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Secondary malnutrition in patients with oropharyngeal tumors can be the cause of substantial morbidity. The present, prospective study examined 30 patients receiving treatment for an oropharyngeal tumor. Percutaneous endoscopic gastrostomy (PEG) was performed 1 wk prior to the start of therapy in 15 patients, and 15 patients were temporarily fed by nasogastric tube after surgery. Anthropometric and laboratory parameters were measured in both patient groups at five defined times. Based on these parameters, the nutritional status of the PEG patients was found to be substantially better. The present study was able to show that the prophylactic placement of a PEG tube greatly improves the nutritional status of the patients before and after surgery and minimizes the catabolism of the body's fat depots. [ABSTRACT FROM AUTHOR]

The effect of a single oral dose of 25 mg bemetizide on renal function without and with concomitant administration of the prostaglandin synthesis inhibitor indomethacin was investigated in ten healthy volunteers during sustained water diuresis. Bemetizide induced a significant increase in urinary sodium and chloride excretion from 196 +/- 30 and 163 +/- 28 mumol/min to 690 +/- 54 and 537 +/- 51 mumol/min (P less than 0.01). This effect occurred in the absence of changes in glomerular filtration rate, urinary excretion of phosphate or the delivery of chloride beyond the proximal nephron to the distal tubules (distal delivery) [(CH2O + CCl)/GFR . 100], but was associated with a significant decrease in distal fractional chloride absorption (DFACl) [CH2O/(CH2O + CCl)] from 0.84 +/- 0.02 to 0.63 +/- 0.02 (P less than 0.01). Bemetizide also increased urinary excretion of prostaglandin (PG) E2. Concomitant indomethacin administration significantly suppressed urinary excretion of PGE2 and markedly decreased urinary excretion of sodium and chloride during control and following bemetizide administration. Indomethacin had no effect on glomerular filtration rate, urinary excretion of phosphate, distal delivery or the urinary excretion of bemetizide but significantly increased DFACl both during control and after bemetizide administration. Our results show that bemetizide as a thiazide-diuretic acts in the diluting segments of the nephron. Indomethacin administration induces retention of sodium and chloride and blunts the renal effects of bemetizide via increased absorption in the diluting segments. The interaction of both drugs most likely represents a pharmacodynamic interaction. [ABSTRACT FROM AUTHOR]

Background/aims: Prostaglandin E2 (PGE2) plays an important role in the inhibition of gastric acid production and exerts cytoprotective action. The in vitro and in vivo effect of magaldrate, an aluminum containing antacid, on PGE2 synthesis in the gastric mucosa was investigated., Methodology: In the first part of the study, magaldrate was added to a suspension of isolated gastric mucosal cells. In the second part, the antacid gel was applied to the gastric mucosa during gastroscopy and biopsies were taken from the same site 5 and 10 min later., Results: The antacid significantly stimulated PGE2 release from the suspension of isolated gastric cells in vitro. The biopsies obtained after the application of magaldrate showed an increased PGE2 production compared to specimens obtained before., Conclusions: The data suggest that in addition to its neutralizing capacity as an antacid, magaldrate contributes to the cytoprotective activity of the mucosa by stimulating endogenous PGE2 synthesis.

Background/aims: The effect of calcium on colonic prostaglandin E2 synthesis was investigated in 26 healthy volunteers., Material and Methods: Biopsy specimens were obtained by colonoscopy and the mucosal cells were separated biochemically. The cells were incubated in EDTA or CaCl2 containing media for 15 and 30 minutes., Results: The PGE2 synthesis was significantly (p < 0.001) diminished in the calcium free suspension (EDTA) compared to the CaCl2 containing suspension. To increase intracellular Ca2+ concentration, calcium ionophore A 23187 was added for the last 15 minutes. It significantly stimulated the prostaglandin production. In addition, the calcium channel blocker verapamil did not alter the PGE2 synthesis, whereas trifluoperazine, a calmodulin inhibitor, markedly decreased the production rate., Conclusion: Calcium is an important stimulus of prostaglandin synthesis and inhibition of calmodulin by trifluoperazine decreases the arachidonic metabolism. In these regards, colonic tissue shares features with other tissues. However, in contrast to smooth or cardiac muscle, intracellular calcium concentration in colonic mucosa is not affected by verapamil, indicating that colonic calcium channels have a different affinity to this drug.

