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Biomedical subjects

M B Goldstein

Publications and source records attributed to M B Goldstein.

At least 37 records · Page 2Linked to original sources
PubMed1990

Increased local antitumor effects of interleukin 2 liposomes in mice with MCA-106 sarcoma pulmonary metastases.

The effects of liposome formulations of interleukin 2 (IL-2) and local route were studied in C57BL/6 mice with MCA-106 sarcoma pulmonary metastases. IL-2 liposomes made by hydration of powdered dimyristoyl-phosphatidylcholine with aqueous recombinant IL-2 had 95% of the IL-2 associated with the lipid fraction. When mice with pulmonary micrometastases were treated once daily with free cytokine on days 5, 6, and 7 after tumor inoculation, the intrathoracic route was superior to the i.p. or s.c. routes. When IL-2 liposomes were administered by the local intrathoracic route, significantly better antitumor effects (P less than 0.01) were seen compared to empty liposomes or free IL-2 as determined by (a) increased survival and (b) reduced numbers of pulmonary metastases. Minimal toxicity was observed. Results indicate that local route and incorporation of IL-2 in liposomes may enhance therapeutic efficacy and facilitate more practical daily dosing regimens.

Animals↗
PubMed1990

College students' definitions of social and problem drinking.

College students (N = 276) completed surveys describing two common drinking situations. One scenario described a student alone in an apartment after a weekday class; the other, the same student at a weekend party. Sex of the drinker in the scenario was systematically varied. Students estimated the number of drinks a social drinker and a problem drinker would have in each situation. Results indicated that: 1) definitions of social and problem drinking are strongly influenced by drinking context, and 2) male and female subjects estimated that problem drinkers of the opposite sex drank more than problem drinkers of their own sex. Problem drinkers were regularly estimated to consume three to four more drinks than the subject would in the same situation. Implications for education and prevention are discussed.

Adult↗
PubMed1989

A study of the basic principles determining the performance of several high-flux dialyzers.

The clearance characteristics of several commercially available high-flux dialyzers made from cellulose acetate, polyacrylonitrile, polysulphone, and polymethylmethacrylate were studied in vivo. The impact of increasing surface area and adding ultrafiltration on the clearances of small- and larger-molecular-weight species was assessed. The results show there are major differences in large-molecular-weight substance substance handling by different dialyzers as shown by differences in beta 2-microglobulin clearance, independent of ultrafiltration capacity. Membranes made from similar material, eg, Asahi's PAN and Hospal's AN-69 membrane, both made from polyacrylonitrile, differ significantly in their beta 2-microglobulin clearance. Increased surface area results in much greater increase in large-molecular-weight substance clearance. The present study clearly demonstrates that high water flux is not related to high large-molecular-weight permeability. Decisions with respect to impact on dialysis must be based on a knowledge of both the large- and small-molecular-weight permeabilities of the various membranes.

Acrylic Resins↗
PubMed1987

A controlled trial of cyclophosphamide in patients with membranous glomerulonephritis.

Patients with membranous glomerulonephritis (MGN), impaired renal function and the nephrotic syndrome are at high risk of developing renal failure. Twenty-six such patients were studied with serum creatinine concentrations exceeding 135 microM, and 24-hour urine protein excretion of at least 3.5 g/day to determine the potential benefit of cyclophosphamide therapy. Cyclophosphamide (mean 1.5 mg/kg/day) was given to nine patients for 23 +/- 4 months. These patients were compared with 17 concurrent controls. The two groups did not differ in clinical or laboratory features at the time of biopsy or start of treatment or its equivalent. Six of the nine cyclophosphamide treated patients and 15 of the 17 controls had received prednisone therapy. The total follow-up was 49 +/- 10 months in the treated group and 50 +/- 6 months in the controls. At last observation, serum creatinine values exceeded 400 microM in eight controls (4 on dialysis) and in none of the treated patients. The mean serum creatinine level was significantly lower (P less than 0.02) in the treated group (173 +/- 24 microM) than in controls (433 +/- 71 0.02) in the treated group (173 +/- 24 microM) than in controls (433 +/- 71 microM). The mean serum albumin level and 24-hour urine protein excretion both improved significantly with treatment as compared with controls. There were four complete remissions, five partial remissions and no patient with persistent nephrotic syndrome after treatment. In the controls, there were no complete remissions, six partial remissions and 11 patients had persistent nephrotic syndrome (P less than 0.001). Thus, cyclophosphamide therapy appears to be of benefit in patients with MGN, the nephrotic syndrome and impaired renal function.

