Probable multigeneric resistance to macrocyclic lactone anthelmintics in cattle in New Zealand.

AIM: To establish the efficacy of topical formulations of eprinomectin and abamectin against naturally acquired abomasal and small intestinal nematode infections in cattle purchased from a North Island bull-beef property. METHODS: A controlled slaughter trial, involving eighteen 6-8-month-old mixed breed calves, was conducted in May 2002.The animals were randomly allocated on the basis of faecal egg count to one of three equal-sized groups (n=6), consisting of an untreated control group and two treatment groups. One of the treatment groups was treated with a topical formulation of eprinomectin, the other with abamectin. Both anthelmintics were administered as a single topical treatment on an individual liveweight basis, at the manufacturer's recommended dose rates of 0.5 mg/kg. All calves were housed in separate groups with no access to pasture throughout the entire trial and were slaughtered 7-10 days after treatment. RESULTS: Both anthelmintic treatments were highly effective(worm count reduction >98%) against Ostertagia ostertagi, Trichostrongylus axei and Cooperia punctata, but were not effective at reducing worm counts significantly of either Cooperia oncophora or Trichostrongylus longispicularis. Against these latter two parasites, worm count reductions of only 72% and 79%, and 81% and 76%, respectively, were recorded following treatment with eprinomectin or abamectin, respectively (all p>0.05). CONCLUSIONS: These results demonstrate evidence of resistance to macrocyclic lactone anthelmintics by C. oncophora and probably T. longispicularis also. CLINICAL RELEVANCE: As well as perhaps providing the first record of resistance to any anthelmintic by T. longispicularis, the present findings may also represent the first case of resistance to macrocyclic lactone anthelmintics exhibited by more than one parasite species at a time in cattle in New Zealand.

The Boston experience.

In April 2000, three nurses from Chesterfield (UK) were successful in an application for a travel scholarship. The scholarship was to examine emergency nurse practitioner (ENP) schemes in Boston USA after completion of my dissertation based on the same subject, in the course of which the broad span of ENP work had become obvious to me. Leading up to the trip overseas, we discussed specific objectives we hoped to meet but we did not expect the range of experiences we were exposed to within this busy city. It became apparent while in Boston, that we should avoid becoming too focused otherwise we might miss valuable information or experiences which would benefit practice back in the UK. Six of the most striking issues, which impressed all three of us, are covered in this paper. These are then reflected back to UK practice in an attempt to discover whether these experiences can benefit our own profession. Subjects covered include: student training; ENP training and role parameters; physician assistants; primary care and the effect of information technology on the emergency care culture.

Applying outpatient protocols in febrile infants 1-28 days of age: can the threshold be lowered?

The purpose of this study was to determine the applicability of two accepted outpatient management protocols for the febrile infant 1-2 months of age (Boston and Philadelphia protocols) in febrile infants 1-28 days of age. We retrospectively reviewed charts of patients 1-28 days of age with a temperature greater than or equal to 38.0 degrees C. Criteria from each of the above-cited management protocols were applied to the patients to determine their applicability in screening for serious bacterial infection (SBI). An SBI was defined as bacterial growth in cultures from blood, urine, cerebrospinal fluid (CSF), stool, or any aspirated fluid. Overall, 372 febrile infants were included in the study. Ages ranged from 1 to 28 days of age. The mean age was 15 days. SBI occurred in 45 patients (12%). The mean age of the patients with an SBI was 13 days. Thirty-two infants (8.6%) had a urinary tract infection; 12 (3.2%), bacteremia; five (1.3%), bacterial meningitis; three (0.8%), cellulitis; one (0.3%), septic arthritis; one (0.3%), bacterial gastroenteritis; and one (0.3%), pneumonia. Ten infants had more than one SBI. Of 372 patients, 231 (62%) met the Boston's laboratory low-risk criteria; eight (3.5%) would have been sent home with an SBI with these criteria. Philadelphia's laboratory low-risk criteria would have been met by 186 patients (50%); six (3.2%) would have been sent home with an SBI with these criteria. The negative predictive value of both the Boston and Philadelphia protocols for excluding an SBI was 97%. We conclude that current management protocols for febrile infants 1-2 months of age when applied to febrile infants 1 to 28 days of age would allow 3% of febrile infants less than 28 days of age to be sent home with an SBI. Current guidelines recommending admitting all febrile infants less than 28 days of age should be followed until the outcome of those 3% of febrile infants with an SBI treated as outpatients can be determined.

Induction of apoptotic cell DNA fragmentation in human cells after treatment with hyperthermia.

