Cyclosporine blood monitoring after heart transplantation: a prospective comparison of monoclonal and polyclonal radioimmunoassays.

Management of heart transplant patients who are being given cyclosporine is complicated by the variety of methods available for measuring cyclosporine levels and the current trend toward exclusive use of monoclonal assays. To facilitate clinical decisions regarding cyclosporine levels when converting from a polyclonal system to monoclonal system, 79 heart transplant patients underwent a prospective study to compare the polyclonal radioimmunoassay with the monoclonal-specific parent compound and nonspecific radioimmunoassays. Multivariable regression analyses were performed to generate best-fit equations for conversion of one assay to another. The closest correlation was noted in converting the measurement of cyclosporine parent compound with metabolites by the polyclonal method to the monoclonal method (nonspecific), R2 = 0.93. Considerable variability existed in the relationship between polyclonal and monoclonal-specific levels (R2 = 0.66) and between monoclonal-nonspecific and monoclonal-specific levels (R2 = 0.66), and both relationships were affected by hepatic function. Inferences: (1) The conversion of numeric cyclosporine levels from parent compound to parent plus metabolites is not completely predictable and must be empirically determined with the generation of appropriate regression equations. (2) Caution is advisable when a transplant team adopts a new cyclosporine assay for clinical use; formal study between existing assay methods and any newly adopted assay is warranted to prevent inadvertent underdosing or overdosing with cyclosporine.

Chemiluminescence immunoassay of aldosterone in serum.

A chemiluminescence immunoassay (CLI) for the direct measurement of aldosterone in serum was developed with aminobutylethyl isoluminol (ABEI) as the label. In this competitive assay the samples are incubated with sample, antibody, aldosterone-carboxymethyl oxime-ABEI, and paramagnetic particles coated with second antibody. After magnetic separation and washing, the samples are incubated with 200 microL of NaOH (2 mol/L) at 60 degrees C for 30 min. In the luminometer the chemiluminescence is produced by the serial injection of 150 microL each of microperoxidase and H2O2 solutions. Comparison of results with an RIA method showed excellent agreement: CLI = 1.001 RIA + 0.020 (r = 0.99, n = 93). The method is simple and avoids the hazards and costs associated with isotopic waste. The label has a shelf life of at least two years.

Chemiluminescence immunoassay of cyclosporine in whole blood.

We describe a chemiluminescent immunoassay (CLI) for measuring cyclosporine in whole blood. Its sensitivity and accuracy are comparable with those of an RIA method that makes use of the same specific monoclonal antibody. The comparison with the RIA method was excellent: y(RIA) = x(CLI) + 11.24 (r = 0.99). In our procedure the samples are incubated with cyclosporin C-hemisuccinate-aminobutyl-N-ethylisoluminol, antibody, and paramagnetic particles coated with second antibody. After magnetic separation and washing, the samples are incubated with 200 microL of NaOH (2 mol/L) at 60 degrees C for 30 min. The chemiluminescence generated by automated serial injections of solutions of microperoxidase and dilute (2 mL/L) H2O2 is measured for 5 s. The data are processed by using a spline fit of log B/Bo log conversion. This method is easy to perform and avoids the hazards and costs associated with isotopic waste disposal. The label is stable for at least three years.

Vaginal wall sling.

We describe a new technique for the treatment of urinary incontinence due to intrinsic sphincteric damage in which a sling constructed from vaginal wall is used to provide compression and support of the urethra. A rectangular island of in situ anterior vaginal wall underlying the urethra and bladder neck is developed, the 4 corners are anchored with polypropylene sutures and a ligature carrier is used to transfer the sutures to a suprapubic location. An anterior vaginal wall flap proximal to the island is advanced to cover the island. When the sutures are tied the resulting sling will support the urethra and increase urethral resistance by compression, restoring continence. The advantages are its simplicity, need for only a small incision, short operative time and hospital stay, and reliance on healthy, well vascularized, in situ tissue. Continence has been achieved in 29 of 32 cases. All patients voided spontaneously except for those with neuropathic urethral incompetence who required self-catheterization.

Female urinary incontinence. Therapeutic approaches.