Background: Eicosanoid mediators play an important role in the pathogenesis of chronic inflammatory bowel disease., Materials and Methods: The synthesis of prostaglandin E2 and leukotriene B4 in biopsied colonic specimens from patients with inflammatory bowel disease was compared with that from healthy controls. In contrast to surgical resection, biopsy by colonoscopy enabled patients with milder disease to be investigated., Results: In subjects with Crohn's disease or ulcerative colitis, the synthesis of PGE2 was significantly (p < 0.05) increased, whereas synthesis of LTB4 remained unaltered. In addition, no differences in PGE2 and LTB4 production were found in different age groups or sex., Conclusion: We conclude that prostaglandin E2, compared to leukotriene B4, is the dominant eicosanoid in moderate inflammatory bowel disease.

Background/aims: Prostaglandin inhibits gastric acid secretion and exerts protective action on the mucosa of the stomach. We studied the synthesis of prostaglandin E2 (PGE2) to determine the role of PGE2 in peptic ulcer disease., Materials and Methods: Mucosal biopsies from 22 persons were obtained and incubated. PGE2 was then determined by radioimmunoassay., Results: Compared to healthy subjects, patients with gastric ulcers or gastritis show diminished accumulation of PGE2 in the incubation medium. Other factors like age, gender, and alcohol consumption were also investigated, however, they do not influence endogenous prostaglandin production. In contrast, PGE2 synthesis was found to be decreased in smokers., Conclusions: Our data indicates a deficiency in endogenous PGE2 synthesis as one cause of gastric ulcerations and offer an explanation of the higher incidence of gastric ulcer disease in subjects with nicotine abuse.

A 52 year old patient was admitted for retrosternal pain not responding to nitroglycerin. Two years before he had suffered myocardial infarction. He had known cholecystolithiasis. Reinfarction was excluded, but the patient developed right upper quadrant abdominal pain with rebound tenderness, fever and leukocytosis. Abdominal sonography supported the diagnosis of acute cholecystitis. Acute illness resolved rapidly without complications under treatment with antibiotics. The patient underwent cholecystectomy during the free interval four weeks after discharge from the hospital. Intraoperative diagnosis was empyema of the gallbladder with cholecystolithiasis.

In the present investigation biographic and test-psychologically collected variables in patients with chronically recurrent and chronically continuous forms of colitis ulcerosa are described and analysed. While in patients with a chronically recurrent course of the disease coincident reactions upon situations and/or constellations of situations considered as encumbrance or stress in the sense of the onset of the disease or its recurrence could be discovered, such correlations were found in less than 20 per cent of the patients with a primarily chronic course of the disease. In the latter patients, however the "psychosomatic phenomenon" according to Stephanos [16] could be observed. An analysis of both groups of patients revealed a high correlation between the factors course of the disease and alexithymic characteristics.

Concentration of total thyroxine, normalized thyroxine ratio, T3-RIA, and Serum TSH before and 30 minutes after stimulation with 0,2 mg TRH i.v. in various forms of euthyroid goiter were determined. There were no significant differences between the three clinical groups of goiter patients. We draw the conclusion that the dependence on TSH, as one important factor in pathogenesis, can on the one hand lead to a diffuse goiter and, on the other hand lead to a nodous goiter. That means, that different developments of goiter are determined by specific thyroid tissue factors.

