Biomedical subjects

C K Murray

Publications and source records attributed to C K Murray.

13 recordsLinked to original sources

PubMed1992

Lethal Staphylococcus aureus-induced shock in primates: prevention of death with anti-TNF antibody.

A successful experimental treatment for gram-positive sepsis to our knowledge has not been achieved. The objectives of this study were to develop a nonhuman primate model of lethal gram-positive sepsis employing the micro-organism Staphylococcus aureus and to determine the efficacy of treatment using monoclonal antibody (MAb) to tumor necrosis factor alpha (TNF). The antibody was administered intravenously, 15 mg/kg, 30 minutes after the beginning of a 2-hour infusion of S. aureus, 4 x 10(10) colony forming units/kilogram. The baboons infused with S. aureus demonstrated the release of the cytokines TNF and interleukin-6 (IL-6), but endotoxin was not observed in the plasma at any time. Treatment with antibody to TNF abolished the rise in serum TNF levels and reduced the increased levels of IL-6. Treatment with MAb to TNF prevented multiple organ failure and achieved permanent (> 7 day) survival of all baboons.

Animals↗

PubMed1990

Early detection of colorectal cancer by quantitative fluorescence image analysis of exfoliated cells.

Early-stage colorectal cancer is potentially curable. In the present study, we applied quantitative fluorescence image analysis (QFIA) cytology to the detection of experimental colorectal cancer in a rodent model. QFIA cytology combines visual cytologic examination with quantitation of DNA content in single exfoliated cells. Cancer was induced by treating 110 rats with subcutaneous 1,2-dimethylhydrazine. Sequential colon washes were obtained weekly from each animal for 20 weeks. Control animals were treated identically except for the administration of carcinogen. Cells that were cytologically abnormal or had increased DNA content were found starting in the second week. By the eighth week, roughly 50 percent of animals had positive results, and this level remained approximately constant for the duration of the study. Tissue pathologic results were normal during weeks 1 to 7. Dysplasias became common during weeks 8 to 15 whereas most cancers appeared during weeks 16 to 21. These results indicate that QFIA cytology is a highly sensitive method for detecting even preneoplastic changes resulting from carcinogen administration and may prove useful in detecting human colorectal cancer.

Animals↗

PubMed1990

Survival of primates in LD100 septic shock following therapy with antibody to tumor necrosis factor (TNF alpha).

The purpose of this study was to determine the efficacy of treatment with anti-TNF monoclonal antibody in preventing the deleterious effects of sepsis in a nonhuman primate. Experiments were carried out on anesthetized baboons intravenously infused with a lethal dose of Escherichia coli (E. coli). Twelve baboons (six control and six experimental) received 2 hr infusions of E. coli. The experimental group was administered a bolus of anti-TNF antibody, 15 mg/kg, 30 min after beginning the E. coli infusion. Control baboons lived an average of 19 hr (12-34 hr). All antibody-treated baboons survived more than 7 days with a significantly improved quality of life compared to the control group. Although some adverse changes occurred during the monitoring period in surviving baboons, they maintained nearly normal arterial pressures, and serum urea nitrogen and creatinine concentrations. The severe histopathologic changes in lungs, liver, adrenals, kidneys, and spleen documented at death in baboons receiving E. coli only were absent after 7 days in baboons given E. coli and early post-treatment with antibody to TNF.

Animals↗

PubMed1990

Length of hospital stay in veteran surgical service patients with nosocomial infections.

Four hundred ninety-nine nosocomial infections (with 657 isolates) in 288 Surgical Service patients were monitored from February 1986 to June 1987 (17 months) to determine the influence that pathogen or site of infection had on the length of hospital stay. Patients with upper respiratory and skin infections were more likely to have significantly longer length of stay than those with infections in other sites. Infections with Haemophilus influenzae and Pseudomonas aeruginosa were more likely to yield longer culture to discharge periods than other organisms in certain settings. Extended lengths of stay were common in patients with nosocomial infections.

Cross Infection↗

PubMed1989

A statistical analysis on the relationship of organism and site of infection to antimicrobial susceptibilities.

Disc agar diffusion tests were performed on 1340 clinical isolates (six common pathogens) to determine if the site of infection influenced antimicrobial susceptibility results for a given organism. There were several mathematically significant differences among sites and organisms, however the most important included cefoperazone (wound), piperacillin (sputum and urine) and tobramycin (sputum) against P. aeruginosa. Of these, only piperacillin was significantly less susceptible against P. aeruginosa lower respiratory tract isolates at our hospital. The impact of this on treatment (empiric) efficacy is unknown.

Anti-Bacterial Agents↗

PubMed1988

Staphylococcus aureus-induced shock: a pathophysiologic study.

