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Post-heparin plasma lipoprotein lipase and a triglyceride lipase of hepatic origin were partially purified in a new case of Tangier disease. No deficiency in either of these enzymes could ...

An association between chronic liver disease and monoclonal gammopathy is described in 7 patients. Three cases had cold precipitable IgG-IgM complexes. Two of them manifested a syndrome of ulcerative purpura, Raynaud's phenomena, arthritis, neuropathy, encephalopathy, myopathy, and terminal glomerulonephritis. Two additional cases had occasional purpura and in 2 cases the gammopathy was asymptomatic. In 1 patient, monoclonal gammopathy developed from polyclonal gammopathy in the course of the disease, and transition to malignant lymphoma occurred several months later. Prednisone, ACTH, and azathioprine, had no appreciable effect on the cryoglobulinemia. In 2 cases, the monoclonal fraction disappeared or decreased with prednisone alone and prednisone and chlorambucil respectively.

Two cases are reported, one of multiple myeloma and the other of erythrodermia (malignant reticulosis?), the former associated with a Bence-Jones paraprotein and the latter with IgM paraproteinemia. With an in vitro culture technique and/or the immunofluorescence method it could be demonstrated that the paraprotein present in the serum was synthesized not only in the bone marrow but also in the lesional skin.

The Haema-Count MK-4S system consists of an electronic platelet particle detector and a low-speed centrifuge to prepare platelet-rich plasma. It had greater day-to-day and within-day precision than the phase chamber reference method. In general, it had a good agreement on patient specimens but, in common with other automatic platelet-counting instruments, it was affected by abnormal proteins and by extremes of platelet size. Centrifugation was more rapid and neater than sedimentation in the preparation of platelet-rich plasma. It was not uniformly more accurate, and at high counts may have caused small losses; but in cases of very slow erythrocyte sedimentation it yielded more accurate counts than those obtainable by sedimentation. Users of automatic systems should be alert to occasional spurious counts, and a suitable chamber method should be available to investigate results in disagreement with clinical findings or with the estimate on differential smear.

Bile acid kinetics were determined in 15 normolipidemic and 61 hyperlipidemic subjects with the aid of [(14)C]cholic acid and [(3)H]chenodeoxycholic acid. The diet was standardized and of natural type. The total bile acid formation was within normal limits in patients with hyperlipoproteinemia types IIa and IIb. On the average the production of cholic acid (C) represented less than 50% of the total bile acid synthesis in both groups. The corresponding value recorded for the controls was 64+/-2% (mean+/-SEM). The synthesis of C in hyperlipoproteinemia type IIa was significantly below normal. Of the 27 patients with the type IV pattern, 18 had a synthesis of C and C + chenodeoxycholic acid (CD) that exceeded the upper range recorded for the controls. In these subjects the C formation represented 73+/-3% of the total bile acid synthesis. Similar findings were also encountered in the five patients with the type V lipoprotein pattern studied. The bile acid pool size of the 11 patients with hyperlipoproteinemia type IV, who had been cholecystectomized or suffered from cholelithiasis, was 900 mg smaller on the average than that of the other subjects with the same type of hyperlipoproteinemia. However, the pool size in the former subjects still tended to be higher than that of the control subjects without evidence of gallbladder "disease". In all groups of subjects the formation of bile acids tended to be higher in the male than in the female subjects. Bile acid synthesis showed no linear correlation to actual body weight, relative body weight, or body surface area. A moderate weight reduction in five patients (one with type IIb and four with type IV pattern) was followed by a 50% reduction of the C and CD synthesis.

T HE PLASMA CELL DYSCRASIAS are a group of related diseases that are characterized by proliferation of immunoglobulin-producing cells, usually from a single clone or strain. These cells secrete immunoglobulins or their components as a homogenous protein detectable by serum protein electrophoresis as a single spike (designated M-protein for monoclonal), or by urine protein electrophoresis as a peak (urinary light chains). Synonyms for these disorders are monoclonal gammopathy, dysgammaglobulinemia, and paraimmunoglobulinopathy. In this paper, we will review the clinical and laboratory aspects and bone radiology of three disorders of this group, macroglobulinemia, amyloidosis, and heavy chain disease.

