When physicians forego the doctor-patient relationship, should they elect to self-prescribe or curbside? An empirical and ethical analysis.

BACKGROUND: The American Medical Association, the British Medical Association and the Canadian Medical Association have guidelines that specifically discourage physicians from self-prescribing or prescribing to family members, but only the BMA addresses informal prescription requests between colleagues. OBJECTIVE: To examine the practices of paediatric providers regarding self-prescribing, curbsiding colleagues, and prescribing and refusing to prescribe to friends and family. METHODS: 1086 paediatricians listed from the American Academy of Paediatrics 2007 web-based directory were surveyed. RESULTS: 44% (430/982) of eligible survey respondents returned usable surveys. Almost half (198/407) of respondents had prescribed for themselves. An equal number (198/411) had informally requested a prescription from a colleague. Three-quarters (325/429) stated they had been asked to prescribe a prescription drug for a first-degree or second-degree relative, and 51% (186/363) had been asked by their spouse. Eighty-six per cent (343/397) stated that they had refused to write a prescription on at least one occasion for a friend or family member. The following reasons "strongly influenced" their decision to refuse a prescription request: (1) outside of provider's expertise (88%); (2) patient's need for his or her own physician (70%); (3) not medically indicated (69%); (4) need for a physical examination (65%). CONCLUSION: These data confirm that most physicians have engaged in self-prescribing or curbside requests for prescriptions. It can be argued that curbsiding is more morally problematic than self-prescribing because it implicates a third party, and should be discouraged regardless of whether the requester is a colleague, family member or friend.

Lack of effect of microinjection of noradrenaline or medetomidine on stimulus-evoked release of substance P in the spinal cord of the cat: a study with antibody microprobes.

1. Experiments were performed on barbiturate anaesthetized, spinalized cats to investigate the effect of microinjected noradrenaline or medetomidine on the release of immunoreactive substance P in the dorsal spinal cord following peripheral nerve stimulation. The presence of immunoreactive substance P was assessed with microprobes bearing C-terminus-directed antibodies to substance P. 2. Noradrenaline or medetomidine were microinjected into the grey matter of the spinal cord, near microprobe insertion sites, at depths of 2.5, 2.0, 1.5 and 1.0 mm below the spinal cord surface with volumes of approximately 0.125 microliters and a concentration of 10(-3) M. 3. In the untreated spinal cord, electrical stimulation of the ipsilateral tibial nerve (suprathreshold for C-fibres) elicited release of immunoreactive substance P which was centred in and around lamina II. Neither noradrenaline nor medetomidine administration in the manner described produced significant alterations in this pattern of nerve stimulus-evoked release. 4. In agreement with recent ultrastructural studies these results do not support a control of substance P release by catecholamines released from sites near to the central terminals of small diameter primary afferent fibres.

Evidence for localized release of substance P within rat spinal cord evoked by physiological and electrical stimuli.

Antibodies immobilized onto the outer surface of glass microelectrodes were used to measure and localize substance P (SP) release in the spinal cords of anaesthetized rats. Utilizing a C-terminally directed antibody, significant levels of SP were not found in the lumbar spinal cord in the absence of peripheral noxious stimulation. Following noxious heating or pinch of the ipsilateral hind paw or electrical stimulation of the ipsilateral tibial nerve at C-fibre strength, significant amounts of released SP were detected. This noxious stimulus-evoked release of SP was primarily in the region of the substantia gelatinosa. In conclusion, the antibody microprobe technique can be employed to focally detect the release of neuropeptide in vivo, even in structures as small as rat spinal cord. The technique reveals that SP release in the rat follows broadly the same pattern as that previously reported in the cat.

Release of immunoreactive galanin in the spinal cord of rats with ankle inflammation: studies with antibody microprobes.

