Kelfiprim versus co-trimoxazole in recurrent and persistent urinary tract infections: multicenter double-blind trial

Kelfiprim (KP) is a new bactericidal agent containing trimethoprim (T) and sulfametopyrazine (S), a long-acting sulfonamide (ratio 5:4). The posology is one capsule (T 250 mg + S 200 mg) daily, after a loading dose of two capsules on the first day. To evaluate the clinical value of Kelfiprim (KP) vs co-trimoxazole (CO) in urinary tract infection (UTI) a controlled multicenter double-blind trial (MDBT) was carried out in 76 patients suffering from persistent and recurrent UTIs. About 90 per cent response rate (sterile urine at the end of treatment) was obtained for KP and about 85 per cent for CO in recurrent UTI. In persistent UTI the rate of recovery was 66.8 per cent and 53 per cent for KP and CO, respectively. Safety of treatments was excellent in 97 per cent of patients treated with Kelfiprim and 87 per cent treated with co-trimoxazole. Two patients, one in each group, were dropped from the study because of adverse reactions.     

Long-term oral treatment of urinary tract infections with single daily doses of a new antibacterial drug combination (Kelfiprim)

Of 30 patients with severe, complicated U.T.I. 27 have been given single daily doses of Kelfiprim (KP), a new sulfatrimethoprim combination, for 8 weeks. In 24 bacteriuria was lastingly controlled, one had a relapse, one had a reinfection, and in one, with bladder carcinoma, bacteriuria persisted. Three other patients received KP for shorter periods, as they presented gastric intolerance or skin hypersensitivity, but in two of them a lasting sterilization of the urine has been obtained. The usefulness of a single daily dose schedule is stressed.     

Lower risk of urinary tract infection with low‐dose trimethoprim/sulfamethoxazole compared to dapsone prophylaxis in older renal transplant patients on a rapid steroid‐withdrawal immunosuppression regimen

Giullian JA, Cavanaugh K, Schaefer H. Lower risk of urinary tract infection with low‐dose trimethoprim/sulfamethoxazole compared to dapsone prophylaxis in older renal transplant patients on a rapid steroid‐withdrawal immunosuppression regimen.
Clin Transplant 2009 DOI: 10.1111/j.1399‐0012.2009.01129.x
© 2009 John Wiley & Sons A/S. Abstract: Background: Urinary tract infections (UTI) are common in renal transplant recipients. Trimethoprim/sulfamethoxazole (TMP/SMZ) in moderate to high daily doses prevents Pneumocystis jiroveci (PCP) and reduces the risk of UTI in renal transplant patients. Low‐dose TMP/SMZ also reduces the risk of PCP, although its ability to reduce the risk of UTI is uncertain. Design: Retrospective review of 158 patients who received a renal transplant without corticosteroids for maintenance immunosuppression. Results: Forty percent of patients initially prescribed TMP/SMZ ultimately stopped this medication early because of an adverse reaction. Urinary infection occurred in 16% without a significant difference in the risk of UTI between those treated with dapsone vs. those treated with TMP/SMZ (HR [95%CI]: 1.7 [0.75, 3.9], p = 0.2). In the subset of patients who were older than age 47 yr (mean age for this cohort, SD ± 6.2 yr), those treated with dapsone originally or who switched from TMP/SMZ to dapsone had a greater risk of UTI compared to patients who remained on TMP/SMZ (HR [95%CI]: 4.3 [1.2, 15.5], p = 0.024). Conclusions: For renal transplant recipients over the age of 47 yr, treated without long‐term glucocorticoids, our retrospective data suggest that low‐dose TMP/SMZ is associated with a lower risk of UTI compared to dapsone prophylaxis.     

