Urinary tract infections and pregnancy in women who underwent antireflux surgery in childhood

PURPOSE: For several decades ureteroneocystostomy has been performed in children to correct primary vesicoureteral reflux. A purported indication for antireflux surgery is to prevent significant upper urinary tract infection during pregnancy. We performed a long-term followup of women who underwent antireflux surgery during childhood to determine outcome in regard to urinary tract infection history and pregnancy. MATERIALS AND METHODS: We identified 227 women of childbearing age who underwent ureteral reimplantation for primary vesicoureteral reflux from 1964 through 1981. Of the 122 women contacted 41 had been pregnant (77 total pregnancies). Cystitis or asymptomatic bacteriuria and pyelonephritis developed during 18 and 5 pregnancies, respectively. The 77 pregnancies resulted in 57 term births, 7 voluntary pregnancy interruptions and 13 spontaneous abortions. RESULTS: Patients who previously underwent successful antireflux surgery continued to have a significant number of urinary tract infections through the intervening years. Despite a higher than expected incidence of pyelonephritis, they had relatively little hypertension and renal insufficiency. During pregnancy the incidence of pyelonephritis was only slightly higher than that of the general population. However, severe complications of pregnancy, such as preeclampsia, premature birth and acute renal failure, occurred more frequently in women with a history of renal scarring or hypertension (7 of 12) than in those with a history of recurrent infection alone (3 of 10). CONCLUSIONS: When renal scarring is present, reflux should be corrected before pregnancy to minimize maternal and fetal morbidity. When scarring is not present, the literature suggests that women with a history of reflux are at increased risk for pyelonephritis during pregnancy whether or not ureterocystostomy was performed. Pregnant women with a history of reflux may benefit from prophylactic antibiotics and women with reflux nephropathy should be followed throughout life.     

Elevated interleukin-8 levels in the urine of children with renal scarring and/or vesicoureteral reflux

PURPOSE: Elevation of urinary levels of interleukin-6 and 8 has been observed in patients with acute urinary tract infections. However, to our knowledge there have been no studies concerning the secretion of interleukin-6 and 8 into the urine after acute inflammation has resolved and renal scarring has occurred. On the other hand, it is well known that cytokines are variously related to glomerular diseases and, thus, it is possible that the progression of reflux nephropathy depends on interleukin-6 or 8. Therefore, we assessed urinary levels of interleukin-6 and 8 in children with vesicoureteral reflux and/or renal scarring. MATERIALS AND METHODS: We evaluated interleukin-6 and interleukin-8 levels in the urine of 32 children without a urinary tract infection who presented or were admitted to our hospital because of vesicoureteral reflux between April and December 1994. Interleukin-6 and 8 were determined using a commercially available human enzyme-linked immunosorbent assay kit and the 2-step sandwich method. RESULTS: Urinary interleukin-6 levels were below the lower detection limit (less than 10 pg./ml.) in all samples. There were statistically significant differences between urinary interleukin-8 levels in children with and without renal scarring (p = 0.001), and with and without vesicoureteral reflux (p = 0.0246). CONCLUSIONS: Urinary interleukin-8 is an effective marker for renal scarring and vesicoureteral reflux.     

Alternative approaches to the prognostic stratification of mild to moderate primary vesicoureteral reflux in children

PURPOSE: We compared the prognostic stratification of primary vesicoureteral reflux by performing staging voiding cystourethrography in all children with a urinary tract infection or only in those with renal scarring on 99mtechnetium-dimercapto-succinic acid (DMSA) scintigraphy. MATERIALS AND METHODS: Staging voiding cystourethrography and DMSA scintigraphy were performed in 105 children with a urinary tract infection and reflux persistence was assessed by radionuclide cystography after a 2-year followup. RESULTS: Staging voiding cystourethrography revealed no reflux in 51 children (DMSA positive in 3), grades I to II reflux in 21 (DMSA positive in 6) and grade III reflux in 33 (DMSA positive in 19). On followup radionuclide cystography no new reflux was detected, and it was no longer demonstrated in 23 children (8 with grade III and 15 with grades I to II reflux). The finding of grade III reflux on staging voiding cystourethrography had a 76% positive and a 92% negative value for predicting persistent reflux with an 87% predictive accuracy. Limiting the evaluation of voiding cystourethrography data to the 28 children with a positive DMSA scan the combination of renal scarring and grade III reflux had an 84% positive and an 83% negative predictive value with 83% accuracy. This approach would have prevented 77 children from having to undergo voiding cystourethrography. CONCLUSIONS: Performance of staging voiding cystourethrography exclusively in children with renal scarring on a DMSA scan resulted in predictive accuracy that was close to what was achieved by performing voiding cystourethrography in all children with a urinary tract infection. To be able to limit cystourethrography to a select population could prove to be cost-effective.     