The purpose of the present study was to determine the effects of lethal intravenous infusions of Staphylococcus aureus (SA) in adult dogs. Animals were maintained under anesthesia for 6 hr and observed until death following the 1-hr infusions of SA organisms. Findings unique to SA administration compared to those with Escherichia coli were the absence of significant necrosis of the mucosal intestinal glands of the small and large intestines; widespread intravascular colonization of bacteria in lung, heart, kidney and adrenal tissues often associated with neutrophil sequestration, microabscess formation, and necrosis; relative constant blood pressure, fibrinogen, fibrin degradation products (FDP), serum glutamic pyruvic transaminase (SGPT), blood (serum) urea nitrogen (BUN), creatinine, pH, and PO2, all of which remained relatively unchanged for 6 hr. Rapid early increases were observed in temperature, respiration rate, lactate, and hematocrit, while PCO2, platelet and white blood cell concentrations decreased. Results suggest unique qualitative differences in responses to Staphylococcal-induced shock compared to those caused by gram-negative bacteria.

Animals↗

PubMed1987

Scombrotoxic fish poisoning in Britain: features of over 250 suspected incidents from 1976 to 1986.

Between 1976 and 1986, 258 incidents of suspected scombrotoxic fish poisoning were reported in Britain. Histamine analysis was carried out on 240 fish samples from these incidents, and 101 were found to contain greater than 5 mg histamine/100 g fish. The symptoms most consistently reported were rash, diarrhoea, flushing and headache. In recent years there has been a decrease in the number of confirmed scombrotoxic outbreaks and a trend towards more sporadic incidents. Of fish samples with greater than 20 mg histamine/100 g, 94% were from incidents in which scombrotoxic symptoms were characteristic, but where fish had 5-20 mg/100 g only 38% of incidents were clinically distinctive. Guidelines are presented based on the interpretation of quantitative histamine analysis of fish samples from scombrotoxic poisoning incidents.

Animals↗

PubMed1986

Tobramycin therapy for lethal sepsis in the dog.

Antimicrobial effectiveness and effect on survival of single-dose vs. multiple-dose aminoglycoside antibiotic therapy (with and without steroid) for lethal sepsis were evaluated. Adult dogs of either sex were anesthetized, divided into five groups, and infused iv for one hour with Escherichia coli. Group A was given no drug. Group B was given a 45-mg/kg, 10-min iv injection of tobramycin (TOB) at 65 min. Group C was given a 3-mg/kg, 10-min TOB injection at 65 min, followed by an 8.25-mg/kg iv infusion for 285 min, and three 11.25-mg/kg intramuscular injections at 6, 12, and 18 h (total 45 mg/kg). Group D was given the same TOB regimen as B, plus a 30-mg/kg iv injection and 30-mg/kg iv infusion of methylprednisolone sodium succinate (MPSS) from 15 to 360 min. Group E was given the same TOB regimen as C, plus the same MPSS regimen as D. Treated dogs also received 11.25 mg/kg of TOB daily for 4 days. The percent surviving more than 7 days was 0, 0, 17%, 83%, and 83%, for groups A through E, respectively. By 4 h, TOB-treated groups had significantly (p less than .05) lower E. coli blood levels than group A. Also E. coli levels in group B were significantly (p less than .05) lower than those in groups C, D, or E. High trough serum TOB concentrations were associated with death and very low levels with recovery. Serum urea nitrogen and creatinine concentrations increased in all groups, but returned to normal by 7 days in survivors.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1985

Senning repair for transposition of the great arteries in the first week of life.

Infants with D-loop transposition of the great arteries (D-TGA) may have unacceptable results after the balloon septostomy while awaiting surgery. It has been our policy to repair defects in infants with D-TGA and intact ventricular septum or small ventricular septal defect at the time of diagnosis. We report our experience with the Senning operation in 18 newborns less than 1 week of age. The mean age at operation was 3 days (range 12 hr to 7 days) and the mean weight was 3.5 kg (range 2.8 to 4.8). There were two early postoperative deaths (11%) and one late death (5%). Early mortality was associated with preoperative acidosis and congestive heart failure. Late mortality was associated with severe left ventricular outflow tract obstruction (LVOTO). The 15 long-term survivors have been followed for an average of 27 months and 11 of the 16 perioperative survivors have undergone postoperative catheterizations. There was no evidence of systemic or pulmonary venous obstruction. One patient developed LVOTO that led to his death. Two patients had residual atrial shunts. Electrocardiograms revealed no major arrhythmias. All patients are clinically asymptomatic. Good hemodynamic, electrocardiographic, and clinical results can be obtained with correction of D-TGA in the first week of life.

Arteries↗

PubMed1985

Corticosteroid/antibiotic treatment of adrenalectomized dogs challenged with lethal E. coli.