Biomechanical assessment of new surgical method instead of kyphoplasty to improve the mechanical behavior of the vertebra:Micro finite element study

AIM To reduce post treatments of kyphoplasty, as a common treatment for osteoporotic vertebrae.METHODS This study suggests a new method for treating vertebrae by setting the hexagonal porous structure instead of the rigid bone cement mass in the kyphoplasty(KP). The KP procedure was performed on the fresh ovine vertebra of the level L1. Micro finite element modeling was performed based on micro computed tomography of ovine trabecular cube. The hexagonal porous structure was set on one cube instead of the bone cement mass. For the implant designing, two geometrical parameters were considered: Spacing diameter and thickness.RESULTS The results of micro finite element analyses indicated the improvement in the mechanical behavior of the vertebra treated by the hexagonal porous structures, as compared to those treated by vertebroplasty(VP) and KP under static loading. The improvement in the mechanical behavior of the vertebra, was observed as 54% decrease in the amount of maximum Von Misses stress(improvement of stress distribution), in trabecular cube with embedded hexagonal structure, as compared to VP and KP. This is comparable to the results of the experimental study already performed; it was shown that the improvement of mechanical behavior of the vertebra was observed as: 83% increase in the range of displacements before getting to the ultimate strength(increasing the toughness) after setting hexagonal pearls inside vertebrae. Both the material and geometry of implant influenced the amount of Von Mises stress in the structure.CONCLUSION The new proposed method can be offered as a substitute for the KP. The implant geometry had a more obvious effect on the amount of Von Mises stress, as compared to the implant material.     

Evaluation of tumor growth in vivo in a rat model of liver metastasis, using a newly devised index obtained by positron emission tomography with [18F] FDG

Background/Purpose [¹⁸F] fluorodeoxyglucose-positron emission tomography (FDG-PET) is regarded as a unique imaging modality, because the images reflect tumor activity. This characteristic of PET encouraged us to use it to develop a novel method of quantitatively measuring liver metastasis viability. Methods F344 rats were injected with rat colon adenocarcinoma cells (RCN-9 cell line) via the portal vein, and some of them were treated with 5-fluorouracil (5-FU). Tumor growth and tumor activity were measured by PET. We used a tumor viability index (TVI) to evaluate changes in tumor activity and to quantitatively evaluate tumor proliferation activity, instead of using the standardized uptake value (SUV) of the tumor tissue. The TVI was compared with the number of tumor nodules and the proliferating cell nuclear antigen (PCNA) index 28 days after RCN-9 cell inoculation. Results [¹⁸F] FDG uptake by the liver tumors was measured by PET, and the TVI was found to increase as the tumor nodules increased in number and size. The TVI values in the experimental model represented the viability of tumors suppressed by chemotherapy, and the values were significantly correlated with the number of nodules and the PCNA index. Conclusions The TVI was concluded to be superior to the SUV, the commonly used indicator, for evaluating tumor growth, especially that of multiple, small tumors.     

Virtual unenhanced phase with spectral dual-energy CT: Is it an alternative to conventional true unenhanced phase for abdominal tissues?

PurposeTo compare attenuation measurements and image quality of virtual unenhanced phase (VUP) images with those of conventional true unenhanced phase (TUP) images on spectral dual energy computed tomography (DECT) with dual layer detector on abdominal tissues and to assess potential reduction in radiation dose.Material and methodA total of 295 patients (185 men, 110 women; mean age 61 ± 17.6 [SD] years [range: 17–95 years]) who had undergone abdominal or thoraco-abdominal CT with pre- and post-contrast imaging (portal phase) with spectral DECT with dual layer detector were retrospectively analyzed. VUP images based on portal-venous phase DECT acquisition were generated. Regions of interest were defined in abdominal tissues (liver, spleen, kidney, muscle and fat) by two independent readers. Inter-technique agreement (VUP images vs. TUP images) on attenuation measurements was assessed. Signal-to noise ratio (SNR) and image quality of TUP and VUP images were compared. The radiation dose delivered to patients was compared with the radiation dose of protocols without TUP images.ResultsA total of 9880 ROIs were drawn in the abdominal tissues. The difference in mean attenuation values between TUP and VUP images was less than 15 HU in 98.3% and less than 10 HU in 92.3% of all measurements. VUP images overestimated attenuation in fat comparatively to TUP images. Image quality was evaluated as good or excellent in 77% (37/48) of TUP images and 54% (26/48) of VUP images. Using VUP images instead of TUP images could decrease the radiation dose by 32%.ConclusionVUP images demonstrate good agreement with TUP images in different abdominals tissues and can be obtained with similar image quality as TUP. VUP images appear as an alternative to TUP images, resulting in reduction of radiation dose delivered to the patient.     

