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Biomedical subjects

K H Rand

Publications and source records attributed to K H Rand.

At least 19 recordsLinked to original sources
PubMed1992

Quantitative tip culture methods and the diagnosis of central venous catheter-related infections.

The diagnostic usefulness of two quantitative catheter culture methods was compared in a prospective study of central venous arterial catheters. The roll-plate method followed by sonication was used to culture 177 catheters from 85 patients, and the sonication method was used to culture 136 catheters from 68 patients. All patients were evaluated for catheter-related infections. Catheter-related infections were associated with greater than or equal to 100 colony-forming units (CFU) isolated from catheter tips by either roll plate (p = 0.01) or sonication (p less than 0.001). The sensitivity, specificity, and positive and negative predictive values of greater than or equal to 10(3) CFU by roll plate for catheter-related septicemia were 56%, 97%, 63%, and 96% compared with 93%, 95%, 76%, and 99%, respectively, for the same level by sonication. For central venous and arterial catheters, the sonication method can distinguish infection from contamination and is superior to the roll-plate method in that it may offer a more sensitive and predictive alternative in the diagnosis of catheter-related septicemia.

Bacterial Infections↗
PubMed1992

Vancomycin is not an essential component of the initial empiric treatment regimen for febrile neutropenic patients receiving ceftazidime: a randomized prospective study.

The use of vancomycin as part of the initial antibiotic therapy of febrile neutropenic patients has become a controversial issue. Some studies support its incorporation in the initial regimen, and others suggest that vancomycin can be added later. We examined this issue in a prospective, randomized trial. We randomized 127 febrile neutropenic patients to receive either ceftazidime alone or ceftazidime plus vancomycin as the initial empiric antibiotic treatment. We added vancomycin to the ceftazidime arm of the study when fever persisted after 96 h of monotherapy, when new fever occurred after this time, or when a moderately ceftazidime-resistant gram-positive bacterium was isolated. Each of these regimens had similar initial response rates, similar durations of initial fever, similar frequencies of new fever during therapy, similar microbiological cure rates, similar superinfection rates, and similar survival rates. We observed more renal and cutaneous toxicities in patients receiving vancomycin and ceftazidime as initial therapy. We conclude that ceftazidime is appropriate as initial therapy for febrile neutropenic patients and that the addition of vancomycin is appropriate when fever persists after 4 days of monotherapy or when fever recurs following an initial response.

Adolescent↗
PubMed1991

Pharmacokinetics of intravenous immunoglobulin (Gammagard) in bone marrow transplant patients.

The pharmacokinetics of an intravenous immunoglobulin (IVIG), Gammagard (Baxter Healthcare Corp., Glendale, CA), were measured in 31 cytomegalovirus (CMV) antibody negative bone marrow transplant (BMT) patients as part of a multicenter efficacy trial of 2 weekly dose regimens. Since all patients lacked antibody to CMV and received only screened CMV negative blood products, the half-life of the exogenous CMV antibody could be measured with an ELISA assay. The CMV antibody titer was related to the immunoglobulin concentration using a standard curve. Compared with the 22-day half-life in normal subjects, the half-life in BMT patients was approximately 6 days for either the 250 mg/kg or 500 mg/kg dose regimen. The half-life did not change over the subsequent 3 weekly doses. Peak concentrations were 3.5 +/- 1.4 and 2.6 +/- 0.7 mg/mL of IVIG in week 1 as well as 5.5 +/- 2.6 and 3.4 +/- 1.2 mg/mL in week 3 after the 250 mg/kg and 500 mg/kg, respectively. Total body clearance of IVIG was 0.61 and 0.46 mL/kg/hr for the 500 mg/kg and 250 mg/kg, respectively.

Adolescent↗
PubMed1991

A psycho-behavioral model of genital herpes recurrence.

