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Biomedical subjects

R J Creger

Publications and source records attributed to R J Creger.

32 records · Page 2Linked to original sources
PubMed1991

Contamination during in vitro processing of bone marrow for transplantation: clinical significance.

We determined the prevalence and clinical significance of positive microbiologic cultures obtained from 194 consecutive bone marrow harvests intended for infusion in 188 consecutive adult bone marrow transplant patients. Microbiologic cultures were obtained at harvest, after manipulation in vitro (for ABO imcompatibility or purging procedures), and at the time of thawing and infusion (after earlier cryopreservation). Only one of 194 marrow harvests was culture-positive intra-operatively (from an ABO-compatible allogeneic marrow that was infused without manipulation). None of 39 other allogeneic marrows (including 21 ABO-incompatible marrows which were manipulated in vitro) and none of 154 autologous marrows (including 40 which were purged in vitro) grew bacteria or fungi. On the other hand, 12 of 153 (8%) bone marrow samples were positive for micro-organisms after thawing at the time of infusion. The predominant organisms cultured were gram negative bacilli (including five Pseudomonas sp.), probably introduced during the thawing process in a water bath. In only one of 13 contaminated marrows was the same organism(s) (Pseudomonas picketti and Pseudomonas paucimobilis) recovered in vivo during the transplant course. This patient experienced a bacteremia which was eradicated without sequelae. Contamination of marrow can occur during the procurement and in vitro handling processes. With proper sterile technique bone marrow infusion does not pose a significant infectious risk for the immunocompromised transplant patient.

Adolescent↗
PubMed1990

Phase I trial of high-dose etoposide, high-dose cisplatin, and reinfusion of autologous bone marrow for lung cancer.

We undertook a phase I trial using fixed-dose cisplatin, escalating doses of etoposide, and reinfusion of previously obtained autologous bone marrow in 29 relapsed or refractory small cell and non-small-cell lung cancer patients. Median age was 59 years (range of 38-68 years). Three patients had small-cell and 26 patients had non-small-cell lung cancer. Patients received i.v. cisplatin 200 mg/m2 over 5 days and i.v. etoposide 600 mg/m2/day for 3 days (total of 1,800 mg/m2) that was escalated to 800, 1,000, 1,200, 1,400, and 1,600 mg/m2/day for 3 days (total of 2,400-4,800 mg/m2). Cryopreserved autologous bone marrow was thawed and reinfused through a central venous catheter the second day after the completion of chemotherapy. Toxicities included nausea, vomiting, alopecia, high-tone hearing loss, mucositis, diarrhea, renal insufficiency, metabolic acidosis, and severe myelosuppression. The duration of neutropenia (less than 500 neutrophils/microliter) ranged from 5 to 22 days (median of 11 days) and the duration of severe thrombocytopenia (platelets of less than 20,000/microliters untransfused) ranged from 2 to 19 days (median of 9 days). Reversible renal insufficiency (peak serum creatinines of 6.7, 6.6, 4.3, and 3.5 mg/dl) occurred in four patients who completed the therapy. In three patients, death occurred within 4 weeks of chemotherapy and marrow reinfusion. Three complete and 12 partial remissions (range of 1+(-)22+ months, median of 3 months) were observed. No response was noted in eight patients and tumor progression within 1 month of transplant occurred in two patients. The maximally tolerated dose of etoposide was 1,400 mg/m2/day (total of 4,200 mg/m2), since two of three patients developed life-threatening diarrhea at the 1,600 mg/m2/day (total of 4,800 mg/m2) dose. The encouraging antitumor effects of this regimen suggest that this approach may be useful therapy for lung cancer and other tumors sensitive to VP-16 and cisplatin.

Adult↗
PubMed1990

Infusion of high doses of undiluted etoposide through central venous catheters during preparation for bone marrow transplantation.