Comparison of recovery following rapacuronium, with and without neostigmine, and succinylcholine

The neuromuscular blocking effects of a single dose of rapacuronium 1.5 mg x kg(-1) with or without reversal with neostigmine have been examined in the present study and compared with a dose of succinylcholine 1.0 mg x kg(-1). Neuromuscular block was measured mechanomyographically using train-of-four stimulation. Complete block occurred within 1 min with both agents. Twenty-five per cent recovery of the first response of the train-of-four occurred in a median [range] time of 7.6 [5.7-11.3] min in the succinylcholine group and in 14.2 [8.8-23.6] and 15.1 [9.6-23.4] min in the rapacuronium groups with and without neostigmine reversal, respectively. Spontaneous recovery to a train-of-four ratio of 0.8 took 33.4 [20.0-79.0] min with rapacuronium but this was reduced to about 21.2 [13.9-33.7] min when neostigmine was administered at 25% recovery of first twitch of the train-of-four.     

Effects of Radolmidine, A Novel α2-Adrenergic Agonist Compared with Dexmedetomidine in Different Pain Models in the Rat

Background: Intrathecally administered [alpha]2-adrenoceptor agonists produce effective antinociception, but sedation is an important adverse effect. Radolmidine is a novel [alpha]2-adrenoceptor agonist with a different pharmacokinetic profile compared with the well-researched dexmedetomidine. This study determined the antinociceptive and sedative effects of radolmidine in different models of acute and chronic pain. Dexmedetomidine and saline served as controls.

Methods: Male Sprague-Dawley rats were studied in acute pain (tail flick), carrageenan inflammation, and the spinal nerve ligation model of neuropathic pain. Mechanical allodynia was assessed with von Frey filaments, cold allodynia with the acetone test, and thermal hyperalgesia with the paw flick test. Locomotor activity-vigilance was assessed in a dark field. Dexmedetomidine and radolmidine were administered intrathecally in doses of 0.25 [mu]g, 2.5 [mu]g, 5 [mu]g, and 10 [mu]g.

Results: In the tail flick test, radolmidine showed a dose-dependent antinociceptive effect, being equipotent compared with dexmedetomidine. In carrageenan inflammation, intrathecal doses of 2.5 [mu]g or 5 [mu]g of dexmedetomidine/radolmidine produced significant antinociception compared with saline (P < 0.01). The two drugs were equianalgesic. In the neuropathic pain model, an intrathecal dose of 5 [mu]g dexmedetomidine-radolmidine had a significant antiallodynic effect compared with saline (P < 0.01). The two drugs were equipotent. Intrathecal administration of both dexmedetomidine and radolmidine dose dependently decreased spontaneous locomotor acitivity-vigilance, but this effect was significantly smaller after intrathecal administration of radolmidine than after intrathecal dexmedetomidine.     

Impact of dose reduction and iterative reconstruction algorithm on the detectability of pulmonary nodules by artificial intelligence

