Kidney involvement and renal manifestations in non-Hodgkin's lymphoma and lymphocytic leukemia: a retrospective study in 700 patients.

Renal involvement as part of systemic lymphoma (LY) is quite frequent, however, primary extranodal renal non-Hodgkin's lymphoma (NHL) is extremely rare, and only about 65 cases have been reported in the world literature. In a retrospective study of renal manifestations in 700 patients with documented LY and chronic lymphocytic leukemia (CLL) seen at our hospital during 1986-95, 83 patients had signs of acute renal failure. Only five of these had proven renal infiltration, but none of them satisfied the criteria for primary renal LY. Glomerulonephritis (GN) has also rarely been reported in association with LY and CLL, and only 37 glomerular lesions in NHL and 42 in CLL have been documented, respectively. GN may precede, coexist, or follow the diagnosis of LY by several years. Of the 42 cases of CLL reported worldwide, 36 had nephrotic syndrome. Renal failure was seen in about one third. The most common glomerular lesion reported is membranoproliferative GN, followed by membranous GN. In our study, we found only five biopsy-proven cases with GN amongst the 700 patients seen. In this report we also briefly describe some rare interesting associated renal syndromes in CLL and NHL.

Immunotactoid glomerulopathy with massive bone marrow deposits in a patient with IgM kappa monoclonal gammopathy and hypocomplementemia.

A case of immunotactoid glomerulopathy with an amyloid-like material in the glomeruli and bone marrow is described. Clinically the patient was diagnosed as having severe nephrotic syndrome, hypocomplementemia, and IgM kappa monoclonal gammopathy. Immunotactoid glomerulopathy is an unusual cause of glomerulonephritis, characterized by Congo red-negative, amyloid-like deposits in the glomeruli. This unusual case presentation shows that immunotactoid glomerulopathy may be a manifestation of systemic disease. This patient also presented with hypocomplementemia, an extremely rare associated finding that has been reported previously in only four cases of immunotactoid glomerulopathy.

Side effects of ovarian hyperstimulation: hormonal and lipid profile changes.

OBJECTIVE: Ovarian hyperstimulation is associated with a significant increase in ovarian steroid hormone production. Since such high levels of sex steroids may influence the activity of other endocrine glands, as well as affecting lipid metabolism, we studied the effect of ovarian hyperstimulation on the hormonal and lipid profile. STUDY DESIGN: In ten patients who were treated with human menopausal gonadotropins (hMG) for in vitro fertilization (IVF), the serum levels of dehydroepiandrosterone (DHEA), 17-hydroxyprogesterone, insulin, cortisol, growth hormone, thyroid-stimulating hormone, and prolactin, as well as total cholesterol, low-density-lipoprotein cholesterol (LDL-C), high-density-lipoprotein cholesterol (HDL-C), triglycerides, and free fatty acids were monitored. These were correlated with estradiol and free and total testosterone levels. RESULTS: Increased estradiol and free testosterone levels were associated with an increase in DHEA concentration. A correlation was found between increased estrogen level and decreased total cholesterol, triglyceride, and LDL-C levels; HDL-C levels remained unchanged. There was a positive correlation between the estradiol levels and free fatty acid elevation. CONCLUSION: Ovarian hyperstimulation induced changes in lipoprotein lipid content. However, the treated women faced no increase in cardiovascular risk, since their lipoprotein lipid levels were not affected.

The effect of desogestrel for hormone replacement therapy on the blood lipid profiles of postmenopausal women.

OBJECTIVE: To determine the effect of a hormone replacement protocol containing conjugated equine estrogens and desogestrel (which has a highly selective progestogenic and low androgenic effect) as the progestogen, on the plasma lipid profile, as compared with two other hormone replacement treatments (HRT). METHOD: Eighty-nine healthy postmenopausal women were divided prospectively into four groups. A control group of 24 women did not receive HRT. Twenty-nine women received conjugated equine estrogen and medroxyprogesterone, and 13 women received a protocol containing estradiol, estriol and norethisterone acetate. Fasting blood lipid was taken at the end of each third cycle. The cumulative therapeutic response was calculated in each group as compared with initial values and between groups. Significance was analyzed by t-tests. RESULTS: A protocol containing desogestrel significantly decreased low-density lipoprotein cholesterol (27%; P < 0.05) and increased high-density lipoprotein cholesterol (HDL-C) by 30% (P < 0.05%) after 9 months. The ratio of total cholesterol to HDL-C also decreased significantly (44%; P < 0.05). CONCLUSION: The most beneficial effect on plasma lipid profile was obtained with an HRT protocol containing desogestrel as the progesterone.

