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Biomedical subjects

G R Siber

Publications and source records attributed to G R Siber.

At least 145 records · Page 8Linked to original sources

Stability of trimethoprim-sulfamethoxazole injection in two infusion fluids.

The concentrations over time of trimethoprim (TMP) and sulfamethoxazole (SMZ) in solution after preparations of admixtures of TMP-SMZ in 5% dextrose injection (D5W) and in 0.9% sodium chloride injection (NS) were measured. Admixtures (50 ml) containing three TMP concentrations (0.64 mg/ml, 1.6 mg/ml, and 3.2 mg/ml) and three SMZ concentrations (3.2 mg/ml, 8.0 mg/ml, and 16 mg/ml) were prepared in D5W or NS, representing 1:25 v/v, 1:10 v/v, and 1:5 v/v dilutions of TMP-SMZ injection, respectively. Aliquots of each admixture were obtained immediately upon dilution and after 0.5, 1, 2, 4, 8, and 24 hours. The aliquots were filtered and assayed for TMP and SMZ by high-pressure liquid chromatography. Each mixture was inspected visually for any changes in clarity or color, and the pH of each admixture was measured over time. The concentration of SMZ in all admixtures remained constant over 24-hour study period. The TMP concentration did not change significantly (less than 10% of initial concentration) after 1:25 v/v dilutions in either D5W or NS for up to four hours. With a dilution of 1:10 v/vv D5W TMP was stable at D5W for up to two hours. TMP precipitated rapidly in dilutions of 1:5 v/v in either D5W or NS. The pH of the admixtures ranged from 9.39 to 10.10. D5W is the preferred diluent for TMP-SMZ injection if a dilution ratio of 1:10 v/v is desired. Either D5W or NS may be used if a dilution ratio of 1:25 v/v is desired.

Drug Combinations↗

Correlation between serum IgG-2 concentrations and the antibody response to bacterial polysaccharide antigens.

We measured serum concentrations of immunoglobulin classes and IgG subclasses in 53 patients who had completed treatment for Hodgkin's disease and in 10 healthy adults. We wished to determine the relation of these classes and subclasses to the subjects' antibody responses to bacterial polysaccharide and viral protein antigens. Mean levels of the IgG-2 subclass were significantly lower in patients treated with both radiation and chemotherapy than in controls (P less than 0.05). The level of IgG-2 before immunization correlated directly with the mean antibody response both to 11 pneumococcal antigens (r = 0.71, P less than 0.001) and to the Haemophilus influenzae Type b antigen (r = 0.40, P less than 0.01). The correlation between IgG-2 concentration and pneumococcal antibody response was also significant in the 10 healthy adults ( r = 0.70, P less than 0.05). The levels of no immunoglobulin class or subclass correlated significantly with antibody responses to influenza A/Victoria/75 and A/New Jersey/76 hemagglutinins, both of which are protein antigens. The serum concentration of IgG-2 appears to provide a marker for predicting the ability to produce antibodies to polysaccharide, but not viral protein, antigens.

Adult↗

Bacteremias due to Haemophilus influenzae and Streptococcus pneumoniae: their occurrence and course in children with cancer.

Nine Haemophilus influenzae and 24 Streptococcus pneumoniae bacteremias occurring in children with cancer during the years 1968 to 1977 were reviewed. The number of bacteremias due to these organisms remained relatively constant, in contrast with a sharp decrease in bacteremias caused by other organisms during this period. The highest incidence of bacteremia occurred in patients with acute leukemias and the lowest incidence in patients with solid tumors. Twenty-seven of 33 episodes occurred while patients were receiving chemotherapy. Nine bacteremias were fatal, but concurrent or superinfections contributed to death in six of these. Children with cancer who are receiving chemotherapy seem to be at higher risk of bacteremia and meningitis due to H influenzae and Strep pneumoniae than are normal children. New approaches to the prevention of these infections, such as the use of bacterial polysaccharide vaccines, deserve investigation.

Adolescent↗

Increased gastrointestinal absorption of large molecules in patients after 5-fluorouracil therapy for metastatic colon carcinoma.