The role of human atrial natriuretic peptide (alpha-hANP) in chronic blood pressure (BP) and extracellular fluid volume (ECFV) regulation remains elusive. Hence, the role of alpha-hANP in chronic renal failure is of particular interest since in this pathological condition: (1) increased sodium and water retention plays a major pathogenetic role in the development of hypertension and (2) altered secretion and/or metabolism of alpha-hANP may contribute to fluid volume and BP regulation. To evaluate the relationship between the degree of renal insufficiency, BP and circulating alpha-hANP, we determined plasma alpha-hANP concentrations by radioimmunoassay in 16 nondialyzed patients with progressive chronic renal failure (CRF) of various degrees; subsequently analysis of potential molecular heterogeneity of immunoreactive (ir) ANP was performed by means of gel permeation of plasma extracts from patients with CRF without concomitant hypertension. Serum creatinine concentrations ranged from 127 to 1187 (435 +/- 76) mumol/l, systolic BP from 135 to 200 (158 +/- 4) and diastolic BP from 80 to 110 (94 +/- 2) mmHg, respectively. Plasma alpha-hANP concentrations ranged from 5 to 75 (23 +/- 4) pmol/l which was thus significantly higher as compared to 9 +/- 2 pmol/l found in healthy volunteers (p less than 0.05). A highly significant linear correlation between plasma alpha-hANP and serum creatinine concentrations (r = 0.92; p less than 0.01) was observed; a weaker correlation was found between mean arterial pressure and alpha-hANP (r = 0.66) and serum creatinine concentration (r = 0.59), respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

1. The effects of jaundice on renal and circulatory function were investigated in chronic bile duct ligated (CBDL) rats 6 days after surgery. Sham operated (SO) animals served as controls. 2. Body weight was significantly reduced, whereas blood pressure remained unaltered, 6 days after bile duct ligation when serum bilirubin had risen to 169 +/- 18 (SEM) as compared with 2.8 +/- 0.3 mumol/l in SO rats. When compared with control values before surgery, urinary volume had significantly increased and absolute excretion of sodium, potassium, chloride and phosphate had decreased on day 6 after CBDL. Endogenous creatinine clearance was markedly depressed when compared with SO rats. Whereas fractional excretion of potassium remained unaltered, fractional excretion of sodium and of phosphate was significantly increased. 3. Except for a significant increase in urinary thromboxane B2 (TXB2) excretion in CBDL rats, no significant changes were observed in urinary excretion of prostaglandin (PG) E2, in the synthesis of PGE2, 6-keto-PGF1 alpha and TXB2 by isolated aortic tissue in vitro, nor in renal and cardiac adenosine triphosphatase activities or renal cortical mitochondrial function. 4. The adenosine triphosphate content of kidney cortex and cardiac mitochondrial function were significantly depressed in CBDL rats. 5. The results demonstrate that jaundice in CBDL rats is associated with functional and metabolic disturbances of the kidney and cardiac muscle, which may contribute to the renal and haemodynamic characteristics observed in jaundiced animals and humans.

We have previously shown that a natriuretic factor which is present in a small molecular weight fraction (IV) of serum and urine from salt loaded animals and healthy subjects, respectively, inhibits the Na-K-ATPase enzyme in vitro and also binds to a specific digoxin antibody. In the present study digoxin-like immunoreacting activity (DLIA) was therefore determined in the serum of healthy volunteers during low (35 nmol/day) and high (greater than 400 mmol/day) sodium intake and of patients with chronic renal failure and serum creatinine concentrations ranging from 127 to 757 mumol/l. DLIA was determined with a radioimmunoassay for digoxin in native serum and in the salt (III) and post-salt (IV) serum fractions eluted from a Sephadex G-25 column. DLIA in native serum of healthy subjects was less than 0.125 ng/ml. After gel filtration DLIA eluted exclusively in the small molecular weight salt (F III) and post-salt (F IV) fractions. Whereas DLIA increased in F III and decreased in F IV, total DLIA in F III + IV slightly increased from 0.37 +/- 0.03 to 0.49 +/- 0.05 ng/ml (p less than 0.01) with the change from low to high sodium intake. DLIA in native serum of uremic patients ranged from 0 to 1.70 ng/ml and was detectable consistently only in patients with serum creatinine concentrations above 250 mumol/l. DLIA in F III which averaged 0.22 +/- 0.04 ng/ml and total activity which ranged from 0.11 to 0.88 ng/ml closely correlated with the degree of renal impairment (p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