The biological significance of apoptosis is becoming increasingly clear. Its relevance in tumor response to treatment as well as recent evidence for its important function as a regulating mechanism in tumorigenesis has also been demonstrated. One of the most prominent biological features of apoptosis is nucleosomal DNA fragmentation. In this communication, we present a study of DNA fragmentation in Raji cells which have been subjected to hyperthermia treatment to induce apoptosis. We found that the induction and onset of fragmentation is swift, and consistent with previous reports that fragmentation must be a rapid event.

Intrathecal baclofen therapy for adults with spinal spasticity: therapeutic efficacy and effect on hospital admissions.

A prospective trial to demonstrate the efficacy of intrathecal baclofen therapy by implanted pump for adults with spasticity due to spinal cord injury or multiple sclerosis was initiated in our hospital. Of the 140 patients assessed, 7 met the following criteria for inclusion in the study: a modified Ashworth score > 3, a spasm frequency score > 2, and an inadequate response to oral anti-spasticity drugs, (i.e., baclofen, clonidine and cyproheptadine). All patients responded to intrathecal bolus injection of baclofen in the double blind, placebo-controlled screening phase (mean bolus dose = 42.8 micrograms). Programmable Medtronic pumps were implanted in 4 patients while 3 patients received non-programmable Infusaid pumps. Post-implantation, a marked decrease in spasticity occurred with a significant reduction of the Ashworth score (mean = 1.8, p < .005), a reduced spasm score (mean = 0.8, p < .005), and an improved leg swing in the pendulum test. These effects were maintained during a follow-up of 24-41 months (average infusion dose = 218.7 micrograms/day). The gross cost-savings due to reduced hospitalizations related to spasticity was calculated by comparing the cost for the two year period before pump implantation to the same period after treatment for 6 of the 7 patients. The cost of in-hospital implantation as well as the cost of the pumps were deducted from the gross savings. There was a net cost-saving of $153,120. Our findings agree with the reported efficacy and safety of intrathecal baclofen treatment, and illustrate the cost-effectiveness of this treatment.

Steady-state ventilatory responses to expiratory resistive loading in quadriplegics.

Patients with quadriplegia have a limited capacity to recruit expiratory muscles and are deprived of respiratory-related feedback from the rib cage and abdominal wall. We wished to evaluate the compensatory strategies available to such patients during expiratory resistive loading (ERL) and to compare their responses with those of normal healthy individuals. In addition, to determine whether the quadriplegic subjects have a blunted sensory appreciation of added ERL, we also compared sensory detection thresholds (delta R50). Steady-state ventilatory responses to ERL (delta R = 12 cm H2O/L/s) were compared in seven quadriplegic patients (level of injury, C6, C7) and six age-matched normal subjects. Highly significant intergroup differences were evident in the extent of prolongation of expiratory time (TE) and total cycle duration (Ttot) during ERL; values of delta TE and delta Ttot in quadriplegics were, on average, 46% of those of normals (p < 0.001). Minute ventilation (VE) was defended to an equal or better extent in quadriplegics. ERL-induced changes in tidal volume, inspiratory duration, mean inspiratory and expiratory flows, and end-expiratory lung volume (EELV) were not significantly different. Average delta R50 in quadriplegics and normals were (mean +/- SD), 1.73 +/- 0.039 cm H2O/L/s and 1.62 +/- 0.4 cm H2O/L/s, respectively (p = ns). Quadriplegics, therefore, despite substantial sensory and motor deficits, defend ventilation and EELV as effectively as normal individuals and show no attenuation in the ability to detect an added expiratory resistance.

Breathing pattern adjustments during the first year following cervical spinal cord injury.

The alterations in lung function and breathing pattern were examined in 6 quadriplegics at 3, 6 and greater than 12 months post injury, and were compared to 6 able bodied controls. Subjects were studied in both the seated and supine positions. Functional residual capacity (FRC), forced vital capacity (FVC), inspiratory capacity (IC), and maximum mouth pressure (Pimax) at FRC were measured. Total lung capacity (TLC) and residual volume (RV) were calculated. Resting breathing pattern was assessed for 20 minutes from a spirogram derived from summed rib cage and abdominal strain gauge signals. At 3 months in quadriplegics, TLC was reduced (p less than 0.05), RV increased (p less than 0.01) and FRC was normal in sitting; in supine, only TLC was reduced (p less than 0.05); Pimax was decreased (p less than 0.01) in both positions in quadriplegics at 3 months, but increased over the first year in the seated position (p less than 0.01). There were no alterations in breathing pattern at any time interval in quadriplegics in supine. In contrast, at 3 months post injury in sitting, expiratory time (Te) was shortened (p less than 0.05), tidal volume (Vt) was decreased, and heart rate elevated as compared to controls (p less than 0.05). Inspiratory time (Ti) was not significantly shortened at 3 months in quadriplegics, but a lengthening of Ti occurred between 3 and 6 months (p less than 0.025) resulting in increased Vt, and heart rate decreased to normal. Vt/Ti was reduced, and did not alter with time. The lengthening of Ti/Ttot observed in supine in control subjects (p less than 0.025), was not observed in quadriplegics. Quadriplegics sighed as frequently in supine as did controls at all stages post injury, whereas they decreased sighing frequency in sitting at 3 and 6 months post injury (p less than 0.05). The improvement in resting breathing pattern observed in quadriplegics in sitting with time, may be due to increased accessory muscle function, improved chest wall stability and thoracoabdominal coupling, or a combination of these factors. It is also possible that the alterations in breathing pattern were a response to cardiovascular adjustments occurring in the same time frame. Quadriplegics retain the sigh reflex, but do not take as many big breaths in sitting as they do in supine, probably due to the increased work of breathing in the seated posture.