The effects of two fixed hormonal replacement therapy protocols on blood lipid profile.

Hormonal Replacement Therapy (HRT) is known to be accompanied by changes in blood lipid profile. The present prospective cohort study compared the blood lipid profile of healthy postmenopausal women treated with either (a) a preparation containing a fixed regimen of estradiol, estriol and norethisterone acetate (EENA, marketed under the trade name Trisequens); (b) a fixed protocol of conjugated equine estrogen and medroxyprogesterone acetate (CEEMPA, marketed under the trade name Premaril Plus); or with (c) a concurrent group which underwent no treatment. Blood lipid profiles (total cholesterol (TC), low-density lipoprotein-cholesterol (LDL-C), high-density lipoprotein-cholesterol (HDL-C), and triglycerides (TG)) were performed at the beginning of the study and at 3-month intervals, for 9 months. The EENA-treated women showed a significant and profound decrease in TC and LDL-C when compared with their initial values, with the control group, and with the CEEMPA group. The CEEMPA group showed an increase in HDL-C values and a decrease in LDL-C values when compared with their initial values and with the control group, but no increase was shown when compared with an EENA group. There was a favorable decrease in the TC/HDL-C and LDL-C/HDL-C ratios in both treatment protocols. As the primary goal of prevention of coronary artery disease is total cholesterol reduction, the EENA protocol seems to be preferred.

Correlation between serum lipids and stroke in an Israeli population.

The role of blood lipids as a risk factor for cerebrovascular disease remains uncertain. In the present prospective study, 202 patients admitted with stroke to a community hospital in Jerusalem were evaluated. All patients had a full clinical and neurological evaluation, and a risk factor analysis. The study protocol included routine blood evaluation, fasting blood lipid analysis, brain imaging, 2D echocardiography and carotid Doppler ultrasonography. Stroke risk factors were correlated to stroke types as defined by the modified NINCDS Stroke Data Bank Criteria. Lacunar and atherosclerotic ischaemic infarctions were the most frequent type of stroke in both sexes. Lipid values were in general lower in males than in females. Comparison of stroke patients to age and sex matched controls disclosed lower LDL-C values in male and female patients (p less than 0.001), and lower cholesterol levels in women with strokes than in control subjects (p less than 0.001). Our study corroborates previously reported risk factors for stroke: hypertension (major risk factor in both sexes), smoking (more prevalent in males) and diabetes (more frequent in females).

Regional specificities of monoclonal anti-human apolipoprotein B antibodies.

The usefulness of monoclonal antibodies as probes of protein structure is directly related to knowledge of the structures and locations of the epitopes with which they interact. In this report we provide a detailed map of 13 epitopes on apoB-100 defined by our anti-apoB monoclonal antibodies based on current information on the amino acid sequence of apoB-100. To localize antibody specificities to smaller regions along the linear sequence of the apoB-100 molecule we used a) thrombin- and kallikrein-generated fragments of apoB-100; b) beta-galactosidase- apoB fusion proteins; c) heparin; and d) antibody versus antibody competition experiments. Most of the monoclonal antibodies elicited by immunization with LDL were directed towards epitopes within the first 1279 amino terminal (T4/K2 fragments) or last 1292 carboxyl terminal amino acid residues (T2/K4 fragments) of apoB-100. One epitope localized to the mid-portion of apoB-100 was elicited by immunization with VLDL (D7.2). Saturating amounts of heparin bound to LDL did not inhibit the binding of any of the monoclonal antibodies to their respective epitopes on apoB-100, indicating that none of the antibody determinants is situated close to any of the reported heparin binding sites on LDL apoB. We examined the expression of apoB epitopes on VLDL subfractions and LDL isolated from a normolipidemic donor. The apparent affinities with which the antibodies interacted with their respective epitopes on the VLDL subfractions and LDL uniformly increased as follows: LDL greater than VLDL3 greater than VLDL2 greater than VLDL1, suggesting that each of the major regions of apoB-100 is progressively more exposed as normal VLDL particles become smaller in size and epitopes are most exposed in LDL. Previous experiments utilizing hypertriglyceridemic VLDL subfractions yielded similar results, but the rank order of VLDL subfractions and LDL was not the same for all antibodies tested. Thus, differences in apoB epitope expression on VLDL particles of differing sizes is a general phenomenon, but the expression of apoB epitopes in hypertriglyceridemic VLDL appears to be more heterogeneous than is the case for VLDL from normolipidemic donors.(ABSTRACT TRUNCATED AT 400 WORDS)