To develop a model of how stress and other psychosocial constructs may interact to explain recurrences of genital herpes, assessments of major and minor life stress, locus of control, arousal or stimulation seeking, and social support were given to 153 university students (33% male; 67% female) who were seropositive for genital herpes. Retrospective and concurrent indices of illness vulnerability were evaluated. Serum levels of thymosin-alpha-1, a peptide sensitive to psychosocial stress, were measured at the beginning of the study. A causal model suggested by previous research was not supported by the data. An alternate model showed that psychosocial stress did not affect herpes recurrence directly, but instead predisposed subjects to more generalized illnesses, which in turn mediated recurrences. Social support increased rather than decreased the likelihood of illness vulnerability, thus increasing the risk of recurrence. Higher levels of both arousal seeking and external locus of control increased illness vulnerability but moderated the likelihood of herpes recurrence. Higher levels of thymosin-alpha-1 were related to greater illness vulnerability but this peptide was not associated with psychosocial stress as originally predicted. Additional construct validation of the role of illness vulnerability in increasing the risk of herpes recurrence is recommended.

Adolescent↗
PubMed1990

Taq polymerase contains bacterial DNA of unknown origin.

The polymerase chain reaction (PCR) was carried out with the highly conserved E. coli ribosomal RNA gene sequences 1376-1395 and 1521-1540. Using these primers and reaction conditions specified by the manufacturer(s), a 165 bp fragment was synthesized using Taq polymerase from three different sources in the absence of any added template. Restriction enzyme analysis suggests the source of this bacterial DNA is neither E. coli nor Thermus aquaticus. A variety of different methods to eliminate it such as treatment with DNase, restriction enzyme digestion, and CsCl2 density gradient centrifugation were unsuccessful. Since the bacteria in which the Taq polymerase is produced are not the source of the DNA, some step(s) in the purification or reagents added to the enzyme must be involved. Thus it is likely other biological products are similarly contaminated. Although the problem is easily dealt with by running a no-template control and choosing other primers if a problem exists, it is important to recognize the potential for a false-positive result.

Base Sequence↗
PubMed1990

Group A beta-hemolytic streptococcal bacteremia and HIV infection.

We describe a case of group A beta-hemolytic streptococcal bacteremia in an individual infected with the human immunodeficiency virus (HIV). The organism was also recovered from the stool, but not from the throat. A review of 19 cases of group A beta-hemolytic streptococcal bacteremia shows an association between an underlying immunologic defect and the occurrence of serious group A beta-hemolytic streptococcal infection in adults. We review evidence in the literature suggesting that there is a predisposition to infection caused by pyogenic bacteria in HIV-infected individuals.

AIDS-Related Complex↗
PubMed1990

Three-year experience with sonicated vascular catheter cultures in a clinical microbiology laboratory.

Using a quantitative sonication method, we cultured 1,681 consecutive vascular catheters submitted to a clinical microbiology laboratory in a 36-month period. A total of 46% of the cultures were positive; the most common organisms isolated were coagulase-negative staphylococci (36.4%), Pseudomonas aeruginosa (13.9%), enterococci (10.0%), yeasts (9.2%), Staphylococcus aureus (5.8%), and Enterobacter species (4.4%). The frequencies of positive blood cultures within 48 h prior to a positive catheter culture result were as follows: Candida albicans (68.4%), S. aureus (60%), Enterobacter cloacae (42.9%), Staphylococcus epidermidis (32.1%), P. aeruginosa (27.7%), and enterococci (23.3%). The sonication method allowed quantification of the number of CFU removed from a catheter for between 10(2) and 10(7) CFU. For catheter cultures in which greater than or equal to 10(2) CFU grew, a linear regression equation could be calculated: (risk of positive blood culture for the same organism) = 14 [log10 (number of organisms removed from the catheter)] -21 (r = 0.93). For catheter cultures in which less than 10(2) CFU grew, positive blood cultures for the same organism were strongly associated with a proven infection at a site distant from the catheter (P = 0.001) or probable contamination (S. epidermidis). Our findings indicate that this technique has considerable potential for use in clinical microbiology laboratories to aid in the diagnosis of vascular catheter infections and for clinical investigations into the pathogenesis of these infections.

Bacteria↗
PubMed1990

Daily stress and recurrence of genital herpes simplex.

