Indications of proton-dominated cosmic-ray composition above 1.6 EeV.

We report studies of ultrahigh-energy cosmic-ray composition via analysis of depth of air shower maximum (X(max)), for air shower events collected by the High-Resolution Fly's Eye (HiRes) observatory. The HiRes data are consistent with a constant elongation rate d/d[log(E)] of 47.9+/-6.0(stat)+/-3.2(syst) g/cm2/decade for energies between 1.6 and 63 EeV, and are consistent with a predominantly protonic composition of cosmic rays when interpreted via the QGSJET01 and QGSJET-II high-energy hadronic interaction models. These measurements constrain models in which the galactic-to-extragalactic transition is the cause of the energy spectrum ankle at 4x10(18) eV.

Impact of renal donation. Long-term clinical and biochemical follow-up of living donors in a single center.

Forty-six renal donors who responded to a questionnaire and two additional donors with nephrotic syndrome and renal insufficiency were studied. The mean age was 46 +/- 2.0 years (mean +/- SE). Duration of follow-up was 6 +/- 0.5 years. Serum creatinine levels increased from 1.0 +/- 0.03 mg/dl before donation to 1.2 +/- 0.04 mg/dl at follow-up. The incidence of proteinuria (more than 150 mg over 24 hours) was 39 percent. The serum creatinine level was 1.0 +/- 0.08 mg/dl and 1.2 +/- 0.06 mg/dl in the proteinuric and nonproteinuric groups, respectively. The incidence of hypertension was 31 percent with a serum creatinine level of 1.1 +/- 0.11 mg/dl and 1.2 +/- 0.07 mg/dl in the hypertensive and normotensive groups, respectively. One patient with nephrotic syndrome had proliferative glomerulonephritis. It is concluded that renal donation is associated with a minimal but statistically significant increment in serum creatinine levels. The incidence of mild hypertension and proteinuria is increased, but impact on renal function is minimal as assessed by serum creatinine determination.

Soft drink consumption and urinary stone recurrence: a randomized prevention trial.

The object of this study was to determine if a strong association between soft drink (soda) consumption and recurrence of urinary stone disease, found in an earlier case-control study of adult males, had a causal component. The study sample consisted of 1009 male subjects, who completed an episode of urinary stone disease, who were aged 18-75 at that time, and who reported consuming at least 160 ml per day of soft drinks. Half of the subjects were randomized to refrain from consuming soft drinks, while the remaining subjects served as controls. The intervention group had an observed 6.4% advantage in actuarial 3 yr freedom from recurrence (p = 0.023 one-sided) over the control group. One important secondary finding was that for those who reported at the time of the index stone that their most consumed drink was acidified by phosphoric acid but not citric acid, the experimental group had a 15% higher 3 yr recurrence-free rate than the controls, p = 0.002, while for those who reported at the time of the index stone that their most consumed drink was acidified by citric acid with or without phosphoric acid, the experimental group had a similar 3 yr recurrence-free rate to the controls, p = 0.55. This interaction was significant, p = 0.019.

Spontaneous rupture of a hydronephrotic kidney during pregnancy.

Acute abdominal pain during pregnancy can be of urologic origin. Hydronephrosis of pregnancy can be complicated by symptomatic renal colic, pyelonephritis, and secondary renal abscess formation. In this report, rupture of a hydronephrotic kidney with retroperitoneal urinoma formation was treated by retroperitoneal drainage and internal ureteral until a term delivery was achieved. However, if severe renal hemorrhage accompanies renal rupture, surgical exploration of the kidney with partial or complete nephrectomy may be necessary.

Immersion anesthesia for extracorporeal shock wave lithotripsy. Review of two hundred twenty treatments.

