Fourteen Caucasian families with 81 affected individuals have been assessed in which polycystic ovaries/male pattern baldness (PCO/MPB) segregates as an autosomal dominant phenotype (1). The gene CYP17, coding for P450c17 alpha (17 alpha-hydroxylase; 17/20 lyase) on chromosome 10q24.3 is the rate-limiting step in androgen biosynthesis. We have identified a new single base change in the 5' promoter region of CYP17 by heteroduplex analysis. This creates an additional SP1-type (CCACC box) promoter site, which may cause increased expression. This base change also creates a recognition site for the restriction enzyme MspA1 allowing a simple screening procedure. There is a significant association between the presence of this base change (A2) and the affected state for consecutively identified Caucasian women with PCO as compared either to consecutively matched controls (P = 0.03) with an odds ratio for those with at least one A2 allele of 3.57, or to a random population (P = 0.02) with an odds ratio of 2.50. Within the fourteen families, members with PCO or MPB have a significant association with the occurrence of at least one A2 allele compared to their normal relatives, with an odds ratio of 2.20 (P = 0.05). The base change does not cosegregate with the affected phenotype within the families showing association, demonstrating that this mutation of CYP17 does not cause PCO/MPB. Variation in the A2 allele of the CYP17 gene is a significant factor modifying the expression of PCO/MPB in families where it has been demonstrated to segregate as a single gene disorder, but it is excluded as the primary genetic defect.

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The amount and nature of the total nondialyzable solids (TNDS) of normal human urine have been parametrically defined (1). This report is concerned with a technique for separation of the TNDS into three reproducible primary fractions, which are suitable for subfractionation by other methods, and their composition. MATERIALS AND METHODS MaterialsSubjects. Twelve young adult individuals (seven male, five female), who had no history or clinical evidence of renal disease or current evidence of other disease, served as subjects for this study. Each subject continued the usual daily activities and diet during the collection of three 24 hour urine specimens. Female subjects submitted specimens near the midportion of the menstrual cycle.Membranes for ultrafiltration. The solvent for collodion membranes was prepared from analytical grade reagents by mixing 96.1 ml. absolute ethanol, 40.5 ml. diethyl ether, and 13.5 ml. glacial acetic acid. One hundred ml. of collodion2 was then added and thoroughly mixed.Discs of the best grade of plate glass, 15 cm. in diameter, scratch-free, and hand-rubbed to provide a polished surface, were stored in bichromate cleaning solution. The edges of the glass plates were unbeveled. Prior to use, the plates were rinsed thoroughly with distilled water and air dried. The lint-free plate was then floated on mercury in a glass dish in a desiccator containing 75 ml. of concentrated sulfuric acid in the bottom. Exactly 12 ml. of the collodion solution was poured onto the center of the plate and allowed to dry for exactly 20 minutes in a closed desiccator. The collodion-covered disc was lifted out and slid into a vessel of distilled water. The gelled membrane floated free to the surface of the water and was transferred on a piece of filter paper for storage in distilled water saturated with thymol. The sulfuric acid was changed after preparation of each membrane.These membranes have a "T" value of 14 to 34 seconds, i.e., the period required for 100 ml. Ultrafilters. Ultrafilters of 4 L. capacity, having porous steel supporting plates 15 cm. in diameter, were used.4 Methods Fractionation and recovery. The collection and dialysis of 24 hour urine specimens was by the previously described technique (1). A 'Ao aliquot was removed for TNDS determination and the remainder of the 24 hour specimen was ultrafiltered at approximately 30 C., under a maximum pressure of 30 to 40 lbs. per sq. inch. This required about 24 hours. The solids in the ultrafiltrate were recovered by stepwise lyophilization, as previously described (1). The resultant brown powder was designated UFO (ultrafiltrate 0). The residue, designated RO (residue 0), was removed from the membrane and extracted three times with five volumes of barbital-sodium barbital buffer, ionic strength 0.1N, pH 8.6. The veronal insoluble fraction of RO, recovered by centrifugation (relative centrifugal force = 1,000 X G, 20 minutes) and designated as R1 (residue 1), was immediately suspended in distilled water and dialyzed against cold distilled water for no...

One hundred and thirty‐one patients undergoing 142 carotid endarterectomy procedures were randomized to have their operation performed either with or without intra‐operative electroencephalographic (EEG) monitoring. Patients with EEG monitoring were shunted if both the internal carotid back pressure (ICBP) was less than 50 mmHg and ipsilateral change was evident on the EEG after clamping. Patients without EEG monitoring were shunted if ICBP was less than 50 mmHg. There was one postoperative death (0.7%) with neurological deficits occurring in five patients (3.5%). There were significantly fewer neurological deficits (P = 0.02) in patients with no EEG change (one of 59) compared with those with EEG change (two of 13). There was a highly significant increase (P = 0.005) in incidence of neurological deficit (two of five patients) when ICBP was considered ‘adequate’ at 50 mmHg or greater but EEG change occurred. No neurological deficit occurred in 14 patients who were not shunted with ICBP < 50 mmHg but with no EEG change. There was no difference in the incidence of neurological deficit in patients with low and high ICBP when both 50 and 55 mmHg were used as the cut‐off points. It is concluded that EEG monitoring is useful in identifying patients requiring shunting during carotid endarterectomy. Use of a shunt is recommended if there is EEG change regardless of ICBP; conversely, if ICBP is low but there is no EEG change it would appear safe to proceed without shunting.

