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Biomedical subjects

R Birch

Publications and source records attributed to R Birch.

At least 19 recordsLinked to original sources
PubMed2001

Sodium channel beta1 and beta2 subunits parallel SNS/PN3 alpha-subunit changes in injured human sensory neurons.

Voltage-gated sodium channels consist of a pore-containing alpha-subunit and one or more auxiliary beta-subunits, which may modulate channel function. We previously demonstrated that sodium channel SNS/PN3 alpha-subunits were decreased in human sensory cell bodies after spinal root avulsion injury, and accumulated at injured nerve terminals in pain states. Using specific antibodies for immunohistochemistry, we have now detected sodium channel beta1 and beta2 subunits in sensory cell bodies within control human postmortem sensory ganglia (78% of small/medium (< or = 50 microm) and 68% of large (> or = 50 microm) cells); their changes in cervical sensory ganglia after avulsion injury paralleled those described for SNS/PN3 alpha-subunits. Our results suggest that alpha- and beta-subunits share common regulatory mechanisms, but present distinct targets for novel analgesics.

Adult↗
PubMed2001

Plasticity of TTX-sensitive sodium channels PN1 and brain III in injured human nerves.

Sensory neurones co-express voltage-gated sodium channels that mediate TTX-sensitive (TTX-S) and TTX-resistant (TTX-R) currents, which may contribute to chronic pain after nerve injury. We previously demonstrated that TTX-R channels were decreased acutely in human sensory cell bodies after central axotomy, but accumulated in nerve terminals after peripheral axotomy. We have now studied the TTX-S channels PN1 and Brain III, using specific antibodies for immunohistochemistry, in dorsal root ganglia (DRG) from 10 patients with traumatic central axotomy, nerves from 16 patients with peripheral axotomy, and controls. PN1 showed temporal changes similar to the TTX-R channels in sensory cell bodies of injured DRG. In contrast, Brain III was found only in injured nerves (not control nerves, or control/central axotomy DRG). PNI and Brain III are distinct targets for novel analgesics.

Adult↗
PubMed2001

Long-term results of tibialis posterior tendon transfer for drop-foot.

Twelve patients with drop-foot secondary to sciatic or common peroneal nerve palsy treated with transfer of the tibialis posterior tendon were followed-up for a mean of 90 (24-300) months. In 10 patients the results were 'excellent' or 'good'. In 11 patients grade 4 or 5 power of dorsiflexion was achieved, although the torque, as measured with a Cybex II dynamometer, and generated by the transferred tendon, was only about 30% of the normal side. Seven patients were able to dorsiflex their foot to the neutral position and beyond. The results appeared to be better in men under 30 years of age with common peroneal palsies. A painful flatfoot acquired in adulthood does not appear to be a significant long-term complication despite the loss of a functioning tibialis posterior tendon.

Adolescent↗
PubMed2001

Immunolocalisation of sodium channel NaG in the intact and injured human peripheral nervous system.

The voltage-gated 'glial' sodium channel NaG belongs to a distinct molecular class within the multi-gene family of mammalian sodium channels. Originally found in central and peripheral glia, NaG has since been detected in neurons in rat dorsal root ganglia (DRG) and may play a role in Schwann cell-axon interactions. We have studied the presence of NaG-like immunoreactivity in the intact and injured human peripheral nervous system using a specific affinity-purified antibody. Nerve fibres in normal and injured peripheral nerves and normal skin exhibited intense NaG-immunoreactivity. Numerous NaG-immunoreactive nerve fibres surrounded neuronal cell bodies within postmortem control DRG, and in DRG avulsed from the spinal cord (i.e. after traumatic central axotomy). There were no significant differences in the pattern of NaG immunostaining between control and avulsed DRG, or with delay after injury. Generally, the neuronal cell bodies were only very weakly immunoreactive to NaG, indicating that the NaG immunoreactivity was predominantly in Schwann cells/myelin. In accord, we demonstrated NaG immunostaining in cultured human and rat Schwann cells, and in distal nerve after wallerian degeneration. NaG thus appears to be a useful new marker for Schwann cells in the human PNS, and a role in neuropathy deserves investigation.