Antibody microprobes bearing antibodies to the carboxy-terminus of rat galanin were inserted into the spinal cords of anaesthetized normal rats and those in which ankle inflammation had been induced by the unilateral subcutaneous injection of Freund's adjuvant four to six days previously. In normal rats, a basal presence of immunoreactive galanin was detected in the dorsal horn. Similar levels of immunoreactive galanin were found in the dorsal horn of both sides of the spinal cord in animals with unilateral ankle inflammation. Flexing the ankle or compressing the foot in normal rats failed to alter levels of immunoreactive galanin detected by microprobes. In animals with ankle inflammation, prolonged periods of ankle flexion did release immunoreactive galanin in the ipsilateral dorsal horn. Subsequent noxious ankle compression in these animals did not increase but rather decreased immunoreactive galanin in the dorsal horn to below basal levels. The reason for this decrease is unknown but it may represent an inhibition of release or a depletion of spinal stores of galanin.

Noxious mechanical stimulation of the hind paws of the anaesthetized rat fails to elicit release of immunoreactive beta-endorphin in the periaqueductal grey matter.

As a test of the hypothesis that an animal responds to a severe peripheral painful stimulus by a central release of beta-endorphin, antibody microprobes were inserted stereotactically into the midbrain of urethane anesthetized rats. These microprobes bore antibodies to beta-endorphin immobilized to their outer surfaces. While microprobes were in the brain for periods of 10 to 30 min either no stimulus was delivered or alligator clamps were applied to both hind paws. Microprobes were then incubated with 125I-beta-endorphin. Quantitative image analysis of microprobe autoradiographs showed no differences between the no-stimulus and noxious-stimulus groups. Thus these experiments found no evidence for beta-endorphin release following a severe peripheral painful stimulus.

Effect of peptidase inhibition on the pattern of intraspinally released immunoreactive substance P detected with antibody microprobes.

Antibody microprobes bearing antibodies to the C-terminus of substance P (SP) were used to measure release of immunoreactive (ir) SP in the dorsal horn of barbiturate anaesthetized spinal cats. Electrical stimulation of unmyelinated primary afferents of the ipsilateral tibial nerve produced a relatively localised release of ir SP in the superficial dorsal horn. Prior microinjection of the peptidase inhibitors kelatorphan and enalaprilat in the dorsal horn resulted in ir SP being detected over the whole of the dorsal horn and the overlying dorsal column. This pattern had previously been observed with evoked release of ir neurokinin A and supports the proposal that a slow degradation results in a neuropeptide accessing many sites remote from sites of release.

Failure to detect a putative oestrus-indicating pheromone in the urine or vaginal secretions of female sheep.

Extensive use of gas chromatographic analysis of the volatile and non-volatile components of sheep urine and sheep vulvovaginal secretions at different stages of the oestrous cycle has not succeeded in identifying the putative oestrus-indicating pheromone produced by the ewe. However the putative pheromone is probably not a low molecular weight alcohol, diol, phenol, amine, amide, aldehyde, ketone, fatty acid or steroid.

Calcitonin Gene-related Peptide Causes Intraspinal Spreading of Substance P Released by Peripheral Stimulation.

Experiments were performed in barbiturate-anaesthetized, spinalized cats to investigate the effect of calcitonin gene-related peptide (CGRP) on the spatial distribution of immunoreactive substance P (ir-SP) in the spinal cord released by electrical nerve stimulation and noxious mechanical stimuli. The presence of ir-SP was assessed with microprobes bearing C-terminus-directed antibodies to SP. CGRP was microinjected into the grey matter of the spinal cord near microprobe insertion sites at depths of 2500, 2000, 1500 and 1000 microm using minute amounts (in total 0.2 - 0.5 microl) of Ringer solution containing CGRP at a concentration of 10-5 or 10-3 M. In the untreated cord electrical stimulation of the tibial nerve (suprathreshold for all C fibres) elicited release of ir-SP which was centred in and around the lamina II. After microinjection of CGRP, stimulation-associated ir-SP was detected in a region extending from the cord surface down to the ventral horn. This pattern was similar to that observed after the microinjection of synthetic peptidase inhibitors (Duggan et al., Brain Res., 579, 261 - 269, 1992). The large expansion of sites accessed by ir-SP was time-dependent, reaching a maximal effect within 10 - 40 min after microinjection of CGRP, and reversal was observed in subsequent probes. A similar expansion of the regions accessed by ir-SP after microinjection of CGRP was also observed when release of ir-SP was evoked by noxious mechanical stimulation of the toes. These results indicate that one important function of CGRP in the spinal cord may be the control of the intraspinal sites and neuronal circuits accessed by released substance P, possibly by inhibition of endopeptidases responsible for peptide degradation.

