Hormonal evaluation of boys born with undescended testes during their first year of life.

We studied pituitary-gonadal function during the first year of life in 48 boys born with 56 undescended testes in order to test the hypotheses that functional insufficiency of the hypothalamo-pituitary-gonadal axis and disorders of testosterone (T) biosynthesis occur in such boys. Cryptorchidism persisted for longer than 1 yr in 29 boys (30 testes; group I), whereas spontaneous descent occurred in 19 boys (20 testes; group II), in 6 after the sixth month. A control group (group III) included 160 boys. Basal and peak LHRH-stimulated serum LH and FSH and basal serum T values were determined at 3, 6, and 12 months. Serum T, dihydrotestosterone (DHT), progesterone (P), 17-hydroxypregnenolone, 17-hydroxyprogesterone, dehydroepiandrosterone sulfate, and androstenedione before and after hCG administration were determined at age 1 yr. Comparing the 3 groups, cross-sectional evaluation revealed no significant differences in basal or peak LHRH-stimulated serum LH and FSH levels, except that basal serum LH levels were slightly higher in group II than in group III. Comparing groups I and II, longitudinal evaluation revealed similar basal and peak LHRH-stimulated serum LH and FSH values, with comparable changes with time. Basal serum T, DHT, and T precursor levels were similar in all three groups, with similar rises of T and DHT and variable minimal increases in androstenedione and dehydroepiandrosterone sulfate after hCG stimulation. We conclude that during the first year of life, boys with cryptorchidism have no functional insufficiency of the hypothalamo-pituitary-gonadal axis or disorders in T biosynthesis.

Radiation nephropathy in young and adult rats.

The effects of bilateral kidney irradiation were compared in young and adult rats. During a 1 year period after a single dose of 0, 7.5, 10, 12.5, or 15 Gy on both kidneys, renal function (glomerular filtration rate and effective renal plasma flow), urine composition, and systolic blood pressure were measured periodically. The first changes after irradiation were observed in the glomerular filtration rate and urine osmolality. One month after 10, 12.5, and 15 Gy, glomerular filtration rate (GFR) and urine osmolality had declined below control values in the young rats. After this initial decline, renal function increased at control rate or even more during the third and fourth month after irradiation but decreased progressively thereafter. In the adult rats, GFR and urine osmolality started to decrease 3 months after 10, 12.5, and 15 Gy. A rise in systolic blood pressure and proteinuria started 2-3 months after 12.5 and 15 Gy in both age groups. Early changes in the glomerular filtration rate with a drop in urine osmolality in young rats, occurring during a period of rapid renal development indicated an irradiation-induced inhibition of glomerular and tubular development. Although renal function deteriorated at a later time in adult rats, dose-response relationships obtained in young and adult rats did not show significant differences.

Proteinuria is an early marker in the development of progressive renal failure in hypertensive fawn-hooded rats.

Male spontaneously hypertensive fawn-hooded (FH) rats can be divided into two classes on the basis of their proteinuria. We investigated the relationship between early proteinuria and the impairment of renal function later in life. Urinary protein excretion (UpV), systolic blood pressure (SBP) and parameters of renal function were sequentially determined in male FH rats. A significant difference in UpV was already present from the age of 10 weeks. Class I rats excreted less protein than class II animals. Initially, the glomerular filtration rate (GFR) of class II animals was somewhat higher than that of class I rats, but from week 50 onwards a decrease in GFR of class II rats was noted and from then on rats died due to uraemia. The GFR of class I animals fell from week 75. The fall in GFR was preceded by a concomitant increase in UpV and SBP. The increase occurred earlier and the rate of increase was higher in class II rats. We conclude that a number of hypertensive FH rats die prematurely from end-stage renal failure. The presence of an increased UpV at an early age is an early marker for the development of renal failure.

Prednisolone and posttransplantation hypertension in rat renal allograft recipients.

Rat recipients of renal allografts and unilaterally nephrectomized control rats were studied to evaluate the response in blood pressure to prednisolone in diverse doses, and to determine the dosage required to achieve adequate immunosuppression without undue complication of hypertension. While a continuous infusion of 2 mg/kg/day or more of prednisolone proved effective in prolonging allograft survival time, this dosage increased the blood pressure of recipients as well as unilaterally nephrectomized control rats. In contrast to control rats, the recipients remained hypertensive after the cessation of prednisolone administration. This suggests that the high blood pressure observed during prednisolone administration was due to its hypertensive action. On the other hand, the high blood pressure remaining after cessation of the prednisolone administration is likely to be caused by an incomplete prevention of rejection. If recipients had received a transfusion of donor-strain blood prior to transplantation in combination with the infusion of 2 mg/kg/day or more of prednisolone, they became normotensive when the prednisolone infusion was ceased. By reducing the prednisolone dosage to 1 mg/kg/day in combination with donor-strain blood pretreatment, hypertension could also be eliminated during the first two weeks. In conclusion, effective immuno suppression can be achieved with prednisolone in rats, without inducing hypertension, provided prednisolone is administered at a low dosage in combination with adjuvant immunosuppression--i.e., donor-strain blood pretreatment.