Animals↗
PubMed2001

Imaging of adult brachial plexus traction injuries.

Closed, high-energy transfer traction injuries of the adult brachial plexus lead to rupture or avulsion of the spinal nerves. Accurate preoperative diagnosis is crucial for surgical planning and reconstruction. Myelography, computerised tomographic myelography and magnetic resonance imaging are the main radiological methods for preoperative diagnosis of the lesion. This article reviews the current status of imaging of traction injuries of the adult brachial plexus.

Adult↗
PubMed2001

A method for evaluating the results of tendon transfers for foot drop.

A system for assessing the results of tibialis posterior tendon transfers in the treatment of foot drop secondary to nerve palsy is proposed. There are seven sections to this scoring system: pain, need for orthosis, ability to wear normal shoes, activity level, muscle power of ankle dorsiflexion, degree of active ankle dorsiflexion, and foot posture. The total score is 100. The results are classified as excellent for scores between 85 and 100, good between 70 and 84, fair between 55 and 69, and poor for scores below 55. The results of 18 patients (mean followup, 64.6 months) who had a tibialis posterior tendon transfer were assessed using this method. Four patients (22.2%) had an excellent result, seven (38.8%) had a good result, two (11.1%) had a fair result, and five (27.7%) had a poor result. The average score was 67.2, suggesting an overall fair result for this operation. In nine patients, there was correlation between the outcome when assessed with this method and with patient rating. In two patients, the outcomes were better when assessed with this method than with patient rating, whereas the reverse was true in seven other patients. Thus, this system may provide a more objective and critical evaluation of tibialis posterior transfers for foot drop.

Adolescent↗
PubMed2001

Tibialis posterior tendon dysfunction: a primary or secondary problem?

Seventeen patients with a mean follow-up of 64.4 months following a tibialis posterior tendon transfer to regain active foot dorsiflexion were clinically examined specifically for signs of tibialis posterior tendon dysfunction. The results show that 8 patients (47%) had Grade 4 or better power of eversion but none had a clinical flatfoot on the Harris-Beath footprints. Only 6% had forefoot abduction; 17% exhibited hindfoot valgus and 82% were able to perform the single-heel rise. Tibialis posterior tendon dysfunction therefore does not appear to be an inevitable sequel of tibialis posterior tendon transfer even in the presence of a functioning peroneal muscle. Other studies have noted that a pre-existent flatfoot was often present in patients with tibialis posterior tendon dysfunction. None of the patients in this study had pre-existent flatfoot. We suggest that a predisposition, in the form of a pre-existent tendency to flatfoot may also be a factor in the pathogenesis of tibialis posterior tendon dysfunction. This may explain the long-term failure of flexor digitorum longus and flexor hallucis longus tendon transfers in the treatment for tibialis posterior tendon dysfunction when the biomechanics of the foot has not been altered.

Adolescent↗
PubMed2001

Penetrating missile injuries of the brachial plexus.

We studied a consecutive series of 58 patients with penetrating missile injuries of the brachial plexus to establish the indications for exploration and review the results of operation. At a mean of 17 weeks after the initial injury, 51 patients were operated on for known or suspected vascular injury (16), severe persistent pain (35) or complete loss of function in the distribution of one or more elements of the brachial plexus (51). Repair of the nerve and vascular lesions abolished, or significantly relieved, severe pain in 33 patients (94%). Of the 36 patients who underwent nerve graft of one or more elements of the plexus, good or useful results were obtained in 26 (72%). Poor results were observed after repairs of the medial cord and ulnar nerve, and in patients with associated injury of the spinal cord. Neurolysis of lesions in continuity produced good or useful results in 21 of 23 patients (91%). We consider that a vigorous approach is justified in the treatment of penetrating missile injury of the brachial plexus. Primary intervention is mandatory when there is evidence of a vascular lesion. Worthwhile results can be achieved with early secondary intervention in patients with debilitating pain, failure to progress and progression of the lesion while under observation. There is cause for optimism in nerve repair, particularly of the roots C5, C6 and C7 and of the lateral and posterior cords, but the prognosis for complete lesions of the plexus associated with damage to the cervical spinal cord is particularly poor.

