PubMed Health⌕ Search

Biomedical subjects

F Alexander

Publications and source records attributed to F Alexander.

At least 91 records · Page 5Linked to original sources
PubMed1985

Thromboxane A2 moderates permeability after limb ischemia.

Reperfusion after limb ischemia results in muscle edema as well as excess secretion of thromboxane A2 (TxA2), an agent associated with permeability increase in other settings. This study tests whether TxA2 moderates the permeability following limb ischemia. A tourniquet inflated to 300 mmHg was applied for 2 hours around the hind limb of four groups of dogs. In untreated animals (N = 25), 2 hours following tourniquet release, plasma TxB2 values rose from 320 pg/ml to 2416 pg/ml (p less than 0.001), and popliteal lymph values rose from 378 pg/ml to 1046 pg/ml (p less than 0.001). Platelet TxB2 was unaltered and plasma 6-keto-PGF1 alpha levels did not vary. Following ischemia, lymph flow (QL) increased from 0.07 to 0.37 ml/h (p less than 0.05), while the lymph/plasma (L/P) protein ratio was unchanged at 0.41. These measurements indicate increased permeability since increase in hydrostatic pressure in a second group by tourniquet inflation to 50 mmHg (N = 7) led to a rise in QL from 0.07 to 0.22 ml/h, but a fall in the L/P ratio to 0.32, a value lower than the ischemic group (p less than 0.05). Pretreatment with the imidazole derivative ketoconazole (N = 11) reduced platelet Tx synthesis from 42 ng to 2 ng/10(9) platelets, but lymph TxB2 levels rose to 1703 pg/ml after ischemia, indicating an extravascular or vessel wall site of synthesis not inhibited by ketoconazole. Pretreatment with a lower molecular weight imidazole derivative OKY 046 (N = 9) inhibited all Tx synthesis after ischemia. Prior to tourniquet inflation, both OKY 046 and ketoconazole lowered plasma TxB2 levels as well as the L/P ratio (p less than 0.05). After ischemia, OKY 046, but not ketoconazole, maintained the L/P ratio at 0.33, a value below that of untreated animals (p less than 0.05). These results indicate that nonplatelet-derived TxA2 modulates both baseline and ischemia-induced increases in microvascular permeability in the dog hind limb.

6-Ketoprostaglandin F1 alpha↗
PubMed1985

Membranous glomerulonephritis in a patient with Crohn's disease of the small bowel.

A 12-year-old girl presented with concurrent onset of membranous glomerulonephritis and Crohn's disease of the small intestine. Subsequent investigations failed to implicate any other systemic disease as a cause of the glomerulonephritis. Membranous glomerulonephritis is an immune complex--mediated glomerulopathy frequently associated with underlying systemic disease. The association of immune complex phenomenon with Crohn's disease and the variation of renal abnormalities in parallel with activity of bowel disease in this patient suggest that the glomerulonephritis may be due to the underlying Crohn's disease.

Child↗
PubMed1985

Prostacyclin and thromboxane A2 moderate postischemic renal failure.

Since prostacyclin (PGI2) is known to regulate renal cortical blood flow and since ischemia stimulates thromboxane (Tx) A2 synthesis, the role of these prostanoids in moderating the response to renal ischemia was studied in the rat. At baseline, plasma TxB2 concentration in untreated animals (n = 13) was 357 pg/ml. The left renal pedicle was clamped for 45 minutes after a right nephrectomy (n = 16), which led after 5 minutes of reperfusion to a rise in TxB2 to 2825 pg/ml (p less than 0.001), but there was no change in 6-keto-PGF1 alpha. After 24 hours creatinine levels rose from 0.4 to 3.0 mg/dl (p less than 0.001), and left renal weight rose from 94% to 117% (p less than 0.001) relative to the weight of the right kidney. In nephrectomized but nonischemic sham control rats (n = 7), creatinine level was 0.9 mg/dl and kidney weight 91% after 24 hours. Pretreatment with OKY 046 (n = 13) (2 mg/kg administered intravenously) blocked ischemia-induced TxB2 synthesis, while 6-keto-PGF1 alpha levels rose from 96 to 302 pg/ml (p less than 0.001). There was no increase in creatinine levels or kidney weight relative to the sham group. Pretreatment with ibuprofen (n = 10) (12 mg/kg) or OKY 046 and ibuprofen (n = 9) inhibited TxB2 and 6-keto-PGF1 alpha synthesis, but creatinine levels and renal weight rose (p less than 0.001). Renal histology in OKY 046-pretreated animals was equal to that in nephrectomized controls, while all other ischemic groups showed tubular necrosis. Results indicate that a high PGI2/TxA2 ratio protects against renal ischemia.

