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Biomedical subjects

S Maigaard

Publications and source records attributed to S Maigaard.

50 records · Page 3Linked to original sources
PubMed1980

Penicillanic acid derivatives in the canine prostate.

Distribution of ampicillin, amoxicillin, bacampicillin, mecillinam, pivmecillinam, carbenicillin, indanyl sodium was studied in the canine prostate, prostatic interstitial fluid, and prostatic secretion. All seven antibiotics were found in higher concentrations in the prostatic interstitial fluid than in the prostatic secretion. As expected for weak acids, drug concentrations in these fluids were always lower than the simultaneous serum concentrations. Tissue penetration was enhanced for the penicillin ester, pivmecillinam, as shown by its prostatic secretion/serum and tissue/serum ratios, which were higher than those of the other antibiotics, including the esters, bacampicillin, and carbenicillin indanyl sodium. This results may be due to pivmecillinam's long hydrolysis half-life. The concentrations for these penicillanic acid derivatives in prostatic interstitial fluid were above the minimal inhibitory concentrations for most of the commonly encountered gram-negative bacteria encountered in prostatitis. Therefore, these antibiotics should be effective in the treatment of bacterial prostatitis caused by susceptible organisms. Carbenicillin and carbenicillin indanyl sodium had the highest prostatic interstitial fluid/serum ratios of the compounds tested, and theoretically, therefore, they should be the most effective in the treatment of prostatitis. However, clinical trials should be carried out to confirm this.

Amdinocillin↗
PubMed1980

Mezlocillin pharmacokinetics after single intravenous doses to patients with varying degrees of renal function.

The pharmacokinetics of mezlocillin were examined after single 2- and 4-g intravenous injections to three groups of male patients with creatinine clearances of I >/= 60, II = 21 to 59, and III </= 20 ml min(-1) 1.73 m(-2). The decline in serum antibiotic levels was biphasic in all groups, and serum data were interpreted in terms of the pharmacokinetic two-compartment model. The mean elimination half-life of mezlocillin after the 2-g dose was 1.3, 1.5, and 2.3 h in groups I, II, and III, respectively. Equivalent values after the 4-g dose were 1.2, 1.6, and 4.4 h. In three functionally anephric patients the mean serum half-life of mezlocillin was 1.5 h during hemodialysis. Mean antibiotic levels in serum were greater than 10 mug ml(-1) for 4 h after the 2- and 4-g doses in group I and 8 h in group II. In group III, levels greater than 10 mug ml(-1) were maintained for 6 h after the 2-g dose and over 12 h after the 4-g dose. Mezlocillin distribution characteristics were largely independent of renal function and dose size. The only observable change occurred in the value of V(dss), which was significantly increased to 0.32 with 0.38 liter kg(-1) in severe renal impairment, compared to ca. 0.2 liter kg(-1) in subjects with normal or slightly impaired renal function. Cumulative 24-h urinary excretion accounted for 50, 40, and 3.2% of the dose in groups I, II, and III, respectively. Urine levels of mezlocillin were uniformly greater than the minimum inhibitory concentration for susceptible organisms for 12 h after dosing in all patients who produced urine. Because of the relatively small increase in the mezlocillin elimination half-life with declining renal function, dose reduction is necessary only in cases of severe renal impairment.

Anti-Bacterial Agents↗
PubMed1980

Netilmicin treatment of complicated urinary tract infections.

Netilmicin was investigated in the treatment of complicated urinary tract infection in 169 elderly male patients. It was found to be safe and effective at the dose levels of 1.0-2.5 mg/kg, three times a day, or 2 mg/kg twice a day, eliminating approximately 50-60% of the infections. The serum half-life of netilmicin was 2-3 hours in subjects with normal renal function but increased to 10-14 hours in subjects with severe uremia. When the dosage was adjusted according to the patient's weight and serum creatinine, some nephrotoxicity occurred, possibly due to drug accumulation. Therefore, we suggest that the dose be adjusted according to reduction in creatinine clearance and when possible, monitoring serum concentrations during treatment.

Aged↗
PubMed1979

Co-trimazine distribution in the canine prostate.

Constant infusion experiments were performed on dogs to determine the concentration levels of co-trimazine (a combination of trimethoprim and sulphadiazine) in the dogs' prostatic secretion, prostatic interstitial fluid, prostatic tissue, urine, and other tissues. Trimethoprim concentrations in prostatic secretion, interstitial fluid and tissue were higher than corresponding serum values, whereas the concentrations of sulphadiazine were far below these values. These results were compared to those of a similar study which combined trimethoprim and sulphamethoxazole (co-trimoxazole). The prostatic secretion to serum ratios of sulphadiazine were lower than those for sulphamethoxazole. Urine concentrations of sulphadiazine, however, were much higher than those of sulphamethoxazole. In serum and urine, only co-trimazine had a trimethoprim/sulphonamide ratio approximating the optimal synergy ratio of 1:20. Neither trimethoprim/sulphonamide combination appears to have any theoretical advantage over the other in the treatment of prostatitis. However, co-trimazine may be more effective in the treatment of urinary tract infections in general because of the high concentrations of sulphadiazine in urine.

