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A patient with chronic myelocytic leukaemia (CML) and a new complex Philadelphia chromosome (Ph') translocation, t (10; 14; 22), is described. This three way Ph' translocation not involving chromosome 9 was present in the majority of the bone marrow cells, as well as in a great proportion of metaphases from phytohaemagglutinin (PHA) stimulated peripheral blood cultures. The possibility that the Ph' translocation was present also in lymphocytes is discussed and at this regard the involvement of chromosome 14 is of interest considering the documented non random involvement of chromosome 14 in lymphoid malignancies.

A patient with clinical and haematological findings compatible with congenital dyserythropoietic anaemia (CDA) most porbably type II is described. In contradistinction to previous observations, electron microscope examination of the erythroid cells in the bone marrow showed the concomitant appearance of nuclei at different maturation stages in a single cell. In addition, a marked tendency toward multinuclearity of the megakaryocytes was found. The mature erythroblasts showed an increased uptake of 3H-thymidine less than is normally found in these cells. Thes findings suggest an impairment in RNA and DNA synthesis.

The case of a 40-year-old patient with congenital trisomy 8 and sex chromosome mosaicism is discussed. The main clinical features were: mental retardation, thick and darkly pigmented skin, prominent forehead, convergent strabismus, high arched palate, flexion contractures of the extremities, and numerous skeletal abnormalities. The patient developed severe aplastic anemia followed by an interim period of preleukemia which developed into acute leukemia. Electron microscope examination of the white blood cells at the stage of the aplastic anemia showed ultrastructural abnormalities similar to those observed in other genetic disorders with a predisposition to leukemia, as well as in leukemia.

A 56-yr-old woman with acute lymphocytic leukemia showed the presence of a Philadelphia chromosome in 90% of the bone marrow metaphases and in 10% of the peripheral blood metaphases. Part of the long arm of a G22 chromsome was translocated to the long arm of a C9 chromosome. A second cytogenetic abnormality was found in chromosome 7. Monosomy 7 was found in 60% of the marrow and in 20% of the peripheral blood metaphases. Chromosome 7q- was also found in a small percentage of the metaphases examined. Three months later, when the patient was in partial remission, only 10% of the marrow cells showed chromosome 7 monosomy and a Ph1 chromosome. During complete remission, no chromosomal abnormalities were found, except for a high breakage rate. The finding of a Ph1 chromosome in acute lymphocytic leukemia indicates that different precursors, both granulocytic and lymphocytic, may be involved in the Ph1 process.

The effect of 30% Urografin on platelet aggregation induced by adenosine diphosphate (ADP), epinephrine, and arachidonic acid was examined. In vivo and in vitro experiments in 10 nondiabetic subjects and in vitro experiments in 7 diabetic-uremic patients showed a statistically significant decrease in platelet aggregation 20 minutes after in vitro incubation or in vivo infusion with Urografin. Urografin concentration was about 2.4-2.5%. The possibility of bleeding induced by contrast media and the connection with acute renal failure in diabetic-uremic patients are discussed.

Parathyroid hormone (PTH) is elevated in patients with chronic renal failure (CRF) and was suggested to be one of the factors responsible for the anemic syndrome of these patients because it raises the osmotic fragility of the red blood cells (RBC). In the present study, the youngest and oldest RBC were separated from circulating erythrocytes by high-speed centrifugation. The age distribution was described, and the effect of PTH on the different age groups was investigated. Median density (MD) and glutamic-oxaloacetic transaminase (GOT) activity were chosen as age markers. MD (1.0985 +/- 0.00087) and GOT activity (12.49 +/- 2.083 IU/g Hb) of the young uremic cells did not differ significantly from the values of young normal cells (1.0987 +/- 0.00046 and 10.36 +/- 1.174 IU/g Hb, respectively). The MD of the oldest cells, however, was lower (1.1048 +/- 0.00054) and GOT was higher (6.60 +/- 1.1019 IU/g Hb) in the uremic than in the control cells (1.1093 +/- 0.00175 and 3.77 +/- 0.233 IU/g Hb, respectively). These results indicate that the life span of RBC in uremics is shorter than normal and that an enrichment of circulating RBC by young cells occurs in uremic patients. The median osmotic fragility (MOF) of the young cells was lower in both uremic (0.376 +/- 0.006) and control patients (0.378 +/- 0.003) than the MOF of old cells (0.402 +/- 0.005 and 0.392 +/- 0.004, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

A case of a 50-year-old patient suffering from secondary amyloidosis presenting with amyloid goiter is described. The diagnostic and therapeutic implications are reviewed.