Childhood reflux and urinary infection: a follow-up of 10-41 years in 226 adults

To ascertain the outcome of childhood vesicoureteric reflux (VUR), 226 adults (37 males), mean age 27 years, were studied after 10-35 years, extended to 41 years by postal questionnaire in 161. At presentation (mean age 5 years) all had VUR (grade III-V in 68) and urinary tract infection (UTI); there was renal scarring in 85 (acquired before referral in 11 and during follow-up in 1), hypertension in 6 and impaired renal function in 5. They were managed and followed prospectively by one paediatrician; 63% of these children remained free from UTI; VUR persisted in 63 and had resolved in 69% of 193 children managed medically. At follow-up, 61% of adults had remained free from infection; 17 adults had hypertension and/or raised plasma creatinine, 16 with scarred kidneys. Their deterioration was predictable because of scar type, blood pressure or plasma creatinine levels in childhood. No new scars developed after puberty. Renal growth rates were unaffected by initial severity or persistence of VUR. On the later questionnaire, 9 further adults, mean age 38 years, had moderate hypertension. The adults with complications were those with extensive renal scarring and/or at least borderline hypertension in childhood. Those with VUR, but no scarring, and managed carefully in childhood, did not suffer serious consequences as adults. There is a need for early recognition and treatment of children with VUR and UTI to limit scar development.     

Evaluation and treatment of urinary tract infections in children

Urinary tract infections (UTIs) are among the most common bacterial infections encountered by primary care physicians. Although UTIs do not occur with as great a frequency in children as in adults, they can be a source of significant morbidity in children. For reasons that are not yet completely understood, a minority of UTIs in children progress to renal scarring, hypertension and renal insufficiency. Clinical presentation of UTI in children may be nonspecific, and the appropriateness of certain diagnostic tests remains controversial. The diagnostic work-up should be tailored to uncover functional and structural abnormalities such as dysfunctional voiding, vesicoureteral reflux and obstructive uropathy. A more aggressive work-up, including renal cortical scintigraphy, ultrasound and voiding cystourethrography, is recommended for patients at greater risk for pyelonephritis and renal scarring, including infants less than one year of age and all children who have systemic signs of infection concomitant with a UTI. Antibiotic prophylaxis is used in patients with reflux or recurrent UTI who are at greater risk for subsequent infections and complications.     

The effect of cyclophosphamide on the experimental inflammation induced by the toxic mushroom Cortinarius speciosissimus in the rat kidney

A single intraperitoneal dose of cyclophosphamide (150 mg/kg) given at the same time as an oral dose of Cortinarius speciosissimus prevented the renal inflammation induced by this toxic mushroom in the male rat. Furthermore, a scar formation around dilated collecting ducts was clearly reduced by cyclophosphamide treatment. In general the only lesions observed in the cyclophosphamide treated animals were dilated collecting ducts in the outer medullary zone, the epithelia of which were either in regenerative mitosis or were atrophic. Apparently the primary sites of action of Cortinarius toxins in male rats are the collecting ducts of the outer medullary zone. When inflammation and the subsequent scar formation is prevented by cyclophosphamide, the damaged tubules can regenerate by mitotic activity and perhaps restore normal function.     

Novel environment induced inhibition of corticosterone secretion: physiological evidence for a suprachiasmatic nucleus mediated neuronal hypothalamo-adrenal cortex pathway

The effects of two cognition enhancers on avoidance impairment induced by the tricyclic antidepressant amitriptyline were assessed during shuttle-box avoidance acquisition and in previously trained mice of the DBA/2 strain. The nootropic agent piracetam (50, 100 or 200 mg/kg, i.p.) had slight or no effect in mice receiving amitriptyline (5 or 10 mg/kg, i.p.). Conversely, the acetylcholinesterase inhibitor tacrine (0.5, 1, 2 or 3 mg/kg, i.p.) prevented the avoidance impairment induced by 5 mg/kg amitriptyline on shuttle-box avoidance acquisition as well as on a previously learned avoidance response. The avoidance disrupting action produced by 10 mg/kg of the antidepressant drug was not affected by the anticholinesterase drug. The preventing action of tacrine seems specifically related to the avoidance impairment induced by amitriptyline, since the acetylcholinesterase inhibitor did not reduce, but enhanced the avoidance impairing action of the neuroleptic chlorpromazine. Taken together, the results indicate that amitriptyline-induced avoidance impairment, and the related preventing action of tacrine, may be ascribed to drug effects on the performance of the avoidance response, rather than to interferences with learning processes.     