Lipolysis of LDL with phospholipase A2 alters the expression of selected apoB-100 epitopes and the interaction of LDL with cells.

To assess the effects of perturbing the surface of low density lipoprotein (LDL) on the conformation of apoB-100, LDL (d 1.030-1.050 g/ml) isolated from normal subjects were treated with phospholipase A2 (PL-A2) for 0.5 to 15 min. The resulting P-LDL and concurrent control LDL (C-LDL) incubated without PL-A2 were isolated by gel permeation chromatography. Approximately 50% of LDL-phosphatidylcholine was hydrolyzed in 2 min and approximately 85% in 5 min. Lysophosphatidylcholine compounds (LPC) and free fatty acids (FFA) accumulated during lipolysis but most of the LPC and all of FFA could be removed by adding FFA-free albumin to the lipolysis mixtures. Immunoreactivities of P-LDL and C-LDL were evaluated in competitive radioimmunoassays, using a library of anti-human LDL monoclonal antibodies directed against the major regions of apoB-100 (the T4, T3, and T2 thrombin fragments). One epitope defined by monoclonal antibody 465B6C3 and localized near the carboxyl end of the apoB-100 molecule became less immunoreactive (ED 50s increased); three other epitopes on the T2 fragment near the LDL receptor recognition site and four epitopes localized towards the middle (T3) and amino terminal (T4) regions did not change. Altered immunoreactivities were not related to LPC and FFA contents. Thus, the conformation of apoB-100 was selectively altered by phospholipolysis. The interactions of P-LDL with cultured fibroblasts were grossly altered: P-LDL were bound nonspecifically to fibroblasts of both normal and homozygous familial hypercholesterolemic subjects and P-LDL were not degraded. LPC and FFA retained in LDL did not explain these alterations, nor did changes of epitope expression near the LDL receptor recognition site. It is likely that the apoB-100 aberrant cell interaction is due to loss of surface phospholipids and "uncovering" of core lipids that react nonspecifically with cell surface components.

Abnormal regulation of LDL receptor activity and abnormal cellular metabolism of hypertriglyceridaemic low density lipoprotein: normalization with bezafibrate therapy.

The regulation of LDL (B,E) receptor activity and of cellular LDL protein metabolism by hypertriglyceridaemic (HTG) low density lipoprotein before and during hypolipidaemic therapy (with bezafibrate (BZ] were determined in cultured human skin fibroblasts. Defective binding and subnormal capacity to regulate LDL receptor activity was found for HTG-LDL. Binding affinity (Kd) of HTG-LDL to the receptor was 4.97 x 10(-8) M and of N-LDL, 1.74 x 10(-8) M. When assayed with normal 125I-LDL, the capacity of HTG-LDL to down-regulate receptor activity was 46-68% less than N-LDL. Both abnormalities reverted towards normal during treatment. The cellular metabolism of HTG-, BZ- and N-LDL in cells grown for 48 h with the respective lipoproteins was determined. In spite of their defective binding to the receptor, the metabolism of HTG-LDL in the regulated cells was accelerated in comparison to N-LDL, and equal to that of BZ-LDL. That observation is explained by the inefficient ability of HTG-LDL to depress LDL receptor activities in the cells.

Thymoma presenting as a superior vena cava syndrome remission following therapy.