Adolescent↗
PubMed2001

The radial and posterior interosseous nerves. Results fo 260 repairs.

The outcome of 260 repairs of the radial and posterior interosseous nerves, graded by Seddon's modification of the Medical Research Council Special Committee's system, was analysed according to four patterns of injury; open 'tidy', open 'untidy', closed traction, and those associated with injury to the axillary or brachial artery. We studied the effect on the outcome of delay in effecting repair and of the length of the defect in the nerve trunk. Of the 242 repairs of the radial nerve we found that 30% had good results and 28% fair; 42% of the repairs had failed. The violence of injury was the most important factor in determining the outcome. Of the open 'tidy' repairs, 79% achieved a good or fair result, and 36% of cases with arterial injury also reached this level. Most repairs failed when the defect in the nerve trunk exceeded 10 cm. When the repairs were carried out within 14 days of injury, 49% achieved a good result; only 28% of later repairs did so. All repairs undertaken after 12 months failed. Of the 18 repairs of the posterior interosseous nerve, 16 achieved a good result.

Adolescent↗
PubMed2001

Ribozyme genes protecting transgenic melon plants against potyviruses.

Potyviruses are the most important viral pathogens of crops worldwide. Under a contract with Gene Shears Pty Limited, we are using ribozyme genes to protect melon plants against two potyviruses: WMV2 and ZYMV. Different polyribozyme genes were designed, built and introduced into melons plants. Transgenic melon plants containing a resistance gene were obtained and their progeny was challenged by the appropriate virus. Most of the genes tested conferred some degree of resistance to the viruses in glasshouse trials. Melon plants from one family containing one gene directed against WMV2 were also field-trialed on small plots under natural infection pressure and were found immune to WMV2. Field trial is in progress for plants containing genes against ZYMV. Some of the ribozyme genes used in the plants were also assayed in a transient expression system in tobacco cells. This enabled us to study the sequence discrimination capacity of the ribozyme in the case of one ribozyme target site. We found that a mutated target GUG (non cleavable) was less susceptible to inhibition by the ribozyme gene than the corresponding wild type target GUA (cleavable). Work is now in progress to incorporate multiple resistance genes in melon plants, in constructs designed in compliance with the evolving European regulations concerning transgenic plants. The use of ribozyme genes to protect plants against viruses provides an alternative to the technologies currently used for protecting crops against viruses, based on the concept of Pathogen Derived Resistance (see for example 14). In the light of concerns expressed by some plant virologists (13) about the use of viral genes in transgenic plants, it may be that ribozyme genes will find many uses in this area of agricultural biotechnology.

Agriculture↗
PubMed2000

P2X3 receptor in injured human sensory neurons.

The ATP-gated cation channel P2X3 is expressed selectively by rat sensory neurones, and may play a role in nociception by binding ATP released from damaged or inflamed tissues. However, the distribution of this channel in human sensory neurons is not known. Using a specific antibody, we have demonstrated intense P2X3 immunoreactivity within a subset (60%) of small/medium diameter sensory neurones and fine nerve fibres in intact post-mortem human dorsal root ganglia (DRG). Co-localization studies showed < 15% overlap with the trkA immunostaining in DRG, indicating that P2X3 was expressed predominantly in sensory neurons that are also isolectin B4 positive. There was a significant decrease in numbers of P2X3-like immunoreactive neurons in human DRG after central axotomy (to 36%), similar to the decrease in rat DRG after peripheral axotomy. However, Western blotting demonstrated a specific 66 kDa band in human DRG and peripheral organs, including intestine, where histochemistry showed P2X3 immunoreactivity in myenteric plexus neurons. Thus P2X3 antagonists may be analgesic, but are unlikely to have a selective effect on pain in humans.

Adult↗
PubMed2000

SNS/PN3 and SNS2/NaN sodium channel-like immunoreactivity in human adult and neonate injured sensory nerves.