It is widely believed that emotional stress triggers recurrences of both oral and genital herpes simplex virus. On a daily basis, we studied 64 subjects prospectively for 1 to 3 months; all subjects had at least one culture-proved recurrence of genital herpes simplex virus type 2 before or during the study. All subjects filled out a questionnaire that measured psychological/emotional stress in six areas: physical health, relations with friends, relations with family, relations with sex partner(s), financial, and vocation/education. These questionnaires were mailed back to us daily. Data were analyzed by General Linear Models analysis of variance to compare stress reported on each of the 6 days before a recurrence with that on days during or after a recurrence, as well as days not temporally related to recurrence. Under these conditions, in which retrospective bias was minimized, there was no significant increase in psychological/emotional stress on any day in any area preceding a recurrence of genital herpes simplex virus.

Adult↗
PubMed1989

Pharmacokinetics of cytomegalovirus specific IgG antibody following intravenous immunoglobulin in bone marrow transplant patients.

Cytomegalovirus (CMV) associated interstitial pneumonitis is a major cause of death among bone marrow transplant patients. A variety of intravenous immunoglobulin (IVIg) preparations have shown some promise in preventing this complication. As part of a multicenter trial of Sandoglobulin, the pharmacokinetics of CMV specific IgG was measured in order to guide future dosing schedules. A dose of 500 mg/kg was administered weekly beginning 1 week before transplant and continuing until day 98 following transplant. The half-life of CMV specific IgG was measured by an ELISA method after the first, third and fifth doses of IVIg. CMV seronegative patients received only screened CMV negative blood products, which permitted assessment of the half-life of IVIg CMV antibody. Peak titers achieved were comparable to those of the CMV seropositive patients averaging 1:2702 (range 1:596-1:10 514). Total IgG levels rose to a peak of about 75% above baseline. After the first dose of IVIg, the half-life of CMV IgG antibody was 3.4 +/- 2.0 (SD) days, although it lengthened to 6.1 +/- 5.1 days after the fifth dose of IVIg. The half-life of total IgG was estimated to be between 5 and 10 days, depending on the assumptions made regarding endogenous production. If high levels of IVIg are necessary for protection from CMV associated interstitial pneumonitis, weekly dosing will be important in order to maintain sufficient levels to be protective.

Adolescent↗
PubMed1987

Trifluorothymidine: potential non-invasive diagnosis of herpes simplex infection using 19F nuclear magnetic resonance in a murine hepatitis model.

Trifluorothymidine (TFT) is known to be concentrated in herpes simplex virus (HSV) infected cells in vitro in the form of phosphorylated derivatives. We studied a murine hepatitis model of HSV infection to determine whether this in vitro observation would also be demonstrable in vivo. Following i.v. injection of 100 or 160 mg/kg TFT, TFT was found in significantly higher concentrations in the livers of HSV-2 infected mice than in the livers of uninfected mice, mice infected with murine hepatitis virus (MHV-A59) or mice with hepatitis from carbon tetrachloride treatment. Neither altered renal function, nor altered pharmacokinetics could account for this difference. 19F Nuclear Magnetic Resonance spectroscopy readily detected the 19F from TFT in both liver extracts and whole livers, particularly at higher tissue levels, i.e. greater than 50 micrograms/g tissue. If further studies with living animals support these preliminary observations, clinical application could be pursued.

Animals↗
PubMed1986

Potential treatment of herpes simplex virus encephalitis by brain-specific delivery of trifluorothymidine using a dihydropyridine in equilibrium pyridinium salt type redox delivery system.