Long-term survival of DLA-matched segmental small-bowel allografts in dogs.

The aim of this study was to investigate the combined effect of DLA matching and immunosuppressive therapy on the survival of segmental small-bowel allografts in dogs. Orthotopic segmental small-bowel transplantations (25 to 30% of total small bowel length) were performed in two stages: first a heterotopic segmental small bowel transplantation, followed after 5 to 8 weeks by a second-stage operation during which the heterotopic graft was placed in an orthotopic position and the native small bowel was resected. All dogs received cyclosporine immunosuppression. Control dogs (n = 4), subjected to total enterectomy, survived 37.3 +/- 7.1 days (mean +/- SEM). Recipients of DLA-mismatched small bowel grafts (n = 6) survived 113.2 +/- 37.0 days, which was a significantly shorter time than dogs with a DLA-matched graft (n = 6, 211.5 +/- 38.8 days, P < 0.05). None of the matched allografts was rejected during CsA treatment, whereas four of six mismatched grafts were (P < 0.05). The control dogs uniformly showed progressive weight loss, steatorrhea, and hypoalbuminemia. The dogs with DLA-mismatched grafts did not regain initial body weight, whereas animals with DLA-matched grafts recovered preoperative weight after 20 weeks. Both transplanted groups showed near-normal fecal fat excretions and constant serum albumin, cholesterol, and triglyceride levels, whereas serum total protein levels increased during follow-up. We conclude that segmental small bowel transplantation between DLA-matched donor-recipient pairs results in long-term survivors with an adequate nutritional status. This may have important implications for future living-related small-bowel transplantation.

Detection of canine intestinal allograft rejection by in vivo electrophysiologic monitoring.

The aim of this study was to evaluate the significance of in vivo measurements of electrophysiologic parameters for the detection of canine small bowel (SB) allograft rejection. In dogs of group I (n = 17) a heterotopic SB autotransplantation was performed. Dogs of group II (n = 8) received a heterotopic SB allograft in a fully mismatched donor-recipient combination. No immunosuppression was given. All grafts were monitored regularly by in vivo measurements of transepithelial potential differences (PDs) and by biopsies of the grafts. The overall technical failure rate was 36% caused by thrombosis at the vascular anastomosis in most cases. All successful autografts survived the experimental period and showed physiologic PD responses after stimulation by both a theophylline solution and a glucose solution. The successful allografts survived 5.5 +/- 0.2 days (mean +/- SEM); the transepithelial PDs showed normal responses at postoperative day 3, but showed decreased responses at day 5 (P less than 0.05) and reversed responses at day 6 (P less than 0.05). The diminished PD responses correlated well with the onset of histologic alterations characteristic of rejection. This study demonstrates that serial monitoring of transepithelial PD responses is a noninvasive method to detect acute SB allograft rejection.

The influence of the recipient upon renal function after isogeneic kidney transplantation in the rat.

Little attention has been paid to the changes in renal function that occur after kidney transplantation when donor and recipient differ markedly in size. We studied this phenomenon after isogeneic kidney transplantation in rats of varying body weight (BW). Renal functional parameters, such as the glomerular filtration rate (GFR), the effective renal plasma flow (ERPF), and the plasma levels of creatinine (Pcr) and urea (Pur) were determined at regular intervals following transplantation. In the initial experimental series, juvenile (BW approximately 150 g) and adult (BW approximately 300 g) rats were used. Four groups of transplant recipients were studied. These consisted of 2 groups of adult recipients of juvenile or adult donor kidneys, and 2 groups of juvenile recipients of juvenile or adult donor kidneys. These 4 groups were compared with adult and juvenile control rats, as well as with unilaterally nephrectomized (NX) rats. A comparison between the 2 groups of juvenile recipients revealed no significant difference in the GFR, ERPF, Pcr, or Pur levels after the transplantation of adult or juvenile donor kidneys. Nor were any significant differences found when comparing the functional parameters of the 2 groups of adult recipients after transplantation of adult or juvenile donor kidneys. The transplanted kidneys generally functioned at a level amounting to 80-90% of the GFR and 90-100% of the ERPF of NX rats of comparable BW. These observations are a clear indication of functional adaptation after kidney transplantation. The compensatory functional response is augmented--in case of a young donor kidney transplanted into an adult recipient, or attenuated--in case of an adult donor kidney transplanted into a juvenile recipient. In an additional experiment, kidneys were transplanted from very young rats (BW approximately 50 g) to adult recipients. It appeared that as early as two weeks after transplantation, renal function had reached adult kidney levels, as observed in the first experimental series. In conclusion, after isogeneic kidney transplantation in rats, the transplanted kidney generally adapts rapidly to the size of the recipient and functions like an inherent part of the recipient's body.