Chemotherapeutic agents may damage gastrointestinal epithelium and thereby impair the mucosal barrier to bacteria and their products. In order to obtain an objective measurement of gastrointestinal permeability to large molecules, we measured urinary excretion of [14C]polyvinylpyrrolidone administered p.o. (mean molecular weight 11,000) and tobramycin (molecular weight 467) in ten patients receiving 5-fluorouracil therapy for metastatic cancer of the colon. Base-line absorption of [14C]polyvinylpyrrolidone was 0.013 to 0.048% of the administered dose. Dose-related increases in absorption (range, two to 20 fold) occurred after 5-fluorouracil administration, but the dose response differed markedly between individuals. Absorption was maximal 8 to 15 days after the start of therapy, was correlated in time but not necessarily in severity with the presence of gastrointestinal symptoms, and was unaffected by oral nonabsorbable antibiotics. Tobramycin excretion was 8.5 times greater than [14C]polyvinylpyrrolidone excretion, but the two were highly correlated in simultaneous determinations (r, 0.93; p, < 0.001). With the exception of an episode of Escherichia coli bacteremia, infections coincided not with maximal [14C]polyvinylpyrrolidone absorption but with maximal granulocytopenia 17 to 24 days after the start of therapy. The gastrointestinal absorption of polyvinylpyrrolidone provides an objective measurement of mucosal integrity which may have applications in assessing the gastrointestinal toxicity of other cytotoxic agents.

Colonic Neoplasms↗

Predictability of peak serum gentamicin concentration with dosage based on body surface area.

We examined gentamicin dosage based on body surface area (60 mg/m2 intravenously every eight hours) as a means of attaining therapeutic but nontoxic serum concentrations in 58 patients ranging in age from 0.7 to 73 years. All but one patient had peak serum levels between 3.4 and 8.0 microgram/ml. The mean serum gentamicin half-life was shorter in patients less than 10 years of age (76 minutes) than in patients aged 10 to 50 years (116 minutes) and in patients aged 50 to 63 years (184 minutes) (all significant at P less than 0.01). We conclude that gentamicin dosage based on body surface area produces uniform peak serum gentamicin concentrations in both children and adults, and that the safety and efficacy of a shorter dosage interval for children deserves investigation.

Adolescent↗

Comparison of two antigen detection techniques in a primate model of Haemophilus influenzae type b infection.

Rapid diagnosis of Haemophilus influenzae type b meningitis is possible using immunological tests for capsular antigen (polyribophosphate, PRP), such as countercurrent immunoelectrophoresis (CIE) and latex particle agglutination (LPA). We compared two tests in monkeys with evolving, serially quantitated H. influenzae type b bacteremia (n = 23) and meningitis (n = 21). In vitro, the LPA test was sensitive to 0.5 ng of PRP/ml of saline, and the CIE test was sensitive to 1.0 ng/ml; in serum, however, CIE detected 5.0 ng of PRP/ml, whereas the sensitivity of LPA was unchanged. LPA detected PRP earlier in the course of bacteremia (mean, 12 h after onset; range, 4 to 36 h) than did CIE (mean, 45 h; range, 4 to 168 h) (P less than 0.01). A positive LPA test required greater than or equal to 100 bacteria per ml of blood, whereas CIE required greater than or equal to 1,000/ml. PRP accumulated with continuing blood stream infection, aiding detection of low-grade bacteremia. LPA detected antigen in cerebrospinal fluid (CSF) earlier in the course of meningitis and at a lower bacteria density than did CIE. Both methods detected antigen reliably with greater than or equal to 1,000 bacteria per ml of CSF. A close correlation existed between CSF concentrations of capsular antigen and bacteria (r = 0.90, P less than 0.001). We conclude that the LPA method permits earlier diagnosis of H. influenzae type b infection in part because of its greater sensitivity.

Animals↗

Impaired antibody response to pneumococcal vaccine after treatment for Hodgkin's disease.

To determine if a normal antibody response can develop after therapy for Hodgkin's disease, we immunized 53 patients and 10 normal controls with dodecavalent pneumococcal vaccine. Antibody concentrations three weeks after immunization (geometric mean of 11 serotypes) were 1566 ng of protein nitrogen per milliliter in controls, 963 ng per milliliter after subtotal radiation (P less than 0.05 compared to controls), 658 ng per milliliter after chemotherapy (P less than 0.05), 377 ng per milliliter after subtotal radiation plus chemotherapy (P less than 0.01) and 283 ng per milliliter after total nodal radiation plus chemotherapy (P less 0.001). Low levels of antibody before immunization correlated with a poor response (r = +0.73, P less than 0.001). The ability to respond to immunization improved significantly but did not return to normal as long as four years after combined therapy. The antibody response to pneumococcal vaccine is profoundly impaired in patients who have received intensive treatment for Hodgkin's disease: the ability of this vaccine to protect them from overwhelming postsplenectomy infections remains in doubt.

Adolescent↗

Rapid diagnosis of Hemophilus influenzae type b infections by latex particle agglutination and counterimmunoelectrophoresis.