The automated immunonephelometric assay (AINA) was compared with double immunodiffusion (DIDA) and single radial immunodiffusion (SRID) for the quantitation of differential protein clearance of proteins in sera and urine of patients with malignant paraproteinemia and with nephrotic syndrome. The correlation coefficient between the methods for all the proteins was high. The results indicate that the automated immunonephelometric assay is particularly suitable for differential protein clearance investigations and that the protein selectivity index may be also related to prognosis in patients with paraproteinemia.

IgG paraproteins were detected in the serum of three patients with the Wiskott-Aldrich syndrome (WAS). Two distinctly different monoclonal IgG paraproteins occurred in one patient separated by an interval of four years. One of the patients who had a paraprotein also had reticulum-cell sarcoma. However, no evidence of malignant disease was present in the other two patients with monoclonal immunoglobulins, nor did the sera of five additional WAS patients with malignancy contain detectable paraproteins. The development of monoclonal gammopathy is discussed in relation to the unique immunodeficiency found in this disorder and to the high frequency of malignant reticuloendotheliosis in these children.

Palmitate, glucose, and glycerol oxidation to CO(2) have been investigated in the fasted state in ten normal subjects and nine patients (six hyperlipoproteinemias, one xanthomatosis, and two glycogenosis) after intravenous injection of [1-(14)C]palmitate, [1-(14)C]glucose, or [1-(14)C]glycerol in tracer amounts. The specific activities and concentrations of plasma palmitate, glycerol, or glucose and expired CO(2) were measured at various intervals after the injection for a period of 24 h. All the studies were analyzed in terms of a multicompartment model describing the structure for each of the subsystems, the transfer of carbon label between subsystems, and the oxidation to CO(2). A bicarbonate subsystem was also included in the model to account for its role in shaping the CO(2) curves. All the CO(2) activity following a palmitate injection could be accounted for by a direct oxidative pathway from plasm FFA with the addition of a 20-min delay compartment. The same also applied to glucose, except that the delay compartment had a mean time of about 150 min. Only about a third of the injected glycerol was directly oxidized to CO(2) from plasma; the delay time was about 4 min. Most of the remainder was converted to glucose. In normals about 45% of the FFA is oxidized to CO(2) directly. This constitutes about 30% of the total CO(2) output. In hyperlipemia the CO(2) output is nearly unchanged and the contribution from FFA is nearly the same. There is a considerable increase (factor of 2), however, in FFA mobilization, most of which is probably diverted to triglyceride synthesis. The glucose and glycerol subsystems are roughly the same in normals and hyperlipemics. About 50% of glucose is oxidized by the direct pathways which accounts for about 35% of the CO(2) output. Glycerol accounts for only 1.5% of the CO(2) produced. Major changes occurred in the glycerol and glucose subsystems in glycogenosis. The changes are consistent with the known deficiency in glucose-6-phosphatase in this disorder. There is a considerable reduction (factor of 2 or more) in the release of glucose to plasma (gluconeogenesis) and in the conversion of glycerol to glucose. Despite the integration of the kinetics of the glucose, glycerol, and FFA subsystems over a 24-h period, 36% of the CO(2) production was still unaccounted for in normals and 50% in hyperlipemics. Thus, some of the carbon must wind up in very slowly turning-over pools which supply CO(2) through subsystems not covered in these studies (triglycerides, glycogen, amino acids, etc.). All the modeling was carried out with the aid of the SAAM25 computer program.

