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Biomedical subjects

N Craven

Publications and source records attributed to N Craven.

36 records · Page 2Linked to original sources
PubMed1983

Antibiotic activity against intraleukocytic Staphylococcus aureus in vitro and in experimental mastitis in mice.

The activities of a range of antibiotics on Staphylococcus aureus organisms that survive within bovine neutrophils in vitro were studied in mice. Cloxacillin, floxacillin, and cephradine failed to kill intracellular staphylococci but increased the organisms' sensitivity to killing by lysostaphin after neutrophil disruption. Fusidate and clindamycin caused an apparent small reduction in viable intraleukocytic S aureus, whereas novobiocin did not demonstrate intracellular activity. Substantial intracellular bactericidal effects were shown in vitro by rifampin and rifamycin SV, even at concentrations in slight excess of the minimum inhibitory concentration. In a mouse model of chronic mastitis, intramammary therapy with rifampin was more effective in reducing viable S aureus in infected glands than was therapy with rifamycin SV.

Animals↗
PubMed1983

Generation of neutrophil chemoattractants by phagocytosing bovine mammary macrophages.

Macrophages from bovine mammary gland were cultured in vitro and the growth medium collected at intervals. Using an in vitro system in which neutrophils migrated under agarose, both chemotactic and chemokinetic activity for bovine neutrophils was detected in supernatants of macrophage cultures to which heat killed preopsonised Staphylococcus aureus had been added. The suspensions of killed bacteria were not themselves chemotactic for neutrophils and no chemotactic activity was present either in supernatants from unstimulated macrophage cultures or in sonicated macrophages. The chemotaxin(s) was generated within two hours of the addition of staphylococci to the cultures and was largely stable to heating at 56 degrees C for 45 minutes, although its activity was reduced by boiling for 15 minutes. Traces of proteolytic activity were also detected in some supernatants. Substantial proteolytic activity was found in lysates of neutrophils. Unlike chemotaxis, proteolytic activity was suppressed by addition of milk from early lactation and containing high natural levels of protease inhibitors. Proteolytic activity was destroyed by boiling for 15 minutes.

Animals↗
PubMed1983

Penicillin (cloxacillin)-tolerant Staphylococcus aureus from bovine mastitis: identification and lack of correlation between tolerance in vitro and response to therapy in vivo.

Twenty-four isolates of Staphylococcus aureus from naturally occurring cases of bovine mastitis were examined in vitro for resistance to cloxacillin. All strains produced penicillinase and none showed intrinsic resistance (methicillin resistance) to cloxacillin. The minimum inhibitory concentration of cloxacillin for all these strains was normal (low) but differences were found between them in their sensitivities to the bactericidal action. Three were considered to be tolerant to cloxacillin and a further five possibly so. In a mouse model of mastitis there was no difference in the response to intramammary therapy with cloxacillin between cloxacillin-sensitive or tolerant strains of S aureus and a known methicillin-resistant strain was similarly sensitive to cloxacillin therapy in vivo. It is concluded that cloxacillin tolerance may have little clinical significance in mastitis therapy.

Acute Disease↗
PubMed1982

Enhanced killing of penicillin-treated S. aureus by host defences: effects of amoxycillin, cloxacillin and nafcillin in vitro and in experimental mastitis.

The effects of pretreatment of Staphylococcus aureus with subMIC or 10 x MIC amoxycillin, cloxacillin and nafcillin on subsequent killing by bovine neutrophils or sensitivity to lysostaphin were examined in vitro, using penicillinase positive and negative strains. All penicillins increased the susceptibility of S. aureus to bovine neutrophils; with amoxycillin this was most marked with the penicillinase negative strain. Cloxacillin pretreatment was significantly more effective than nafcillin or amoxycillin in some tests and equally effective in others. The sensitivity of S. aureus to lysostaphin was increased following cloxacillin or nafcillin exposure. In a mouse model of mastitis, more cloxacillin and nafcillin-treated S. aureus (at 1/4 MIC) were killed than untreated bacteria 1 hr after infection but by 4 hr no differences were found. No differences were seen after intramammary infection with 10 x MIC penicillin-treated S. aureus. In glands with established chronic mastitis both cloxacillin and nafcillin at high doses failed to kill staphylococci. These findings indicate that prior exposure to penicillins increases staphylococcal susceptibility to killing by neutrophils but following phagocytosis, intracellular bacteria are protected from the lethal action of penicillins.

Amoxicillin↗
PubMed1982

pH-dependent penicillin tolerance may protect intraleukocytic Staphylococcus aureus from killing by cloxacillin.

