Metabolism of deltamethrin and cis- and trans-permethrin by human expressed cytochrome P450 and carboxylesterase enzymes

1. The metabolism of the pyrethroids deltamethrin (DLM), cis-permethrin (CPM) and trans-permethrin (TPM) was studied in human expressed cytochrome P450 (CYP) and carboxylesterase (CES) enzymes.

2. DLM, CPM and TPM were metabolised by human CYP2B6 and CYP2C19, with the highest apparent intrinsic clearance (CL_int) values for pyrethroid metabolism being observed with CYP2C19. Other CYP enzymes contributing to the metabolism of one or more of the three pyrethroids were CYP1A2, CYP2C8, CYP2C9*1, CYP2D6*1, CYP3A4 and CYP3A5. None of the pyrethroids were metabolised by CYP2A6, CYP2E1, CYP3A7 or CYP4A11.

3. DLM, CPM and TPM were metabolised by both human CES1 and CES2 enzymes.

4. Apparent CL_int values for pyrethroid metabolism by CYP and CES enzymes were scaled to per gram of adult human liver using abundance values for microsomal CYP enzymes and for CES enzymes in liver microsomes and cytosol. TPM had the highest and CPM the lowest apparent CL_int values for total metabolism (CYP and CES enzymes) per gram of adult human liver.

5. Due to their higher abundance, all three pyrethroids were extensively metabolised by CES enzymes in adult human liver, with CYP enzymes only accounting for 2%, 10% and 1% of total metabolism for DLM, CPM and TPM, respectively.

     

Apramycin and gentamicin resistance in Escherichia coli and salmonellas isolated from farm animals

Since the aminoglycoside antibiotic apramycin was licensed for veterinary use in 1980, all isolates of Escherichia coli and salmonellas received at the Central Veterinary Laboratory have been monitored for resistance to apramycin and the related antibiotic gentamicin. During the period 1982-4, the incidence of resistance in E. coli to apramycin increased from 0.6% in 1982 to 2.6% in 1984. In salmonellas the incidence of resistance to apramycin increased from 0.1% in 1982 to 1.4% in 1984. Resistance to both apramycin and gentamicin was detected in six different salmonella serotypes, although an isolate of Salmonella thompson from poultry was resistant to gentamicin but not apramycin. Most of the cultures were isolated from pigs, although the incidence of apramycin resistance in S. typhimurium (DT 204C) from calves has shown a recent dramatic increase. All the isolates with one exception produced the enzyme aminoglycoside 3-N-acetyltransferase IV (ACC(3)IV). The resistance was transferable by conjugation in most of the strains examined, and the plasmids specifying the resistance have been found to belong to a number of different incompatibility groups. Plasmids from three E. coli strains were compatible with all the reference plasmids and belonged to a previously undescribed group which was investigated further. It is suggested that bacteria from humans should be examined for resistance to apramycin and gentamicin to determine the possibility of the antibiotic-resistance bacteria, and their genes, spreading from animals to humans.     

Lps Genotype in the C57 Black Mouse Blackground and its Influence on the Interleukin-6 Response to E. coli Urinary Tract Infection

The present study examined the influence of the mouse Lps genotype on the interleukin-6 (IL-6) and polymorphonuclear leucocyte (PMN) responses to mucosal Escherichia coli infection. Lipopolysaccharide (LPS) responder C57BL/6J (Lpsn, Lpsn) and LPS non-responder C57BL/10ScCr (Lpsd, Lpsd) mice were inoculated intravesically with Escherichia coli Hu734. The secretion of IL-6, the recruitment of PMNs into urine, and the bacterial clearance from the kidneys and bladders were compared between the two mouse strains at 2, 6 and 24 h after infection. The C57BL/6J mice showed a high PMN response and rapid clearance of bacteria from the kidneys and bladders. In the C57BL/10ScCr mice the PMN response was low and infection remained. This supported a role of the Lps genotype in these events. The IL-6 levels remained low after infection in both LPS responder and non-responder mice, but became elevated in the animals which were accidentally traumatized during infection. The IL-6 response to trauma alone was independent of Lps genotype, but the response to trauma and infection combined differed between the mouse strains. The IL-6 response to trauma and infection was more rapid in the C57BL/6J than in the C57B1/10ScCr mice. The traumatized and infected animals did not clear the infection as efficiently as the non-injured animals in both backgrounds. The difference in PMN recruitment and susceptibility of infection between LPS responder and non-responder mice in the C57 Black background followed the pattern previously seen in the C3H mouse background and suggested that these events were under Lps gene control. An effect of the Lps locus on the IL-6 response could be detected only in traumatized and infected animals.     