Adult↗
PubMed1986

The urine anion gap: a clinically useful index of ammonium excretion.

In patients with a normal plasma anion gap type of metabolic acidosis, knowledge of the rate of ammonium excretion can provide valuable information to determine if there is a renal cause for the disorder. Unfortunately, few hospital biochemistry laboratories offer routine determination of the urine ammonium concentration. Data are presented that demonstrate a direct linear relationship between the urine anion gap (Na+ + K+ - Cl-) and the urine ammonium concentration. In a 24-hour urine collection, the relationship is urine ammonium equals -0.8 (urine anion gap) +82 (r = 0.97 p less than 0.01). The applications of this index of ammonium excretion are discussed.

Acid-Base Equilibrium↗
PubMed1986

Influence of mannitol and dopamine on renal function during elective infrarenal aortic clamping in man.

The impact of elective infrarenal aortic clamping on parameters of renal function was evaluated in 27 extracellular fluid volume expanded patients. Significant transient decreases (p less than 0.05) in glomerular filtration rate were observed in all three groups either in the early or late post-clamp release period, despite maintenance of hemodynamic stability. This study documents transient decreases in glomerular filtration rate which occurred following release of the infrarenal aortic cross-clamp. No clinically important benefit from the use of mannitol and dopamine over extracellular fluid volume expansion with saline alone was demonstrated in the prevention of the changes in renal function associated with aortic cross-clamping.

Adult↗
PubMed1985

Distal renal tubular acidosis syndromes: a pathophysiological approach.

Ammonium is the most important component of renal acid excretion. A reduced rate of ammonium excretion is the common feature of the group of diseases called distal renal tubular acidosis. We have presented an alternative approach to patients with distal acidification defects based upon the pathophysiology of these disorders. Accordingly, the purpose of this review is to describe a revised classification based on our current understanding of collecting duct hydrogen ion secretion and ammonium addition to the lumen of the distal nephron. We have subdivided these defects into four groups: disorders of the collecting duct proton pump (pump defects); failure to generate and/or maintain an appropriate electrical gradient to favor hydrogen ion secretion (voltage defects); back-leak of hydrogen ions across an abnormally permeable collecting duct membrane (gradient defects), and diminished availability of NH3 in this nephron segment (NH3 defects). These four subtypes can be identified by measuring the urine pH and PCO2 under appropriate circumstances and evaluating the renal excretion of ammonium and potassium.

Acidosis, Renal Tubular↗
PubMed1983

Acute renal failure.

The diagnosis and therapy of acute renal failure should be approached in concert, bearing in mind that more than one cause may co-exist in a patient. Therapy includes reversing prerenal and postrenal failure, removing any nephrotoxins, adjusting drug dosages, correcting acidemia, maintaining good nutritional status, and using dialysis when necessary.

Acute Kidney Injury↗
PubMed1983

Effect of acute changes in the PaCO2 on acid-base parameters in normal dogs and dogs with metabolic acidosis or alkalosis.

