Biomedical subjects

P B Wels

Publications and source records attributed to P B Wels.

15 recordsLinked to original sources

PubMed1993

The development of a bedside algorithm capable of targeting anti-endotoxins to the responder subpopulations.

The published selection criteria for use of anti-endotoxin antibodies are modeled on the criteria used in protocol enrollment of patients. These criteria are not suitable for therapeutic decision-making, because the trials themselves prove that the enrollment criteria have both low sensitivity and low specificity. In order to develop a selection method with greater sensitivity and specificity, we examined the charts and records of 23 patients that we enrolled in the multicenter trials of E5 and HA-1A. We retrospectively determined that seven of our 23 enrolled patients were optimal candidates, based on a pattern of rapid clinical deterioration followed by improvement in 24-96 h. We then explored a variety of different modes of bedside patient selection, in search of a method to select as many of the seven optimal candidates as possible while at the same time rejecting the greatest number of the 16 who showed no benefit when treated. None of the resulting selection methods has perfect performance, but nearly all were better than the original protocol enrollment criteria. In our patients, bacteremia had 57% sensitivity and 56% specificity, which was quite similar to the findings in the HA-1A multicenter trial. Shock had 100% sensitivity and 44% specificity, while a baseline organ dysfunction score of > or = 5 had 100% sensitivity and 69% specificity. A new algorithm that we developed based on a patient's need for vasopressors and baseline organ dysfunction had 100% sensitivity and 81% specificity. This algorithm could identify all seven of the optimal candidates, plus three more.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

PubMed1990

Comparative evaluation of the pharmacokinetics of N-methylthiotetrazole following administration of cefoperazone, cefotetan, and cefmetazole.

The comparative pharmacokinetics and in vivo production of N-methylthiotetrazole (NMTT) were evaluated following administration of cefoperazone, cefotetan, and cefmetazole. In a randomized-crossover manner, 11 healthy male volunteers received single 2-g intravenous doses of each agent and serial blood and urine samples were collected. Concentrations of NMTT and the parent compound in plasma, urine, and the reconstituted antibiotic solution were determined by high-pressure liquid chromatography. The amounts of NMTT administered were 6.06 +/- 0.46, 14.4 +/- 0.87, and 17.4 +/- 1.06 mg for cefoperazone, cefotetan, and cefmetazole, respectively (P less than 0.05). The mean NMTT plasma concentration-time profiles following administration of each cephalosporin were markedly different. Six hours after dosing, NMTT concentrations in plasma following cefoperazone administration were higher than those following administration of cefmetazole and cefotetan. Urinary recoveries of NMTT averaged 137.0 +/- 37.1, 38.3 +/- 6.98, and 25.2 +/- 5.95 mg following administration of cefoperazone, cefotetan, and cefmetazole, respectively (P less than 0.01). The apparent amount of NMTT produced in vivo, calculated by subtracting the amount of NMTT administered from the amount of NMTT excreted in urine, was significantly lower following cefmetazole administration than after administration of cefoperazone and cefotetan (P less than 0.01). The discrepancy between in vitro NMTT production (cefmetazole greater than cefotetan greater than cefoperazone) and the amount of NMTT formed in vivo and excreted unchanged (cefoperazone greater than cefotetan greater than cefmetazole) suggests that in vivo production of NMTT is dependent on the disposition of the parent cephalosporin. These results further suggest that cephalosporins which undergo extensive biliary excretion, such as cefoperazone, are associated with the greatest amount of in vivo NMTT release, whereas cephalosporins which are primarily renally excreted, such as cefmetazole, are associated with the lowest in vivo production of NMTT.

Adult↗

PubMed1985

Clinical risk factors for prolonged PT/PTT in abdominal sepsis patients treated with moxalactam or tobramycin plus clindamycin.