In six healthy subjects the role of renal prostaglandins (PG) in modulating the actions of the renin-angiotensin and renal adrenergic nervous systems on renal function was investigated. During high dietary sodium intake (350 mmol/day) for 4 days no changes in urinary excretion of PGE2, PGF2 alpha, noradrenaline or adrenaline were noted, whereas plasma renin activity (PRA) and urinary aldosterone excretion were suppressed. After 4 days of low sodium intake (35 mmol/day) urinary excretion of PGE2, aldosterone and noradrenaline, as well as PRA, had significantly increased. Inhibition of PG synthesis with indomethacin (2 mg/kg body weight) had no effects on renal function on day 5 of high sodium intake. Despite suppression of PRA and urinary aldosterone, indomethacin significantly reduced p-aminohippurate (PAH) clearance, glomerular filtration rate (GFR) and urinary sodium excretion on day 5 of low sodium intake, when urinary noradrenaline excretion remained high. The results point to the crucial role of the renal adrenergic nervous system in controlling renal vascular resistance and sodium conservation in healthy subjects during low sodium intake, which is unmasked when renal PG synthesis is blocked by indomethacin. Enhanced renal PG synthesis during sodium restriction therefore not only attenuates the vascular and tubular effects of the renin-angiotensin system but, more importantly, also those of the highly stimulated renal adrenergic nervous system.

In patients with chronic uremia we have previously demonstrated a significant inhibition of the Na-K-ATPase enzyme which represents the specific receptor protein for cardiac glycosides. Since an endogenous inhibitor of this enzyme was previously shown to react with a digoxin antibody, in the present study we determined digoxin-like immunoreacting activity(ies) (DLIA) by a radioimmunoassay in 15 nondialyzed patients with chronic renal failure. In native serum, DLIA ranged from 0 to 1.70 ng/ml and was unrelated to the degree of renal failure. After gel filtration of serum, DLIA exclusively eluted in the small molecular weight salt (FIII) and post-salt (FIV) fractions and averaged 0.22 +/- 0.04 and 0.20 +/- 0.05 ng/ml in fractions III and IV, respectively. Total activities ranged from 0.11 to 0.88 ng/ml with a mean of 0.42 +/- 0.06 ng/ml and closely correlated with the degree of renal impairment (p less than 0.001). The results confirm the presence of small molecular weight digoxin-like immunoreacting substance(s) in uremic serum. The variable activities in native serum and the lack of correlation between the degree of renal failure and DLIA in serum fraction IV previously shown to possess the Na-K-ATPase-inhibiting activity, however, indicate that DLIA may not reflect specifically the endogenous sodium pump inhibitor and that unspecific binding to this digoxin antibody of uremic toxins or other endogenous compounds, such as steroids other than aldosterone, may have occurred.

Synthetic L-thyroxine (100-150 micrograms/d) was administered for 18 months to 110 female patients with normothyroid diffuse goitre size II. Reduction of size was observed in 60 patients after one year, in a further 10 there was no increase in size. Increase of neck circumference and thyroid gland size in 40 patients could be explained by patient non-compliance in 35 females. Renewed assessment of treatment results after another 6 months showed decrease of neck circumference and thyroid gland size in 98 out of the 110 patients. There were no significant differences among in vitro parameters (total thyroxine, normalisation of thyroxine ratio and triiodothyronine) assessed at 12 and 18 months among patients treated successfully and without success. However, the TRH test for delta TSH (TSH stim-TSH basal) showed significantly higher values after 12 months in the non-compliant group treated without success initially. These differences could not be demonstrated after 18 months. The results show that consideration of compliance behaviour in conjunction with the intravenous TRH test clearly improve results of conservative treatment of normothyroid diffuse goitre.