MEASUREMENTS OF INTERFACE PRESSURE BETWEEN BODY SITES AND THE SURFACES OF FOUR SPECIALISED AIR MATTRESSES

SUMMARY Four specialised air mattresses had interface pressure measured under six body sites prone to pressure sores in 10 subjects, supine and sitting. The mattresses were the Clinirest (SSI) and FirstStep (KCI) continuous airflow mattress overlays, and Airwave (Pegasus) and Nimbus (Huntleigh) alternating pressure air mattresses. On the mattress overlays, average supine interface pressures were 2.33 kPa (scapula), 4.15 kPa (elbow), 1.94 kPa (sacrum) and 2.79 kPa (buttock), although they were higher at the occiput (7.97 kPa) and heel (11.7 kPa). The alternating pressure air mattresses had an average minimum interface pressure close to zero for three sites, rising to 4.28 kPa under the heel. Average maximum interface pressures were 8.61 kPa (occiput), 5.21 kPa (scapula), 4.90 (elbow), 4.85 kPa (sacrum), 4.61 kPa (buttock) and 13.2 kPa (heel). No accepted scientific method exists for comparing the two types of mattress. Our data suggest a clinical benefit at the occiput and heel (supine) in using an alternating pressure air mattress and a benefit in using a continuous airflow mattress overlay at other sites.     

Analysis of trauma intubations

The timing of trauma patient intubation is dependent on clinical presentation and clinician judgment. We sought to correlate the timing of intubation with the presenting of physiologic parameters and clinical outcome to identify potential quality assurance audit filters. Patients (n = 82) were grouped by timing of intubation: PREHOSPITAL, paramedic intubation; IMMEDIATE, within 10 minutes of arrival; DELAYED, beyond 10 minutes but within 2 hours of arrival; and NONURGENT, beyond 2 hours or at the time of surgery. While mean revised trauma scores and Glasgow Coma Scale (GCS) scores differed for the groups, the mean length of hospital stay and the incidence of aspiration pneumonia were not significantly different. In the DELAYED group, 80% of those who developed aspiration pneumonia had a GCS < or = 13. Patients in the NONURGENT group were older and commonly presented with tachypnea. The survival rate for the NONURGENT group was lower than predicted by the TRISS method (P = .004). A GCS < or = 13 and age greater than 50 years with presenting respiratory rates of more than 25 breaths/min represent potential trauma intubation audit filters.     

Fresnel prisms--their value in the rehabilitation of homonymous hemianopsias

The use of press-on Fresnel prisms is described as a simple inexpensive technique to rehabilitate patients with homonymous hemianopsia. The optical principle of prismatic displacement from the blind to the seeing fields is detailed herein. Forty-one patients were evaluated over a 10 year period. Twenty per cent benefited from the prism. Many of those who found limited or little value from their use expressed appreciation that something had been tried in order to improve visual function. Those patients with good acuity and an otherwise normal neurological status are the best candidates. Proper motivation and instruction are essential.     

Radiology and the Health Policy Agenda for the American People

Eleven radiologists appointed by the major radiological societies participated for the past 5 years in the development of the Health Policy Agenda for the American People. The Agenda is an action plan to address a wide variety of serious problems in medicine. The first phase involved establishment of 159 principles, broad value statements that were the foundation of the project. Phase 2 involved the development of policy proposals on 38 urgent issues for action in medical science; education; health resources; delivery mechanisms; evaluation, assessment, and control; and payment for services. These proposals are summarized in this report. The activities and recommendations of representatives for the field of radiology are described. The Agenda has been released, and an implementation phase has begun. It will likely be of great importance to the practice of radiology over the next decade. Important issues can be addressed by acting with the coalitions that are being formed from among the more than 150 participating organizations.