Two hundred twenty extracorporeal shockwave lithotripsy (ESWL) treatments at the New York Hospital-Cornell Medical Center between September, 1984, and April, 1985, were reviewed with respect to anesthetic management. One hundred seventy-four treatments (79%) were performed under a regional anesthetic technique (RA), either with an indwelling epidural catheter (155 treatments), or with a single spinal injection (19 treatments). Forty-six treatments (21%) were performed under general anesthesia (GA). Ninety per cent of the patients were classified as ASA I or II. Hypotension during treatment, defined as blood pressure falls greater than 20 per cent of baseline mean arterial pressure, was recorded with 19.5 per cent of the regional anesthetic treatments (18.7% of the epidurals and 26.3% of the spinals) and 13.0 per cent of the general anesthetic treatments. Blood pressure falls were larger in the regional group than in the general group. The average recovery room stay was longer for the bupivacaine (0.25-0.5%) epidurals and the tetracaine (0.4%) spinals (252 min and 212.1 min, respectively) than for the lidocaine (1.5-2.0%) epidurals and the general anesthetics (101.7 min and 102.1 min, respectively). General anesthesia, with controlled ventilation, was advantageous in minimizing renal excursion and stone movement during treatment. Yet, in appropriately selected and sedated patients, regional anesthesia with continuous lidocaine epidural techniques was found to provide acceptable anesthesia for patients undergoing ESWL.

Impact of shockwave lithotripsy on upper urinary tract calculi.

Extracorporeal shock wave lithotripsy (ESWL) currently is performed in selected urologic centers to treat over 80 per cent of patients with symptomatic upper urinary tract calculi. This noninvasive technique utilizing shockwaves to disintegrate stones into sand-sized particles allows the patient to pass the particles with spontaneous urination and replaces most surgery or percutaneous endoscopy for stone removal. However, stone-free success rates must be individualized depending on stone position, stone size, and composition. Lithotripsy of renal stones prior to migration and proximal ureteral stones early in their symptomatic course may alter significantly the incidence of distal ureteral calculi requiring hospitalization, cystoscopy, or ureteroscopy.

Computed tomography in urologic patients: preliminary assessment.

Computed tomography (CT) body scanning has specific application to the precise diagnosis of urologic disease. The advantage of visualizing the density of normal and abnormal tissue provides new accuracy in evaluation of renal, retroperitoneal, and pelvic masses. The penetration of the pelvic cavity allows the urologist to assess local, nodal, and skeletal involvement from prostatic and bladder neoplasms in a single diagnostic examination. Cost/efficacy analysis and the role of computed tomography in patient managment must await further review and experience.

Variables influencing radiation exposure during extracorporeal shock wave lithotripsy. Review of 298 treatments.

Retrospective review of 298 extracorporeal shock wave lithotripsy (ESWL) treatments was undertaken to determine the factors which influence radiation exposure during ESWL. Fluoroscopy time averaged 160 seconds (3-509), and the average number of spot films taken per patient was 26 (5-68). The average stone burden was 19.3 mm (3-64). Average calculated skin surface radiation exposure was 17.8 R per treatment. Radiation exposure increased with increasing stone burden and patient weight. Stones treated in the ureter resulted in a higher average patient radiation exposure than for renal stones (19 R vs 16 R), even though the average size of these ureteral stones (11.3 mm) was significantly less than the mean. However, type of anesthetic (general or regional) used was not a significant factor. Operator training, experience, and familiarity with radiation physics should significantly decrease the amount of imaging time and consequent patient radiation exposure during ESWL.

Cost-effectiveness of extracorporeal shock-wave lithotripsy.

A study was done comparing the charges and outcomes for extracorporeal shock-wave lithotripsy (ESWL) with those for percutaneous nephrostolithotomy (PCN), which was the treatment of choice at our hospital for stones of the upper urinary tract when ESWL was introduced. Using a retrospective cohort design, patients were matched for age, sex, physical status index (American Society of Anesthesiologists), stone size, and urinary tract obstruction. Twenty-nine pairs of PCN and ESWL patients with complete data were matched. The groups were not significantly different in the matching parameters. Seventy-two per cent of patients in each group (21/29) were stone-free after the initial hospitalization. PCN patients required more auxiliary procedures per patient than did the ESWL patients; in addition, 5 (17%) of the PCN patients had perforation of the renal pelvis and 5 (17%) required transfusions. On discharge, 48 per cent (14/29) of the PCN patients had nephrostomies compared with none of the ESWL patients. The ESWL group had a shorter mean length of stay (2.9 vs 8.7 days, p less than 0.0005) and lower charges in all categories. Total charges were significantly less for ESWL ($9,290 vs $11,796 for PCN, p less than 0.005) as were physicians' fees ($3,391 vs $5,607, p less than 0.0005), room and board charges ($825 vs $2,164, p less than 0.0005), and operating room fees ($313 vs $1,452, p less than 0.0005). We conclude that ESWL is a cost-effective means for treating stones of the kidney and upper urinary tract.