Long-term survival of auxiliary partial liver grafts in DLA-identical littermate beagles.

Auxiliary heterotopic transplantation of 60% of the liver in the beagle, using a technique in which all requirements for optimal graft survival are met, is described. The autologous liver is left in situ. Transplants were performed in non-tissue-typed and matched donor-recipient combinations. Postoperatively the recipients were treated with a standard schedule of 2 mg azathioprine and 1 mg prednisolone i.v. daily for 75 days--thereafter, the immunosuppressive drugs were gradually withdrawn. HIDA-hepatobiliary scanning proved to be useful for the assessment of graft function. In eight non-tissue-typed donor-recipient combinations, median graft survival was 7 days, most transplants being subject to acute rejection. However, in nine experiments in which donor and recipient were DLA-identical littermates, the median graft survival was 112 days (P less than 0.005). In these animals signs of chronic rejection developed after tapering the immunosuppressive drugs. It is concluded that, in this model, graft survival is improved by histocompatibility matching. The feasibility of partial heterotopic liver transplantation indicates that this method must be reconsidered for clinical application, especially for patients with acute liver failure. For the recipient, it is a relatively minor operation that--by its temporary life sustaining function--may allow for the regeneration or restoration of function of the recipient's own liver.

Interaction of cis-diamminedichloroplatinum and renal irradiation on renal function in the young and adult rat.

The interaction between single low doses of cis-diamminedichloroplatinum(II) (c-DDP) and renal irradiation (7.5, 10, 12.5 Gy) on renal function and systolic blood pressure (SBP) was investigated in young (3-4 weeks old, BW 45-65 g) and adult rats (over 12 weeks old, BW 230-290 g). The glomerular filtration rate (GFR) and effective renal plasma flow (ERPF), plasma creatinine, urea and SBP were measured over 24 weeks. Changes in ERPF, plasma creatinine and urea concentrations paralleled GFR changes, but tended to be less pronounced. In young rats, BW and GFR were 10-20% below control values after c-DDP administration (5 mg/kg BW). Irradiation caused a dose-dependent drop in GFR, starting 4 weeks after irradiation in young rats. When c-DDP was given immediately after irradiation to the young rats, the loss of renal function was more pronounced than after either treatment modality alone. Dose-effect curves for a greater than 25% reduction of the GFR relative to controls (ml/min) after 24 weeks gave an ED50 of 9.8 Gy for irradiation alone and 4.6 Gy for irradiation followed by c-DDP. After correction for the drug effect, dose-effect curves were similar for renal irradiation given alone or followed by c-DDP administration in young rats. In adult rats, c-DDP (2.5 mg/kg BW) or irradiation alone did not significantly alter renal function during the follow-up period. Only 12.5 Gy in combination with c-DDP, caused a significant reduction in GFR after 16 weeks in adult rats. In adult rats data were too limited for probit analysis.(ABSTRACT TRUNCATED AT 250 WORDS)

The importance of mesenteric vascular insufficiency in meconium peritonitis.

The etiology of bowel perforations leading to meconium peritonitis was investigated in an attempt to explain the occurrence of such perforations in the absence of primary intestinal obstruction. Bowel specimens from 22 patients who had presented with meconium peritonitis during a 15-year period, as well as specimens from five patients with intestinal atresia without associated meconium peritonitis, were re-evaluated microscopically. An extensive review of the literature concerning meconium peritonitis, involving 1,084 patients, was compared with the results of a retrospective study of 69 patients from The Netherlands. In approximately 50 per cent of these cases there was no detectable primary cause of the bowel perforation. The pathologic findings, in combination with earlier experimental studies, indicate that vascular insufficiency may result in bowel wall perforation without prior intestinal obstruction. It is suggested that temporary decrease of mesenteric blood flow could lead to intestinal atresia and/or meconium peritonitis.