To investigate a tubular action of atrial natriuretic peptide (ANP), in the present study the effects of rat atrial extract (AE) and of synthetic rat atriopeptin III (AP III) were assessed in conscious rats during hypotonic saline infusion. Renal plasma flow (RPF) and glomerular filtration rate (GFR) were estimated by the clearances (C) of PAH and of endogenous creatinine, respectively. CPO4 was used as a marker of proximal tubular function. Distal delivery (DD) and distal fractional absorption of chloride (DFACl), a measure of solute absorption in the diluting segments, were calculated from CH2O and CCl. AE and AP III increased RPF in all groups of animals. Low doses of AP III (40 ng/100 g B.W.) significantly increased urine flow rate and CCl, whereas GFR, CNa, CPO4, and CK remained unaltered. The marked natriuresis at high doses of ANP was associated with a rise in GFR and in absolute and fractional CPO4 as well as an increase in DD and CK. AE and AP III (1 microgram/100 g B.W.) decreased DFACl from 0.94 +/- 0.03 and 0.87 +/- 0.03 to 0.80 +/- 0.07 (p less than 0.05) and 0.54 +/- 0.07 (p less than 0.01), respectively. Some of the effects on tubular reabsorptive capacity probably result from medullary wash-out which thereby contributes to the natriuresis by potentiating the rise in the filtered load of sodium at high ANP levels. In the absence of changes in GFR and CPO4, the tubular action of ANP is more accurately reflected by CCl which may result from decreased absorption in the medullary collecting tubule.

Recent experimental and clinical findings indicate that immunoreactive human Atrial Natriuretic Peptide (alpha-hANP) is involved in the regulation of blood volume and arterial blood pressure (BP). Whereas the potential regulatory role of alpha-hANP in acute changes of extracellular fluid volume (ECFV) and in the modulation of BP has been demonstrated in various studies, their involvement in the chronic maintenance of sodium and water homeostasis is still equivocal. Moreover the role of alpha-hANP is of particular interest in chronic renal failure, since in this pathological condition increased sodium and water retention plays a major pathogenetic role in the development of hypertension and altered secretion and/or metabolism of alpha-hANP may contribute to fluid volume and BP regulation. To evaluate the relationship between the degree of renal insufficiency, BP and circulating alpha hANP we determined plasma alpha-hANP concentrations in 16 nondialyzed patients with progressive chronic renal failure (CRF) of various degree. Serum creatinine concentrations ranged from 127 to 1187 (435 +/- 76) mumol/l, systolic BP from 135 to 200 (158 +/- 4) and diastolic BP from 80 to 110 (94 +/- 2) mm Hg respectively. Plasma alpha-hANP concentrations ranged from 49 to 753 with a mean of 228 +/- 42 pg/ml which was thus significantly higher as compared to 90.0 +/- 16.2 pg/ml found in healthy volunteers (p less than 0.05). A highly significant linear correlation between plasma alpha-hANP and serum creatinine concentrations (r = 0.92) was observed; a weaker correlation was found between mean arterial pressure and alpha-hANP (r = 0.66) and serum creatinine concentration (r = 0.59), respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Various studies point to a role of the renal prostaglandin (PG) system in the regulation of renal NaCl excretion. In the present experiments, distal delivery of proximal tubular fluid (DD) [CH20 + CC1)/GFR x 100] and distal fractional chloride absorption (DFAC1) [CH20/(CH20 + CC1)] were studied in 6 healthy volunteers undergoing sustained water diuresis. Studies of renal function were performed during intravenous infusion of hypotonic (0.45%) saline and during additional treatment with indomethacin, furosemide and furosemide plus indomethacin. Hypotonic saline was infused at increasing rates of 0.09, 0.18, and 0.36 ml min-1 kg-1 body weight each for a 45-min period. DD over all three clearance periods averaged 8.27 +/- 0.71 ml min-1 100 ml-1 glomerular filtration rate (GFR) during saline infusion alone and was unchanged by indomethacin (8.09 +/- 0.63 ml min-1 100 ml-1 GFR). DFAC1 averaged 0.79 +/- 0.02 during saline and significantly increased to 0.87 +/- 0.01 (p less than 0.002) during concomitant indomethacin treatment. Increased NaCl absorption in the diluting segment during indomethacin was paralleled by a decrease in urinary excretion of chloride (UC1V) from 221 +/- 29 during control to 124 +/- 19 muEq/min (p less than 0.025) and in urinary excretion of PGE2 (UPGE2V) from 1.45 +/- 0.12 to 0.51 +/- 0.09 pmol/min (p less than 0.025). Furosemide increased UPGE2V to 2.94 +/- 0.34 pmol/min (p less than 0.05) and UC1V to 2,590 +/- 128 muEq/min (p less than 0.001). This effect was associated with an increase in DD to 26.70 +/- 1.33 ml min-1 100 ml-1 GFR (p less than 0.001) and a decrease in DFAC1 to 0.19 +/- 0.02 (p less than 0.001). Neither DD and DFAC1 nor UC1V were altered during furosemide+indomethacin as compared to furosemide in spite of a marked suppression of UPGE2V to 0.56 +/- 0.13 pmol/min. Our results support the concept that renal PG participate in the regulation of NaCl absorption in the diluting segments of the nephron. Furthermore, the tubular effects of furosemide appear not to be mediated by the PG system.