Animals↗
PubMed1979

Renal lymph and interstitial fluid concentration of co-trimazine: an experimental study in dogs.

Renal clearance and renal hilar lymph and interstitial fluid concentrations of co-trimazine were investigated in dogs during constant intravenous infusion. The lymph was obtained by direct cannulation of the lymphatics, and the interstitial fluid from small plastic tissue chambers, implanted 4--6 weeks before the experiments. The clearance values for trimethoprim and sulphadiazine, compared to the glomerular filtration rate, as measured by 125I-iothalamate clearance, showed a net tubular secretion of trimethoprim and tubular re-absorption of sulphadiazine. Renal lymph and interstitial fluid concentrations were found to be lower than the plasma concentrations, corresponding well with earlier findings for several other antimicrobial agents. We found a statistically significant difference between lymph/plasma and interstitial fluid/plasma ratios, indicating different composition and origin of lymph and interstitial fluid.

Animals↗
PubMed1979

Netilmicin treatment of complicated urinary tract infection in patients with renal function impairment.

The efficacy and tolerance of netilmicin was studied in 28 elderly male patients with varying degrees of renal function impairment who suffered from complicated urinary tract infections. Doses of netilmicin, equivalent to 2 mg/kg divided by milligrams of creatinine per 100 ml, were administered every 12 h. A 62% cure rate, defined as negative urine culture at 1-week follow-up, was obtained. Treatment failure correlated with impaired renal function. Nephrotoxic reaction, defined as any significant increase in serum creatinine during treatment, was found in 6 of 28 patients (21%). The increase in serum creatinine was transient in all except one of these patients. Apart from the finding of a significant correlation between nephrotoxic reaction to netilmicin and postoperative urinary tract infection, no clinical or therapeutic features correlated with nephrotoxicity; trough concentrations correlated with serum creatinine.

Aged↗
PubMed1979

Cinoxacin: pharmacokinetics and tolerance in patients with normal and impaired renal function.

The pharmacokinetics of cinoxacin, a new antibacterial compound related to nalidixic acid and oxolinic acid, were investigated in 22 patients with varying degrees of renal impairment. After oral administration of cinoxacin at 500 mg every 12 h for 7 days to all patients, the drug was found to be well tolerated. The urine concentrations of cinoxacin in all patients far exceeded the minimal inhibitory concentrations for susceptible organisms commonly found in urinary tract infections. The serum half-life of cinoxacin in patients with normal renal function was approximately 2.7 h but increased to approximately 8.5 h in patients with creatinine clearance less than 30 ml/min. No undue drug accumulation was demonstrated in any patient group during the treatment. Highly significant correlations were found between the elimination rate constant and creatinine clearance and also between the elimination half-life and serum creatinine. The bioavailability of cinoxacin was independent of renal function.

Aged↗
PubMed1979

Rosoxacin and cinoxacin distribution in prostate, vagina, and female urethra. An experimental study in dogs.

Rosoxacin and cinoxacin, two new compounds structurally related to nalidixic acid, were investigated in dogs. Our primary interest was in the beneficial effects of the two drugs when used in the treatment of urinary tract infections. The distribution of rosoxacin and cinoxacin was investigated in prostatic tissue, prostatic interstitial fluid, and prostatic secretion, and in vaginal and female urethral secretions. Concentrations of both antibiotics were also measured in plasma, various tissues, and spinal fluid. The amounts of rosoxacin and cinoxacin in all tested tissues, fluids, and secretions were in the range of the minimal inhibitory concentrations for most Gram negative organisms found in urinary tract infections. This suggested possible beneficial effects of these drugs when the infection involves the above tissues. Rosoxacin concentration ratios were higher than those of cinoxacin relative to plasma concentration in prostatic, vaginal, and urethral secretions, as well as in prostatic and other tissue. These ratio differences were explained by the different physiochemical properties of the two drugs.

Animals↗
PubMed1978

Comparison of netilmicin and amikacin in treatment of complicated urinary tract infections.