Examination of the bone marrow of a 63-year-old man who had acute lymphoblastic leukemia revealed a population of cells with 32 chromosomes and another population with 64 chromosomes, the karyotypical exact duplicate of the first clone. The karyotypic evolution was studied and the findings compared with those described in two similar cases previously reported. It is postulated that severe hypodiploidy is associated with reduced capability of cellular survival, promoting a strong tendency for duplication.

Two cases of hypercalcemia associated with transitional cell carcinoma and negative bone scan are described. In both cases hypercalcemia appeared while there was evidence of tumor spread. Although hypercalcemia was controlled, both patients died shortly thereafter. Hypercalcemia rarely occurs in transitional cell carcinoma and its appearance may suggest spreading of the tumor and poor prognosis.

A Jewish Iraqi woman with familial isolated renal tubular uricosuria, urate clearance of 60.5 +/- 5.7 ml/min and hypouricemia of 1.0 +/- 0.2 mg/dl is described. The combined pyrazinamide-probenecid test suggested a presecretory defect in urate reabsorption. Four offspring were moderately affected. This family represents the sixth Jewish Iraqi family with familial isolated presecretory uricosuria, and emphasizes the marked prevalence of this disease among the Iraqi Jewish population. Since the inheritance of the presecretory defect is autosomal recessive, we suggest that this family is an example of pseudodominant transmission. The combined pyrazinamide-probenecid test may cause a reduction in glomerular filtration rate and filtered load of urate and thereby affect urinary excretion rate of urate in patients with urate wasting.

Six of 102 patients with end-stage renal disease (ESRD) who underwent hemodialysis treatment from 1972 to 1980 developed active tuberculosis (TB). Three of six patients were Yemenite Jews, an ethnic group constituting only 10.8% of the dialysis population; thus, Yemenite Jews appear to be especially at risk among Israeli dialysis patients. Fever of unknown origin was the most frequent presenting symptom. In four patients, previous TB of the lungs was documented. These data support the view of reactivation of dormant TB as the main pathogenetic pathway for the development of the active disease. Two patients died, whereas four recovered on triple therapy with isoniazid, rifampicin and ethambutol.

The effect of metabolic acidosis on the intestinal absorption of calcium (Ca) and phosphorus (P), plasma vitamin D metabolites and urinary excretion of Ca in adult rats treated with a small dose of 1,25(OH)2D3 were investigated. The rats in the experimental group received 1.8% ammonium chloride (NH4Cl) and a commercial chow, and their pair-fed controls received 0.45% NaCl. Both groups were given subcutaneously 1,25(OH)2D3. Intestinal absorption of Ca and P was measured by gut sac uptake of 45Ca and 32P. In the acidotic rats, duodenal, jejunal and ileal 45Ca uptake as well as jejunal and ileal 32P uptake were significantly increased. Plasma 1,25(OH)2D, 25(OH)D and 24,25(OH)2D were similar in both groups. 1,25(OH)2D3 treatment induced a greater calciuria in acidotic rats and increased their fractional excretion (FE) of Ca. An additional experiment showed increased 45Ca uptake by duodenum at a pH of 7.0 compared to pH 7.4. The present study suggests that NH4Cl-induced metabolic acidosis may enhance the effect of 1,25(OH)2D3 on intestinal absorption of Ca and P in the rat. However, the data from the study cannot exclude the possibility that acidosis may have a direct, vitamin D-independent effect on the intestine.

A liver biopsy specimen from a patient with intrahepatic cholestatic jaundice had marked dilation of the bile capillaries, disappearance of the microvilli, and thickened ectoplasm. The unusual finding was a great increase in the number of Kupffer cells that contained masses of electron-dense material, most probably bile. A second examination of the liver, performed one month later when the liver test results had returned to normal, showed only remnants of the Kupffer cells. We report the possible role of the Kupffer cells in the clearance of the blood from the bile pigments.

Epidemiological studies suggest an association between reduced calcium uptake and hypertension, while clinical trials and rat experiments indicate a small but significant hypotensive effect with oral calcium supplements. These data imply that calcium deficiency has a role in genetic hypertension. We reasoned that if the hypothesis is correct, the hypertension should be aggravated by further reducing calcium balance but attenuated by augmenting calcium balance. We tested this hypothesis by evaluating the blood pressure response in spontaneously hypertensive rats (SHR) as calcium balance was decreased by dietary restriction of calcium or increased by supplementation with magnesium or 1 alpha, 25-dihydroxycholecalciferol (calcitriol). A low calcium diet within the physiological range did not accentuate the hypertension in SHR during the 11 weeks of treatment, even though calcium balance was reduced by half. Similar results were obtained with dietary calcium restriction in parathyroidectomized SHR, which excludes any offsetting effects of changes in parathyroid hormone levels. Conversely, 7 weeks of a high magnesium diet, which increased calcium balance without reducing PO4 balance, did not correct the hypertension of SHR. Similarly, long-term administration of calcitriol failed to reduce the blood pressure of parathyroidectomized SHR and normotensive Wistar-Kyoto (WKY) controls, despite the presence of increased serum calcium levels comparable to those produced by oral calcium loading. Finally, external calcium balance was measured directly in 25-day-old, prehypertensive SHR. As a result of the increased calcium absorption and reduced calcium excretion, SHR retained more calcium than did the normotensive WKY, which directly refutes the existence of calcium deficiency at this normotensive stage. These data do not support the role of calcium deficiency in genetic hypertension.

