Reversible crescentic glomerulonephritis following an acute exacerbation of chronic relapsing pancreatitis.

A patient had recurrent episodes of acute glomerulonephritis following exacerbations of chronic relapsing pancreatitis. Light microscopy of the renal biopsy performed during the episode of acute glomerulonephritis showed fibroepithelial crescents involving 70% of the glomeruli. The patient recovered without specific therapy. The time interval involved and the presence of subendothelial deposits with mesangial deposition of C3 complement and IgM suggest immune complex injury.

BP changes in obese hypertensive subjects during rapid weight loss. Comparison of restricted v unchanged salt intake.

A controlled prospective study compared two groups of obese hypertensive subjects during 12 weeks of a hypocaloric protein-supplemented fast containing 40 mEq of sodium daily. One group received additional sodium chloride sufficient to maintain baseline sodium intake measured prior to the fast (210 m/Eq/day). Sodium restriction resulted in greater weight loss and slightly greater BP reduction only during the initial week of fasting. Thereafter, despite sodium equilibrium, further substantial weight loss and BP reduction were identical in both groups, the decrement in weight being linear (1.89 kg/wk) and the BP reduction asymptotic. Although the initial reduction in BP during the first week of supplemented fast may be attributable to negative salt and water balance, the further reduction in BP during a period of constant sodium balance must be caused by weight loss per se or by the triggering of other antihypertensive mechanisms associated with weight reduction.

The effect of weight loss on reproductive hormones in obese men.

The effects of weight reduction on reproductive hormones were investigated in 24 moderately obese men, 18-108% above ideal body weight. Serum estrone (E1), estradiol (E2), testosterone (T), percent free T (%FT), sex hormone binding globulin (SHBG) capacity, and, in 9 subjects, androstenedione (A) were measured serially before and during an outpatient supplemented fasting program (320 kcal/day) for 8-20 weeks. In the baseline state mean E1 was elevated to 100 +/- 7 pg/ml (normal, 30-60 pg/ml). The E2 was slightly elevated to 36 +/- 3 pg/ml (normal, 8-35 pg/ml). The mean T of 400 +/- 20 ng/dl was at the lower end of normal (400-1000 ng/dl). The mean %FT was elevated to 4.1 +/- 0.2% (normal 1.6-3%). The calculated free T was normal. The mean SHBG binding capacity was 0.99 +/- 0.05 micrograms dihydrotestosterone bound/dl (normal, 1.0-1.8 micrograms/dl). The mean A of 52 +/- 5.8 ng/dl was normal. These data were in accord with previous findings in much heavier men. Eight weeks of weight loss (mean, 19.5 kg) were associated with normalization of all the measured parameters. The mean E1 decreased to 48 +/- 23 pg/ml, E2 to 28 +/- 2.1 pg/ml. T increased to 536 +/- 35 pg/dl and %FT fell to 3.2 +/- 0.2%. Data on men remaining on the program for 16 or 20 weeks showed a continued fall of estrogens and stabilization of T and %FT. SHBG and A did not change significantly over the entire time period. In conclusion, increased circulating estrogens and reduced androgen binding were found in moderately obese men, which were completely corrected with weight loss.

Role of the sympathetic nervous system in blood pressure maintenance in obesity.

A group of 10 borderline hypertensive obese subjects had higher (P less than 0.05) supine plasma norepinephrine (NE), epinephrine, and PRA levels as well as greater (P less than 0.05) NE responses to upright posture and isometric handgrip exercise than 12 nonobese controls. Plasma NE as well as mean arterial pressure (MAP) responses to posture and handgrip in the obese patients demonstrated a significant decrement at week 2 after the onset of a low calorie diet. Decrements in plasma NE and MAP responses to posture were correlated (r = 0.61; P less than 0.05) throughout an 8-week period of weight loss in these borderline hypertensive obese subjects. In 15 normotensive obese subjects as well as in the 10 borderline hypertensive obese subjects, weight reduction associated with a very low calorie intake was accompanied by a reduction in supine plasma NE, epinephrine, and MAP 2 weeks after the onset of dieting. PRA decreased after 8 weeks of dieting in both obese groups, and these PRA decrements were correlated with reductions in MAP and decrements in plasma NE. We conclude that enhanced sympathetic activity may play a role in the maintenance of elevated blood pressure in obese individuals. Decreases in PRA and blood pressure associated with weight loss in both normotensive and hypertensive obese individuals occurs, in part, secondary to reductions in plasma NE levels.

