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Abstract: Immunoassays are widely used to determine hormone levels. Antibodies directed against components of the immunoassay system can interfere with analyte concentration estimates. When unrecognized by clinicians, inappropriate clinical intervention may follow. The case of a young child with premature thelarche and elevated basal and stimulated luteinizing hormone (LH) levels is presented, in whom it is hypothesized that heterophile antibodies (HAs) caused interference in the LH immunoassay. LH concentrations were measured in two different assays: LH-microparticle enzyme immunoassay (MEIA) and LH-immunochemiluminometric assay (ICMA). To detect HA interference, LH level was remeasured after both preincubation with mouse serum to neutralize human anti-mouse antibodies, and treatment with a heterophile-blocking tube. The mean basal LH concentration by LH-MEIA was 7.4 mIU/mL and for LH-ICMA was 0.08 mIU/mL (normal range for age: 0.02–0.3 mIU/mL). LH concentration by MEIA was 0.08 mIU/mL after preincubation with mouse serum and 2.7 mIU/mL after preincubation with a heterophile blocking tube. In conclusion, HAs were identified in the serum of a child with premature thelarche. The presence of HAs led to spuriously elevated basal and gonadotropin-releasing hormone-stimulated LH concentrations, resulting in a diagnosis of central precocious puberty and unnecessary therapy. To avoid similar cases in the future, clinicians should consider the possibility of assay interference when the clinical picture is incongruent with the laboratory data.

Intracellular hyaluronic acid binding protein (RHAMM/IHABP), which was recently identified as a novel member of the microtubule‐associated protein (MAP) family, has the capacity to interact not only with microtubules but also with microfilaments. The molecule, which is known to be expressed in mammary carcinoma cells, might, through virtue of its intracellular interactions, influence tumour cell morphology and motility. This possibility was examined in a series of 189 mammary carcinomas by immunohistochemistry, using a polyclonal antibody to RHAMM/IHABP. Tumours were selected to include approximately equal numbers of consecutive grade I, II and III ductal carcinomas and invasive lobular carcinomas. Higher grade tumours had significantly lower expression of RHAMM/IHABP in the cytoplasm (p=0.02), but significantly increased expression in trabeculae (p=0.002) and further enhancement at the tumour island edges (p=0.002). Tumours of infiltrating lobular type had stronger expression in the overall cytoplasm (p=0.02) and trabeculae (p=0.08) than carcinomas of ductal type. The presence of strong trabecular expression was associated with a reduced overall survival time (p=0.017). These results suggest that RHAMM/IHABP expression may contribute to the motility and invasiveness of a tumour cell sub‐population in breast cancers. Copyright © 2001 John Wiley & Sons, Ltd.

The potential impact of local intracoronary infusion of streptokinase (SK) on vascular prostaglandin synthetic pathways was studied in a canine model. Control animals (n = 10) underwent left coronary artery (LCA) infusion of 50,000 units SK for 90 minutes; experimental animals (n = 10) underwent LCA infusion of normal saline. Plasma samples for radioimmunoassay (RIA) of prostacyclin (PGI-2) and thromboxane (TXA-2) were obtained from the coronary sinus (C5) as follows: one sample preinfusion, six samples during infusion, and three samples postinfusion in each animal. Comparisons between control and experimental plasma levels of PGI-2 and TXA-2 were made for each sampling time. The PGI-2 levels remained at or below the lower limits of detectability by RIA (the most sensitive assay available) in both control and experimental animals. TXA-2 levels were higher in experimental than in control animals at all sampling times, with the most significant differences occurring in samples 3 (after 30 minutes of infusion, 001 < P.01), 4 (after 45 minutes of infusion, .05 < P< .10), and 5 (after 60 minutes of infusion, .02 < P< .05).

OBJECTIVE: To determine the relationship of serum theophylline concentration with electrolyte and glucose abnormalities across a broad range of theophylline concentrations.DESIGN: Retrospective review of a computerized laboratory database between June 1, 1984 and June 1, 1986.SETTING: A midwestern university medical center.PATIENTS: Eight hundred sixty-nine patients with serum theophylline concentrations of >5.5 μmol/L and a random unmatched sample (control group) of 350 in- and outpatient adults and children with no history of reactive airways disease or theophylline exposure.RESULTS: Patients with measurable theophylline had a higher risk of hypokalemia, hyponatremia, hyperglycemia, hypophosphatemia, and hypomagnesemia compared with the unexposed control group. Unadjusted odds ratios (OR) were: (1) hypokalemia OR=4.2 (95 percent CI 2.2 to 7.9); (2) hyponatremia OR=5.4 (95 percent CI 2.0 to 12.9); (3) hypomagnesemia OR=1.6 (95 percent CI 1.0 to 2.5); (4) hyperglycemia OR=2.3 (95 percent CI 1.7 to 3.0); and (5) hypophosphatemia OR=2.7 (95 percent CI 1.2 to 5.3). A linear concentration—response relationship was documented between serum theophylline concentration and all metabolic disturbances.conclusions: Measurable theophylline was associated with increased risk for glucose and electrolyte abnormalities in a concentration-related fashion across a broad range of theophylline concentrations from 5.5 to ≥110 μmol/L.

Serum calcium can markedly influence the phagocytic activity of the hepatic Kupffer cell. Specifically, depletion of calcium by chelators induced impairment of phagocytosis but elevation of serum calcium levels above normal leads to a progressive inhibition of phagocytosis. The findings suggest that alterations of serum calcium may induce significant R.E.S. functional changes which may produce a state of altered host resistance. The relationship of these observations to disturbances of the macrophage system during malignancy, which is known for its ability to alter dramatically the serum calcium concentration, warrants further investigation.

No abstract.

We report on 2 patients who became deeply comatose after transurethral resection of the prostate. Both patients were severely hyponatremic and hyperammonemic but the course of the comas followed serum ammonia concentrations more closely than serum sodium concentrations. The genitourinary irrigant used in both procedures was a 1.5 per cent glycine solution. Serum amino acid analyses in 1 patient suggested that the postoperative hyperammonemia was due to catabolism of glycine absorbed during surgery. The inadequate activation of normal pathways of ammonia metabolism in this patient may have been caused by a partial deficiency of the urea cycle enzyme arginosuccinate synthetase. We believe that hyperammonemia should be considered as a cause of encephalopathy after transurethral resection of the prostate. The 1.5 per cent glycine genitourinary irrigating solution may not be as nontoxic as generally believed.

The association between increased serum angiotensin converting enzyme (ACE) activity and active sarcoidosis is well documented. During a recent outbreak of acute histoplasmosis, a disease that shares many of the clinical and roentgenographic features of sarcoidosis, we examined serum ACE activity. Twenty-one (25%) of 86 patients with histoplasmosis had increased serum ACE activity. There were neither roentgenographic nor other substantive clinical differences between the groups of patients with increased and normal ACE values. Therefore, an increase in serum ACE activity must not be assumed to be caused by sarcoidosis unless histoplasmosis had been excluded.(JAMA 1983;249:1888-1889)