Brainstem auditory evoked responses (BAER) were recorded in patients with chronic renal failure before commencement of chronic dialysis treatment, and in patients with end-stage renal failure on chronic hemodialysis for several years. Both groups of patients had delayed latencies of the third and fifth waves. The patients on hemodialysis revealed delayed latency of interpeak I-V as well. There was no correlation between wave latency, serum urea, creatinine, PTH or duration of chronic hemodialysis treatment. A hemodialysis session led to a slight shortening of the third wave. This study suggests that neural conduction along the brainstem in patients with chronic renal failure is delayed even before hemodialysis is started. Although 1 dialysis session may have some beneficial effect, long-term hemodialysis treatment does not seem to shorten the delay in neural conduction observed in patients with chronic renal failure.

Heart studies were carried out in 7 patients with end-stage renal disease (ESRD) who underwent parathyroidectomy for secondary hyperparathyroidism. The studies, which included echocardiography and equilibrium radionuclide angiography (ERNA), were performed prior to parathyroidectomy and 2 weeks, 3 months, and 6 months following it, on a nondialytic day. Heart rate decreased from 89.3 +/- 1.3 to 81.4 +/- 1.5 min-1 (p less than 0.001) following parathyroidectomy and returned to the initial level at 3- and 6-month examination. Cardiac output decreased from 3170 +/- 68 to 2943 +/- 57 ml/min (p less than 0.01) following parathyroidectomy and returned to basal level on 3 and 6-month determinations. End-diastolic dimension (EDD), end-systolic dimension (ESD), septal and posterior wall thickness and shortening fraction (SF) as measured by echocardiography were normal prior to parathyroidectomy and remained unchanged following it. Left ventricular ejection fraction (LVEF), end-diastolic and end-systolic volumes measured by ERNA did not change following parathyroidectomy. This study suggests that hyperparathyroidism has little effect on cardiac performance and, except for a short-lived decrease in heart rate and cardiac output, parathyroidectomy does not affect cardiac performance when performed in patients with preoperatively normal cardiac output.

Calcium absorption in spontaneously hypertensive rats (SHR) has been reported to be increased, decreased or not different from their normotensive Wistar Kyoto (WKy) control. One postulated reason for these conflicting results is an abnormal sensitivity to the intestinal effects of 1,25(OH)2D3 (1,25D3). Previous studies in everted duodenal sacs and perfused duodenum examined the acute response to 1,25D3 only in 12-week-old SHR, which however already had higher basal rates of calcium absorption. Inability to stimulate Ca absorption further was an unexcluded possibility. To test this hypothesis more vigorously, balance and in situ duodenal 45Ca uptake studies were performed in SHR and WKy using four separate protocols yielding the following results. First, in response to pharmacological doses of 1,25D3 (25 ng/100 g body wt/day X 3), four-week-old normotensive female SHR had higher net calcium absorption (41.4 vs. 31.1 mg/day; 61.6 vs. 48.1%), similar to the increases seen in the untreated state. These results suggest intrinsic epithelial differences independent of 1,25D3. Ca absorption was similarly higher in 1,25D3 treated male SHR (42.9 vs. 36.7 mg/day; 60.1 vs. 53.7%). Second, at 12 to 14 weeks of age, low doses of 1,25D3 (8 ng/100 g body wt/day X 6) stimulated net Ca absorption in the female SHR (33.0 to 39.1 mg/day), but not in WKy (26.8 to 29.3 mg/day). In the male, positive effects were again seen only in the SHR (25 to 45 mg/day). Third, in response to three weeks of dietary Ca deprivation, in situ duodenal 45Ca uptake, measured in the conscious awake state, was higher in 35-week-old SHR (70.9 vs. 53.0%).(ABSTRACT TRUNCATED AT 250 WORDS)

Electron microscope examination of the liver biopsies of 33 patients revealed the presence of intramitochondrial crystalline inclusions (IMCI) in ten of them. Three patients suffered from iron deficiency anemia, porphyria, and malignant melanoma, conditions not reported to be associated with IMCI. Comparison of the clinical and laboratory findings of patients with and without IMCI did not show significant difference, or a clue for clarifying the nature of this phenomenon. Although these inclusions were reported in normal individuals, the possibility that they are the result of liver damage is not excluded.