Long-term effects of urinary tract infections. The need for a controlled trial

Two series of children with urinary tract infections are compared: in one the infections were primarily covert, while in the other they were predominantly overt. Grade III reflux occurred only in the overt infection group, and the development or progression of renal clubbing and scarring was much more common in these patients. Now that effective, long-term prophylactic therapy for infection is available, the author urges that controlled trials be established to determine whether or not sterile reflux is harmful and whether or not ureteral reimplantation for reflux is of value.     

Acute childhood pyelonephritis: predictive value of positive sonographic findings in regard to later parenchymal scarring

RATIONALE AND OBJECTIVES: The authors evaluated the importance of positive sonographic findings in acute childhood pyelonephritis. MATERIALS AND METHODS: A total of 290 children (91 boys, 199 girls, aged 4 days to 15 years [median, 394 days]) with clinically suspected acute pyelonephritis underwent initial renal gray-scale ultrasound (US) and dimercaptosuccinate scintigraphic examination within 3 days of onset. A total of 173 patients underwent color or energy US examination. One hundred fifteen children with normal scintigraphic or pathologic findings (other than acute pyelonephritis) were excluded from further study; 170 patients with abnormal scintigraphic findings underwent follow-up scintigraphic scanning 60-90 days later. RESULTS: When pathologic structures other than acute pyelonephritis were not considered, the diagnostic value of gray-scale US was poor, with a sensitivity of 45.5%, a specificity of 86.6%, a positive predictive value of 88.8%, and a negative predictive value of only 40.6%. In regard to future renal scarring, gray-scale US had a positive predictive value of 67.7%, a negative predictive value of 40%, and a likelihood ratio of 1.16. Abnormal Doppler findings helped predict future scarring with a positive predictive value of 85.7%, a negative predictive value of 37.2%, a very low sensitivity of 26.9%, a high specificity of 90.6%, and a likelihood ratio of 2.87. CONCLUSION: Positive US Doppler findings in children with clinically suspected acute pyelonephritis indicate the need for immediate treatment. A positive initial gray-scale US examination does not predict future renal scarring, but a positive Doppler examination indicates a high probability of scarring. Negative gray-scale or Doppler US does not exclude a diagnosis of acute pyelonephritis and it cannot predict an absence of future scarring.     

Hypertension as complication of vesicoureteral reflux in children

Eight cases are reported of female children presenting with hypertension and found to have primary vesicoureteral reflux with chronic pyelonephritis. In 6 patients renal function was essentially normal while 2 had azotemia and progessive renal deterioration. As a result of early surgical intervention in the form of antireflux procedures, occasionally combined with unilateral nephrectomy for renin-dependent lesions, 5 of the 8 had complete disappearance or amelioration of hypertension with stabilization of renal function. The interactions of each member of the triad--vesicoureteral reflux, pyelonephritis, and hypertension--are reviewed with emphasis on pertinent pathophysiologic concepts regarding their roles in the production of progressive renal deterioration.     

Omeprazole. A review of its use in Helicobacter pylori infection, gastro-oesophageal reflux disease and peptic ulcers induced by nonsteroidal anti-inflammatory drugs