Effects of weight loss on the dexamethasone suppression test.

The authors studied postdexamethasone cortisol secretion in 18 depression-free, healthy, obese subjects before and after weight loss. Although all subjects suppressed cortisol normally before weight loss, 5 of 18 (27.5%) failed to suppress cortisol after an average loss of 13.5 kg. This failure to suppress cortisol was not associated with any change in depression ratings.

Pomegranate juice consumption reduces oxidative stress, atherogenic modifications to LDL, and platelet aggregation: studies in humans and in atherosclerotic apolipoprotein E-deficient mice.

BACKGROUND: Dietary supplementation with nutrients rich in antioxidants is associated with inhibition of atherogenic modifications to LDL, macrophage foam cell formation, and atherosclerosis. Pomegranates are a source of polyphenols and other antioxidants. OBJECTIVE: We analyzed, in healthy male volunteers and in atherosclerotic apolipoprotein E-deficient (E(0)) mice, the effect of pomegranate juice consumption on lipoprotein oxidation, aggregation, and retention; macrophage atherogenicity; platelet aggregation; and atherosclerosis. DESIGN: Potent antioxidative effects of pomegranate juice against lipid peroxidation in whole plasma and in isolated lipoproteins (HDL and LDL) were assessed in humans and in E(0) mice after pomegranate juice consumption for

Pomegranate juice consumption inhibits serum angiotensin converting enzyme activity and reduces systolic blood pressure.

Consumption of pomegranate juice which is rich in tannins, possess anti-atherosclerotic properties which could be related to its potent anti-oxidative characteristics. As some antioxidants were recently shown to reduce blood pressure, we studied the effect of pomegranate juice consumption (50 ml, 1.5mmol of total polyphenols per day, for 2 weeks) by hypertensive patients on their blood pressure and on serum angiotensin converting enzyme (ACE) activity. A 36% decrement in serum ACE activity and a 5% reduction in systolic blood pressure were noted. Similar dose-dependent inhibitory effect (31%) of pomegranate juice on serum ACE activity was observed also in vitro. As reduction in serum ACE activity, even with no decrement in blood pressure, was previously shown to attenuate atherosclerosis, pomegranate juice can offer a wide protection against cardiovascular diseases which could be related to its inhibitory effect on oxidative stress and on serum ACE activity.

Mechanisms of hypertension in obesity.

We conclude that the following may explain the rise in blood pressure with obesity and the subsequent fall in blood pressure (Fig. 2): (1) An increase in calories, protein, or carbohydrate leads to an increase in plasma catecholamines, sympathetic nervous system activity, and insulin secretion. (2) These factors, in turn, lead to increased renal sodium retention and stimulation of the renin-aldosterone system which, in turn, leads to: (3) An increased cardiac output with an inability to appropriately adjust the peripheral resistance to maintain normotension with resultant hypertension. Conversely, the fall in blood pressure with weight reduction can be explained by (Fig. 3): (1) A decrease in calorie, carbohydrate, or protein intake which leads to: (2) A decrease in circulating plasma catecholamines, sympathetic nervous system activity, and insulin secretion which results in: (3) A natriuresis and decrease in the renin-aldosterone system, which causes a decrease in circulating blood volume and in cardiac output. This, in turn, lowers blood pressure towards normal. The unanswered question still remains: why do some obese patients become hypertensive and others remain normotensive? Perhaps there are weight-sensitive individuals and weight-resistant individuals just as there appear to be salt-sensitive and salt-resistant hypertensive patients. Perhaps the answer is genetic. These questions also remain to be answered.

Pre- and postoperative renal failure.