Two tetrodotoxin-resistant voltage-gated sodium channels, SNS/PN3 and SNS2/NaN, have been described recently in small-diameter sensory neurones of the rat, and play a key role in neuropathic pain. Using region-specific antibodies raised against different peptide sequences of their alpha subunits, we show by Western blot evidence for the presence of these channels in human nerves and sensory ganglia. The expected fully mature 260 kDa component of SNS/PN3 was noted in all injured nerve tissues obtained from adults; however, for SNS2/NaN, smaller bands were found, most likely arising from protein degradation. There was increased intensity of the SNS/PN3 260 kDa band in nerves proximal to the site of injury, whereas it was decreased distally, suggesting accumulation at sites of injury; all adult patients had a positive Tinel's sign at the site of nerve injury, indicating mechanical hypersensitivity. Injured nerves from human neonates showed similar results for both channels, but neonate neuromas lacked the SNS2/NaN 180 kDa molecular form, which was strongly present in adult neuromas. The distribution of SNS/PN3 and SNS2/NaN sodium channels in injured human nerves indicates that they represent targets for novel analgesics, and could account for some differences in the development of neuropathic pain in infants.

Adolescent↗
PubMed2000

Immunolocalization of SNS/PN3 and NaN/SNS2 sodium channels in human pain states.

The tetrodotoxin-resistant (TTX-R) voltage-gated sodium channel SNS/PN3 and the newly discovered NaN/SNS2 are expressed in sensory neurones, particularly in nociceptors. Using specific antibodies, we have studied, for the first time in humans, the presence of SNS/PN3 and NaN/SNS2 in peripheral nerves, including tissues from patients with chronic neurogenic pain. In brachial plexus injury patients, there was an acute decrease of SNS/PN3- and NaN/SNS2-like immunoreactivity in sensory cell bodies of cervical dorsal root ganglia (DRG) whose central axons had been avulsed from spinal cord, with gradual return of the immunoreactivity to control levels over months. In contrast, there was increased intensity of immunoreactivity to both channels in some peripheral nerve fibers just proximal to the site of injury in brachial plexus trunks, and in neuromas. These findings suggest that the expression of these sodium channels in neuronal cell bodies is reduced after spinal cord root avulsion injury in man, but that pre-synthesized channel proteins may undergo translocation with accumulation at sites of nerve injury, as in animal models of peripheral axotomy. The latter may contribute to positive symptoms, as our patients all showed a positive Tinel's sign. Nerve terminals in distal limb neuromas and skin from patients with chronic local hyperalgesia and allodynia all showed marked increases of SNS/PN3-immunoreactive fibers, but little or no NaN/SNS2-immunoreactivity, suggesting that the former may be related to the persistent hypersensitive state. Axonal immunoreactivity to both channels was similar to control nerves in sural nerve biopsies in a selection of neuropathies, irrespective of nerve inflammation, demyelination or spontaneous pain, including a patient with congenital insensitivity to pain. Our studies suggest that the best target for SNS/PN3 blocking agents is likely to be chronic local hypersensitivity.

Adult↗
PubMed2000

Intact myelinated fibres in biopsies of ventral spinal roots after preganglionic traction injury to the brachial plexus. A proof that Sherrington's 'wrong way afferents' exist in man?

Bell-Magendie's law of separation of spinal function states that afferent and efferent fibres join the spinal cord separately in ventral and dorsal spinal nerve roots. For over 100 years there have been reports that challenge the exclusiveness of this law in mammals; very few studies have referred to man. We conducted a prospective morphological study in patients with preganglionic traction injuries of the brachial plexus to address this question. Avulsed ventral and dorsal roots were examined after variable intervals from the injury for histological and ultrastructural evidence for myelinated afferent fibres entering the cord via the ventral roots. Intact myelinated fibres were found in all ventral root specimens, but the majority of fibres in later biopsies are regenerative. A small number of fibres could be demonstrated that are likely to be 'wrong way ventral afferents'. Their number is falsely low due to wallerian degeneration of dorsal and ventral afferents following the mechanical and ischaemic effects of traction injury. Our findings are the first morphological evidence in human material that Bell-Magendie's law might not entirely be correct and they underline the difficulties in comparing traumatic with experimental rhizotomy.

Adult↗
PubMed2000

HSE performance tests for dosimetry services.