PurposeThe purpose of this study was to assess whether the performances of an automated software for lung nodule detection with computed tomography (CT) are affected by radiation dose and the use of iterative reconstruction algorithm.Materials and methodsA chest phantom (Multipurpose Chest Phantom N1; Kyoto Kagaku Co. Ltd, Kyoto, Japan) with 15 pulmonary nodules was scanned with a total of five CT protocol settings with up to 20-fold dose reduction. All CT examinations were reconstructed with iterative reconstruction algorithms ADMIRE 3 and ADMIRE 5 and were then analyzed for the presence of pulmonary nodules with a fully automated computer aided detection software system (InferRead^TM CT Lung, Infervision), which is based on deep neural networks.ResultsThe sensitivity of fully automated pulmonary nodule detection for ground-glass nodules at standard dose CT was greater (70.0%; 14/20; 95% CI: 51.6-88.4%) than at 10-fold and 20-fold dose reduction (30.0%; 6/20; 95% CI: 0.0%-62.5%). There were less false positive findings when ADMIRE 5 reconstruction was used (4.0 ± 2.8 [SD]; range: 2–6) instead of ADMIRE 3 reconstruction (25.0 ± 15.6 [SD]; range: 14–36). There was no difference in the sensitivity of detection of solid and subsolid nodules between standard dose (100%; 95% CI: 100–100%) and 10- and 20-fold reduced dose CT (92.5%; 95% CI: 83.8–100.0%). Image noise was significantly greater with ADMIRE 3 (81 ± 2 [SD] [range: 79–84]; 104 ± 3 [SD] [range: 101–107]; 114 ± 5 [SD] [range: 110–119]; 193 ± 10 [SD] [range: 183-203]; 220 ± 16 [SD] [range: 210–238]) compared to ADMIRE 5 (44 ± 2 [SD] [range: 42–46]; 60 ± 2 [SD] [range: 57–61]; 66 ± 1 [SD] [range: 65–67]; 103 ± 4 [SD] [range: 98–106]; 110 ± 1 [SD] [range: 109–111]), respectively in each of the five CT protocols.ConclusionThis phantom study suggests that dose reduction and iterative reconstruction settings have an impact on detectability of pulmonary nodules by artificial intelligence software and we therefore encourage adaption of dose levels and reconstruction methods prior to widespread implementation of fully automatic nodule detection software for lung cancer screening purposes.     

Stereotactic body radiation therapy versus radiofrequency ablation in patients with small hepatocellular carcinoma: a systematic review and meta-analysis

BackgroundThis study aimed to compare the clinical outcomes and toxicity between small hepatocellular carcinoma (HCC) patients treated with stereotactic body radiation therapy (SBRT) and those treated with radiofrequency ablation (RFA).MethodsWe searched databases for relevant clinical studies. The primary outcomes of interest were overall survival (OS) at 1 and 2 years, freedom from local progression (FFLP) rate at 2 years, and complications.ResultsFive cohorts from 5 retrospective studies and 4,814 patients with HCC were included. Pooled OS at 2 years was significantly lower for SBRT than for RFA [odds ratio (OR): 0.63; 95% confidence interval (CI): 0.51–0.79; P<0.0001], but the pooled FFLP rate at 2 years was higher for SBRT than for RFA (OR: 1.66; 95% CI: 1.05–2.61; P=0.03). In addition, there was no significant difference in the local and liver toxicities of the two treatments. The contradictory conclusion between the OS and FFLP outcome may be attributed to the difference in radiological dose and location, but there were no uniform criteria to illustrate the radiological dose and location in the included studies.ConclusionsSBRT had a higher local control ratio but poorer prognosis than RFA in patients with small HCC. The local toxicity was comparable in both treatments. Further trials should be designed with uniform standards for SBRT and RFA treatments.     

Opportunistic infections in children following renal transplantation

Opportunistic infections following renal transplantation in children are a major cause of severe morbidity and mortality. These infections account for the majority of early post renal-transplant deaths in children. General risk factors which affect the incidence and severity of these infections include: transmission of the infectious agent by the donor organ; history of immunity in the recipient prior to transplantation; type and amount of immunosuppression including treatment for rejection episodes; availability of specific treatment for the infection. Children are at particular risk because of the lack of exposure to certain pathogens prior to transplantation. There have been recent advances in the prevention and treatment of important infections which occur in children following transplantation, including varicella,Pneumocystis carinii pneumonia (PCP) and cytomegalovirus (CMV) disease. Varicella is treatable with acyclovir, often without decreasing immunosuppression and placing the graft at risk. Prophylaxis against PCP may be achieved by provision of alternate-day trimethoprim sulpha, but clear guidelines for determining who should be treated are lacking. Treatment of this disease with high-dose trimethoprim sulfa or pentamidine is usually successful. CMV disease is frequently severe, especially when the donor is seropositive and the recipient seronegative. In these situations, prophylactic CMV immunoglobulin reduces the morbidity and the mortality of the disease and prophylactic oral acyclovir may decrease its incidence. Treatment of severe CMV disease with gancyclovir is promising.     