The acute onset of oliguria and azotemia in the postoperative setting may be caused by pre-renal causes or intrinsic renal damage. The first step in arriving at a diagnosis is to review the history as noted above for clues regarding fluid balance, treatment with nephrotoxins, etc. The typical patient with prerenal azotemia will present with evidence of the recent onset of worsening of pre-existing cardiac disease, renal or gastrointestinal fluid loss, or the accumulation of acites, edema, or retroperitoneal fluid. In the absence of very recent diuretic therapy, he will be excreting a scant amount of concentrated (greater than 400 mOsm per L) sodium free (less than 10 to 20 mEq per L) urine. The serumBUN/Cr ratio is often greater than 15 to 20:1, and their urinary sediment will be bland. In an occasional patient in whom these studies give equivocal results, additional help may be obtained with measurements of central venous pressure (CVP) or pulmonary wedge pressure (PWP) and by noting their response to intravenous fluid loading. A rising CVP or PWP in the face of salt loading is, of course, evidence against prerenal azotemia. Patients with obstructive uropathies may be oligoanuric or polyuric-occasionally a characteristic alternating polyuria and oliguria is found (due to displacement of a stone or relief of edema). When oliguric their urine typically contains substantial amounts of sodium (greater than 20 mEq per L), is isotonic, and their OsmU:OsmP is les s than or equal to 1.2. Their urinary sediment will reflect the cause of their obstruction as noted above. A renal scan, ultrasound study, or infusion IVP are mandatory to rule out the possibility of obstructive uropathy. If these nonivasive studies are equivocal, one must consider doing a unilateral retrograde. The development of ATN usually occurs in the setting of hypotension, sepsis, dehydration, and with exposure to nephrotoxins. Most patients with be excreting scant amounts of isotonic urine containing more than 20 to 30 mEq per L of sodium. Their CrU:CrP is less than or equal to 20:1 and their urinary sediment reveals many epithelial cells and casts. Those patients with nonoliguric ATN have urine outputs which may exceed 2 liters per day. Despite this output they demonstrate a stepwise increase in serum urea and creatinine. Urine sodium and osmolality are not very helpful in this setting. Many such patients do have low (less than 20 mEg per L) urine sodium concentration and excrete isotonic urine.

Dietary restriction on serum thyroid hormone levels.

To determine the long term effects of a protein sparing fast on serum thyroid hormone levels, the authors studied 38 obese patients ingesting a diet of 320 kcal for up to 13 weeks. The high baseline serum triiodothyronine (T3) levels decreased significantly by the first week, further decreased by the third week, and this lower level persisted for the duration of the fast until realimentation. Serum free T3 index followed the same general pattern as did serum T3 levels. Serum reverse T3 increased significantly by the first week, but by week three, the reverse T3 level had begun to fall, although still significantly increased above baseline. By week seven, reverse T3 had decreased to almost baseline and remained not significantly changed from the baseline to 13 weeks. Serum thyroxine (T4) increased significantly by the first week in all patients, but by the third week had returned to baseline levels which persisted to 13 weeks. The free T4 index and free T4 concentrations showed the same increment at week one and then returned to baseline levels. There were no significant changes in serum thyroxine-binding globulin (TBG) or thyroid-stimulating hormone (TSH) concentrations. The changes in serum T3 and reverse T3 levels are attributable to alterations in peripheral 5'-monodeiodination of T4 and reverse T3 induced by the protein sparing fast.

Pomegranate juice flavonoids inhibit low-density lipoprotein oxidation and cardiovascular diseases: studies in atherosclerotic mice and in humans.

The beneficial health effects attributed to the consumption of fruit and vegetables are related, at least in part, to their antioxidant activity. Of special interest is the inverse relationship between the intake of dietary nutrients rich in polyphenols and cardiovascular diseases. This effect is attributed to polyphenols' ability to inhibit low-density lipoprotein (LDL) oxidation, macrophage foam cell formation and atherosclerosis. Pomegranate polyphenols can protect LDL against cell-mediated oxidation via two pathways, including either direct interaction of the polyphenols with the lipoprotein and/or an indirect effect through accumulation of polyphenols in arterial macrophages. Pomegranate polyphenols were shown to reduce the capacity of macrophages to oxidatively modify LDL, due to their interaction with LDL to inhibit its oxidation by scavenging reactive oxygen species and reactive nitrogen species and also due to accumulation of polyphenols in arterial macrophages; hence, the inhibition of macrophage lipid peroxidation and the formation of lipid peroxide-rich macrophages. Furthermore, pomegranate polyphenols increase serum paraoxonase activity, resulting in the hydrolysis of lipid peroxides in oxidized lipoproteins and in atherosclerotic lesions. These antioxidative and antiatherogenic effects of pomegranate polyphenols were demonstrated in vitro, as well as in vivo in humans and in atherosclerotic apolipoprotein E deficient mice. Dietary supplementation of polyphenol-rich pomegranate juice to atherosclerotic mice significantly inhibited the development of atherosclerotic lesions and this may be attributed to the protection of LDL against oxidation.