Pervenous hepatic transplant angiography using a new low osmolar contrast medium: an experimental study in dogs.

The patency of the vascular anastomoses in a canine liver transplantation model was imaged by serial pervenous angiography using ioxaglate, which is a new ionic low osmolar contrast medium. No premedication or general anesthesia was administered. No major adverse reaction was noted, not even after repeated angiography. Except for the occurrence of one hematoma formation and one paravenous injection, which resolved without leaving sequellae, no local complications occurred. Sufficient information regarding the patency of the hepatic artery anastomosis was obtained in 94% of the angiographic studies, while in 70% the patency of the caval anastomoses could be determined. In addition, portal vein patency was imaged in 21% of the angiograms. Even better visualization results can be expected when combining this method with video subtraction techniques, although patient cooperation or general anesthesia would then be mandatory.

Pathologic explanation for postoperative obstipation in Hirschsprung's disease revealed with monoclonal antibody staining.

Until now, no pathologic explanation could be found for the postoperative obstipation occurring in some patients with intestinal aganglionosis. Twenty-two of 108 infants treated for intestinal aganglionosis suffered from postoperative obstipation. Resected material from these 22 patients and from 17 control subjects was investigated with monoclonal anti-neurofilament antibody staining. An abnormal staining pattern was revealed in 18 of the constipated patients. Consequently, this new immunohistochemical staining technic has revealed a hitherto unsuspected cause for postoperative obstipation in aganglionosis. The monoclonal antibody may provide early warning of such postoperative constipation.

Hypertension after bilateral kidney irradiation in young and adult rats.

The mechanism of a rise in blood pressure after kidney irradiation is unclear but most likely of renal origin. We have investigated the role of the renin-angiotensin system and dietary salt restriction in the development of systolic hypertension after bilateral kidney irradiation in young and adult rats. Three to 12 months after a single X-ray dose of 7.5 or 12.5 Gy to both kidneys of young and adult rats, the systolic blood pressure (SBP) and plasma renin concentration (PRC) were measured regularly. A single X-ray dose of 12.5 Gy caused a moderate rise in SBP and a slight reduction in PRC in both young and adult rats. A dose of 7.5 Gy did not significantly alter the SBP or PRC during the follow-up period of 1 year. In a second experiment, the kidneys of young rats received an X-ray dose of 20 Gy. Subsequently, rats were kept on a standard diet (110 mmol sodium/kg) or a sodium-poor diet (10 mmol sodium/kg). On both diets, SBP started to rise rapidly 3 months after kidney irradiation. Sodium balance studies carried out at that time revealed an increased sodium retention in the irradiated rats compared to controls on the same diet. In rats on a low sodium intake, there was neither a delay nor an alleviation in the development of hypertension. Compared to controls, the PRC tended to be lower in irradiated rats up to 4 months after irradiation. Subsequently, malignant hypertension developed in all 20 Gy rats, resulting in pressure natriuresis, stimulating the renin-angiotensin system. Our findings indicated that hypertension after bilateral kidney irradiation was not primarily the result of an activation of the renin-angiotensin system. Although there were some indications that sodium retention played a role, dietary sodium restriction did not influence the development of hypertension.

Potentiation of cis-diamminedichloroplatinum nephrotoxicity by amikacin in rats.

The nephrotoxic interaction between cis-diamminedichloroplatinum (CDDP) and amikacin (AMI) was studied in rats. Following a single dose of CDDP (5 mg/kg i.v.), AMI (60 mg/kg s.c.) was given for 14 days. When given alone CDDP caused a 40% fall in the glomerular filtration rate (GFR), whereas AMI alone had no effect on GFR. This nonnephrotoxic course of AMI potentiated the CDDP-induced fall in GFR. Only a limited recovery of renal function was observed during a 15-week follow-up period.

Function of pediatric Nissen-Rossetti fundoplication followed up into adolescence and adulthood.

BACKGROUND: We analyzed the very long-term results of the Nissen-Rossetti fundoplication performed in young children. Little has been reported about follow-up longer than 5 years in homogeneous populations. This study concerns a homogeneous group with a minimum follow-up of 10 years; these former patients, therefore, are now adolescents or adults. STUDY DESIGN: In 24 consecutive patients without other congenital or acquired anomalies of the esophagus or stomach, we evaluated the primary postoperative diagnoses, symptoms of recurrent reflux, and their state of health in 1994. RESULTS: After a median follow-up of 16 years, the result was excellent in 18 patients, good in 5, and poor in I (graded according to Visick). Patients with recurring reflux symptoms had evidence of failure of the fundoplication. All but 1 had been given a diagnosis of recurrent reflux within 2 years after the operation. The situation after 2 years seems predictive for the later outcome. CONCLUSIONS: In almost all cases, the Nissen-Rossetti fundoplication is a long-lasting, effective treatment for young children with symptomatic gastroesophageal reflux.

