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Biomedical subjects

D McCracken

Publications and source records attributed to D McCracken.

17 recordsLinked to original sources

Polymerase chain reaction aids in the diagnosis of an unusual case of Aspergillus niger endocarditis in a patient with acute myeloid leukaemia.

Endocarditis secondary to Aspergillus niger has not been described in a leukaemic patient. We describe a case of A. niger endocarditis in a patient with acute myeloid leukaemia and refractory fever. The microbiological cause of his endocarditis was initially misdiagnosed because he fulfilled the Duke criteria for enterococcal endocarditis. A polymerase chain reaction test utilizing pan-fungal primers detected a product from an Aspergillus sp. The DNA was subsequently sequenced and was found to have 100% homology with A. niger. A postmortem revealed fungal endocarditis secondary to disseminated aspergillosis, without evidence of bacterial endocarditis. The patient was found to have a lung aspergilloma that was possibly occupationally acquired, and may have been long standing.

Aspergillosis↗

Cluster of cases of Mycobacterium chelonae bacteraemia.

Mycobacterium chelonae was isolated from the blood of four immunosuppressed patients over a period of 10 weeks. Three patients had intravascular catheters in situ and the other had a biliary stent. All presented with recurrent fever despite treatment with broad-spectrum antibiotics. Blood cultures using standard bacteriological medium yielded a gram-positive bacillus from each patient. Ziehl-Neelsen staining of these cultures demonstrated a branching acid-fast bacillus that was subsequently identified as Mycobacterium chelonae in each case. The isolates were sensitive to clarithromycin and, although success of treatment with clarithromycin monotherapy has been variable, this antibiotic combined with removal of the intravascular catheters was used to treat those three patients. The treatment was successful with no recurrence of symptoms after 12 months of follow-up. The patient with the biliary stent died soon after Mycobacterium chelonae was isolated. Pyrolysis mass spectrometry analysis indicated the isolates were of two distinct strains. Radiological insertion of the Hickman lines and biliary stent was implicated epidemiologically as the source of infection.

Adult↗

US probes: risk of cross infection and ways to reduce it--comparison of cleaning methods.

After their use at ultrasonography (US) in the intensive therapy unit, probes were used to directly inoculate blood agar plates before and after various cleaning procedures. The uncleaned probes transmitted large numbers of clinically important microbes. Simple cleaning methods were effective in reducing transmission among certain patients: fit patients, double paper wipe; patients at risk of contracting infection, single paper wipe followed by alcohol wipe; patients with a potential source of infection, single paper wipe followed by alcohol wipe.

Bacteria↗

Effect of hypoinsulinemia on growth in the fetal rabbit.

Insulin is an important regulatory hormone in the control of fetal growth. In a fetal rabbit model, a non-ruminant species, the effects of insulin deprivation on glucose, growth and protein metabolism were studied. The fetuses of 10 pregnant New Zealand white rabbits in one uterine horn received a subcutaneous injection on day 25 of gestation (term = 30 days) of 0.1 mg streptozotocin (STZ)/gm fetal weight. The fetuses in the opposite horn received a sham injection of buffer. The dams were then killed on day 29. The fetal insulin concentration was depressed by 38%, and the serum glucose concentration was elevated by 28% in animals given STZ when compared to control animals. Fetal weights, carcass weights and skeletal growth, as measured by crown-rump length and tibial length of STZ-treated fetuses, were significantly reduced by 7-13%. However, organ weights were not significantly different, except for the kidneys which were 17% lighter. Protein and mineral contents of the carcasses were also reduced compared to the control fetuses. Thus, insulin deprivation in fetal rabbits results in significant growth impairment in a pattern similar to that of human asymmetric intrauterine growth retardation.

Animals↗

Efficacy of insulin eyedrops.