Cobalt as a gastric juice volume marker: comparison of two methods of estimation

We investigated the use of cobalt-EDTA, a novel, nonabsorbable liquid phase marker, in the estimation of secretory volumes during topical misoprostol (synthetic PGE, analog) administration in the canine chambered gastric segment. We compared atomic absorption spectrophotometry (AAS) and instrumental neutron activation analysis (INAA) in the estimation of [Co]. Mucosal bathing solutions containing cobalt-EDTA were instilled into and recovered from the chamber by gravity every 15-min period as follows: (i) basal--60 min; (ii) misoprostol periods--150 min (plus 0.1-, 1-, 10-, 100-, and 1000-micrograms doses of misoprostol for two periods per dose). The recovered solutions were analyzed for [Co] by AAS and INAA. Total cobalt recovery by AAS after chamber washout was 102.97 +/- 0.98%. Mean +/- SE volumes (12.14 +/- 0.33 and 13.24 +/- 0.60 ml/15 min) obtained respectively from AAS and INAA were significantly higher (P less than 0.001) than the recovered mean volumes (10.51 +/- 0.17 ml/15 min). The percentage error in volume collection increased (range: 9.3-52.7%) with the volume of secretion. Values of [Co] obtained by the two techniques were comparable and not significantly different from each other (P greater than 0.05). INAA-estimated mean +/- SE [Co] showed consistently higher coefficients of variation. Spectra obtained for all samples during INAA measurements showed significant Compton background activity from 24Na and 38Cl. Cobalt-EDTA did not grossly or histologically damage the gastric mucosa. We conclude that cobalt is not adsorbed, absorbed, or metabolized, and is a suitable and reliable volume marker in this model.(ABSTRACT TRUNCATED AT 250 WORDS)     

Fibrinolytic inhibitors in off-pump coronary surgery: a prospective, randomized, double-blind TAP study (tranexamic acid, aprotinin, placebo).

OBJECTIVE: To evaluate and compare hemostatic effects of tranexamic acid vs. aprotinin vs. placebo in off-pump coronary artery bypass (OPCAB) surgery and, in addition, to assess the safety of fibrinolytic inhibitors therapies. METHODS: In a prospective, randomized, double-blind study finally 91 patients undergoing OPCAB were investigated (group A, n=32, tranexamic acid 1g before skin incision and continuously 200mg/h; group B, n=29, aprotinin 1,000,000IU before skin incision and 250,000IU/h; group C, n=30, placebo). RESULTS: Highly significant inter-group differences were found in cumulative blood loss within 4h (geometric means [95% confidence intervals]-group A: 89.3 [72.7, 109.8] mL, group B: 72.3 [49.2, 106.3] mL and group C: 192.3 [151.8, 243.5] mL) (P<0.001), within 8h (group A: 152.1 [120.7, 191.6] mL, group B: 130.3 [88.1, 192.8] mL and group C: 283.8 [226.0, 356.3] mL) (P=0.001), and within 24h postoperatively (group A: 410.3 [337.6, 498.6] mL, group B: 345.8 [256.0, 398.2] mL and group C: 619.8 [524.3, 732.8] mL) (P<0.001). At all time points, placebo group C was significantly distinct from the groups treated with fibrinolytic inhibitors (groups A and B). However, no differences between groups A and B were found. Both mean hemoglobin and hematocrit values 24h postoperatively were different between the groups (P=0.018 and P=0.077, respectively), acheiving the lowest value in group C. Number of re-transfuzed patients was highest in group C, but without statistical significance (either packed red blood cells, P=0.119 or fresh-frozen plasma, P=0.118). We observed one postoperative myocardial infarction in aprotinin treated group B and one temporary postoperative myocardial ischemia in placebo group C, no cerebrovascular or pulmonary embolism was noticed. Treated groups A and B did not demonstrate postoperative increase in mean levels of myocardial enzymes, compared with group C. Significantly higher mean values of D-dimer were found in group C 24h postoperatively (P<0.001). CONCLUSIONS: Both tranexamic acid and aprotinin seem to be similarly effective in the reduction of postoperative blood loss in OPCAB. Tranexamic acid appears to be cost-effective and safe alternative to aprotinin.     