Radiographic evidence of bronchopulmonary dysplasia in high-risk congenital diaphragmatic hernia survivors.

Congenital diaphragmatic hernia is a congenital malformation associated with pulmonary hypoplasia. It often leads to respiratory failure, requiring artificial ventilation with high inflation pressures and high percentages of oxygen. We evaluated radiographic evidence of bronchopulmonary dysplasia (BPD) in survivors, who presented with respiratory distress within 6 hours after birth, by a radiographic scoring system measuring the severity of BPD by the Toce score and the degree of pulmonary hypoplasia by the Touloukian score. Fifteen of 45 survivors (33 percent) had clinical and radiological lung disease resembling BPD. As a group they had significantly higher Touloukian and Toce scores than survivors without BPD. Morbidity expressed as the duration of artificial ventilation, supplemental oxygen, and hospital stay was much higher in the BPD group. The hypoplastic lung in infants with congenital diaphragmatic hernia appears to be as susceptible to barotrauma and pulmonary oxygen toxicity as the lungs of prematurely born infants. To what extent BPD occurring in congenital diaphragmatic hernia survivors might influence the future development of lung function is not yet known.

Prenatal diagnosis and management of omphalocele.

The prenatal diagnosis of omphalocele by real-time sonography is important for intrauterine and neonatal management and prognosis. The prognosis and mortality rate is determined rather by the presence of serious associated anomalies such as cardiovascular and chromosomal defects, than by the omphalocele itself. Obstetric management in the presence of an omphalocele should therefore include immediate amniocentesis for chromosomal analysis and ultrasonic scanning of the fetus for other structural abnormalities. The obstetric management should be coordinated by the neonatologist and pediatric surgeon to ensure timely and optimal care of the infant.

Postoperative care after craniofacial surgery: evaluation of routine laboratory testing.

In this study, two protocols for monitoring children after major craniofacial surgery were compared. The first protocol consisted of repetitive laboratory testing in 37 children to detect surgical and medical complications during a 2-year period. None of the complications were predicted by abnormal test results, and abnormal results of routinely performed tests never led to a change in management. The second protocol, an adapted version of the first protocol, was continued for 5 years as a prospective study in 98 children: Patients were routinely tested only once, and further testing was initiated either after an abnormal test result or because of clinical symptoms. Clinical management and the incidence of postoperative complications did not differ between groups. The second protocol considerably reduced the mean number of tests per patient from 42.5 to 7.0, but in contrast with the first protocol, 84 percent of abnormal test results led to changes in clinical management. In conclusion, in the first group the test results were not used and were not predictive of complications. In the second group, tests were more apt to have abnormal results and often initiated treatment. This shows that indiscriminate routine laboratory testing is of limited value in covering the postoperative period after craniofacial surgery.

Continence after posterior sagittal anorectoplasty.

Posterior sagittal anorectoplasty (PSARP) was introduced in 1982 by Peña and De Vries as a new operation for patients with a high anorectal malformation. The degree of postoperative continence is reported to be high. During the past decade, too, new insights have been gained into the embryology of anorectal malformations. Evaluation of PSARP in relation to current understanding of the development and anatomy of the anorectum and the pelvic floor has led us to conclude that optimal continence cannot be expected. Fifty patients with a high anorectal malformation underwent PSARP between June 1983 and May 1990. Postoperative follow-up consisted of anamnesis (subjective) and electrostimulation, defecography, and anorectal manometry (objective). All patients are alive, and all but one are being evaluated regularly. Subjectively, the majority of patients were more or less incontinent, with soiling of pants at least once a day. On the basis of objective criteria, virtually all patients appeared to be incontinent, and in only one patient was the mechanism of defecation almost unimpaired after PSARP. From this study, we conclude that although PSARP provides a good aesthetic result, patients will never acquire normal continence.

The management of a fistula between the rectum and the lower urinary tract.

Ten boys with a fistula between the rectum and the urinary tract are presented. Six resulted from complications of imperforate anus surgery, three were various congenital abnormalities, and one was associated with an inflammatory pelvic mass. The management of these patients is described and the problems are discussed.