Omeprazole is a well studied proton pump inhibitor that reduces gastric acid secretion. This review examines its use in Helicobacter pylori infection, gastro-oesophageal reflux disease (GORD) with or without oesophagitis and gastrointestinal damage caused by nonsteroidal anti-inflammatory drugs (NSAIDs). Optimal omeprazole regimens for anti-H. pylori therapy are those that administer the drug at a dosage of 40 mg/day (in 1 or 2 divided doses) for 7, 10 or 14 days in combination with 2 antibacterial agents. As a component of 3-drug regimens in direct comparative studies, omeprazole was at least as effective as lansoprazole, pantoprazole, bismuth compounds and ranitidine. However, a meta-analysis suggests that triple therapies with omeprazole are more effective than comparable regimens containing ranitidine, lansoprazole or bismuth. Omeprazole also appears to be successful in triple therapy regimens used in children with H. pylori infection. In patients with acute GORD with oesophagitis, omeprazole is at least as effective as lansoprazole or pantoprazole in promoting healing, and superior to ranitidine, cimetidine or cisapride in oesophagitis healing and symptom relief. Omeprazole was similar to lansoprazole and superior to ranitidine in preventing oesophagitis relapse in patients with all grades of oesophagitis, but may be superior to lansoprazole or pantoprazole in patients with more severe disease. More patients with symptomatic GORD without oesophagitis experienced symptom relief after short term treatment with omeprazole than with ranitidine, cisapride or placebo, and symptoms were more readily prevented by omeprazole than by cimetidine or placebo. Omeprazole was effective in healing and relieving symptoms of reflux oesophagitis in children with oesophagitis refractory to histamine H2 receptor antagonists. Omeprazole is superior to placebo in preventing NSAID-induced gastrointestinal damage in patients who must continue to take NSAIDs. It is also similar to misoprostol and superior to ranitidine in its ability to heal NSAID-induced peptic ulcers and erosions, and superior to misoprostol, ranitidine or placebo in its ability to prevent relapse. In long and short term studies, omeprazole was well tolerated, with diarrhoea, headache, dizziness, flatulence, abdominal pain and constipation being the most commonly reported adverse events. Usual omeprazole dosages, alone or combined with other agents, are 10 to 40 mg/day for adults and 10 to 20 mg/day for children. CONCLUSIONS: Omeprazole is a well studied and well tolerated agent effective in adults or children as a component in regimens aimed at eradicating H. pylori infections or as monotherapy in the treatment and prophylaxis of GORD with or without oesophagitis or NSAID-induced gastrointestinal damage.     

Clinical survey of congenital cytomegalovirus infection in Japan

Contrast media-induced nephropathy is one of the leading causes of hospital-acquired renal failure, occurring most frequently in patients with pre-existing renal insufficiency. We prospectively studied 55 patients with chronic renal insufficiency (serum creatinine concentration 1.4 to 3.5 mg/dl) who underwent abdominal aortography and arteriography of the lower extremities. The patients were randomized into two groups. Group 1, 28 patients, received dopamine 2.5 mcg/kg beginning 1 hour before arteriography and continuing for 12 hours. Group 2 received an equal volume of saline for the same period of time. Serum creatinine and 12-hour creatinine clearance were measured before arteriography and for 4 consecutive days afterward. Acute contrast-induced decrease in renal function was defined as increase in the baseline serum creatinine concentration > or = 0.5 mg/dl. On day 1 postarteriography the serum creatinine increased from baseline .193 mg/dl for controls while the dopamine group decreased slightly from baseline .018 mg/dl (p = 0.002). Excepting day 1 postarteriography, there was no statistical difference between groups, and serum levels for both groups increased linearly from baseline across time (dopamine p = 0.028, control p = 0.025). In patients with pre-arteriography baseline serum levels greater than or equal to 2.0 mg/dl, however, the increase in serum creatinine from baseline levels was consistently and significantly greater in the control group through the fourth day (0.012 < or = p < or = 0.049). Creatinine clearance did not change significantly from baseline after arteriography in the dopamine group (baseline versus days 1 through 4, 0.238 < or = p < or = 0.968); however, the control group showed a significant linear decrease in creatinine clearance from baseline through the fourth day after arteriography (p = 0.016). Dopamine infusion prevented a rise in serum creatinine 24 hours after angiography in patients with pre-existing renal insufficiency, and protected against contrast-induced decrease in renal function in patients whose baseline serum creatinine was > or = 2.0 mg/dl.     

Urinary tract infections in girls: the cost-effectiveness of currently recommended investigative routines