Factors associated with prolongation of the prothrombin time were analyzed in 94 patients with intra-abdominal sepsis. Patients were randomized prospectively to receive either the combination of tobramycin and clindamycin (TM/C) or moxalactam (MOX). This paper presents a retrospective review designed to compare the frequency of prolonged clotting times and to analyze predisposing factors. Prothrombin time (PT) prolongation occurred more frequently in patients given moxalactam (19 of 47 patients) than in patients given the combination of tobramycin and clindamycin (9 of 47 patients) (p less than 0.05). Prolongation of the partial thromboplastin time (PTT) occurred in all patients with a prolonged PT. Liver disease, upper gastrointestinal surgery, and use of cimetidine were more frequent in those patients with abnormal PT/PTT values (p less than 0.05). Two moxalactam-treated patients with subsequent PT/PTT prolongation had individual clotting factors assayed before moxalactam treatment and at the time of detection of the abnormal PT. The activity of clotting factors II, VII, VIII, IX, X, and XII was reduced during MOX therapy. Treatment with vitamin K reversed the abnormality. In view of underlying abnormalities and rapid response to parenteral vitamin K, the mechanism is probably an acute vitamin K deficiency superimposed upon chronic vitamin K deficiency. In patients with intra-abdominal infection, those treated with MOX are more likely to develop abnormal PT than those treated with TM/C. Since abnormal PT/PTT was common even in TM/C patients, supplemental vitamin K should be considered for all seriously ill, older patients with abdominal infections.

Abdomen↗

PubMed1984

C-reactive protein as an indicator of infection relapse in patients with abdominal sepsis.

C-reactive protein (CRP) concentrations were monitored serially in 97 patients with abdominal sepsis to determine if differences in infection type or site would produce diagnostic or prognostic CRP level elevations. After surgery and abdominal infection, the average (+/- SD) CRP peak values were 21.2 +/- 9.0 mg/dL. The CRP values rose markedly with infection, rose further with surgery, and subsided to less than 10 mg/dL with cure. Persistent levels of more than 10 mg/dL indicated abscess formation or continued infection. The average normal value at complete tissue healing after resolution of infection was 1.2 mg/dL, which was not different from that for healthy volunteers. Analysis suggested that CRP concentrations were not predictive of the type, site, or severity of abdominal infection; however, since persistent elevations were frequently associated with new or unresolved bacterial infection, serial determinations may be helpful in monitoring the course of disease and response to treatment.

Abdomen↗

PubMed1983

Steady-state moxalactam pharmacokinetics in patients: noncompartmental versus two-compartmental analysis.

Moxalactam pharmacokinetics at steady state was examined in a group of 40 patients with presumed or proven abdominal sepsis. Mean steady-state serum concentrations ranged from 27.0 to 211.0 mcg/ml and correlated inversely with creatinine clearance (r = 0.91, p less than 0.0001). Terminal half-life ranged from 1.27 to 8.27 hr and reflected the varying renal function of the patients. Moxalactam total body clearance (CL) displayed excellent correlation with creatinine clearance as 92% (r2 x 100) of the variance in clearance could be accounted for by renal function (p less than 0.0001). Pharmacokinetic parameters were estimated using noncompartmental analysis based on statistical moment theory. Noncompartmentally determined CL was in agreement with CL determined by nonlinear least squares regression (r = 0.99, p less than 0.0001). Moxalactam total body clearance is best predicted from creatinine clearance corrected for body surface area.

Biological Assay↗

PubMed1983

A randomized clinical trial of moxalactam alone versus tobramycin plus clindamycin in abdominal sepsis.