Our patient had no features of phenytoin toxicity despite a concentration of 31-3 mg/I. After starting tolbutamide the phenytoin concentration decreased to 27-4 mg/I. The total concentration was measured, not the free level. Neither the Committee on Safety of Medicines nor the manufacturer knows of any other cases of phenytoin toxicity produced by tolbutamide.

A number of high molecular weight compounds have been separated as constituents of normal urine. Regardless of the investigators' intention, in practically all of these studies only one or a few components were isolated. Interpretation and correlation of these numerous data, obtained by various procedures, would be greatly facilitated by the quantitative determination of the amount and composition of the total biocolloid content of normal 24 hour urine specimens. Hamerman, Hatch, Reife, and Bartz (1) have reported the recovery of the total nondialyzable solids (TNDS) from three 24 hour urine specimens by alternate dialysis and vacuum distillation with final lyophilization. The following experiments were designed to expand these data and to study individual variations in TNDS, in order to establish the limits of such variation in normal human urine. MATERIALS AND METHODSSubjects for the study were laboratory workers who were in excellent health, had no history or clinical evidence of renal or urinary tract disease, and who were within the average weight and height range for their age group. Each followed his daily routine without special diet, variation in fluid intake, or alteration in physical activity.Twenty-four hour urine specimens were collected into chemically clean containers, with 10 ml. of phenylmercuric nitrate 1: 1,000 as an inhibitor of enzymatic and bacterial activity. As soon as the collection was completed, each specimen was measured and the total specimen (or a 1,200 ml. aliquot) divided into 150 ml. portions. Each portion was placed in a 35 cm. Visking cellulose tubing 2 of 2.8 cm. inflated diameter. The sacs were knotted to include a 35 ml. volume of air in each bag. This arrangement kept the sac upright, absorbed mechanical shock, and permitted agitation of the urine during dialysis. The sacs were completely submerged in a closed carboy con-

The total nondialyzable solids (TNDS) of normal human urine have been found to have an approximate composition of 47 per cent protides, 16.6 per cent glucides, 9.7 per cent sialic acid, 6.2 per cent hexosamine, 3.3 per cent lipids, 12.2 per cent bound water and 8.5 per cent ash (1). The mean TNDS excretion in two series of determinations has been found to be 433 mg. and 505 mg. per 24 hours, with a value of 472 (S.D. ± 108) mg. per 24 hours for the combined series (1, 2). Methods have been described for separation of the TNDS into three reproducible fractions (2). Figure 1 is a flow sheet illustrating the technique and approximate percentage weight distribution of each fraction. Boundary electrophoretic studies, at pH 8.6, have demonstrated the presence of concentration gradients in the RS-l fraction which have mobilities closely approximating each of the gradients of normal blood plasma under similar conditions (3). The Cohn Method 10 for fractionation of plasma proteins has been modified by Lever and co-workers to permit separation of small quantities of plasma proteins (4). The present report concerns the application of this technique to the fractionation of RS-l solids from normal human urine. MATERIALS AND METHODSSubjects. Ten to 12 subjects (seven male and five female) submitted 24 hour urine specimens, which were pooled daily for rapid processing (2).Reagents. The reagents were prepared from stock solutions at room temperature and cooled to -50 C. immediately before use. The reagents A and A' of Lever gave an initial precipitation medium of pH 5. amount of acid-citrate-dextrose (ACD) plasma. The aqueous solution of RS-1 urinary fraction was found to lack the buffering action of ACD plasma; hence, in order to achieve the above conditions for urinary RS-1, the reagents A and A' of Lever and co-workers were combined to form Reagent I.Reagent I. This reagent contained 250 ml. 95 per cent ethanol, 20 ml. of M sodium acetate, 1.75 ml. of M acetic acid and water to make 1,000 ml. When necessary, the pH of this solution was adjusted to pH 5.80 ± 0.05 by addition of approximately 0.05 ml. of 10 M acetic acid.Zinc reagent. This reagent contained 54.8 Gm. of zinc acetate dihydrate dissolved in 500 ml. of water, to which 200 ml. of 95 per cent ethanol was added and then sufficient water to make 1,000 ml. The final pH was 6.5 ± 0