Adrenalectomized animals are extremely sensitive to endotoxin and die quickly when given small doses. A six hour administration of the corticosteroid, methylprednisolone sodium succinate (MPSS), combined with the antibiotic, gentamicin sulfate (GS), promotes complete recovery of dogs with intact adrenals administered LD100 E. coli. The aim of the present study was to determine if this early administered treatment would protect adrenalectomized dogs from overwhelming lethal doses of E. coli. Dogs were infused with MPSS from fifteen minutes to six hours after the onset of E. coli administration and with GS after administration of all E. coli. Animals given only E. coli died in 2.6 (+/- 0.3) hours, while those given no E. coli, or E. coli plus steroid/antibiotic, survived longer than 100 hours. Arterial pressure, pH, pO2, hematocrit, lactate, and glucose concentrations were maintained near control values in animals receiving steroid/antibiotic infusions. Adrenalectomized dogs infused with corticosteroid/antibiotic recovered completely from shock even though the treatment period was limited to the first 6 hours after lethal E. coli infusion. Findings indicate that animals treated with MPSS/GS after E. coli ultimately succumbed to adrenal insufficiency rather than from the E. coli insult and thus recovery from shock itself was complete.

Adrenal Cortex Hormones↗

PubMedDate not supplied

The importance of endogenous histamine relative to dietary histamine in the aetiology of scombrotoxicosis.

Deliberately spoiled mackerel samples and mackerel samples implicated in outbreaks of scombrotoxicosis were, under medical supervision, tested blind on normal, healthy volunteers of both sexes. These experiments identified batches of fish which could induce nausea/vomiting and/or diarrhoea when 50 g samples were consumed. It was also established that the fillets in a batch were neither of equal potency nor homogeneous with respect to histamine content. Strong evidence was obtained that dietary histamine is not a major determinant of scombrotoxicosis since potency was not positively correlated with the dose, and volunteers appeared to fall into susceptible and non-susceptible subgroups. However, there is no reason to suspect allergy as being solely responsible for these differences in sensitivity. It is also possible to discount body weight as a factor. While the data suggest that females may be more susceptible than males, this effect cannot be confirmed at the present time. Studies with susceptible volunteers predosed with either placebo or H1 antagonist (chlorpheniramine 4 mg) demonstrated convincingly that the antihistamine can abolish vomiting and diarrhoea associated with the ingestion of 50 g of scombrotoxic fish. It is therefore postulated that endogenous histamine released by mast cell degranulation has a significant role in the aetiology of scombrotoxicosis, whereas the role of dietary histamine is minor. The nature and origin of the agent responsible for mast cell degranulation is being investigated.

Chlorpheniramine↗

PubMedDate not supplied

Is there a role for amines other than histamines in the aetiology of scombrotoxicosis?

Mackerel fillets associated with an outbreak of scombrotoxicosis have been analysed for their contents of cadaverine, histamine, putrescine, spermidine, spermine and tyramine, and fed to informed, healthy volunteers of both sexes under medical supervision. Of the 86 fillets examined, 30 rapidly induced nausea/vomiting and/or diarrhoea when 50 g were consumed. The remaining fillets failed to provoke such symptoms, even though 17 of them were tested by volunteers proven to be susceptible to scombro-intoxication. Statistical analysis failed to detect any differences in amines content between fillets shown to be scombrotoxic and those failing to induce nausea/vomiting and/or diarrhoea, and failed also to establish any significant relationships between the amines doses and volunteer responses, even after manipulations to simulate additive or synergistic interactions. Accordingly it is concluded that the content of such amines in mackerel have little or no role in the aetiology of scombrotoxicosis.

Amines↗

PubMedDate not supplied

Do saxitoxin-like substances have a role in scombrotoxicosis?

Evidence is presented which establishes that mackerel fed in captivity can, by relay from contaminated shellfish via sand eels, accumulate paralytic shellfish poisons (PSP) in the edible flesh at a level (250 micrograms saxitoxin equivalents per kg) similar to that in the contaminated shellfish. Data from ELISAs performed independently in two laboratories show that commercial mackerel fillets which have been associated with incidents of scombrotoxicosis contained 0.02-1.30 micrograms saxitoxin equivalents per kg, concentrations some two to four orders of magnitude below that normally detectable by the mouse bioassay. The doses, expressed as saxitoxin equivalents, administered inadvertently during volunteer testing of such fillets ranged up to 0.5 ng/kg bw, at least four orders of magnitude less than the fatal oral dose for an adult. The doses associated with the rapid induction of nausea/vomiting and/or diarrhoea, 0.11-1.0 ng/kg bw, could not be distinguished from the doses which failed to produce such symptoms in susceptible volunteers (up to 0.5 ng/kg bw). Factors that might explain this lack of correlation between dose (saxitoxin equivalents) and volunteer response are discussed along with previously published reports of PSP relay through the food web. It is suggested that the relay of algal toxins, particularly PSP, but possibly in combination with diarrheic shellfish poisons, may be responsible for scombrotoxicosis.

Animals↗