Breathing pattern in chronic quadriplegia.

The resting breathing pattern in 14 chronic C6 and C7 traumatic quadriplegics was compared with six age-matched healthy controls. All quadriplegics had complete motor loss below the lesion level and were at least two years postinjury. Tests were performed with subjects seated. Forced vital capacity (FVC), forced expiratory volume in one second (FEV1.0), inspiratory capacity (IC), and maximum inspiratory mouth pressure (Pimax) were measured. Resting breathing pattern was assessed for 20 minutes using mercury in rubber strain gauges and a computer-assisted data acquisition and analysis program. Inspiratory time (Ti), expiratory time (Te), and tidal volume (Vt) were measured, and the remaining timing components were calculated from these values. The variability of breathing was assessed by comparing the coefficients of variation of each variable. The FVC, IC, and Pimax were significantly reduced; Vt was significantly lower (p less than 0.01) and frequency significantly elevated (p less than 0.05) in quadriplegics. The decreased Vt in quadriplegics was due entirely to a significantly decreased mean inspiratory flow (p less than 0.01); Ti was the same in quadriplegics as in controls. The ratio of mean Ti to total cycle time (Ti/Ttot) was significantly longer in quadriplegics (p less than 0.005). There was no difference in variability of breathing between the two groups for any timing component of ventilation. There was no significant difference in sighing frequency between groups for either breaths greater than 2x mean Vt or breaths greater than 3x mean Vt. Chronic quadriplegics demonstrated a rapid, shallow breathing pattern, probably due to the mechanical restrictions resulting from paralysis of the thorax musculature. They retained the ability to sigh, suggesting that chest wall afferents may not be required in this process.

Ventilatory muscle endurance training in quadriplegia: effects on breathing pattern.

We examined the effects of ventilatory muscle endurance training on resting breathing pattern in 12 C6-C7 traumatic quadriplegics at least 1 year post-injury. All subjects had complete motor loss below the lesion level. Subjects were randomly assigned to a training (N = 6), or a control group (N = 6). Baseline tests included measurement of resting ventilation and breathing pattern using mercury in rubber strain gauges for 20 minutes in a seated position; maximum inspiratory mouth pressure (MIP) at FRC, and sustainable inspiratory mouth pressure for 10 minutes (SIP); lung volumes, and arterial blood gases (ABG's). The training protocol consisted of breathing through an inspiratory resistor equivalent to 85% SIP for 15 minutes twice daily, 5 days a week for 8 weeks. Both trainers and controls attended the lab every 2 weeks for reassessment of MIP and SIP and the inspiratory resistance was increased in the training group as SIP increased. At the end of 8 weeks, baseline tests were repeated. All subjects had normal ABG's. There was a significant increase in mean MIP and SIP in both the control group (30% +/- 19% and 31% +/- 18% respectively), and in the training group (42% +/- 24% and 78% +/- 49% respectively). Although the absolute values for both MIP and SIP were greater in the training group than in the control group, the differences were not significant. The alterations in resting breathing pattern were also the same in both groups. Mean frequency decreased significantly in the control group (20.2/minute to 16.9/minute) and, while insignificant, the change in frequency in the training group was the same, 19.4/minute to 16.4/minute. Mean tidal volume (Vt) increased 18.2% of baseline Vt in the control group and 17.0% baseline in the trainers, resulting in no change in minute ventilation. As MIP and SIP increased similarly in both groups, the data from the control and trainers was pooled and timing changes re-evaluated pre- and post-study. A significant decrease in mean Ti/Ttot was observed, while no change in Vt/Ti was found. We concluded that the testing procedure itself provided the stimulus resulting in a significant increase in MIP and SIP. The addition of training did not increase MIP and SIP further. The increased MIP and SIP resulted in a slower and deeper breathing pattern and a significantly shorter Ti/Ttot in both trainers and control subjects.

Alteration in breathing pattern with progression of chronic obstructive pulmonary disease.