Exposure of Staphylococcus aureus to cloxacillin at neutral pH rendered the bacteria more susceptible to subsequent lysis by lysostaphin. This sensitization effect also occurred at lower pH levels which were nonpermissive for the bactericidal action of cloxacillin, but the effect disappeared at pH 5.0. These findings elucidate previous observations on the protection of intraleukocytic S. aureus from killing by cloxacillin and indicate that low pH in the phagolysosomes may be involved.

Cloxacillin↗
PubMed1981

A membrane filtration method for estimating the number of viable bacteria in solutions containing antibiotic.

The method involves filtration of dilutions of the mixture through a membrane filter followed by replication on ox blood agar and enumeration of organisms. This method was compared with the conventional drop count method, and a significant correlation was found (r = 0.985). When solutions containing antibiotic were used, the membrane filtration method gave a more reliable estimate of the viable count at the time of sampling.

Animals↗
PubMed1981

Therapy of experimental staphylococcal mastitis in the mouse with cloxacillin and rifampicin, alone and in combination.

Cloxacillin effectively killed Staphylococcus aureus in vitro and in experimental acute mastitis in the mouse, but was ineffective in reducing bacterial counts in those with experimental chronic mastitis. Rifampicin was similarly bactericidal for staphylococci in vitro and in acute mastitis but it also significantly reduced numbers of viable bacteria in chronic mastitis. Exposure of multiplying staphylococci in vitro and in vivo to rifampicin alone led to the emergence of resistant bacteria, but this was prevented by the use of a combination of rifampicin with cloxacillin. This combination showed neither antagonism nor synergy in vitro, was more effective than either antibiotic alone in acute mastitis and killed S aureus in the chronic infection as effectively as rifampicin alone.

Animals↗
PubMed1980

The effects of cloxacillin on staphylococci phagocytosed by bovine neutrophils.

The effects of cloxacillin on staphylococci within neutrophils from the peripheral blood of cattle were examined. When cloxacillin was added to a preparation of intracellular staphylococci suspended in nutrient broth at 37 degrees C in the presence of lysostaphin, significantly more staphylococci were killed than in the controls without the antibiotic. Cloxacillin entered the neutrophils and made the intracellular staphylococci sensitive to lysis by lysostaphin when the neutrophils were disrupted. The intracellular action of cloxacillin was greater than when Hanks' balanced salt solution was the suspending fluid or when the broth was incubated at 4 degrees C. Failure to observe the effect in these circumstances was possibly due to a very low rate of metabolism in the staphylococci.

Animals↗
PubMed1979

The location of Staphylococcus aureus in experimental chronic mastitis in the mouse and the effect on the action of sodium cloxacillin.

Chronic staphylococcal mastitis was established in the mouse and electron miscroscopic examination of mammary tissue showed that the staphylococci were within epithelial cells, neutrophils and macrophages. Suspensions of cells containing staphylococci were prepared from chronically infected glands and incubated with sodium cloxacillin in vitro. This procedure resulted in a reduction in bacterial numbers, but a significantly greater reduction was obtained if the somatic cells were disrupted by sonication before the addition of cloxacillin. The results imply that the intracellular location of the staphylococci protects them against the action of the antibiotic.

Animals↗
PubMed1976

Computer analysis of the single-breath nitrogen washout curve.

A computerized system has been developed to analyze the parameters that can be derived from the nitrogen washout curve. Analog signals for air flow, volume, and nitrogen concentration are entered either on-line or off-line into a 24,000 mini-computer. The program calculates vital capacity, total lung capacity, and residual volume, as well as the slope of phase III, closing volume in liters, total lung capacity, residual volume, closing capacity, closing volume/vital capacity ratio, and closing capacity/total lung capacity ratio. Validation tests showed excellent correlation between hand- and computer-calculated values of closing volume(r=0.864), vital capacity (r=0.997), total lung capacity (r=0.991), and slope of phase III (R=0.926). We concluded that the computerized system for analysis of the expired nitrogen washout curve is as reliable as hand calculations and is immeasurably faster.

Diagnosis, Computer-Assisted↗
PubMed1975

Learning pulmonary function interpretation: deductive versus inductive methods.

Volunteer undergraduate medical students were randomly divided into 2 groups. One group were given pulmonary function data and the correct diagnoses from 18 patients. They were told to try to derive the rules by which the diagnoses were made. The other group were given the data from the same 18 patients, but were required to use a computer-assisted instructional program to arrive at the diagnoses in a deductive fashion. Both groups were pre- and post-tested. The deductive method provided higher post-test results. The inductive method took longer and produced more dropouts from the study.

Analysis of Variance↗