6-Ketoprostaglandin F1 alpha↗
PubMed1984

Evolution of the albumin: alpha-fetoprotein ancestral gene from the amplification of a 27 nucleotide sequence.

The genes for alpha-fetoprotein and albumin arose by duplication of an ancestral gene that contained three genetic domains. These domains were generated by the triplication of a primordial genetic domain composed of five exons or subdomains. That the primordial domain itself arose by amplification of a simpler sequence is suggested by nucleotide sequence homologies among the subdomains of the mouse alpha-fetoprotein gene. A detailed analysis of these homologies reveals that each of the five subdomain families contains remnants of a 27-base-long repeat from which the entire alpha-fetoprotein coding sequence has been assembled. A consensus sequence for the 27 nucleotide repeat is derived, and the positions of the repeats within each subdomain are described. A model is proposed for the evolution of the primordial domain by the amplification and divergence of the 27 base-pair sequence, along with the condensation of the repeats into subdomains separated by intervening sequences. It is postulated that the role of intervening sequences may be to limit sequence amplification in genes such as alpha-fetoprotein and albumin whose protein products cannot tolerate size variation.

Albumins↗
PubMed1984

Biliary carcinoma. A review of 109 cases.

One hundred nine patients operated on for bile duct carcinoma were reviewed. Herein, we reported 83 proximal duct tumors, 12 mid-duct tumors, and 14 distal third tumors. Resectability was 10 percent, 33 percent, and 100 percent, respectively, with an operative mortality of 0 percent, 25 percent, and 23 percent. The median survival time and 5 year survival rate for these resected groups were 21 months and 25 percent for proximal duct tumors, 8 months and 0 percent for mid-duct tumors, and 16 months and 20 percent for distal third tumors. Eighty-three patients were treated with strictly palliative procedures with an operative mortality of 19 percent, an adjusted median survival rate of 10.9 months, and a 5 year survival rate of 0. The 2 and 5 year survival rates of patients with well-differentiated tumors were 73 percent and 15 percent, respectively, whereas for patients with poorly differentiated lesions, it was 6 percent and 0. Although most patients require palliative decompressive procedures, resection should be attempted whenever possible. It is expected that nonoperative techniques will have an increased role in the treatment of poor-risk patients or those who have unresectable disease.

Adenocarcinoma↗
PubMed1984

Arachidonic acid metabolites mediate early burn edema.

Standard burns were sequentially produced on the backs of Sprague-Dawley rats at 0, 1, 2, and 2 1/2 hr, followed by the IV injection of Evans blue dye. All animals were killed at 3 hr, and burns evaluated by wet/dry weight ratios, and Evans blue extravasation scored 1-4 by two observers. Five groups of rats were compared to controls. Rats made neutropenic by exposure to 137cesium showed no significant difference in wet/dry weight ratio or Evans blue extravasation compared to controls. At 1 1/2 hr four other groups were treated with various inhibitors of arachidonic acid metabolism including ibuprofen, a cyclo-oxygenase inhibitor; FPL 55712, a leukotriene (LT) receptor antagonist; ketoconazole, an inhibitor of thromboxane (Tx) synthetase; and lodoxamide, a calcium channel inhibitor. All treated groups showed significant reduction of Evans blue dye extravasation. Wet/dry weight ratios were significantly reduced in rats treated with FPL 55712 and ketoconazole before or after burning. These data support the postulate that oxygenation products of arachidonic acid, particularly Tx and LT, are important mediators in early burn edema.

Animals↗
PubMed1984

Short term variability in FEV1: relation to pretest activity, level of FEV1, and smoking habits.

The natural variability in forced expiratory volume in one second (FEV1) over 20 minutes was determined in 54 fit hospital employees and 13 patients with restrictive lung disorders. Initial FEV1 ranged from 1.1 to 6.3 1 BTPS. Variability when expressed as absolute change was similar at all levels of FEV1, so that, when expressed as percentage change, variability decreased with increasing FEV1. Smoking habits did not appear to affect variability but activity before the test did. On the basis of these results an absolute change in FEV1 of 190 ml would be necessary for 95% confidence that the change in FEV1 occurred other than by chance in any one individual. This suggests that the absolute change in FEV1 might be a more reliable criterion than percentage change when distinguishing between natural variability and a response to inhalation of bronchodilators.