Comparison of Predicted Induction Dose with Predetermined Physiologic Characteristics of Patients and With Pharmacokinetic Models Incorporating those Characteristics as Covariates

Background: The relationship between patient characteristics and anesthesia induction dose at a high administration rate is unclear. This study was designed to investigate the relation between induction dose and patient characteristics and to compare it to the predicted induction dose using the previously reported pharmacokinetic model.

Methods: Diluted propofol (0.5 mg/ml) dose required to reach loss of consciousness, when infused at an infusion rate per lean body mass (LBM) of 150 mg [middle dot] kg-1 [middle dot] h-1 (high rate), was determined in 82 patients, ages 10-85 yr. Cardiac output, blood volume, central blood volume (CBV), and hepatic blood flow were measured with indocyanine green pulse spectrophotometry. Stepwise multiple linear regression models were used to investigate the relations between the patient characteristics and induction dose. These were compared with our previously reported parameters at the rate of 40 mg [middle dot] kg-1 [middle dot] h-1 (low rate) and with predicted induction doses with two previously reported pharmacokinetic models.

Results: Significant factors for predicting the induction dose at a high rate were age, LBM, and CBV. Induction dose with one pharmacokinetic model was 1.5 times that of the measured one and the other was half that of the measured one at a high rate. At a low rate, one pharmacokinetic model provided an accurate induction dose.     

Effective postcoital prophylaxis of recurrent urinary tract infections in premenopausal women: A review

A total of 77 sexually active premenopausal women, susceptible to recurrent urinary tract infections (UTI) but otherwise healthy, were subjected to postcoital prophylaxis consisting of a single oral dose of either cotrimoxazole (80 mg trimethoprim+400 mg sulfamethoxazole), 50 mg nitrofurantoin macrocrystals, 500 mg nalidixic acid, 250 mg cinoxacin or 250 mg cephalexin. Postcoital prophylaxis reduced the incidence of recurrent UTI from 5-8 UTI per patient/year prior to prophylaxis, to a mere 0.03 UTI per patient/ year following prophylaxis. The differences in the incidence of UTI prior to and following institution of postcoital prophylaxis were statistically highly significant. A mean of 106–120 antibacterial tablets per patient were administered per year.Postcoital prophylaxis of recurrent UTI in premenopausal women is highly effective because of easy compliance, the high urinary concentration achieved and the minimal induction of resistance in the introital Gram-negative bacterial flora, irrespective of the length of time this prophylaxis is used. Furthermore, postcoital prophylaxis is significantly more effective than daily, as it achieves the same effect but requires only one third or fewer of the antibacterial tablets used in daily prophylaxis. At present, postcoital prophylaxis with cotrimoxazole, nitrofurantoin macrocrystals or cephalexin is recommended.     

Switch from cyclosporine A to mycophenolate mofetil in nephrotic children

Nephrotoxicity is a well-known adverse effect of cyclosporine A (CyA) treatment in children with steroid-dependent (SD) and steroid-resistant (SR) nephrotic syndrome (NS). We analyzed nine children (age: 3.3–15.7 years, two girls) with SD or SR NS who experienced a significant decrease in their GFR under CyA treatment as measured by inulin clearance (C_IN). Mycophenolate mofetil (MMF) was introduced progressively until doses of 1 g/1.73 m² twice daily were reached. CyA treatment was stopped after introduction of MMF and oral steroids were reduced if possible. After a median follow up of 261 days, no adverse effects of MMF such as diarrhea or hematological anomalies occurred in our patients. After switching from CyA to MMF, those children with SD NS remained in remission without proteinuria and those with SR NS did not show any significant changes in their residual proteinuria. The serum protein level did not change significantly in any of the children analyzed. GFR increased from a mean of 76.9±4.8 to 119.9±5.9 mL/1.73 m² per min (P<0.001). Oral steroid treatment could be reduced from a median [range] prednisone dose of 0.85 [0.26–2.94] mg/kg/d pre-MMF to 0.29 [0–1.1] mg/kg per day (P=0.026), and blood pressure decreased moderately after CyA withdrawal, but the difference did not reach statistical significance. We conclude that a switch from CyA to MMF seems to be safe for children with SDNS and SRNS in terms of side effects as well as disease control, at least in the short term. Interruption of CyA treatment lead to rapid amelioration of kidney function in these children, often associated with steroid sparing, which may lead to additional benefit for growth velocity, blood pressure and physical appearance.     