Des anciennes theories sur les fondements anatomiques de la douleur supposaient l'existence d'une voie-douleur(pain Pathway) directe, reliee a des recepteurs peripheriques specifiques. D'apres des etudes anatomiques, celle-ci etait reliee a de petites fibres medullees et non medullees dans les nerfs peripheriques. Des hypotheses subsequentes admirent que la douleur ne dependait pas d'ensembles specifiques de fibres, mais plutot de configurations particulieres spaciales et temporales de l'activite sensorielle dans le systeme nerveux. Des etudes physiologiques plus recentes ont mis en evidence certains recepteurs peripheriques qui repondent uniquement aux stimulations nociceptives; et des etudes morphometriques de neuropathies peripheriques chez l'homme attribuent clairement aux petites fibres medullees et aux fibres non medullees un role dans la conduction de la douleur. Les etudes morphometriques ont demontre, d'autre part, une association vraissemblable de la douleur spontanee des neuropathies, a la perte selective de patites fibres. Ces constatations appuient la these precedente de l'existence d'une voie nociceptive specifique comprenant des fibres de calibre fin dans les nerfs peripheriques. Il est evident que cette voie afferente est susceptible de modifications au niveau de la moelle epiniere, d'une part a cause d'apports energetiques peripheriques, et d'autre part a cause de pulsions descendantes. Il demeure probable qu'il faille abandonner la notion de voie-douleur (pain pathway) en tant que telle.

Kinetics of T3 and T4 were studied in a case of TBG deficiency with hypothyroidism. Serum total and free T4 of 35-year-old man were 0.6 μg/100ml and 0.54 ng/100ml, respectively. Serum total and free T3 were 18 ng/100ml and 74 pg/100ml, respectively. BMR was -27%. Thyroidal 24-hr uptake of 131I was 7%. Resin-sponge 131I-T3 uptake was 52%. Binding capacity of TBG was O. Binding capacities of TBPA measured by two different methods were 240 and 223 μg/100ml. The half-life of T4 was shortened, the T4 distribution space, turnover rate and clearance rate increased. Extrathyroidal organic iodine pool and degradation rate decreased. The half-life of T3 was slightly shortened, turnover rate, distribution space and clearance rate increased. Extrathyroidal T3 pool and degradation rate decreased. During the treatment with 75 μg/day of l-T3, the patient's complaints disappeared. When administration of l-T3 was switched to 400 μg/day of l-T4, elevated serum T3 remained higher than the preadministration level. His mother and a younger sister had decreased T4-binding capacity of TBG.

• How prevalent is hyperlipoproteinemia in children and adolescents?• What is the most common secondary cause of blood lipid elevation and how might it be counteracted?• How can you identify children and adolescents with hyperlipoproteinemia?

Eighty-one patients with sera positive for antinuclear antibodies were studied to determine the clinical significance of serum antinuclear antibody titers and immunofluorescent nuclear staining patterns. Attempts were made to (1) determine clinically significant serum ANA titers for various connective tissue diseases; (2) note the specificity of immunofluorescent nuclear staining patterns among various connective tissue diseases; (3) observe the spectrum of serum ANA titers and immunofluorescent nuclear staining patterns among various non-rheumatic diseases; (4) correlate serum ANA titers and immunofluorescent nuclear patterns with the clinical courses of connective tissue diseases. No clinically significant serum ANA titer could be determined either for specific connective tissue diseases or for connective tissue diseases in general, although patients with titers of 1:160 or above more often than not had clinically evident connective-tissue disease. Furthermore, no pattern of nuclear fluorescence proved to be specific for any given clinical syndrome, with a variety of nuclear fluorescent patterns being observed in specific connective-tissue disorders and other non-rheumatic diseases. Only a few correlations could be made between serum ANA titer, nuclear fluorescent pattern, and the clinical courses of connective-tissue disorders. These correlations occurred most frequently with lupus nephritis.