Adolescent↗
PubMed1984

Five cephalosporins: pharmacokinetics and their relation to antibacterial potency.

In a group of adult volunteers, pharmacokinetic profiles of five cephalosporins were correlated with their minimal inhibitory concentrations (MICs90) against Staphylococcus aureus, Streptococcus pyogenes, Streptococcus pneumoniae, Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, and Enterobacter aerogenes. Subjects received the following intravenous regimens in a randomized, crossover fashion: (1) 0.5 gm, 1 gm, or 2 gm of cefazolin; (2) 2 gm of cephalothin; (3) 1 gm of cephapirin; (4) 1 gm of cefoxitin; or (5) 0.5 gm of cefamandole. The 500-mg dose of cefazolin produced serum concentrations that exceeded those of any of the other cephalosporins at 0.5, 1, 2, 4, and 6 hours after administration. The area under the curve for this dose of cefazolin was at least twice that of any of the other antibiotics. Two hours after a 500-mg dose of cefazolin, serum levels exceeded the MIC90 for all seven groups of pathogens; at six hours, the 500-mg dose of cefazolin continued to achieve serum levels above the MIC90 against the majority of bacterial groups. In contrast, at two hours after administration none of the other cephalosporins maintained serum levels above the MIC90 for all pathogens; at six hours, the levels of cephapirin were adequate to inhibit the two streptococci, but serum levels of all other cephalosporins were inadequate to inhibit any of the pathogens. These data indicate that a 500-mg dose of cefazolin maintains serum levels above the MICs90 longer than any of the other cephalosporins tested and support the use of a 500-mg dose of cefazolin every eight hours for surgical prophylaxis and treatment of most community-acquired infections. Such a comparatively low dosage offers substantial savings to both patient and hospital.

Adult↗
PubMed1984

Ulcerative colitis: why is the mortality from cardiovascular disease reduced?

A recent mortality study of patients with ulcerative colitis showed significant deficits in deaths from cardiovascular disease and from respiratory disease in males. The reasons for the observed deficits have been examined by studying the risk factors in a consecutive series of 103 patients with ulcerative colitis using matched controls. The patients and controls were assessed for age, sex, social class, alcohol and tobacco consumption. Height, weight and blood pressure were recorded and fasting blood samples were taken for serum lipid estimation. Patients with ulcerative colitis had significantly lower systolic and diastolic blood pressures and the changes were particularly marked in patients with extensive colitis and after panproctocolectomy. After matching for age, sex and social class the patients with ulcerative colitis smoked significantly less than controls. Serum lipid measurements were similar in both groups. The lower blood pressure may be related to sodium and water depletion particularly in ileostomy patients and those with extensive colitis.

Adult↗
PubMed1983

A new oral renal vasodilator, fenoldopam.

Fenoldopam, a dopamine agonist, was evaluated in renal clearance studies during water diuresis after oral doses of 25, 50, and 100 mg. After the 100-mg dose there was an increase in urine flow rate, paraaminohippurate clearance, free water clearance, and an increase in the fractional excretion of sodium, calcium, and uric acid. These effects were evident within the first hour, peaked during the second hour, and lasted about 3 hr. Doses of 50 and 25 mg induced smaller increases. There was no significant change in inulin clearance at any dose. To elucidate the mechanism of action, the studies were repeated after treatment with a dopamine-receptor antagonist (metoclopramide). Metoclopramide greatly diminished the renal effects of fenoldopam. These findings indicate that fenoldopam is an active renal vasodilator in man and increases urine volume, free water clearance, and fractional excretion of sodium by stimulation of renal dopamine receptors.

Adult↗
PubMed1982

Effect of phenylbutazone on electrolyte metabolism in ponies.

Phenylbutazone administered in therapeutic doses to ponies decreased urinary sodium and chloride excretion. The volume and osmolality of the urine was unaffected as was potassium excretion. Faecal excretion of chloride decreased and that of potassium increased, while faecal sodium excretion was unaffected. Plasma pH, bicarbonate and total carbon dioxide decreased after phenylbutazone administration. Packed cell volume, plasma sodium, potassium, carbon dioxide tension and chloride were unchanged.

Animals↗
PubMed1982

Ceftizoxime kinetics and renal handling.