We employed a new method to administer etoposide in high doses to 51 patients undergoing autologous bone marrow transplantation. Undiluted etoposide (20 mg/ml) was sterilely drawn into Luer-Lok plastic syringes, connected to IV extension tubing, and infused intravenously by a syringe pump over 3-4 hours. Patients received etoposide at doses ranging from 400 to 1600 mg/m2 per day (median dose: 800 mg). Total actual etoposide doses infused during the transplant period ranged from 2200 to 9000 mg. The infusion rate range was 4.1-13.4 mg/min. No episodes of hypotension, bronchospasm, or hemorrhagic cystitis were noted during or within 3 days of the etoposide infusion. In addition, no cracking of the infusion apparatus was observed in any of the 148 separate infusions. Serum bicarbonate concentrations fell significantly in 6 patients who received the higher etoposide doses. This procedure is superior to the standard method of etoposide drug delivery, since large doses of etoposide may be given without the concomitant administration of large volumes of fluid over short periods of time.

Adenocarcinoma↗
PubMed1990

Percutaneous placement of femoral central venous catheter in patients undergoing transplantation of bone marrow.

Five patients undergoing transplantation of autologous bone marrow underwent percutaneous placement of a double lumen central venous catheter into the inferior vena cava by way of the femoral vein. All had conditions that precluded access to the superior vena cava or other sites in the upper part of the torso. Patients ranged in age from 18 to 59 years. The double lumen central venous catheter was inserted using aseptic technique in the operating room, and the catheter exit site was dressed using sterile technique every 48 hours afterward. Patients received all irradiated blood product transfusions, intravenous fluids, intravenous antibiotics, parenteral alimentation and autologous bone marrow reinfusion through the catheter. The duration of severe neutropenia (less than 500 neutrophils per microliter) and severe thrombocytopenia (less than 20,000 platelets per microliter) ranged from zero to 24 days (median of 22 days) and five to 20 days (median of 15 days), respectively. Catheters remained in the groin area 23 to 45 days (median of 35 days). Complications included one catheter-related Streptococcus species infection and one Escherichi coli bacteremia. These infections resolved with the catheter in place after appropriate institution of antibiotics. No episodes of thrombosis, kinking, migration, extravasation of drugs or local infection were noted. Central venous catheters can be safely inserted and maintained in the groin area even in severely immunocompromised patients receiving bone marrow transplants.

Adolescent↗
PubMed1989

High-dose melphalan, misonidazole, and autologous bone marrow transplantation for the treatment of metastatic colorectal carcinoma. A phase I study.

To augment the antitumor effect of high-dose melphalan and determine pharmacokinetics we conducted a phase I trial of escalating doses of high-dose IV melphalan with the chemosensitizer misonidazole for patients with advanced colorectal carcinoma. Fourteen patients with modified Dukes D adenocarcinoma of the colorectum were treated with a single course of melphalan (40-60 mg/m2 i.v. bolus q.d. X 3 days) and misonidazole (1-3 g/m2 p.o. q.d. X 3 days) followed by autologous bone marrow transplantation. Toxicity consisted of severe myelosuppression, moderate nausea and vomiting, and mild mucositis and diarrhea. One patient developed unexplained renal tubular acidosis, and a diffuse encephalopathy occurred in another patient. Three patients died within the first 30 days after the start of treatment, two due to tumor progression and one due to sepsis and disseminated intravascular coagulation-induced intracerebral hemorrhage. Six of 14 patients achieved a partial response, and the median response duration was 4 months (range 3-10 months). Analysis of misonidazole serum concentrations showed similar pharmacokinetics to those previously reported, suggesting no significant drug interaction with intravenous melphalan. Mean peak serum concentrations ranged from 81.8 micrograms/ml to 115.2 micrograms/ml at the second and third misonidazole dose levels, which approximate those known to provide effective chemosensitization with melphalan in animal models. In this phase I study, we showed that maximally tolerated doses of intravenous melphalan can safely be combined with oral misonidazole. In view of the large volumes of oral misonidazole required at the highest dose level, subsequent studies to determine the maximally tolerated dose of misonidazole should employ the intravenous form.

Adenocarcinoma↗
PubMed1989

Infectious emergencies in oncology patients.