We examined the relationship between breathing pattern and severity of disease in patients with chronic obstructive pulmonary disease (COPD). Resting breathing pattern was recorded for 45 min using the respiratory inductance plethysmograph (RIP) in 22 patients with stable COPD. Six subjects (moderate group) had FEV1 25 to 50% predicted, 8 subjects (severe group) had FEV1 less than 25% predicted, and 8 subjects (respiratory failure group) had FEV1 less than 25% predicted and were hypoxemic. Seven of the subjects with respiratory failure were also hypercapnic. Subjects with respiratory failure were studied with and without supplemental O2. All subjects were studied in the seated position. There were no significant differences in breathing pattern between the moderate and severe groups. Tidal volume (VT) was 120 ml lower in the severe group, but breathing frequency (f) was slightly elevated, allowing minute ventilation (VI) to be maintained. The respiratory failure group demonstrated a significant decrease in VT compared with that in the moderate group and a significant decrease in VT/TI as compared with both moderate and severe groups; TI was unchanged in subjects with respiratory failure, and, as f did not increase significantly, VI was decreased. Acute relief of hypoxemia had no effect on breathing pattern in respiratory failure. Variability was assessed by comparing the coefficients of variation for each timing component. There was no difference in intraindividual variability of breathing pattern between all groups. These results suggest that changes in ventilatory control as reflected by breathing pattern are to some extent independent of mechanical abnormalities.

Breathing patterns in patients with chronic obstructive pulmonary disease.

The respiratory inductance plethysmograph (RIP) was used to record resting breathing for 45 min in 12 patients with stable chronic obstructive pulmonary disease (COPD) and 8 age- and sex-matched control subjects. The COPD group had mean FEV1.0 of 31% predicted (range: 15 to 49%), mean PaO2 of 70 mmHg (56 to 83 mmHg), and mean PaCO2 of 37 mmHg (31 to 47 mmHg). All subjects were studied in the sitting position, and the rib cage (RC) and abdomen (ABD) RIP signals were simultaneously recorded on a polygraph and sampled at 20 Hz by a microcomputer. The summed RC and ABD signals were processed to create a spirogram from which the timing components of the respiratory cycle were subsequently analyzed. The mean number of breaths analyzed per subject was 702 +/- 213 (SD). Mean tidal volumes were identical in both groups. Inspiratory and expiratory times were significantly less (p less than 0.01), and mean inspiratory flow was significantly greater (p less than 0.01) in the COPD group. Frequency and minute ventilation also were significantly greater in the COPD group (p less than 0.005). Variability of breathing pattern, assessed in terms of coefficients of variation, was significantly less for TI, TI/Ttot, and VI in COPD patients than in normal subjects, even after sighs had been excluded from the analysis. We suggest that alterations in breathing pattern and its variability reflect changes in neural control of breathing consequent to disease.

Single-position calibration of the respiratory inductance plethysmograph.

Since we intended to use the respiratory inductance plethysmograph (RIP) to study breathing patterns in a single body position, we developed a method to calibrate the RIP in one position (seated) and verified the stability of this calibration procedure during a 60-min period. The subject breathed spontaneously through a pneumotachograph for 1 min during all calibration and verification runs. All inspiratory data from the abdomen and rib cage RIP transducers was analyzed using multiple linear regression analysis to calculate calibration factors for the transducers. Eight normal subjects were studied, and the stability of calibration at 20, 40, and 60 min was determined. The correlation coefficients were all greater than 0.94. The mean slope and mean intercept describing the relationship of the RIP volume to the pneumotachograph volume for all calibration and verification runs were 0.995 +/- 0.074 and 0.012 +/- 0.018 liter, respectively. This calibration method allows a spirogram to be generated from the RIP signals. Therefore, this technique may be valuable in further investigating resting breathing patterns in humans.

Physiotherapy management of patients with chronic obstructive airways disease.

Various physiotherapy techniques have long been advocated as therapeutic tools for patients with chronic obstructive airways disease (COAD). The purpose of this review is to present an outline of the different techniques, a definition of the present controversies, and an illustration of the possible new directions for physiotherapy in the future. The following aspects of the disease are reviewed: pathophysiology; research; patient education; secretion removal (including techniques of coughing, postural drainage, and percussion); breathing control exercises (including use of the abdominal muscles, nasal inspiration, pursed lip breathing, positioning, alteration of regional ventilation, and the related short and long-term benefits); and thoracic mobility exercises. The authors conclude not only that the physical therapeutic techniques used with COAD patients are extremely diverse in nature, but that the investigations of their validity have been neither comprehensive nor conclusive. Immediate study is needed to define more specific physiological aims for each modality; more selective and effective treatment can then be performed and the true potential of chest physiotherapy realized.