Using DNA samples obtained from two unrelated patients, diagnosed as having familial dysalbuminaemic hyperthyroxinaemia (FDH), exons 1-14 which span the entire coding region of the human serum albumin (HSA) gene were amplified by the polymerase chain reaction. The sequence of each of the 14 DNA fragments was then determined. In each case a point mutation was identified at nucleotide 653 which causes an Arg to His substitution at amino acid position 218 The major hazard for FDH patients is that they can be misdiagnosed as hyperthyroid and subjected to unwarranted treatment. ' The raised serum TT4 in FDH patients results from the presence of an abnormal human serum albumin (HSA) which exhibits enhanced binding to thyroxine (T4).28 Our study on intrinsic fluorescence properties of purified normal HSA and HSA obtained from an FDH patient, hereafter referred to as patient 1, using both steady state and time resolved methodologies, showed that the patient had two HSA species with different affinities for T4.9 Until now the specific molecular defect of FDH HSA was unknown. This study describes a specific amino acid substitution resulting from the same nucleotide change in the HSA gene in two unrelated FDH patients.We have developed a rapid method for identifying FDH patients with the mutation we describe by using polymerase chain reaction (PCR) amplification of exon 7 of the HSA gene followed by restriction endonuclease digestion and gel electrophoresis. Materials and methods SOURCE OF WHOLE BLOODWhole blood drawn up in EDTA was obtained from patient 1 and patient 2, diagnosed as FDH by methods described previously.2

In a double-blind prospective study of 200 sequential urine specimens the sediment count of leukocytes in the centrifuged urine (white blood cells per high power field) was compared to a chamber count of leukocytes in uncentrifuged urine (white blood cells per microliter.). There was good correlation (coefficient of correlation 0.783, sensitivity 91.9 per cent, specificity 97.6 per cent and efficiency 96.6 per cent) between the more precise chamber count and the more commonly performed sediment count if the methodology of the sediment count was standardized. In a double-blind prospective study the results of the sediment count for leukocytes and erythrocytes were compared to the leukocyte esterase and hemoglobin dipstick results of urine specimens from 1,346 adults who underwent multiphasic screening. The dipsticks were found to be sensitive to physiologic limits for leukocytes and erythrocytes, with only 0.9 per cent false negative results for each. Formed elements in the urine not detectable by dipstick, such as casts and crystals, were present in 3 per cent of the specimens. Among patients who had significant pyuria, hematuria or formed elements not detectable by dipstick chemical urinalysis, no significant pathological condition was detected upon retrospective review. Because the chemical dipstick is not quantitative and because the sensitivity of the dipsticks resulted in many false positive findings compared to the sediment count (red and white blood cells 16.4 and 13.2 per cent, respectively) a protocol is offered in which results of screening urine specimens that are positive on dipstick culture would be confirmed by a properly performed microscopic urinalysis. This protocol as applied to an adult screening population would be an accurate, cost-effective method of urine testing.

A cost-effective urinalysis test strategy, employing screening dipstick analysis with sediment microscopy performed on urines positive for leukocyte esterase, nitrite, protein, or blood, is evaluated. Screening urine culture is done when greater than or equal to 5 WBC/HPF, greater than 10 bacteria/HPF, or yeasts are found on sediment microscopy. Predictive value, sensitivity, and specificity of the test strategy in predicting significant bacteriuria is compared with sediment microscopy, Gram staining of uncentrifuged urine and leukocyte chamber counting. Employment of the test protocol for routine urine specimens would decrease sediment microscopy by 49%, while effectively screening for significant bacteriuria with a sensitivity of 88.9% and predictive value of a negative result of 98.8%.

We report a case of lovastatin-induced rhabdomyolysis and resulting life-threatening renal failure. Lovastatin, a hypocholesterolemic agent, decreases endogenous cholesterol synthesis by inhibiting 3-hydroxy-3-methylglutaryl coenzyme A reductase (EC 1.1.1.88). This agent has been implicated in causing rare serious side effects in various clinical settings; however, the mechanism of these adverse reactions is not understood. The clinical course of our patient was characterized by profound muscle weakness with marked increases in serum creatine kinase and myoglobin. Light- and electron-microscopic studies of skeletal muscle of our patient demonstrated a noninflammatory myopathy suggestive of ongoing rhabdomyolysis with vacuolization and focal degeneration of myocytes. The patient's symptoms and the laboratory values referable to rhabdomyolysis resolved after discontinuation of the drug. We speculate that the rhabdomyolysis was due to mitochondrial damage secondary to inadequate synthesis of coenzyme Q and heme A, members of the electron-transport system of the inner mitochondrial membrane.

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