A 45-year-old male developed myasthenia gravis 8 years ago. He received prednisone for 3 years, and resumed complete clinical remission. Five years later, he was admitted with obstruction of the superior vena cava. Invasive thymoma was diagnosed by chest X-ray and an open lung biopsy. Radiation followed by combination chemotherapy with cyclophosphamide, vincristine, and prednisone induced a complete remission. The patient remained disease-free for more than 20 months after the first admission to our department. To the best of our knowledge, superior vena cava syndrome as the presenting symptom of thymoma has never been reported previously.

Surgical priorities of abdominal wounded in a combat situation.

It is well established that abdominal wounded should be operated on as soon as possible. Combat conditions or mass casualty situations may dictate a delay in surgery because of higher priorities or lack of surgical facilities. A review of 178 abdominal wounded treated in an evacuation hospital during the 1973 and 1982 Israeli wars evaluates the effects of delay on mortality and complications. Surgery on 141 of the 178 abdominal casualties was delayed from 8 to 17 hours from the time of their injury. They were well supported hemodynamically along the chain of evacuation and none died en route. Mortality for the delay group was 5% and for the entire group 7.9%, which compares favorably with the 8.5% mortality during the latter part of the Vietnam War. Abdominal casualties who can tolerate delay in surgery are those who respond rapidly to vigorous volume replacement and remain stable with the aid of conventional supportive treatment.

Hypolipidemic therapy modulates expression of apolipoprotein B epitopes on low density lipoproteins. Studies in mild to moderate hypertriglyceridemic patients.

Low density lipoproteins (LDL) of untreated moderate to severe hypertriglyceridemic patients (HTG-LDL) are smaller in size and are relatively enriched in triglycerides and proteins compared with normal LDL (N-LDL). HTG-LDL also manifest defective binding to the LDL receptors of normal cultured human fibroblasts. These structural and functional defects are reversible by effective hypolipidemic therapy. The aims of the present study were to confirm the reversibility of the structural and functional defects in mild to moderate hypertriglyceridemic patients and also to test the hypothesis that therapy improved the binding of HTG-LDL to cells by modulating epitopes of apolipoprotein B (apoB-100) on the surfaces of LDL particles. Fasting plasma samples were obtained from five mild to moderate hypertriglyceridemic patients before and 3 weeks after bezafibrate therapy when mean triglyceride levels were 436 and 157 mg/dl (P less than 0.01), respectively. LDL particles were isolated by zonal ultracentrifugation, characterized chemically, and assayed for cell association and proteolytic degradation in-up regulated normal human skin fibroblasts. LDL immunoreactivity was tested in solid phase competitive binding radioimmunoassays (RIA) using three monoclonal antiLDL antibodies (Mab). Mab 464B1B3 and Mab 465B6C3 react against epitopes in the COOH-terminal (T2/K4) fragment of apoB-100. Mab D7.1 reacts with an epitope in the midportion (T3/K3) fragment. Mab 464B1B3 inhibits the binding of LDL to the LDL receptor. Hypolipidemic treatment altered the composition of LDL. Mean LDL triglycerides fell from 9.4 to 5.8% of LDL mass (P less than 0.025).(ABSTRACT TRUNCATED AT 250 WORDS)

Bulimia. An underlying behavioral disorder in hyperlipidemic pancreatitis: a prospective multidisciplinary approach.

Between 1978 and 1985, we conducted a prospective study of 21 patients who survived several attacks of pancreatitis and were diagnosed as having primary hyperlipidemia. None of the patients suffered from chronic alcoholism, primary diabetes, or cholelithiasis or was receiving prolonged steroid therapy. Lowering of plasma lipid values toward normal was achieved in all patients following a program of combined dietary and drug (bezafibrate) therapy. Five patients had recurrent episodes of pancreatitis during the treatment program. These patients were diagnosed subsequently as suffering from bulimia and were all given cognitive behavioral therapy. One patient died following an attack of pancreatitis. An underlying eating disorder should be suspected in patients who relapse after treatment for pancreatitis and hyperlipidemia. Multidisciplinary treatment should be used in these patients to improve therapeutic efficacy and uncover behavioral patterns that have a direct impact on their life expectancy.