The development of neutropenia in a patient undergoing therapy for cancer represents a serious medical problem that rapidly escalates if fever develops. A diligent history and physical examination cannot be overemphasized, since this maneuver may direct the medical person to quickly identify the source of the infection and initiate appropriate therapy. No time should be wasted, but every attempt should be made to quickly obtain body fluids or tissue for microbiologic culture purposes. Appropriate therapy should then be instituted in an empiric manner. The antibacterial agents that are chosen as initial therapy should be selected based on a knowledge of the current local ecology and the antibiotic resistances of endemic strains of bacteria. The empiric therapy should continue until the patient has evidence of recovery of bone marrow function. In those patients who have developed obvious tissue infection, such as pneumonia or bloodstream infection, the therapy should be continued until the infection is eradicated. In patients who have persistent fever despite broad-spectrum antibacterial agents, a painstaking search for the source and type of infection should continue, including repeated blood cultures and other tests. Additional antibiotic or fungal agents should be administered as the need arises. Such an approach to this group of patients has resulted in a significantly better outcome for cancer patients. With the advent of recombinant hematopoietic growth factors, which may allow for a more rapid marrow and immunologic recovery, the therapy for the neutropenic patient should continue to improve.

Agranulocytosis↗
PubMed1989

Rapid infusion amphotericin B: effective and well-tolerated therapy for neutropenic fever.

A retrospective analysis was carried out of the results of 115 intensively-treated cancer inpatients receiving 91 treatment courses of amphotericin B given in an empirical fashion. Amphotericin B was administered over 1.5 to 2 hours at a dose of 0.6 to 0.7 mg/kg/day. Median duration of neutropenic fever before amphotericin B administration was 5 days (range 1 to 32 days) and median total amphotericin B dose was 480 mg (range 10 to 2450 mg). In 56 (61%) of 91 amphotericin B courses, neutropenic fevers resolved; this occurred a median of 3 days (range 1 to 15 days) after amphotericin B was begun and at a median dose of 120 mg (range 10 to 850 mg). Response to amphotericin was independent of positive cultures for fungus or sites of positive culture. Adverse reactions to amphotericin B included rigors (89% of courses), fever (23%), bronchospasm (9%), and transient hypotension (9%). Median increase above baseline serum creatinine in patients given amphotericin B was 0.5 mg/dl (range 0 to 2.6 mg/dl) compared to a median of 0.1 mg/dl (range 0 to 2.9 mg/dl) in a similar group of intensively-treated cancer patients who did not receive amphotericin B. Amphotericin B was well tolerated when given by rapid infusion and was associated with prompt resolution of neutropenic fever in the majority of patients.

Adolescent↗
PubMed1988

Randomized trial of imipenem-cilastatin versus gentamicin plus clindamycin in the treatment of polymicrobial infections.

The comparative efficacy of imipenem-cilastatin versus clindamycin and gentamicin in the treatment of polymicrobial infections was evaluated. Eleven patients completed treatment with the former and nine with the latter. Conditions treated included infected extremity ulcers, peritonitis, perirectal abscess, soft-tissue abscess, abdominal abscess, and acute diverticulitis. Similar rates of bacteriologic and clinical cure or improvement were achieved with the two treatments. Superinfection occurred in two patients who received imipenem-cilastatin and one who received clindamycin and gentamicin. No significant difference in adverse effects was noted. Imipenem-cilastatin appears to be an effective antibiotic in treating polymicrobial infections; however, a much larger patient population would be required to detect a significant difference in the efficacy rates or frequency of adverse effects when comparing the two regimens.

Adult↗
PubMed1985

Pharmacokinetics of tobramycin and gentamicin in abusers of intravenous drugs.

The kinetics of aminoglycoside elimination were determined in 18 hospitalized narcotics abusers receiving gentamicin or tobramycin for treatment of severe infection. Rapid aminoglycoside elimination (requiring doses of greater than 5 mg/kg per day to maintain adequate drug levels) was noted in 12 of the 18 patients (18 of 27 clearance studies). Patients found to have rapid elimination were younger (P less than 0.01) and had larger drug distribution volumes (P less than 0.005), greater measured creatinine clearances (P less than 0.05), and lower creatinine levels in serum (P less than 0.001) than those with normal elimination. Nevertheless, by regression analysis, age, creatinine levels in serum, creatinine clearances, and drug distribution volumes proved to be unreliable predictors of individual aminoglycoside clearance. Measured drug half-life in serum appeared to be the only reliable predictor of drug clearance (r = 0.93). Patients with rapid drug elimination had aminoglycoside clearances 16 to 43% greater than measured creatinine clearances, suggesting an extraglomerular route of drug elimination. We conclude that in drug abuse patients a significant and clinically unpredictable interpatient variation occurs in aminoglycoside elimination and that accurate serum kinetics are needed to determine therapeutic dosing. In addicts younger than 35 years, with a creatinine level of less than 1.0 mg/100 ml in serum, the risk of inadequate therapy is high if standard dosing guidelines are followed. For this group, initial dosing of 8 mg/kg per day, with a drug half-life determination on the first dose, is recommended. Pharmacokinetic analysis is critical for all drug abusers treated with aminoglycosides for serious infection.