Ramipril is a newly synthesized angiotensin converting enzyme inhibitor without a sulfhydryl group in the molecule but with a prolonged duration of action. Efficacy, tolerance and safety of this drug were evaluated in 10 patients with severe essential hypertension. After a treatment period of at least 4 weeks with the conventional antihypertensive drug combination of a diuretic and a beta-blocking agent with the vasodilator dihydralazine, their systolic and diastolic blood pressures averaged 161 +/- 6 and 111 +/- 2 mm Hg, respectively. Because diastolic blood pressure during this drug regimen was still greater than 105 mm Hg in all patients, the patients received ramipril initially at single daily doses of 5 mg in addition to their previous medication. The first dose of 5 mg ramipril resulted in a moderate but significant decrease in systolic and diastolic blood pressure in 9 of the 10 patients to 142 +/- 5 and 104 +/- 4 mm Hg (p less than 0.01), respectively, between 3 and 6 hours after drug administration. In 1 patient blood pressure was unresponsive to ramipril and 1 patient complained of nausea and vomiting within the first week of treatment with ramipril. Within the following 8-week treatment period with a once-daily intake of 5 or, if necessary, 10 mg of ramipril, diastolic blood pressure normalized in the remaining 8 patients to less than 90 mm Hg. Systolic and diastolic blood pressure averaged 130 +/- 5 and 83 +/- 2 mm Hg, respectively, at the end of the 8-week treatment period with ramipril. Severe hypotension and reflex tachycardia were not observed.(ABSTRACT TRUNCATED AT 250 WORDS)

The role of human atrial natriuretic peptide (alpha-hANP) in the regulation of blood pressure (BP) and extracellular fluid volume (ECFV) remains elusive. This is of particular interest in chronic renal failure, in which first, increased sodium and water retention plays a major pathogenetic role in the development of hypertension, and second, altered secretion and/or metabolism of alpha-hANP may contribute to fluid volume and BP regulation. In the present study the relationship between renal function, BP, and circulating alpha-hANP was investigated in 16 non-dialyzed patients with stable chronic renal failure (CRF) without edema. Analysis of potential molecular heterogeneity of immunoreactive (ir) ANP was performed by gel permeation chromatography of plasma extracts from normotensive patients with CRF. Serum creatinine concentrations averaged 435 +/- 76 mumol/l ranging from 127 to 1187 mumol/l, systolic and diastolic BP averaged 158 +/- 4 and 94 +/- 2 mmHg, respectively. Plasma alpha-hANP concentrations ranged from 5 to 75 with a mean of 23 +/- 4 pmol/l as compared to a mean of 10 +/- 1 pmol/l in healthy volunteers (p less than 0.05). A significant linear correlation between plasma alpha-hANP and serum creatinine concentrations (r = 0.92) was observed; a weaker correlation was found between mean arterial pressure and alpha-hANP (r = 0.66). Chromatographic analysis revealed considerable amounts of higher molecular weight circulating ir-ANP, approximately 15,000 Da, in addition to the biologically active small mol wt ANP.(ABSTRACT TRUNCATED AT 250 WORDS)

A 20-year-old female presented with right flank pain she had felt for two weeks. Colics, dysuria and fever were denied. The father and a sister of the patient were known to have cystic kidneys. Abdominal ultrasound revealed symmetrically enlarged kidneys with multiple cysts. Thus, the diagnosis of autosomal dominant polycystic kidney disease (ADPKD) was made. For a follow-up period of four years renal function has remained normal. An intercurrent urinary tract infection was treated with antibiotics. Blood pressure has been normal over the entire follow-up period. As yet, no specific treatment had to be initiated.