There is a linear relationship between the PaCO2 and blood hydrogen ion concentration in normal dogs, but for theoretical reasons to be discussed, we questioned whether this relationship would apply in animals with metabolic acidosis or alkalosis. To study this in more detail, animals were divided into three groups: normal, metabolically acidotic, and metabolically alkalotic. Following anesthesia and bilateral ureteral ligation, dogs were intubated and ventilated to produce acute steady state PaCO2 values corresponding to the range observed during disease states. Changes in the volume and electrolyte composition of the gastrointestinal fluid and urine as well as the concentration and distribution of lactate were evaluated in all experiments. We observed the previously described linear relationship between the PaCO2 and blood hydrogen ion concentration in normal dogs, but the slope of the regression line differed significantly from those of dogs with metabolic acidosis and metabolic alkalosis. On the other hand, there was a consistent relationship between the ratio of the PaCO2 values, but not the absolute PaCO2, and the change in the plasma bicarbonate concentration over a wide range of PaCO2 values in all groups of dogs. The chemical basis for these observations will be discussed.

Acid-Base Equilibrium↗
PubMed1983

Decreased distal acidification in acute hypercapnia in the dog.

The present studies evaluate the effect of acute hypercapnia on distal nephron H+ secretion (DNH+S) in vivo by means of the urine-blood PCO2 difference (U-B PCO2) in alkaline urine. Bicarbonaturia was induced by either a sodium bicarbonate infusion or L-lysine administration. Our results demonstrate that the U-B PCO2, as a function of the urinary bicarbonate concentration, was significantly lower during acute respiratory acidosis; this effect was not dependent on changes in glomerular filtration rate and/or fractional excretion of sodium, potassium, and chloride. Infusion of the sodium salts of sulfate, a nonreabsorbable anion, did not correct the diminished U-B PCO2. Amiloride caused the U-B PCO2 to fall in normocapnic dogs but not in hypercapnic dogs. When hypercapnia was superimposed in dogs with extracellular fluid volume contraction, there were no changes in the U-B PCO2. This study indicates that acute hypercapnia in the intact dog decreases DNH+S and is compatible with an effect of hypercapnia on the voltage-dependent component of urine acidification. The mechanism appears to be direct rather than secondary to factors that influence the rate of sodium delivery to the distal nephron.

Acidosis, Respiratory↗
PubMed1983

Hemorrhage from ileal varices: a delayed complication after total proctocolectomy in a patient with ulcerative colitis and cirrhosis.

A 60-year-old woman presented with recurrent ileostomal hemorrhage 29 years after proctocolectomy for ulcerative colitis. Ileal varices were demonstrated by selective mesenteric angiography, and a portasystemic shunt was performed with control of the bleeding. Stomal varices typically present with repeated episodes of bleeding at and proximal to the mucocutaneous junction of the ileal stoma and attempts at local corrective measures generally meet with only temporary success. A portasystemic shunt to diminish portal hypertension in this situation is currently the most widely accepted therapy for this entity.

Colectomy↗
PubMed1982

Role of acidosis in the protein wasting of fasting in the rat and the rabbit.

The purpose of these experiments was to determine if augmented renal ammoniagenesis in chronic metabolic acidosis could increase the negative nitrogen balance during prolonged fasting. To explore this question, rats and rabbits were fasted for up to 10 days because acidosis would markedly augment ammonium excretion in the rat but not in the rabbit. Since the ketoacidosis of fasting was mild in both species (less than 2 mM) and ketonuria virtually absent, a hydrochloric acid load was given to stimulate renal ammoniagenesis. Under these conditions, nitrogen balance was significantly more negative during acidosis in the rat but not in the rabbit. This increment in nitrogen excretion appeared as ammonium with no detectable difference in urea nitrogen excretion. Therefore, it appears that if more nitrogen is excreted as ammonium, net protein breakdown increases to furnish the substrate for ammoniagenesis rather than reducing the excretion of the other nitrogenous waste component urea. The implications of these findings will be discussed.

Acid-Base Equilibrium↗
PubMed1982

A quantitative analysis of renal ammoniagenesis and energy balance: a theoretical approach.