An assessment of quality of life following radical prostatectomy, high dose external beam radiation therapy and brachytherapy iodine implantation as monotherapies for localized prostate cancer

PURPOSE: Monotherapy with radical prostatectomy, high dose external beam radiotherapy or a (125)I implant is reported to produce equivalent outcomes. We assessed the health related quality of life associated with these 3 treatment approaches. MATERIALS AND METHODS: Extended Prostate Index Composite surveys were mailed to all 960 patients treated with a (125)I implant, high dose external beam radiotherapy or radical prostatectomy with or without hormonal therapy at our institution from 1998 to 2000. A total of 625 patients (65%) completed the surveys. Nerve sparing radical prostatectomy was performed when appropriate. The (125)I implant consisted of 145 Gy and high dose external beam radiotherapy consisted of 78 Gy. For urinary, rectal and sexual domains mean scores were calculated, compared by treatment modality and compared to normative values. RESULTS: A total of 234 patients with radical prostatectomy, 135 with external beam radiotherapy and 74 with a (125)I implant were treated with a monotherapy approach. Median age was 61 years in the radical prostatectomy group, 68 years in the high dose external beam radiotherapy group and 64 years in the (125)I implant group (p <0.001). Of the patients 97% [corrected] had cT1-2 disease and Gleason score 7 or less [corrected] Median time from treatment was 4.0 years for radical prostatectomy, 4.7 years for high dose external beam radiotherapy and 3.5 years for (125)I implantation. Radiation caused significantly worse bowel bother and bowel function than radical prostatectomy (p < or =0.018). Patients with high dose external beam radiotherapy had significantly better urinary function than patients with radical prostatectomy (p <0.001). While patients with radical prostatectomy had significantly worse urinary incontinence than those with a (125)I implant or high dose external beam radiotherapy (p <0.0001), patients with a (125)I implant had more urinary irritation than those with high dose external beam radiotherapy and radical prostatectomy (p <0.01 and <0.0001, respectively). Patients with a (125)I implant had significantly better sexual function than those with high dose external beam radiotherapy and radical prostatectomy (p = 0.01 and 0.0003, respectively). CONCLUSIONS: Of patients with prostate cancer treated with a monotherapy approach we noted better urinary continence in those who underwent radiation based therapies, and better bowel function and less urinary irritation in those who underwent surgery. Sexual function was impaired across all monotherapies but higher scores were seen in men who selected brachytherapy.     

Dobutamine Antagonizes Epinephrine's Biochemical and Cardiotonic Effects: Results of an In Vitro Model Using Human Lymphocytes and a Clinical Study in Patients Recovering from Cardiac Surgery

Background: Patients may receive more than one positive inotropic drug to improve myocardial function and cardiac output, with the assumption that the effects of two drugs are additive. The authors hypothesized that combinations of dobutamine and epinephrine would produce additive biochemical and hemodynamic effects.

Methods: The study was performed in two parts. Phase 1 used human lymphocytes in an in vitro model of cyclic adenosine monophosphate (cAMP) generation in response to dobutamine (10-8 to 10-4 M) or epinephrine (10-9 M to 10-5 M), and dobutamine and epinephrine together. Phase 2 was a clinical study in patients after aortocoronary artery bypass in which isobolographic analysis compared the cardiotonic effects of dobutamine (1.25, 2.5, or 5 [micro sign]g [middle dot] kg-1 [middle dot] min-1) or epinephrine (10, 20, or 40 ng [middle dot] kg-1 [middle dot] min-1), alone or in combination.