Current recommendations for the universal investigation of urinary tract infection (UTI) in children by ultrasonography, voiding cystourethrography, and dimercaptosuccinic acid renal scan (and sometimes intravenous pyelography as well) are not based on any convincing evidence as to the necessity or effectiveness of such a routine. Over 8% of all girls will have a UTI during childhood. About 87 individuals in a million will develop end-stage renal disease (ESRD) by the age of 60 years, caused in about 9% by pyelonephritis (PN) or reflux nephropathy. From these statistics, the maximal risk of a first diagnosed UTI progressing to ESRD is approximately 1:10,000. The risk of developing hypertension following a first UTI in childhood, without eventual evolution to ESRD, appears to be very small. The cost of the widely recommended routine imaging procedures ranges from U.S. $355 in Britain to U.S. $1,090 in the United States. The minimal cost of preventing a single progression to ESRD by early diagnosis of underlying pathology-if this were possible in all cases-would range between U.S. $5 million in Britain and U.S. $15 million in the United States. Since in many instances progressive renal damage can not be prevented, the true cost is considerably higher. Lower UTI in girls is a very common and, in most cases, benign finding in primary-care practice. It is suggested that girls with afebrile UTI, presenting with lower urinary tract symptoms alone, need not undergo any imaging procedures, but should be followed with urine examinations and cultures at the time of febrile illness. The recommended investigative routines should be reserved for UTI in infants and in girls with fever or other symptoms suggesting PN, and for proven recurrent UTI. Such a regimen will allow a marked saving in terms of costs and in terms of unnecessary radiation, psychological stress to children, and stress, inconvenience, and time loss to parents. There is no evidence that this approach will compromise the course or final outcome of this very common condition.     

Reproducibility of drug efficacy predictions by Holter monitoring in the electrophysiologic study versus electrocardiographic monitoring (ESVEM) trial. ESVEM Investigators

The effect of a newly developed free radical scavenger (OPC-15161) on the progression of nephrotoxic serum (NTS) nephritis was evaluated. NTS nephritis rats were sacrificed immediately before and 1, 2, 3, 6, and 24 h and 13 and 19 days after intravenous injection of NTS. The tissue content of phosphatidylcholine hydroperoxide, the activity of superoxide, the activity of superoxide dismutase in the renal cortex, and the serum malondialdehyde levels were measured. The phosphatidylcholine hydroperoxide content in the renal cortex of OPC-15161-treated NTS nephritis rats was lower than that in the control rats 24 h after NTS injection. The activity of superoxide dismutase in OPC-15161-treated rats was sustained in contrast to the decrease in this activity in the control rats 6 h after injection of NTS. The effects of OPC-15161, dipyridamole, and prednisolone on NTS nephritis rats were investigated. OPC-15161 (20 mg/kg p.o.) showed a potent inhibitory effect on the urinary protein excretion, whereas dipyridamole (30 and 100 mg/kg p.o.) and prednisolone (2 mg/kg p.o.) had less suppressive effects. In view of these results, we conclude that OPC-15161 notably ameliorated the urinary protein excretion by way of the suppression of lipid peroxidation in the renal tissue of NTS nephritis rats.     

Meta-MEME: motif-based hidden Markov models of protein families

Sirolimus is a new immunosuppressive drug that has been evaluated in animal experiments. The current study was conducted on humans with reformulated sirolimus in doses from 3 mg/m2 to 15 mg/m2. Sixteen renal transplant recipients were included in this phase I study to determine the safety, tolerance, and preliminary pharmacokinetics of increasing single doses of orally administered sirolimus. All 16 patients had stable renal graft function after a renal transplant at least 6 months before the study. Basal immunosuppression consisted of cyclosporine and prednisolone (n = 10) or cyclosporine, azathioprine, and prednisolone (n = 6). Four groups (I, 3 mg/m2; II, 5 mg/m2; III, 10 mg/m2; IV, 15 mg/m2) of four patients were assigned randomly to receive sirolimus (n = 3) or placebo (n = 1). Among the 12 patients who received sirolimus, five had mild transient study events such as headache, nausea, mild dizziness, hypoglycemia, epistaxis, and decrease in platelets. No serious adverse events occurred and no nephrotoxic effects could be related to the single dose administration of sirolimus. The only study event that was judged as probably related to sirolimus was the single case of thrombocytopenia. The other events were evaluated as possibly related. Thrombocytopenia occurred at the highest dose level (15 mg/m2 sirolimus). In two of the patients in the placebo group, slight elevations of liver enzymes and serum amylase were seen. Blood and plasma sirolimus concentrations were analyzed by an electrospray-high performance liquid/mass spectrophotometric (ESP-HPLC/MS) method Sirolimus showed an extensive red blood cell distribution with a mean blood/ plasma ratio of 49.1. The elimination half-life ranged from 43.8 to 86.5 hours (mean 56.9 hours). The Cmax and the area under the concentration versus time curves (AUC) correlated reasonably with doses from 3 to 15 mg/m2. The oral dose clearance ranged from 42 to 339 ml/h.kg. No clinically significant differences were seen in the trough concentrations of cyclosporine or the AUCs before and after the administration of sirolimus. Administration of single oral doses of sirolimus from 3 to 15 mg/m2 was safe and well tolerated in stable renal transplant recipients. Thrombocytopenia may be the dose-limiting toxicity. Additional phase II and phase III clinical trials will define the immunosuppressive efficacy of sirolimus.     