In the United Kingdom a dosimetry service that measures and assesses whole-body or part-body doses arising from external radiation must successfully complete a performance test. Results of the performance tests for routine whole-body, routine extremity/skin and special accident dosimetry, carried out over the past six years by the AEA Technology Calibration Service at Winfrith, and DRaStaC, the AWE Calibration Service at Aldermaston, are presented. The test involves irradiating groups of dosemeters to known doses of gamma radiation and determining the bias and relative standard deviations for each dose group. The results are compared with the pass criteria specified by the UK Health and Safety Executive. For routine whole-body dosimetry, both the film badge and thermoluminescent dosemeter (TLD) perform adequately for irradiations between 0.6 and 30 mSv. For higher doses up to 250 mSv, where the slow emulsion of the film is used, the film badge shows poorer performance with a tendency to overestimate the dose. For routine extremity/skin dosimetry there is a wider spread of relative standard deviation results than is seen for routine whole-body dosimetry. This is to be expected since the results will include dosemeters that are based on 'disposable' TLDs and ones based on lithium fluoride powder in sachets. For special accident dosimetry the dosemeters are tested between 0.26 and 6 Gy. For the highest dose group the film badge invariably underestimates the true dose, whereas the TLD has a tendency to overestimate it.

Information Services↗
PubMed2000

Randomized trial of filgrastim, sargramostim, or sequential sargramostim and filgrastim after myelosuppressive chemotherapy for the harvesting of peripheral-blood stem cells.

PURPOSE: The purpose of this study was to compare the effects of filgrastim, sargramostim, or sequential sargramostim and filgrastim on CD34(+) cell yields and morbidity after myelosuppressive mobilization chemotherapy (MC). PATIENTS AND METHODS: One hundred fifty-six patients were randomized to receive filgrastim (n = 51), sargramostim (n = 52), or sargramostim for 5 days followed by filgrastim (n = 53) after MC with either cyclophosphamide and etoposide (n = 75) or paclitaxel and cyclophosphamide (n = 81). RESULTS: Compared with those who received sargramostim, patients who received filgrastim had faster recovery of an absolute neutrophil count of 0.5 x 10(9)/L or greater (a median of 11 v 14 days; P =. 0001), with fewer patients requiring RBC transfusions (P =.008), fewer patients with fever (18% v 52%; P = 0.001), fewer hospital admissions (20% v 42%; P =.013), and less intravenous antibiotic therapy (24% v 69%; P =.001). Patients who received filgrastim yielded more CD34(+) cells (median, 7.1 v 2.0 x 10(6)/kg/apheresis; P =.0001), and a higher fraction achieved 2.5 x 10(6) (94% v 78%; P =.021) and 5 x 10(6) (88% v 53%; P =.001) or more CD34(+) cells/kg with fewer aphereses (median, 2 v 3; P =.002) and fewer days of growth-factor treatment (median, 12 v 14; P =.0001). There were no major differences in outcomes between the filgrastim alone and the sequential regimens. After high-dose chemotherapy, patients who had peripheral-blood stem cells (PBSCs) mobilized with filgrastim or the sequential regimen received higher numbers of CD34(+) cells and had faster platelet recovery (P =.015), with fewer patients (P =.014) receiving fewer platelet transfusions (P =.001) than patients receiving sargramostim-mobilized PBSCs. CONCLUSION: It was concluded that filgrastim alone or sequential sargramostim and filgrastim were superior to sargramostim alone for the mobilization of CD34(+) cells and reduction of toxicities after MC.

Adult↗
PubMed2000

Peripheral nerve repairs and their results in children.

It seems that lesions of nerves in children account for 10% to 15% of the total cases seen in this, as in other, specialist units. The prognosis for recovery after repair is defined by the severity of the original injury. The authors' worst results were seen in complete lesions of the supraclavicular brachial plexus and in the untidy wounds of war, in which penetrating missiles destroyed the proximal femur and the adjacent nerves. The outcome for injuries to the lumbosacral plexus, from fractures of the pelvis or from penetrating missile injury, are as bad. The most significant variable in determining prognosis is delay. Evidently, children are at least as vulnerable to the harmfulness of this as are adults. Skillful primary repair, however, is often followed by recovery to near normal levels, even in complex cases. Adequate follow-up is essential to detect and treat progressive deformity, especially at the ankle and foot.

Child↗