Urinary incontinence results from bladder or sphincter dysfunction. Bladder-related incontinence due to a reduced-capacity, unstable, or noncompliant bladder can often be remedied by augmentation techniques. For anatomic incontinence, excellent results are achieved with use of any of the retropubic or transvaginal suspension techniques that restore the bladder neck and proximal urethra to a high, fixed retropubic position. However, when the urethral sphincter is intrinsically damaged, mere restoration of position will fail to cure the problem. Such damage warrants use of a compression procedure that increases urethral resistance, such as one of the many sling techniques, implantation of an artificial urinary sphincter, or periurethral Teflon injection.

Outpatient pediatric urologic procedures.

Outpatient pediatric urologic surgery is not a new concept. However, it has recently become extremely popular. The general experience nationwide and particularly the experience at Children's Hospital of Philadelphia and the University of Virginia Hospital indicate that outpatient surgery can be very safe and satisfactory for patients. The outpatient approach requires close cooperation among anesthesiologists, surgeons, and outpatient personnel. Excellent communication with the patient and family is essential. This includes extensive educational printed material and 24-hour availability by telephone. Once the infrastructure is in place, outpatient pediatric urologic surgery results in efficient use of facilities and a more pleasant surgical experience for the patient. The psychological, social, and economic benefits of outpatient surgery make it imperative that a large percentage of pediatric procedures be done on an ambulatory basis. We do not, however, intend to suggest that all minor procedures can be done on an outpatient basis, as certain special situations will mandate hospitalization.

Outpatient pediatric urological surgery: techniques for a successful and cost-effective practice.

Of 674 operations performed in the pediatric urology division between January and October 1984, 62 per cent were done on an outpatient and 12 per cent on a 1-night stay basis. The outpatient procedures included major proximal hypospadias repairs and intra-abdominal procedures, as well as inguinal, penile, scrotal and endoscopic procedures. No child required subsequent hospitalization. This successful approach was contingent upon proper patient selection, patient and family education, modern anesthetic and monitoring techniques, and careful followup. For elective procedures, such as hypospadias repairs, patients are operated on when they are 6 to 18 months old. Modern anesthetic techniques include isoflurane to maintain a light level of general anesthesia and adjunctive regional blocking procedures. The availability of a physician support service on a 24-hour basis is fundamental to the success of this approach. Benefits include patient, parental and physician satisfaction, diminished potential for nosocomial disease transmission and avoidance of the emotional stress of parent-child separation. Increased use of outpatient surgery is a means to produce a significant decrease in the cost of medical care.

Preputial calculus: a case report.

A preputial calculus developed postoperatively in a child with epispadias. Analysis of the pathophysiological development of this lesion and a review of the literature are presented. The inert subpreputial space may become calculogenic in the presence of phimosis and urinary stasis.

Invasive carcinoma of prostate presenting as rectal carcinoma.

Prostate carcinoma occasionally can present with rectal obstructive symptoms and an annular constricting lesion of the rectum. Discriminating between primary rectal carcinoma and prostate carcinoma locally invasive to the rectum is of obvious importance because of the different treatments and prognoses. History and physical examination play only a marginal role in differentiating between these two lesions. The diagnosis of prostatic malignancy in patients in this circumstance can be supported by an elevated serum acid phosphatase as well as a bone scan that demonstrates a pelvic/vertebral distribution of bony metastases. The rectal mucosa is usually spared, and a barium enema often will demonstrate tapered margins as opposed to a tumor edge in primary rectal malignancy. Excretory urography often demonstrates hydronephrosis. Rectal biopsy with immunohistochemical staining for prostate specific antigen can direct the origin of a poorly differentiated adenocarcinoma to the prostate. Treatment involves hormonal manipulation with estrogen therapy or orchiectomy. Radiation therapy to the obstructed rectum has provided satisfactory palliation when hormonal manipulation fails.

Cushing's syndrome. Screening methods in hospitalized patients.

