG and penile tissues of renal failure rats were significantly higher than those of controls. CONCLUSION: This report demonstrates that impairment of erection in renal failure rats, as determined by ICP-rise, was present in spite of elevated neuronal nitric oxide synthase mRNA and its protein in the MPG and penile tissues. Further studies are needed to determine whether erectile dysfunction is a result of post-translational changes, circulating inhibitory substances or other factors.     

Benchmarking iron dextran sensitivity: reactions requiring resuscitative medication in incident and prevalent patients.

BACKGROUND: Reliable information on the incidence of severe reactions to iron dextran is limited. Administration of agents of resuscitation in acute anaphylaxis may serve as a marker to quantify life-threatening adverse drug reactions. METHODS: To determine the incidence of the most serious reactions to intravenous (i.v.) iron dextran, we searched the Gambro Healthcare US medical database for evidence of same-day administration of both i.v. iron dextran and parenteral adrenaline, corticosteroids or antihistamines. We confirmed each case as an iron dextran sensitivity reaction by direct inquiry. We also determined the total reported number of suspected adverse iron dextran reactions. RESULTS: During the 16 month study period, we determined that 1,066,099 doses of i.v. iron dextran were given to 48,509 patients, including 20,213 patients who had not previously received iron dextran (iron dextran na?ve). We identified seven patients who experienced reactions requiring resuscitative agents, all in response to a test dose (five patients) or first therapeutic dose (two patients), and therefore all in the iron-na?ve (incident) group. Thus, we found the incidence of iron dextran reactions requiring resuscitative agents to be 0.035% (7 out of 20,213). No reaction was fatal. In a combined group of incident and prevalent patients, we found 337 total reports of suspected adverse reactions to iron dextran, without regard to severity of reaction, yielding an overall per patient adverse drug event (ADE) rate of 0.69% (337 out of 48,509) and per exposure rate of 0.03% (337 out of 1,066,099). CONCLUSIONS: The incidence of reactions to iron dextran requiring resuscitative medications, per exposure or per patient, is approximately 0.035%. Reactions of this severity occur after either the test dose or first dose of iron dextran.     

Reducing high phosphate levels in patients with chronic renal failure undergoing dialysis: a 4-week, dose-finding, open-label study with lanthanum carbonate.

BACKGROUND: The majority of patients with end-stage renal disease on dialysis are hyperphosphataemic. Lanthanum carbonate has been shown to be a highly effective phosphate binder in pre-clinical studies. A 4-week, open-label, dose-titration trial was conducted to assess the ability of lanthanum carbonate to control phosphate levels in patients with chronic renal failure. METHODS: This preliminary study was of 6 weeks duration: 2 weeks of washout followed by 4 weeks of dose titration. Patients (n = 59) were titrated on the basis of weekly serum phosphate levels from a daily dose of 375 mg lanthanum carbonate to a maximum dose of 2250 mg. Patients were maintained on the dose that controlled serum phosphate to between 1.30 and 1.80 mmol/l (4.03-5.58 mg/dl). Serum phosphate levels represented the main efficacy assessment. Safety was also evaluated. RESULTS: Most patients were successfully titrated to 1500 and 2250 mg lanthanum/day (mean dose at end of titration: 1278 mg). At completion of the study 70% of patients achieved a serum phosphate of 相似文献   

RIGHT ATRIAL CATHETERS: RELIABLE,IMMEDIATE AND DURABLE VASCULAR ACCESS FOR HAEMODIALYSIS AND PLASMA EXCHANGE

This paper prospectively evaluates 33 dual lumen, right atrial catheters inserted into either an external or internal jugular vein by open operation in 29 patients, of whom 15 required haemodialysis and 14 required temporary plasma exchange. The median (range) catheter survival in the haemnodialysis and plasma exchange groups was 108 days (7–334 days) and 61 days (10–116 days), respectively. Life table analysis demonstrated that overall catheter survival was 58% at 200 days. The main causes of catheter failure were infection (four cases), poor flow (three cases) and accidental removal (one case). Another nine catheters were removed electively because of maturation of alternative methods of vascular access (five cases). completion of plasma exchange treatment (three cases), or successful renal transplantation (one case). Long-term silastic catheters, inserted into the right atrium via a jugular vein. have distinct advantages over temporary subclavian vein catheters and external arteriovenous (AV) shunts; this form of access is the method of choice for hamodialysis and plasma exchange patients who require immediate and short- to medium-term vascular access.