Systemic absorption of insulin delivered via eyedrops has been studied in rats made transiently hyperglycemic by anesthesia with xylazine/ketamine. Insulin at a concentration of 2 mg/ml was not absorbed significantly when saline alone was used as the formulation for the eyedrops (0.04 ml). When various emulsant agents were added to the eyedrop formulation, systemic insulin levels were increased and concomitantly, blood D-glucose levels were decreased. Saponin, Brij-78, BL-9 and several alkylglycosides all increased the systemic absorption of insulin following delivery in eyedrops. Not all surfactant agents were effective in promoting systemic insulin absorption from eyedrops, as evidenced by the failure of some non-ionic surfactants to increase insulin absorption. Similar results were obtained when nosedrops containing insulin plus non-ionic surfactants were administered to rats. In conclusion, systemic insulin absorption was greatly accelerated by the addition of certain emulsants to the eyedrop formulation and physiologically important levels of insulin could be delivered systemically following eyedrop administration.

Absorption↗

Human tumour-associated NK cells secrete increased amounts of interferon-gamma and interleukin-4.

Numerous interactions between malignant and stromal/inflammatory cells take place within solid human tumours, which are mediated, in part, by the release of signalling proteins called cytokines. In the present study, we have compared the secretion of two important immunomodulatory cytokines, IFN-gamma and IL-4 by individual, immunophenotyped NK cells freshly isolated from either malignant tumour biopsies, or peripheral blood samples from patients with ductal invasive breast cancer. Due to the marked heterogeneity amongst cells isolated from these clinical samples, we have employed a technique called the reverse haemolytic plaque assay to identify and enumerate cytokine-secreting cells at the single cell level. Our data indicate that NK cells isolated directly from the tumour site secrete more IFN-gamma and IL-4 than NK cells from the blood of the same patients. However, a greater proportion of CD16+ cells from both sources in breast cancer patients secreted IFN-gamma than of those from the blood of healthy donors. We also show that factors secreted by the human breast cell lines, MCF-7 and MDA-231 PN9, were able to mimic the stimulatory influence of the tumour microenvironment on secretory activity of NK cells.

Antigens, CD↗

Handgrip dynamometry, Cybex measurements and lean mass as markers of the ageing of muscle function.

Isometric handgrip force, isokinetic knee flexion and extension torque, and anthropometric data were obtained on 67 older men and women (ranging in age from 45 to 75 years, mean 59.7 years). Hydrostatic and skinfold estimates of lean body mass were quite closely correlated with each other in this sample (r = 0.93). Handgrip force, isokinetic knee flexion and extension torque, and lean mass all decreased by 6-8% per decade over the age span examined, although in the men the loss was most marked in terms of handgrip and lean mass, whereas in the women the loss of torque in the knee muscles was dominant. Because of these differences, the handgrip data were only weakly correlated with the isokinetic strength measurements (r = 0.22), and the isokinetic data were more strongly related to lean body mass and body mass. The optimum equation for a field prediction of isokinetic strength in this age group (a combination of age, sex, age-sex interaction and lean body mass) has an error approaching 25%, with a multiple r2 of 0.37, and a standard error of the estimate (s.e.e.) of 24.5%. It is concluded that handgrip data and slow isokinetic torque measurements evaluate relatively independent aspects of the ageing of muscular function.

Aged↗

Phase I-II pilot of whole abdominal radiation and concomitant 5-FU as an adjuvant in colon cancer: a Southwest Oncology Group Study.