Results: In phase 1, dobutamine increased cAMP production 41%, whereas epinephrine increased cAMP concentration [almost equal to] 200%. However, when epinephrine (10-6 M) and dobutamine were combined, dobutamine reduced cAMP production at concentrations between 10-6 to 10-4 M (P = 0.001). In patients, 1.25 to 5 [micro sing]g [middle dot] kg-1 [middle dot] min-1 dobutamine increased the cardiac index (CI) 15-28%. Epinephrine also increased the CI with each increase in dose. However, combining epinephrine with the two larger doses of dobutamine (2.5 and 5 [micro sign]g [middle dot] kg-1 [middle dot] min-1) did not increase the CI beyond that achieved with epinephrine and the lowest dose of dobutamine (1.25 [micro sign]g [middle dot] kg-1 [middle dot]-1 min (-1)). In addition, the isobolographic analysis for equieffective concentrations of dobutamine and epinephrine suggests subadditive effects.     

Nefopam, a Nonsedative Benzoxazocine Analgesic, Selectively Reduces the Shivering Threshold in Unanesthetized Subjects

Background: The analgesic nefopam does not compromise ventilation, is minimally sedating, and is effective as a treatment for postoperative shivering. The authors evaluated the effects of nefopam on the major thermoregulatory responses in humans: sweating, vasoconstriction, and shivering.

Methods: Nine volunteers were studied on three randomly assigned days: (1) control (saline), (2) nefopam at a target plasma concentration of 35 ng/ml (low dose), and (3) nefopam at a target concentration of 70 ng/ml (high dose, approximately 20 mg total). Each day, skin and core temperatures were increased to provoke sweating and then reduced to elicit peripheral vasoconstriction and shivering. The authors determined the thresholds (triggering core temperature at a designated skin temperature of 34[degrees]C) by mathematically compensating for changes in skin temperature using the established linear cutaneous contributions to control of each response.

Results: Nefopam did not significantly modify the slopes for sweating (0.0 +/- 4.9[degrees]C [middle dot] [mu]g-1 [middle dot] ml; r2 = 0.73 +/- 0.32) or vasoconstriction (-3.6 +/- 5.0[degrees]C [middle dot] [mu]g-1 [middle dot] ml; r2 = -0.47 +/- 0.41). In contrast, nefopam significantly reduced the slope of shivering (-16.8 +/- 9.3[degrees]C [middle dot] [mu]g-1 [middle dot] ml; r2 = 0.92 +/- 0.06). Therefore, high-dose nefopam reduced the shivering threshold by 0.9 +/- 0.4[degrees]C (P < 0.001) without any discernible effect on the sweating or vasoconstriction thresholds.     

Surgical outcome in biliary atresia: etiology affects the influence of age at surgery

OBJECTIVE: The exact nature of the relationship between age at Kasai portoenterostomy (KP) for biliary atresia (BA) and outcome is controversial. METHODS: Single-center retrospective analysis of consecutive cases (January 1994-December 2005) undergoing KP, using 2 dichotomous measures of outcome (clearance of jaundice to <20 micromol/L and native liver survival at 2 years post-KP). Outcome was analyzed by age cohort (<30 days, 30-40 days, etc) and cumulatively. Data are quoted as median (interquartile range). Statistical analysis was by extended Fisher r x c analysis. P < 0.05 was regarded as significant. RESULTS: Two hundred twenty-five infants with BA were divided into 3 groups based on possible etiology: isolated BA (n = 177), biliary atresia splenic malformation (BASM) syndrome (n = 28), and cystic BA (n = 23). Three infants had both BASM and a cyst. Age at KP was significantly greater in those with isolated BA [58 (48-61)] compared with both BASM [47 (39-59); P = 0.02] and cystic BA [47 (39-54); P = 0.02]. Overall, 127 (56%) cleared their jaundice and 145 (65%) survived to 2 years with their native liver. Children with isolated BA showed no statistical difference by age cohort for clearance of jaundice (P = 0.75) or for native liver survival (P = 0.14). In contrast, there was a marked detrimental effect of age at KP for both BASM and cystic BA groups (P = 0.02). CONCLUSION: There is a marked detrimental effect of age at KP on groups with a presumed "developmental" origin, not seen in the majority with isolated BA.