1. High values for plasma thyrotrophic hormone, which did not correlate with other parameters of thyroid function, were found in patients with abnormally high plasma immunoglobulin concentrations. 2. Results indicate that human IgG interferes with the post-precipitation double-antibody radioimmunoassay of thyrotrophic hormone. It is possible that this interference occurs with similar radioimmunoassays of other substances.

One normal donor has been found whose red blood cells type as I positive with all anti-I sera except those obtained from patients with chronic cold hemagglutinin disease (CCHD). In addition, these cells had more H than other random O cells and may be devoid of i antigen. Complete absorption of non-CCHD anti-I with the unusual cells left an anti-I reactive with other I positive cells. These unique cells have allowed definition of at least two separate I determinants present on adult cells.

Steatorrhea associated with advanced cirrhosis of the liver was studied by means of the I131-labeled oleic acid absorption test. The validity of the use of this test as a measure of fat absorption by the small intestine was reviewed. Malabsorption of oleic acid was demonstrated in each of the 6 cirrhotic patients examined. The impaired absorption of oleic acid was attributed to pathologic changes in the mucosa of the small intestine secondary to portal hypertension. The clinical implications of this finding were discussed. The possibility that a protein-losing enteropathy might contribute to the hypoalbuminemia of advanced cirrhosis was investigated by means of intravenously administered I131-labeled polyvinylpyrrolidone and I131-labeled serum albumin. However, no significant loss of protein through the gastrointestinal tract was demonstrated in the 4 cirrhotic patients examined for this condition.

Two cases of Menetrier's disease with occult gastrointestinal albumin loss, absence of free hydrochloric acid, and increased uropepsinogen excretion are presented. The absence of free hydrochloric acid is explained by the combination of edema and inflammatory reaction interfering with passage of the hydrochloric acid into the gastric cavity and its neutralization by the increased amount of albumin exuded into the stomach. The decrease in gastric pepsinogen secretion associated with an increased uropepsinogen excretion is probably due to a derangement of the normal exocrine-endocrine partition.

In 101 subjectively healthy persons, who at a routine health examination were found to be markedly hyperlipidaemic, the erythrocyte sedimentation rate (E.S.R.) was significantly raised. The E.S.R. was raised above 25 mm/hr in 44, 64, and 23% respectively of subjects with type II A, II B, and IV hyperlipoproteinaemia in comparison to only 6% in sex- and age-matched normolipidaemic controls.Several explanations for this E.S.R. elevation have been studied. The levels of plasma lipoproteins do not appear themselves to influence the E.S.R., as among other things there was no difference in plasma concentrations of cholesterol and triglycerides in hyperlipidaemic persons with high and low E.S.R. The concentration of lysolecithin, which may decrease the E.S.R. was the same in the hyperlipidaemic persons with high E.S.R. as in those with low. However, the incidence of ischaemic exercise E.C.G. changes was 38% in the hyperlipidaemic subjects with E.S.R. below 24 mm/hr and 72% in those with E.S.R. above 25 mm/hr. For the time being one possible reason for the raised E.S.R. thus seems to be that the hyperlipidaemia causes silent vascular disease that in its turn produces the E.S.R. elevations.

Net triglyceride transfer was studied between isolated human very low density and low density lipoprotein, as well as very low density and high density lipoprotein, at their usual plasma concentrations in separate in vitro incubations. No transfer of triglyceride was observed for either the low or high density lipoprotein incubations at 4°. At 37° triglyceride transfer was seen with high density, but not with low density lipoprotein. The transfer of very low density triglyceride to high density lipoprotein was unaffected by changes of buffer pH or ionic strength. Increased transfer was observed by both increasing the incubated concentrations of donor very low density lipoprotein or receptor high density lipoprotein.

A simple vertical polyacrylamide gel electrophoresis method to separate α1-antitrypsin and orosomucoid from other plasma proteins is described. This technique may be useful to screen populations with emphysema for α1-antitrypsin deficiency, to isolate orosomucoid, and to detect genetic variants of these two plasma proteins.