Effect of triethylenepentaminehexaacetic acid on the renal damage in cadmium-treated Syrian hamsters

Cadmium (Cd)-induced nephropathy was treated by triethylenepentaminehexaacetic acid (TTHA) in male Syrian hamsters. Hamsters injected three times a week with 3 mg/kg body wt CdCl2 showed proteinuria, urinary N-acetyl-beta-D-inglucosaminidase (NAG), and fractional excretion of sodium (FENa) when compared to saline-injected control. Cd-treated hamsters injected ip with TTHA 10 mg/kg body wt five times a week showed reduction of renal damage, including reductions in urinary protein (from 6.7 +/- 2.2 to 4.3 +/- 0.5 mg/d) and NAG (0.17 +/- 0.06 to 0.04 +/- 0.02 U/d). Urinary excretion of Cd was significantly increased (from 87 +/- 51.3 to 3052 +/- 1485 mg/L) by TTHA administration. Cd concentration in renal cortical tissue was slightly reduced (26.4 +/- 3.0 to 21.8 +/- 2.7 mg/g. protein). Excretion of malondialdehyde (MDA) was increased only in Cd-injected hamsters (to 2.1 +/- 1.6 nM/L), and elevated MDA in renal cortical tissue was not reduced by the administration of TTHA (1041 +/- 105 vs 1104 +/- 358 nM/g protein). Glutathione (GSH) concentration in the renal cortex was significantly elevated after Cd administration and further increased after TTHA administration (5.5 +/- 2.1 to 9.8 +/- 2.0 micrograms/50 mg protein). There were no marked effects on creatinine clearance (Ccr) and hematocrit. Moreover, renal morphological changes were improved significantly by treatment with TTHA. We demonstrated the efficacy of TTHA in the treatment of Cd-induced nephropathy in hamsters. Although the precise mechanism of the TTHA effects on Cd-induced nephropathy has not been elucidated, it might involve GSH reducing the elevated MDA concentration in renal tissue.     

Non-radioactive detection of K-ras mutations by nested allele specific PCR and oligonucleotide hybridization

PURPOSE: The aim of the study was to evaluate prospectively urinary alpha 1-microglobulin as a marker of proximal tubular damage following acute pyelonephritis and outflow disease of the upper urinary tract in a urological population with minimal exclusion criteria. We also measured the urinary gamma-glutamyltransferase activity, urinary albumin, urinary and serum creatinine, serum IgA and serum alpha 1-microglobulin. PATIENTS AND METHODS: We studied 483 urological patients (age: 1 to 92 years, 297 men, 186 women) excluding patients receiving nephrotoxic drugs, or suffering from type 1 diabetes or renal diseases. There were 141 patients with urinary tract infection but no fever, 36 patients with high fever of non-renal origin, 51 patients with acute pyelonephritis and 156 patients with outflow disease of the upper tract, and 99 patients were included in the reference population. RESULTS: For acute pyelonephritis, vesico-ureteral reflux, and ureteral obstruction, urinary alpha 1-microglobulin had a sensitivity of 94%, 90% and 63% respectively and a specificity of 67%, 77% and 76%. The area under the curve of the receiver operator characteristic curve was significantly (p < 0.001) higher for urinary alpha 1-microglobulin than for albumin or gamma-glutamyltransferase activity. Unexpected positive results were found in acute prostatitis. The urinary alpha 1-microglobulin was the only parameter which differentiated between acute prostatitis and pyelonephritis (p < 0.001). Creatinine clearance or age had little and gender had no influence on the urinary excretion of alpha 1-microglobulin. Urine production rate significantly increases the urinary alpha 1-microglobulin/creatinine ratio. CONCLUSION: Our results suggest that the urinary alpha 1-microglobulin/creatinine ratio is a diagnostically useful marker of tubular damage in acute pyelonephritis and vesico-ureteral reflux in the urological population. Following renal colic and chronic ureteral obstruction, a significant increase in urinary alpha 1-microglobulin excretion was observed.     