Selective use of ureteral stents before extracorporeal shock-wave lithotripsy.

Stents must be judiciously, not indiscriminately, used prior to lithotripsy to maximize successes. The documented advantages for specific stone burdens and patient types should not be taken as an endorsement for pretreatment stenting on a routine basis. Universal stenting is a costly adjunct to an already costly technology, not to mention the substantial number of patients with stents who report bladder or renal discomfort that is relieved when the stents are removed. Certainly, in some cases, the constant discomfort of bladder irritability and reflex voiding secondary to polymer stents may be more incapacitating than mild colic associated with fragment passage. Complications of internal ureteral stents do occur, so judicious selection of patients for pre-ESWL stenting is advised.

Kidney transplantation in insulin dependent diabetic patients: improved survival and rehabilitation.

Between 1977 and 1986, 50 insulin-dependent diabetic patients received a kidney transplant, 19 from living related donors and 31 from cadaveric donors. Cumulative patient survival was 81% and graft survival was 64% and 33% for living related and cadaveric donor kidneys, respectively, at five years. These results are comparable to that of nondiabetic patients. While physical performance and visual acuity significantly improved after a successful kidney transplantation, neuropathies and angiopathies might not improve. Physical performance improved even in those patients whose nerve conduction time had deteriorated. These findings suggest that kidney transplantation is an effective means of improving survival and rehabilitation of diabetic patients with end-stage renal disease.

Polymeric micelles containing reversibly phospholipid-modified anti-survivin siRNA: a promising strategy to overcome drug resistance in cancer.

The discovery that survivin, a small anti-apoptotic protein, is involved in chemoresistance, opens a new scenario to overcome the drug resistance in cancer. It was shown that siRNA can efficiently inhibit the expression of survivin in cancer cells. However, the clinical use of siRNA is still hampered by an unfavorable pharmacokinetic profile. To address this problem, earlier we developed a novel system to deliver siRNA into cancer cells. Namely, we reversibly modified the survivin siRNA with a phosphothioethanol (PE) portion via a reducible disulfide bond and incorporated the resulting siRNA-S-S-PE conjugate into nanosized polyethyelene glycol 2000-phosphatidyl ethanolamine (PEG2000-PE)-based polymeric micelles (PM), obtaining survivin siRNA PM. The activity of these nanopreparations was evaluated by survivin protein down-regulation, tumor cell growth inhibition, and chemosensitization of the treated tumor cells to paclitaxel (PXL). We found a significant decrease of cell viability and down-regulation of survivin protein levels after treatment with survivin siRNA PM in several cancer cell lines. In addition, the down-regulation of survivin by treating cells with survivin siRNA PM, elicited a significant sensitization of the cells to PXL, in both sensitive and resistant cancer cell lines. Finally, we demonstrated successful co-delivery of PXL and survivin siRNA in the same PM leading to superior therapeutic activity compared to their sequential administration. Our results support the use of this new platform for the treatment of the most aggressive tumors.

First observation of the Greisen-Zatsepin-Kuzmin suppression.

The High Resolution Fly's Eye (HiRes) experiment has observed the Greisen-Zatsepin-Kuzmin suppression (called the GZK cutoff) with a statistical significance of five standard deviations. HiRes' measurement of the flux of ultrahigh energy cosmic rays shows a sharp suppression at an energy of 6 x 10(19) eV, consistent with the expected cutoff energy. We observe the ankle of the cosmic-ray energy spectrum as well, at an energy of 4 x 10(18) eV. We describe the experiment, data collection, and analysis and estimate the systematic uncertainties. The results are presented and the calculation of the statistical significance of our observation is described.

Extracorporeal shock wave lithotripsy of ureteral stones.

Shock wave lithotripsy of upper ureteral stones is significantly more successful than ureteroscopy. Successful stone manipulation before ESWL increases the stone-free rate, yet impacted stones disintegrate and pass in the majority of patients. Earlier ESWL treatment of symptomatic ureteral stones will decrease patient morbidity and subsequent complication of distal stone passage. Lithotripsy of small renal stones prior to migration and proximal ureteral stones early in their symptomatic course may significantly alter the incidence of distal ureteral calculi requiring hospitalization, cystoscopy, or ureteral endoscopy. Ureteroscopy will remain the treatment of choice for symptomatic distal ureteral stones.