Analgesic doses of morphine do not reduce noxious stimulus-evoked release of immunoreactive neurokinins in the dorsal horn of the spinal cat.

1. Antibody microprobes were used to detect immunoreactive neurokinin A release in the dorsal spinal cord of barbiturate-anaesthetized spinal cats. 2. Noxious mechanical stimulation of the ipsilateral hind paw and electrical stimulation (suprathreshold for unmyelinated primary afferent fibres) of the ipsilateral tibial nerve evoked immunoreactive neurokinin A release. 3. Systemic morphine, 5 mg kg-1, i.v., did not block immunoreactive neurokinin A release in response to these stimuli. 4. Subsequent naloxone administration, 0.5 mg kg-1, i.v., did not alter this stimulus-evoked release. 5. Basal levels of immunoreactive neurokinin A were unaltered by morphine or naloxone. 6. These results suggest that the analgesic effects of morphine at the spinal cord level are not brought about by activation of presynaptic opiate receptors on neurokinin A containing afferent terminals.

Sustained isometric contraction of skeletal muscle results in release of immunoreactive neurokinins in the spinal cord of the anaesthetized cat.

Antibody microprobes were used to study release of immunoreactive neurokinins in the dorsal horn of the anaesthetized spinal cat following sustained isometric contraction of ipsilateral hindlimb muscles. Microprobes had immobilized antibodies to neurokinin A (NKA) on their outer surfaces and bound a proportion of released molecules when inserted in the central nervous system. Bound molecules were detected in autoradiographs as zones of reduced binding of 125I-NKA in which microprobes were incubated after withdrawal from the spinal cord. The left hindlimb was immobilized using an epoxy bandage splint and isometric contraction of muscles induced by intermittent tetanic stimulation of a ventral root. A basal presence of immunoreactive neurokinins was detected and this was increased by sustained isometric muscle contraction. It is probable that ergoreceptors contain and release neurokinins.

Microinjection of neuropeptide Y into the superficial dorsal horn reduces stimulus-evoked release of immunoreactive substance P in the anaesthetized cat.

In barbiturate anaesthetized spinal cats, antibody microprobes were used to measure release of immunoreactive substance P in the superficial dorsal horn following electrical stimulation of unmyelinated primary afferents of the ipsilateral tibial nerve. Prior microinjection of neuropeptide Y (0.2-0.6 microliters of 10(-5) mol/l solution) in the region of the substantia gelatinosa reduced the evoked release of immunoreactive substance P for up to 40 min. Microinjection of similar volumes of phosphate-buffered saline at similar sites was without effect. This action of neuropeptide Y could contribute to analgesia, particularly if this neuropeptide is co-released with noradrenaline from axon terminals in the superficial dorsal horn.

Persistence of immunoreactive neurokinins in the dorsal horn of barbiturate anaesthetized and spinal cats, following release by tibial nerve stimulation.

Antibody-coated microprobes were used to study the time course of release and disappearance of immunoreactive neurokinins in the dorsal spinal cord, in response to electrical stimulation of unmyelinated fibres of the tibial nerve of the cat. Noxious cutaneous stimuli were not used thereby avoiding potentially uncontrolled tissue damage and inflammation. Microprobes, inserted into the spinal cords of barbiturated anaesthetized spinal cats prior to nerve stimulation, detected a basal level of immunoreactive neurokinins. During nerve stimulation immunoreactive neurokinins were released significantly in the upper dorsal horn and dorsal columns and required at least 1 h to return to prestimulus levels. The persistence of immunoreactive neurokinins in the dorsal horn may underlie the prolonged hyperexcitability of some spinal neurons following brief noxious stimuli.