The ultrastructural findings in a muscle biopsy of a patient with Cushing's disease associated with severe myopathy are described. They included pronounced mitochondrial damage, thickening and deep invaginations of the sarcolemmal basement membrane, and thickening of the basement membrane of the capillaries. In addition, the muscle fibers showed a marked degree of disarray and wide interfibrillar spaces, containing large numbers of vacuoles, which presented degenerated mitochondria. The similarity between these findings and the ultrastructural features of corticosteroid-induced myopathy is discussed.

Two adult women with idiopathic acute interstitial nephritis (AIN) whose presenting symptom was anterior uveitis are described. On histologic examination of the renal biopsy, eosinophilic infiltrates and mononuclear cells were found. Immunofluorescence was negative. Immunological evaluation showed a slight decrease in the number of T cells with a normal subpopulation ratio. AIN responded to steroid treatment.

Previous studies have demonstrated that hypoxemia does not occur during isolated ultrafiltration, but does occur during diffusion dialysis with acetate, whether it is performed alone or following a period of isolated ultrafiltration. To determine if the substitution of bicarbonate for acetate in dialyzate could prevent hypoxemia, we studied the effect of sequential isolated ultrafiltration-diffusion dialysis with bicarbonate on arterial oxygen concentration. There was no significant change in pO2 during isolated ultrafiltration or the subsequent period of diffusion dialysis. In addition, excess body fluid could be removed and effective dialysis achieved without marked tachycardia or fluctuation in blood pressure. We conclude that sequential isolated ultrafiltration diffusion dialysis with bicarbonate is a safe and effective way of dialyzing patients without producing hypoxemia or cardiovascular instability.

Low cell calcium level is essential for preservation of red blood cell (RBC) membrane deformability and survival. RBCs from patients with end-stage renal disease (ESRD) demonstrate reduction in membrane deformability, possibly as a result of increased RBC cellular calcium level. To evaluate calcium homeostasis in RBCs from patients with ESRD, we measured cell calcium level, basal and "calmodulin"-stimulated calcium-stimulated Mg-dependent ATPase (CaATPase) activity, and calcium 45 efflux were measured before and after hemodialysis. The in vitro effect of uremic plasma and of urea on CaATPase activity of normal RBCs was tested, and 45Ca influx into RBCs of patients undergoing hemodialysis also was determined. A morphologic evaluation of red cells from patients with ESRD was performed with a scanning electron microscope. RBC calcium level in patients (mean +/- SEM 21.2 +/- 2.8 mumol/L of cells; n = 28) was higher than in controls (4.9 +/- 0.3 mumol/L of cells; n = 24; p less than 0.001). Hemodialysis had no effect on cell calcium level. Both basal and "calmodulin"-stimulated RBC CaATPase activities in patients with ESRD (n = 9) were reduced by approximately 50% (p less than 0.01), but after hemodialysis, enzyme activity returned to normal. 45Ca efflux from calcium-loaded cells, which was 2574.0 +/- 217.0 mumol/L of cells per 0.5 hours before hemodialysis, increased to 3140.7 +/- 206.8 mumol/L of cells per 0.5 hours after hemodialysis (p less than 0.005). In vitro incubation of normal RBCs with uremic plasma depressed CaATPase activity, but incubation with urea had no effect. RBCs of patients with ESRD revealed increased 45Ca influx, 7.63 +/- 1.15 mumol/L of cells per hour versus 4.61 +/- 0.39 mumol/L of cells per hour (p less than 0.025). RBCs of patients revealed a high incidence of spherocytosis and echynocytosis, which correlated with a high cell calcium level (r = 0.894, p less than 0.01). These results indicate that RBC calcium level is elevated in patients with ESRD and suggest that a dialyzable uremic factor inhibits RBC CaATPase activity and thereby calcium efflux, which may account for the elevated cell calcium level. The increased calcium influx further increases cellular calcium level. These abnormalities are associated with spherocytosis and echynocytosis and may contribute to the shortened survival of RBCs in uremia.

A case of "non-secretory" multiple myeloma is described. The diagnosis was based on the clinical picture, typical radiological findings, and infiltration of the bone marrow by myeloma cells which showed specific immunofluorescence staining mainly with antisera for IgM and kappa light chains. An attempt is made to explain the absence of pathological proteins in the serum, based on the ultrastructural findings of the myeloma cells, which showed "buddings" of the cell membranes containing endoplasmic reticulum and cytoplasmic material. It is suggested that the cells of the "non-secretory" type of multiple myeloma possess a normal excretory mechanism, but the pathological proteins are prevented to be secreted in the serum being surrounded by portions of the cell membrane.