A newly described, drug-carrier delivery system in which a lipophilic derivative is enzymatically converted to a hydrophilic compound was used to treat experimental herpes simplex virus (HSV) encephalitis. Because trifluorothymidine (TFT) does not cross the blood brain barrier, the lipophilic dihydropyridine derivative 3'-(N-methyl-1, 4-dihydronicotinoyl)-5-'pivaloyltrifluorothymidine (DHTFT) was synthesized and characterized by HPLC. After intravenous administration of 20 mg/kg of DHTFT to rats, the quaternary, intermediate compound 3'-N-methyl-1,4-nicotinoyltrifluorothymidine was measured at levels of 7-8 micrograms/g brain at 1 hour and 13.5 +/- 0.8 micrograms/g brain at 4 hours. This compound had antiviral activity equivalent to that of TFT against HSV-1 in a plaque reduction assay (ID 50 = 0.5-1.0 microgram/ml), either directly or by conversion to TFT. Although survival was not prolonged in a rat model of HSV encephalitis, a statistically significant reduction in titer of HSV/g brain was achieved with daily intravenous treatment with DHTFT. TFT was not detected in brains of rats at 1 and 4 hours after intravenous DHTFT, but a low level was observed at 18 hours, 0.3 +/- 0.05 microgram/g brain. These data suggest that the lipophilic compound DHTFT or a lipophilic metabolite crossed the blood brain barrier and was converted to a quaternary compound, which accumulated in the brain and which was either active directly or was converted to TFT. The drug-carrier delivery system described here can potentially be used in the treatment of HSV or other viral encephalitides.

Animals↗
PubMed1986

False positive indirect fluorescent antibody (IFA) tests for antibody to herpes simplex virus 1. Comparison of four commercially available methods.

Four commercially available herpes simplex virus 1 (HSV-1) indirect fluorescent antibody (IFA) kits were compared with the use of sera selected because they were negative for HSV antibody by complement fixation (CF less than 1:8) and by ELISA (less than 1:100). However, 14 of 24 (58.3%) of these HSV-1 antibody-negative sera were positive at greater than or equal to 1:10 with the use of the HSV-1 IFA kit from Electronucleonics, 15 of 24 (62.5%) were positive with the Clinical Sciences HSV-1 IFA kit, 4 of 24 (16.7%) were positive with Zeus Scientific, and 4 of 18 (22.2%) were positive with the Gull Laboratories product. HSV-1 induces Fc receptors that commonly cause false positive IFA tests for HSV antibody. Therefore, further studies were undertaken to determine whether Fc receptors accounted for these false positive results. Staphylococcal protein A (SPA) is known to bind to the Fc portion of human IgG and therefore could be used to distinguish between the binding of an antibody by its Fab or its Fc portion. Thus, when fluorescein isothiocyanate conjugated (FITC) SPA was used as conjugate instead of FITC antibody to human IgG, true HSV-1 antibody-containing sera remained positive, but the false positives identified in the commercial IFA kits did not. The authors conclude that HSV-1-induced Fc receptors are responsible for most of the problem of these false positives and that HSV-1 serology probably should not be done by this type of IFA method until this problem is corrected.

Antibodies, Viral↗
PubMed1985

Rotazyme assay in neonates without diarrhea. Results of screening survey and preliminary analysis of false positive specimens.

One hundred forty-seven stool specimens from 93 infants younger than four months of age in a Neonatal Intensive Care Unit were tested for rotavirus by the Rotazyme ELISA method (Abbott Laboratories, North Chicago, IL). None of the infants had diarrhea at the time of the testing. Ten of 147 (6.8%) specimens were either low or suspect positive. None had rotavirus by electron microscopy. Excluding the suspect positives, which were negative on retesting, the false positive rate was only 6 of 147 (4.1%). Of five specimens with sufficient material and repeatedly positive tests, heat to 56 degrees C for one-half hour eliminated the binding to the Rotazyme bead but had no effect on the rotavirus positive control. One patient was found to have an extremely high positive Rotazyme test, independently of the survey. No virus was found in this specimen by electron microscopy, and the material responsible for the false positive result was not removed by centrifugation (100,000 X g for one hour), heating to 56 degrees C for one-half hour, trypsin, ether/beta-mercaptoethanol, or dialysis. Thus, false positives were encountered, but the overall rate was acceptably low. Such false positives are likely to result from more than one cause and, depending on results of further study, may be confirmed as false positives by loss of reactivity at 56 degrees C for one-half hour and perhaps lack of binding to a control bead.

Enzyme-Linked Immunosorbent Assay↗