Latex particle agglutination and counterimmunoelectrophoresis techniques were compared in a clinical trial to demonstrate their sensitivity, specificity, and usefulness in the rapid diagnosis of invasive Hemophilus influenzae type b disease. LPA, a simplified LPA performed by house officers, and CIE used in this study detected 0.2, 0.5, and 1 to 10 ng/ml of Hib capsular antigen, respectively. One hundred-six illnesses suspected of being caused by Hib were evaluated prospectively by these assays. A total of 39 of these were confirmed by culture or detection of antigen or both. LPA and simplified LPA were more sensitive and specific than CIE in the diagnosis of Hib disease (P less than 0.01), especially in invasive disease other than meningitis. LPA is inexpensive, can be performed quickly, and detects all invasive Hib infections. The results emphasize the usefulness of antigen detection in the rapid diagnosis of Hib infections, demonstrate that LPA is more sensitive and specific than CIE, and can be conveniently performed by physicians.

Antigens, Bacterial↗

Impaired humoral immunity in treated Hodgkin's disease.

To define the contribution of aggressive lymphoma treatment to the risk of post-splenectomy septicemia, we investigated the humoral immunity of 44 patients with Hodgkin's disease. Specific antibody against Haemophilus influenzae Type b was significantly reduced (mean, 147 ng per milliliter, P less than 0.01) in patients receiving combined treatment (radiotherapy and chemotherapy), whereas single treatment reduced titers marginally (chemotherapy) or not at all (radiotherapy). Untreated patients had normal values (396 ng per milliliter), and splenectomy was without effect. In some patients who received combined treatment, titers were reduced to levels seen in infants. IgM levels were likewise normal in untreated patients. Chemotherapy, however, significantly reduced IgM levels (P less than 0.025), an effect potentiated by prior splenectomy. IgG, IgA, alternate-pathway activity, C3, C4 and CH50 were all normal or elevated. Aggressive treatment with chemotherapy and radiation impairs humoral defense against encapsulated micro-organisms, and thus magnifies the risk of post-splenectomy septicemia in patients with Hodgkin's disease.

Adolescent↗

Phycomycotic gangrenous cellulitis. A report of two cases and a review of the literature.

Progressive gangrenous cellulitis due to Rhizopus arrhizus following colostomy destroyed the entire abdominal wall of a young woman and caused her death. A similar infection in an 11-year-old kidney transplant recipient was diagnosed more promptly and treated successfully with extensive debridement and amphotericin B. Nine similar cases found in the literature were reviewed. All 11 patients appeared to have had prior tissue injury at the original site of infection, and seven had diabetes mellitus. The disease was initially misdiagnosed in most of the patients, progressed rapidly in eight, and was fatal in four. Phycomycotic gangrenous cellulitis should be included in the differential diagnosis of progressive necrotizing lesions of the skin, especially in diabetic patients, but it can be identified promptly only by histologic examination of the infected tissue. Urgent radical excision and amphotericin therapy are recommended.

Abdominal Muscles↗

Age-dependent dose response to gentamicin.

Serum gentamicin concentrations were measured 30 minutes after 140 intravenous doses in 60 children and nine adults with normal renal function. Distinct interpatient variation was observed but individual patients tended to have similar pharmacokinetics with repeated doses. Age had a significant effect in that mean peak serum concentrations were 1.58 mug/ml per 1 mg/kg dose in children between 6 months and 5 years, 2.03 mug/ml per 1 mg/kg in those between 5 and 10, and 2.86 mug/ml per 1 mg/kg in children 10 to 15 years of age. The mean calculated single dose of gentamicin necessary to achieve a peak serum concentration between 4 and 5 mug/ml is 2.5 mg/kg for ages 0.5 to 5 years, 2.0 mg/kg for ages 5 to 10 years, and 1.5 mg/kg for individuals over 10 years of age.

Adolescent↗

Pharmacokinetics of gentamicin in children and adults.

Peak concentrations and half-life of gentamicin in serum were measured after 140 intravenous and 13 intramuscular doses in 52 children and 17 adults with normal levels of creatinine in serum. Marked interpatient variation in peak concentrations and half-life of gentamicin was observed, but individual patients tended to have similar values on repeated determinations. Age markedly affected the peak concentrations: a 1-mg/kg dose produced mean peak concentrations of 1.58, 2.03, and 2.81 mug/ml in the one-half to five, five to 10, and greater than 10 year age groups, respectively. This age-related change in dose response was diminished when the dose was calculated on the basis of body surface area. Patients in whom gentamicin had a short half-life, patients with fever, and adults with a high extracellular fluid volume had low peak concentrations. The mean half-life after intravenous administration was 75 min (range, 26-230 min). The mean half-life was 29 min longer after intramuscular dosage (p less than 0.01). A low rate of creatinine clearance was associated with a long half-life; fever and anemia were associated with a short half-life. The dosage of gentamicin necessary to produce mean peak serum concentrations between 4 mug/ml and 6 mug/ml was 60 mg/m2 per dose for all age groups or 2.5 mg/kg per dose for ages one-half to five years, 2.0 mg/kg per dose for ages five to 10 years, and 1.5 mg/kg per dose for ages greater than 10 years.

Adolescent↗