Adult↗
PubMed1985

Cerebrospinal fluid penetration of moxalactam in ventriculostomy patients.

The cerebrospinal fluid penetration of moxalactam was simultaneously investigated in three patients with presumed bacterial meningitis. When ratios of simultaneously drawn ventriculostomy to serum moxalactam levels of 1, 2, 3, and 4 h were examined, the penetration ratios were 7.8 +/- 2.4, 11.2 +/- 1.3, 14.2 +/- 2.5, and 15.0 +/- 4.9%, respectively. These ratios were not statistically different from the penetration of moxalactam calculated by the area under the concentration-time curve technique (8.97 +/- 1.89%).

Drug Administration Schedule↗
PubMed1984

Hydroxylamine technique for in vitro prevention of penicillin inactivation of tobramycin.

Hydroxylamine was evaluated and found to be a highly effective agent for the in vitro prevention of penicillin inactivation of tobramycin. This inactivation reaction resulted in an underestimation of tobramycin concentrations and was dependent on time, temperature, amount and type of penicillin, and amount of tobramycin. Plasma samples containing tobramycin and three clinically relevant concentrations of ticarcillin, carbenicillin, azlocillin, or piperacillin were incubated with and without hydroxylamine, and tobramycin concentrations were monitored at 0, 12, 24, 48, and 72 h. The inactivation reaction was found to be completely inhibited by hydroxylamine (1 mg/ml) compared with a 27 to 50% loss of measured tobramycin concentration in the unprotected tobramycin-penicillin samples. Hydroxylamine did not interfere with the Emit enzyme immunoassay (Syva Co.) at either high or low tobramycin concentrations. Hydroxylamine was effective in inhibiting the tobramycin inactivation at both room and refrigerator temperatures and was 100% effective in protecting tobramycin on a 1:1 molar basis.

Azlocillin↗
PubMed1983

Dose-dependent theophylline elimination in an adult.

A 69-year-old male patient with chronic obstructive pulmonary disease exhibited dose-dependent theophylline elimination. Steady-state serum theophylline concentrations, obtained at five different aminophylline infusion rates, ranged from 2.0 mg/L at an infusion rate of 36 mg/h to 10.1 mg/L at 76 mg/h. These serum concentrations were nonlinearly related to dose, with a Vmax of 89.04 mg/h and Km of 3.96 mg/L (r = 0.983, p less than 0.005). Theophylline clearance fell from a high of 348 ml/kg/h to 145 ml/kg/h as the infusion rate was increased. Although theophylline elimination kinetics in adults are generally assumed to be linear, clinicians should be alert to the possibility of nonlinear theophylline elimination, as has been observed commonly in children.

Aged↗
PubMedDate not supplied

Inadvertent intravenous administration of enteral diet.

Needle catheter jejunostomy feedings were instituted in a 64-yr-old man on postoperative day 1 following subtotal gastrectomy for carcinoma of the antrum. Several days later, the enteral tube catheter was inadvertently connected to the patient's peripheral intravenous cannula which resulted in the intravenous administration of the enteral formula solution. The administration was stopped immediately when recognized, but 4 hr later the patient became febrile, hypotensive, and tachycardic. Cultures from the enteral solution demonstrated Streptococcal viridans and yeast; the patient's blood cultures similarly demonstrated S. viridans. Broad spectrum antibiotics, hemodynamic monitoring, and intravascular support with crystalloid solutions resulted in a favorable outcome. Prevention of the complication could be assured by adopting luer connectors for enteral feeding sets which cannot be connected to intravenous cannulas. Until these are available, the addition of methylene blue to the tube feeding formula or utilization of color coded distal connecting tubing may prevent accidental intravenous administration of tube feeding formulas. The potential for this complication must be recognized by those dealing with enteral feeding.

Enteral Nutrition↗