One hundred patients with intraabdominal infections were assigned randomly in double-blind fashion to receive either the combination of tobramycin plus clindamycin (TM/C) or moxalactam (MOX) alone. Fifty patients comprised each group, but one patient in each group died of infection before 48 hours treatment. In the remaining 98 patients, the average age was 62 years, initial serum albumin was 3.0 mg/dl, serum creatinine was 1.5 mg/dl, and over half of the patients were nutritionally deficient by the prognostic nutritional index criteria. In approximately one-half of the patients, the source of infection was perforated colon or perforated appendix. There were no significant differences in demographic factors between these groups, except that those who were given TM/C were older, while those who were given MOX had a more serious long-term prognosis due to underlying disease. The average length of treatment was 11 days, and the average hospitalization time was 24 days. Clinical response to therapy was identical, since 74% of the TM/C patients and 76% of the MOX patients had satisfactory responses. Bacteria persisted at the site of infection in 63% of the TM/C patients and in 65% of the MOX patients, with the most common isolate being Staphylococcus epidermidis. Pseudomonas infections were the most difficult to cure in both groups. The two regimens differed only in side effects; TM/C was a more frequent (p less than 0.05) cause of nephrotoxicity, and elevated prothrombin time/partial thromboplastin time (PT/PTT) was more frequently (p less than 0.05) observed in MOX. All PT/PTT elevations responded to injections of vitamin K, and no serious bleeding occurred. Choice between these regimens depends on the risk of renal versus hematologic side effects, rather than efficacy.

Abdomen↗

PubMed1983

Antibiotic penetration in liver infection: a case of tobramycin failure responsive to moxalactam.

A 23-year-old man sustained a severe liver laceration which subsequently became infected with Enterobacter aerogenes. Blood cultures were positive for this organism and the patient experienced sepsis. Over the course of 18 days, his bilirubin and serum creatinine increased from normal to 40 and 2.7 mg/dl, respectively. Tobramycin, clindamycin, and penicillin failed to control the infection despite in vitro sensitivity of the organism to tobramycin. Moxalactam was started as a last resort, and the symptoms of infection resolved in 12 h. Both hepatic and renal function returned to normal, and the patient was discharged without complications. Moxalactam concentrations in wound fluid exceeded serum concentrations and the usual minimum inhibitory concentration of the infecting organism. A likely explanation for response to moxalactam, in face of tobramycin failure, was that moxalactam was able to reach the site of infection.

Adult↗

PubMed1982

Renal handling of gentamicin by normal and ischemic canine kidneys.

The purpose of this study was to examine the pharmacokinetics of gentamicin renal uptake in dogs and assess the role of chronic renal ischemia. A stenosing silver clip was place on the left renal artery of four mongrel dogs. Six months later, each dog received an infusion of gentamicin and inulin. Blood and urine samples were collected serially. In each dog, the ischemic left kidney was smaller and had a lower RPF and CCR. The decrease in CCR was highly correlated with the decrease in RPF. Measured gentamicin kidney concentrations were found to be in good agreement with predicted values based on the amount reabsorbed and the kidney weight. Within each animal (control vs. ischemic kidney), there was a significant correlation between the filtered load of gentamicin and both the renal reabsorption and excretion of gentamicin. These relationships exhibited high R2 values, demonstrating that the induced ischemia did not alter the filtration or reabsorbtive mechanisms of gentamicin within the animal, but only decreased the filtered load. Between animals, gentamicin excretion was proportional to filtered load, but gentamicin reabsorption had the lowest r2 value, explaining only 49% of the observed variance. The unexplained variance encountered in gentamicin reabsorption between animals establishes that there are important determinants of renal tissue concentration that are independent of filtration or filtered load. This study suggests that a reduction in glomerular filtration is not an important risk factor for elevated gentamicin renal tissue concentrations, provided that serum concentrations are controlled within the therapeutic range.

Absorption↗

PubMed1981

Coagulum choledocholithotomy: a preliminary report.

Using the technique of coagulum pyelolithotomy, development of which was pioneered by Dees in 1943, we successfully extracted common duct stones from 17 dogs and three human beings. The canine model for pyelolithotomy was developed by producing an autogenous clot. We think Dee's technique could be applicable in common bile duct surgery.

Animals↗

PubMed1973