Netilmicin and amikacin, two recently developed aminoglycosides, were compared in a prospective, randomized study of 57 male patients with complicated urinary tract infections. Both drugs were administered intramuscularly every 12 h for 7 to 10 days, netilmicin at 2 mg/kg and amikacin at 7.5 mg/kg. The two groups were comparable as to infecting bacteria and underlying pathology of the urinary tract. No patients had indwelling catheters. All microorganisms isolated were sensitive to both antibiotics. A total of 69% of the patients treated with netilmicin and 57% of the patients treated with amikacin were cured of the infection, as defined by a negative culture at 7 days after discontinuation of treatment. No major side effects were recorded, and no significant changes were noted in parameters of renal function. Of the patients treated with amikacin, 21% experienced temporary local pain at the injection site; no such effect was noted in the netilmicin-treated group. Therefore, netilmicin appeared to be as effective and better tolerated than did amikacin in the treatment of complicated urinary tract infection.

Adult↗
PubMedDate not supplied

Relaxant effects of hexosamines on isolated small human placental arteries.

Wharton's jelly contains large amounts of hyaluronic acid, and glucosamine is an important constituent of this macromolecule. In order to evaluate the placental vascular effects of this aminosugar, small chorionic and stem villous arteries were dissected from placental specimens obtained at normal term vaginal deliveries (n = 15). Ring preparations were mounted in organ baths, and isometric wall tensions were measured. Glucosamine and its epimer galactosamine (5 X 10(-4) to 10(-2) M) produced marked relaxation of contractions induced by PGF2 alpha (10(-5) M) in both chorionic and stem villous arteries. The effect was unchanged after pretreatment with atropin, propranolol and indomethacin. The relaxant effect of the neutral sugar mannose was less pronounced compared with that of the hexosamines. Total tissue concentrations of placental hexosamines have been reported within the range needed to produce placental vascular relaxation in the present study. However, the major part of these compounds is integrated in macromolecules, and the tissue level of free hexosamine is probably far below the total concentrations. Accordingly, the effects of hexosamines demonstrated in the present study might not be of physiological importance in the regulation of fetal placental medial smooth muscle tension.

Arteries↗
PubMedDate not supplied

Effects of vasoactive intestinal polypeptide and substance P on human intramyometrial arteries and stem villous arteries in term pregnancy.

The effects of vasoactive intestinal polypeptide (VIP) and substance P on isolated human intramyometrial arteries and fetal stem villous arteries obtained from term pregnant women were compared. Ring preparations of small intramyometrial arteries and fetal stem villous arteries obtained at caesarean section were mounted in organ baths, and isometric tension was recorded. None of the peptides affected resting tension. In intramyometrial arteries precontracted by vasopressin (2.8 x 10(-9) M) both substance P (10(-12) to 10(-8) M) and VIP (10(-8) to 10(-6) M) caused relaxation. In fetal stem villous arteries precontracted by prostaglandin F2 alpha (10(-5) M) cumulative addition of substance P (10(-11) to 10(-6) M) did not produce significant changes in tension as compared with controls, while addition of single doses produced moderate relaxation. VIP (10(-8) to 10(-6) M) induced relaxation with similar effects for the addition of cumulative and single doses. The responses to VIP and substance P remained unaffected after pretreatment by atropine (10(-6) M), propranolol (10(-6) M), and indomethacin (10(-6) M). The results support a role for VIP and substance P in the regulation of uteroplacental blood flow in term pregnancy.

Arteries↗
PubMedDate not supplied

Digoxin inhibition of relaxation induced by prostacyclin and vasoactive intestinal polypeptide in small human placental arteries.

Small chorionic plate arteries were obtained from human placentae following normal vaginal delivery. Tubal vascular preparations were dissected, mounted in organ baths, and their isometric tension was recorded. Digoxin (10(-6) M) caused a rise in basic tension, reaching a maximum of 17 per cent of contractions induced by potassium (124 mM) depolarization. Pretreatment with digoxin did not significantly influence the concentration-dependent contractile responses to 5-hydroxytryptamine and prostaglandin F2 alpha (PGF2 alpha). In preparations contracted with PGF2 alpha, cumulative addition of prostacyclin (PGI2) and vasoactive intestinal polypeptide (VIP) produced concentration dependent relaxations. Digoxin (10(-8) to 10(-6) M) inhibited and finally abolished these relaxant effects of PGI2 and VIP in a concentration-dependent fashion. Pretreatment by digoxin (10(-8) to 10(-6) M) diminished the relaxant effect of sodium nitroprusside, but the effect was less pronounced than that on PGI2- and VIP-induced relaxation. As PGI2 and VIP may be of importance for the maintenance of a low resistance of the fetal placental vascular bed, the finding that digoxin decreases the vasodilating effects of these agents might imply effects on placental resistance of cardiac glycosides when used in late human pregnancy.

Arteries↗