Thirty-eight patients with Stage B2, C1 or C2 colon cancer (Astler-Coller Modification of Dukes) received 3000 rads whole abdominal radiation and concomitant intermittent bolus 5-FU as part of a phase I-II adjuvant trial. Patients whose tumor penetrated the serosa (B2 or C2) in addition received a 1600 rad boost to the tumor bed. 5-FU was administered only during radiation. It was given at a dose of 300 mg/m2 days 1-5 and 28-32 in 21 patients (Group A) and day 1-3 and 28-31 in 17 patients (Group B). Median follow-up time for Group A is 44 months. Group A patients have a disease-free survival of 66% and overall survival of 73% at 44 months. The 16 C2 patients in Group A have a disease-free survival of 54% and overall survival of 65% at 44 months. There was a 26% incidence of moderate to severe acute toxicity in Group A but no long term bowel, liver, or hematologic toxicity. One patient developed acute myelogenous leukemia 2 years after treatment. Group B patients had only a 6% incidence of moderate to severe toxicity, but had a disease-free survival of 60% and overall survival of 100% at median follow-up of 23 months. Group B Stage C2 patients had a disease-free survival of 53% and overall survival of 100% at this same follow-up period. Disease-free and overall survival in Group A Stage C2 patients is superior to that in several published trials. Given the manageable toxicity, adjuvant whole abdominal radiation with concomitant 5-FU and tumor bed boost should be tested in a randomized fashion for possible therapeutic benefits.

Abdomen↗

MER-BCG (NSC-143769): immunogenicity and toxicity of single and repeated intradermal injections in dogs.

Intradermal injections of MER-BCG 0.1 mg or 0.2 mg at each of 10 multiple sites, led to local granuloma formation. The nodules reached approximately 10 mm in diameter, ulcerated and were accompanied by granulomatous changes in the regional lymph nodes. Six or twelve successive treatments (each including 10 injections) at 4 week intervals produced the same histopathological lesions but no changes in hematological and blood chemical parameters or general morphology and no changes in general condition with exception of occasional weight loss in a few animals. Injection with 0.01 or 0.001 mg/site produced similar, though less severe, skin lesions but no changes in the draining lymph nodes. The immunogenicity of MER-BCG was characterized by granuloma formation, a positive skin response to old tuberculin, and a positive lymphocyte transformation to PPD tuberculin, thus indicating stimulation of cell-mediated immune responses. However, there was a decreased responsiveness to PHA and PPD with continuing treatment with MER-BCG. The decreased responsiveness and accumulation of numerous depots of antigen would suggest an "immunologic paralysis" contraindicating the administration of excessive amounts of MER-BCG during immunotherapy. A specific humoral response to the administration of MER-BCG was not detected, but an MER-BCG dose independent decrease in albumin associated with a non-specific, dose related elevation in serum IgG was observed.

Adjuvants, Immunologic↗

Paecilomycosis in a nonhuman primate (Macaca mulatta).

Focal granulomas caused by fungi in the genus Paecilomyces occurred at subcutaneous and laryngeal sites in a Rhesus monkey. Slight wheezing was noted 8 months before the monkey died. Death was unexpected and was caused by asphyxiation after occlusion of the larynx by a fungal granuloma.

Animals↗

Adynamic ileus in the rat induced by chloral hydrate.

During neurophysiologic studies in the rat [Crl:COBS CD(SD)BR], chloral hydrate was given intraperitoneally to produce anesthesia for brain electrode implantation. The incidental occurrence of adynamic ileus in six of these rats, 5-16 days after surgery, prompted further investigation. Pathological evaluations and transmission experiments using ingesta and viscera from affected rats failed to reveal an infectious agent. Subsequently chloral hydrate-induced adynamic ileus leading to morbidity or death was experimentally produced in 14 of 27 rats, 3--36 days after intraperitoneal administration of the anesthetic at a dose of 400 mg/kg body weight and concentrations of 125--275 mg/ml. The experimentally produced condition was characterized by lethargy, anorexia, abdominal distension, ruffled hair coat, inactivity, drowsy expression, constipation, and death. Gross pathologic findings included gaseous distension and atony of the cecum and segments of the small intestine. Small intestine contents varied from liquid to solid. The colon and rectum contained only a few dry hard fecal pellets. A few animals showed excess abdominal fluid. Microscopic findings were limited to focal chronic serositis and serosal fibrosis affecting the visceral peritoneum. On the basis of the experimental studies, it was concluded that the condition described was not an infectious disease but was an abnormal physiologic condition produced by the irritating or pharmacologic action of chloral hydrate given at high concentrations in the abdominal cavity.

Anesthesia, General↗