Office laboratory procedures, office economics, patient and parent education, and urinary tract infection

This review provides an update on four important areas in office pediatrics: office laboratory procedures, office economics, patient and parent education, and urinary tract infection. Ball reviews new information about physician office laboratories, with updates on the Clinical Laboratory Improvement Amendments, streptococcal pharyngitis, urinalyses, office stool examination, and information on Helicobacter pylori serology. Shapiro reports on office economics, highlighting new office technologies, physician operated networks, managed care, recent legislation, and the "cost versus quality" debate. Duncan provides a very thought provoking essay on parent and patient education, focusing on improving parenting skills. Wahl reviews the recent literature on urinary tract infections, with emphasis on host-bacteria interactions, diagnostic evaluations, pyelonephritis, renal cortical scarring, and long term follow-up of vesicoureteral reflux. We hope we have provided pediatricians with useful and practical information for their office practices.     

Effects of glucocorticoids on pharmacokinetics and pharmacodynamics of midazolam in rats

We investigated the effect of dexamethasone (80 mg/kg per day for 2 days) and prednisolone (600 mg/kg per day for 2 days, equivalent to dexamethasone for glucocorticoid (GC) potency) on both pharmacokinetics and pharmacodynamics of midazolam (MDZ), a substrate for cytochrome P450 (CYP) 3A, in 8-week-old male Sprague-Dawley rats. Animals received a single injection of MDZ (pharmacokinetic study, 10 mg/kg; pharmacodynamic study, 55.5 mg/kg) in the tail vein 24 h after the last dose of GC or placebo. The elimination half-life (t(1/2)) and the area under the concentration-time curve of MDZ were significantly reduced by pretreatment with dexamethasone to 58.9% and 44.7% of the control value, respectively, and the clearance of MDZ was significantly increased by dexamethasone. Similar changes observed by prednisolone pretreatment did not reach significance. The t(1/2) of the dexamethasone pretreatment group (14.4+/-0.7 min) was significantly shorter than that of the prednisolone group (20.9+/-1.5 min). The amount of CYP3A2 protein and the activity of erythromycin N-demethylase were significantly increased by dexamethasone and prednisolone pretreatments, but dexamethasone showed a greater effect than prednisolone. Sleeping time was significantly shortened by dexamethasone and prednisolone pretreatment to 38.7% and 57.1% of control value, respectively. The current study demonstrates that the anesthetic effect of MDZ would be reduced in patients treated with dexamethasone or prednisolone, and that the CYP3A induction was greater by dexamethasone than by prednisolone, implying that the potency of CYP3A induction may differ among GCs even when GC activity is the same.     

Technetium-99m dimercaptosuccinic acid scintigraphy studies of renal cortical scarring and renal length

The aims of this study were to validate 99mTc-dimercaptosuccinic acid (DMSA) scintigraphy appearances with histopathological features of scarring; to evaluate the sensitivity and specificity of 99mTc-DMSA and ultrasound for the detection of renal scarring; to compare planar, pinhole and SPECT techniques when using 99mTc-DMSA; and to compare 99mTc-DMSA and ultrasound renal length measurement. METHODS: Reflux nephropathy was induced in large white pigs using established methods. To ensure that the abnormalities detected were scars and not inflammatory changes, the pigs were not studied until 3 mo after the treated episode of acute pyelonephritis confirmed by 99mTc-DMSA. RESULTS: Twenty pigs were enrolled in the study. Eleven reached the end point, but only nine pigs (18 kidneys) were available for analysis. Thirty-four scars were identified pathologically; 24 were present macroscopically and a further 10 were seen only on microscopy. Technetium-99m-DMSA abnormalities correlated with scars histopathologically with an accuracy of 92% versus that of ultrasound, 75% (p < 0.001). Technetium-99m-DMSA more accurately identified scarring with a higher sensitivity (76% versus 29%) and specificity (98% versus 92%) than ultrasound. On the 99mTc-DMSA study, pinhole imaging had the highest accuracy (92%) when compared with planar (90%) and SPECT (87%) data. These differences were not statistically significant. Renal lengths as measured on 99mTc-DMSA more closely correlated with length measurement at pathological examination than ultrasound. Technetium-99m-DMSA measurement was, on average, 6% higher than pathology, and ultrasound was, on average, 22% lower. CONCLUSION: Technetium-99m-DMSA appears to be the preferred method for the detection of renal cortical scarring and accurate renal length measurement when compared with ultrasound examination.