The kinetics and renal handling of ceftizoxime were examined after intravenous and intramuscular injection and the effect of probenecid on its excretion was investigated. Peak serum level after 1000 mg IV was 60.5 microgram/ml and half-life (t 1/2) was 1.4 hr. Peak serum level (40.9 microgram/ml) was reached 1 hr after 1000 mg IM. When probenecid was added to the 1000-mg IM dose the peak level was 44.3 microgram/ml at 1 hr and serum levels at 2, 4, 6, and 8 hr were all higher than after ceftizoxime alone (P less than 0.01). The 1.85-hr t 1/2 of ceftizoxime alone was extended to 2.29 hr when probenecid was added. Ceftizoxime was shown to be actively secreted by the renal tubule; this secretion was decreased by probenecid.

Anti-Bacterial Agents↗
PubMed1982

The effect of ethacrynic acid, bumetanide, frusemide, spironolactone and ADH on electrolyte excretion in ponies.

The effect of ethacrynic acid, bumetanide, frusemide, spironolactone and anti-diuretic hormone (ADH) on the urinary and faecal excretion of water and electrolytes by ponies was studied. Ethacrynic acid, bumetanide, and frusemide given intravenously, increased urinary sodium excretion, and, excepting frusemide, decreased faecal sodium excretion. Given by stomach tube ethacrynic acid reduced urinary and faecal sodium. Bumetanide, given intravenously, spironolactone, frusemide and ADH increased urinary sodium and all except frusemide intravenously decreased faecal sodium regardless of route of administration. Ethacrynic acid and bumetanide, given by stomach tube or intravenously decreased urinary and faecal potassium excretion, as did spironolactone and frusemide given orally. Ethacrynic acid and bumetanide given orally or intravenously, frusemide given orally and ADH intranasally reduced urinary chloride excretion; these same drugs by the same routes also reduced faecal chloride excretion. Excepting frusemide given intravenously, and ethacrynic acid orally, the effect of the drugs studied was not the same on urinary sodium excretion as on faecal sodium excretion. This suggested that different mechanisms were involved in the control of sodium excretion by the kidney and in the gut. There were similarities in the treatment of potassium and chloride by these organs.

Animals↗
PubMed1981

Kinetics and renal handling of cefonicid.

Cefonicid kinetics were determined after intravenous and intramuscular injection and the renal handling of the drug was examined, including the effect of probenecid on its excretion. Peak serum levels after 1000 and 500 mg intravenously was 221 and 91 micrograms/ml. The half-life (t1/2) was the same for both regimens (3.5 hr). Intramuscular injection of the 1000- and 500-mg doses resulted in peak serum levels of 112 and 40 micrograms/ml. When probenecid was given with the 500-mg dose, the peak serum level was 61 micrograms/ml and the time to peak level rose from 1.3 to 2.5 hr. The t1/2 after 1000 and 500 mg alone was much the same at 4.8 and 4.9 hr. The addition of probenecid to the 500-mg dose extended the t1/2 and 7.5 hr. Renal clearance, excretion, and secretion rates for cefonicid were reduced by the addition of probenecid. Cefonicid's long t1/2 and high blood levels may provide clinical efficacy with a single daily dose.

Adult↗
PubMed1981

Nephrotic syndrome associated with lithium therapy.

Two patients on long-term lithium therapy developed the nephrotic syndrome. Ultrastructural study of a renal biopsy in each case showed extensive glomerular epithelial cell foot process fusion. Lithium was withdrawn in each case. The nephrotic syndrome cleared without steroid therapy and has not recurred 18 months later in one patient. The other patient required a further course of treatment with lithium and the nephrotic syndrome returned. Further biopsy revealed a more severe glomerular lesion. The nephrotic syndrome responded again to withdrawal of lithium and institution of steroid therapy. Lithium is known to cause acute renal failure and tubulo-interstitial disease, but the recently described association with proteinuria or nephrotic syndrome is little recognized.

Adult↗
PubMed1980

Irreversible attachment of immunoglobulins and F(ab')2 fragments to their specific cell membrane antigens.

Antiserum was raised in sheep against rat kidney glomerular basement membrane, and the antibodies and their F(ab')2 fragments were prepared. These were reacted with one arm of the bifunctional reagent toluene diisocyanate at pH 7.5 and injected into the tail vein of rats. Kidney sections were taken from the rats and, after washing, incubated at pH 8.5 to permit the other arm of the toluene diisocyanate to become reactive. This procedure resulted in the specific irreversible attachment of the antibodies and their F(ab')2 fragments to their corresponding glomerular basement membrane antigens.

Animals↗