Many theories have been proposed to explain the regulation of renal ammoniagenesis during chronic metabolic acidosis but none of these is entirely satisfactory. Since the activity of each of the enzymes in this pathway greatly exceeds the maximum rate of ammonium production in vivo, even when physiological substrate concentrations are used in this calculation, it follows that ammoniagenesis must be inhibited in the intact animal. We shall present a novel hypothesis for the regulation of the maximum rate of ammoniagenesis which emphasizes the fact that ATP is a product of this pathway and that a limited rate of ATP utilization could control its maximum velocity during chronic metabolic acidosis. To test the validity of our hypothesis, a quantitative analysis of the pathways of ATP production and utilization in the kidney will be reviewed. This approach is similar to one already proposed for the regulation of the maximum rate of ketogenesis in the liver.

Acidosis↗
PubMed1982

Protein wasting due to acidosis of prolonged fasting.

During a total fast in obese subjects, the daily rate of nitrogen excretion undergoes only a small further decline after 2 wk, the excretion rate being about 5 g N/day. At this time, ammonium and urea each constitute about one-half of this excretion. The purpose of this study was to consider two alternative hypotheses: first, that the near plateau in nitrogen excretion represents an irreducible minimum rate of net protein breakdown in order to supply essential organs with calories in the form of glucose; second, that protein breakdown could be further reduced by minimizing the requirement to provide nitrogen for ammonium excretion during the ketoacidosis of fasting. Because ammonium excretion is largely controlled by acid-base balance, 150 mmol of sodium bicarbonate plus 60 mmol of potassium chloride were administered daily to decrease ammonium excretion in eight obese subjects who were totally fasting for more than 14 days. Urine ammonium nitrogen fell with this treatment (from 3.8 +/- 0.4 to 2.0 +/- 0.4 g N/g creatinine). In addition, there was a smaller fall in the rate of urea excretion (from 2.5 +/- 0.2 to 2.1 +/- 0.3 g N/g creatinine) together with a fall in the blood urea nitrogen. Therefore, it appears that ammonium excretion contributes to the negative nitrogen balance of a prolonged total fast, as assessed over a 3-day period of observation, is responsible for about one-third of the net lean body mass loss.

Acidosis↗
PubMed1981

Evaluation of the effect of pentobarbitone anaesthesia on the plasma potassium concentration in the rabbit and the dog.

The purpose of these studies was to determine the reasons for the hypokalaemia observed in rabbits studied in our laboratory. The rabbits consumed standard rabbit chow which is rich in potassium and remained in potassium balance. Hypokalaemia was only observed following anaesthesia. A number of additional investigations were undertaken to clarify the mechanisms involved. The hypokalaemia could not be attributed to technical factors, alkalaemia, hyperinsulinaemia or hyperaldosteronism, but seemed to be a function of anaesthesia. This effect of pentobarbitone anaesthesia was not unique to the rabbit, as similar changes also occurred in the anaesthetized dog. The findings reported in this paper have significant implications with respect to the interpretation of plasma potassium concentrations in anaesthetized subjects or animals.

Acid-Base Equilibrium↗
PubMed1981

Sites of ammonia addition to tubular fluid in rats with chronic metabolic acidosis.

The purpose of this investigation was to determine in which nephron segments ammonia was added to or removed from the lumenal fluid of the rat. Ammonium was measured in proximal and distal tubular fluid samples obtained by micropuncture and in collecting duct fluid samples obtained by microcatheterization. Water abstraction was assessed by examining the tubular fluid-to-plasma inulin concentration, (TF/P)In. In normal or acidotic rats, the vast bulk of the final urine ammonium appeared in the proximal tubular fluid samples. Most of this ammonia was lost, however, in transit from the proximal to the distal tubule so that only 20 to 30% of the excreted ammonium was present at the distal site. Ammonia reentered the lumenal fluid primarily in the cortical collecting duct in acidotic rats and in the medullary collecting duct in normal rats. Although the pattern was qualitatively similar in both groups of rats, the absolute quantity of ammonium in each nephron segment of normal rats was about 10 to 20% of that in acidotic animals.

Acidosis, Renal Tubular↗