We studied 18 patients with Cushing's syndrome and 25 patients in which Cushing's syndrome was excluded on follow-up to evaluate screening tests for Cushing's syndrome in hospitalized patients. Plasma cortisol values (at 8 AM) were found least helpful yielding 29% false-positive and 60% false-negative values. Diurnal variation of cortisol was present in 30% of patients with Cushing's syndrome and absent in 18% of patients without Cushing's syndrome. When corrected for total urinary creatinine, 24-hour urinary 17-hydroxycorticosteroids were specific (all patients without Cushing's syndrome had normal values) but not very sensitive (two of 12 patients with Cushing's syndrome had normal values). Similarly, 24-hour 17-ketosteroids were of little help with 17% false-positive and 35% false-negative values. Twenty-four-hour urinary free cortisol was both a sensitive and specific screening test for Cushing's syndrome (no false-positive and no false-negative results). We conclude that urinary free cortisol is the most efficient screening method for Cushing's syndrome in hospitalized patients.

Corticotropin production by tumors of the autonomic nervous system.

Cushing's syndrome in association with a tumor of the autonomic nervous system (ANS) has been reported occasionally. We studied a patient who had an intra-adrenal paraganglioma (pheochromocytoma), and whose plasma corticotropin level was elevated prior to surgery but dropped to a low value following removal of the tumor. Catecholamine levels were elevated preoperatively and catecholamines were extracted from the tumor tissue. Corticotropin was identified in the tumor by immunoperoxidase staining. We also compared the endocrine data of 16 previously reported cases of Cushing's syndrome secondary to the release of ectopic corticotropin from ANS tumors. We concluded that in these patients, the plasma corticotropin level is only modestly elevated but indexes of steroid production frequently are markedly elevated. Also, discrepant responses to dexamethasone suppression tests occur, perhaps via sporadic release of corticotropin. These factors complicate evaluation of the cause of Cushing's syndrome in these patients.

Functional carotid paragangliomas. Biochemical, ultrastructural, and histochemical correlation with clinical symptoms.

To our knowledge, this study is the first to correlate the results of biochemical, electron microscopic (EM), and histochemical analyses of tissues from functional paragangliomas of the upper carotid area with a patient's clinical symptoms. The tumor tissues from our two patients contained epinephrine, norepinephrine, and dopamine. Neurosecretory granules were identified in both tumors by EM and by the Grimelius silver stain. The patient with the most severe symptoms exhibited evidence of higher circulating levels of catecholamines by biochemical, EM, and histochemical analyses.

Simple method for estimating glycosylated hemoglobins, and its application to evaluation of diabetic patients.

Recent reports have suggested that determination of glycosylated hemoglobin may serve as a clinical aid for long-term blood glucose control in diabetes mellitus. We describe a simple procedure for measuring it by ion-exchange chromatography. Hemolysates were subjected to Bio-Rex 70 chromatographic separation on small columns. Percentages in the normal group ranged from 4.7 to 8.8% of total hemoglobin; the mean +/- standard error was 6.61 +/- 0.31%. Values in the diabetic group ranged from 6.9 to 17.4%; the mean was 10.83 +/- 0.34. Plasma glucose concentrations after fasting, plotted vs. the percent of glycosylated hemoglobin, revealed a linear relationship at normal or moderately high glucose concentrations. However, the values for glycosylated hemolgobin approached a plateau with grossly higher plasma glucose concentrations after fasting. Our results support the view that, due to its long half-life, the estimation of glycoylated hemoglobin reflects the integrated glucose concentrations to which the erythrocytes have been previously exposed.

Steric hindrance as a factor in the reaction of labeled antibody with cell surface antigenic determinants.

The binding of rabbit anti-human IgG labeled with 125I, shellfish glycogen or ferritin to human IgG attached to the surface of rabbit RBC with chromic chloride was studied. Maximum binding was noted with 125I labeled antibody. Slightly but consistently less binding was found with shellfish glycogen labeled antibody. The binding of ferritin labeled antibody was strikingly reduced--usually one-third or less of that found with 125I labeled antibody alone. This suggests that under the conditions of these experiments, the attachment of large labels to antibody molecules results in reduced antibody binding to surface antigen. Steric hindrance is probably at least in part responsible for this reduced binding.