Immunologic considerations in renovascular hypertension.

For decades certain diseases, such as glomerulonephritis, polyarteritis nodosa, scleroderma and serum sickness, have been linked with autoimmune pathogenesis. During recent years a host of additional diseases traditionally thought to have some genetic predisposition but with obscure etiology have been suspected of being autoimmune in nature. Rheumatoid arthritis, diabetes, myasthenia gravis and thyroiditis are diseases of widely divergent organ systems, yet may well have common pathways of pathology via immune complexing mechanisms. Herein we present evidence supporting the concept that renal artery stenosis (occurring primarily in association with the middle aortic syndrome or after renal transplantation) is of immune etiology. Although the specific antigenic agent is still to be defined there is growing acceptance of the theory that medium and large vessels are subject to autoimmune vasculitis in many aspects similar to the autoimmune affections of small vessels. Several cases are presented. Some of these suggest an immune reaction by the natural history but without evidence of immunochemical reactants in the involved vessels, presumably because active disease was arrested at the time of study. In other cases immunofluorescent preparations demonstrate reactants in the walls of the vessels to document the hypothesis more convincingly.

Recurrent renovascular hypertension. Report of an unusual case.

A 7-year-old girl with histologically proved fibromuscular dysplasia underwent renal autotransplantation with prompt return of the blood pressure to normal. Two months later, immediately after tonsillectomy, severe hypertension recurred with marked narrowing of the previously patent anastomosis. After 4 weeks on antihypertensive therapy, the patient became normotensive again and remained so for 18 months, with marked widening of the anastomosis. It is possible that this complication might be explained on an immunologic basis.

Solitary intraparenchymal pulmonary plasmacytoma associated with production of an M-protein: report of a case.

A case of a 40-year old man who underwent surgical extirpation of a solitary intraparenchymal pulmonary plasmacytoma is reported. To our knowledge, this is the first reported case associated with the production of an M-protien. The production of protein fell dramatically following removal of the tumor.

Hydralazine therapy in hypertensive patients with idiopathic systemic lupus erythematosus.

Seven hypertensive patients with idiopathic systemic lupus erythematosus were treated with hydralazine. They received a mean daily dose of 203 mg for a mean duration of 21 months. All were taking prednisone alone or in combination with azathioprine. During therapy with hydralazine, there were no new symptoms nor exacerbation of pre-existing symptoms attributable to systemic lupus. Laboratory parameters, including antinuclear antibody titers and complement levels, either improved or remained stable. The results indicate that hydralazine can be safely used in hypertensive patients with systemic lupus who are receiving concomitant immunosuppressive therapy.

Immunologic considerations in renovascular hypertension.

For decases certain diseases, such as glomerulonephritis, polyarteritis nodosa, scleroderma and serum sickness, have been linked with autoimmune pathogenesis. During recent years a host of additional diseases traditionally thought to have some genetic predisposition but with obscure etiology have been suspected of being autoimmune in nature. Rheumatoid arthritis, diabetes, myasthenia gravis and thyroiditis are diseases of widely divergent organ systems, yet may well have common pathways of pathology via immune complexing mechanisms. Herein we present evidence supporting the concept that renal artery stenosis (occurring primarily in association with the middle aortic syndrome or after renal transplantation) is of immune etiology. Although the specific antigenic agent is still to be defined there is growing acceptance of the theory that medium and large vessels are subject to autoimmune vasculitis in many aspects similar to the autoimmune affections of small vessels. Several cases are presented. Some of these suggest an immune reaction by the natural history but without evidence of immunochemical reactants in the involved vessels, presumably because active disease was arrested at the time to study. In other cases immunofluorescent preparations demonstrate reactants in the walls of the vessels to document the hypothesis more convincingly.