Cooperative mechanisms of neurotransmitter action in central nervous sensitization.
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Animals↗
Biomedical subjects
H Rees
Publications and source records attributed to H Rees.
Massive pulmonary tumor emboli in a sarcoma. An unusual cause of sudden death.
Although metastatic spread of tumor to the lungs is common, massive pulmonary tumor emboli are very unusual. Most tumor emboli originate from epithelial-derived tumors. Only a few cases of pulmonary embolism from sarcomata have been reported. We herein describe the case of a 36-year-old woman who died suddenly due to massive pulmonary tumor emboli from a retroperitoneal malignant mesenchymoma. We believe this is the first case report of a mesenchymoma causing sudden death due to massive tumor embolism.
Adult↗
Exposure to sheep dip and the incidence of acute symptoms in a group of Welsh sheep farmers.
OBJECTIVES: To measure the exposure of a group of farmers to organophosphate pesticide in sheep dip, and to record the incidence of symptoms after exposure. DESIGN: A prospective study of the autumn 1992 dipping period. Working methods were assessed by questionnaire. Absorption of organophosphate pesticide was estimated before, immediately after, and six weeks after dipping by measuring plasma cholinesterase, erythrocyte cholinesterase, and dialkylphosphate urinary metabolites of organophosphates. Symptoms were recorded by questionnaire at the same time as biological monitoring. Possible confounding factors were identified by medical examination of the subjects. SETTING: Three community council electoral wards in Powys, typical of hill sheep farming areas in Wales. SUBJECTS: All (38) men engaged in sheep dipping living in the three community council electoral wards. RESULTS: 23 sheep farmers and one dipping contractor completed the study--a response rate of 63%. A sample of seven men who refused to enter the full study had similar working practices to the 24 subjects. Subjects reported inadequate handling precautions, and significant skin contamination with dip. Two men reported under diluting dip concentrate for use. Both had significant depression of erythrocyte cholinesterase after dipping. This indicated some absorption of organophosphate pesticide--but this did not reach levels usually associated with toxicity. It was not clear whether the symptoms of these two mens were caused by organophosphate exposure. Measurement of dialkylphosphate urinary metabolites in a single specimen of urine voided shortly after the end of dipping could not be correlated with individual exposure. CONCLUSIONS: Sheep dipping is strenuous and dirty work and sheep farmers find it difficult to wear personal protective equipment and avoid skin contamination with dip. In this limited study, farmers did not seem to have significant organophosphate toxicity, despite using inadequate handling precautions.
Acute Disease↗
Dorsal root reflexes in articular afferents occur bilaterally in a chronic model of arthritis in rats.
1. Chronic arthritis was produced in rats by the injection of incomplete Freund's adjuvant into one knee joint. By 3-5 days later the rats had developed unilateral swelling of the injected knee and demonstrated bilateral hyperalgesia to radiant heat stimuli applied to the foot. 2. In the same rats anesthetized 3-5 days after the injection, dorsal root reflexes could be recorded bilaterally from the proximal ends of the cut medial articular nerves (MANs) of the knee joint. 3. The dorsal root reflexes consisted of large, medium-sized, and small action potentials evoked in response to phasic mechanical stimulation of the lateral aspect of the knee. The activity was greater in the MAN ipsilateral to the injection than in the contralateral MAN. 4. Local application of capsaicin on the side ipsilateral or contralateral to the arthritis dramatically reduced the dorsal root reflexes recorded from the contralateral MAN, indicating that these dorsal root reflexes depended on activity in fine afferent fibers containing capsaicin receptors, presumably C fibers. Local application of capsaicin on either side did not significantly change the dorsal root reflexes recorded from the ipsilateral MAN. These dorsal root reflexes were presumably conducted in afferent fibers that lacked capsaicin receptors, including A beta- and A delta-fibers.
Action Potentials↗
Mucosal tumor necrosis factor-alpha production and extensive disruption of sulfated glycosaminoglycans begin within hours of birth in neonatal respiratory distress syndrome.
Many of the clinicopathologic features of neonatal respiratory distress syndrome (RDS) may be related to the inflammatory response mounted by the affected infant, although little is known about the interstitial component of this response. We have thus studied the local inflammatory response in this condition by immunohistochemical analysis of whole lung lobes, obtained at postmortem from 40 infants who died from acute RDS in the first week of life. All had demonstrated classical clinical history and histologic features. An archival subgroup from the early 1970s had never received ventilatory support. Immunohistochemical analysis demonstrated rapid temporal increase from birth in the mucosal density of CD68+ macrophages, MAC-387+ monocytes/macrophages, polymorphonuclear neutrophils, and tumor necrosis factor-alpha-immunoreactive cells, maximal in those dying at or after 72 h. Using a cationic probe specific for sulfated glycosaminoglycans (GAGs), the inflammatory infiltration was seen to be associated with striking loss of endothelial, basement membrane, and interstitial GAGs, which was almost complete by 48-72 h. GAG degradation products were found within hyaline membranes in all infants dying after 48 h. This study confirms that neonatal RDS is characterized by intense interstitial inflammation, significantly underestimated on routine staining. This begins within hours of birth and is maximal by 72 h of age. Breakdown of sulfated GAGs within the extracellular matrix follows the same time course and may explain much of the physiologic derangement characteristic of this condition.
Age of Onset↗
Anterior pretectal nucleus facilitation of superficial dorsal horn neurones and modulation of deafferentation pain in the rat.
1. Functional relationships between the anterior pretectal nucleus (APTN) and nociceptive dorsal horn neurones were investigated electrophysiologically in the anaesthetized rat. The effects of APTN lesions were assessed behaviourally in a model of deafferentation pain. 2. Cells in the dorsal and rostral parts of the APTN were excited orthodromically by electrical stimulation of the ipsilateral dorsolateral funiculus or the contralateral dorsal columns, and by noxious and innocuous cutaneous stimuli. 3. Electrical stimulation of the APTN excited nociceptive lamina I spinal neurones. These cells all projected rostrally in the contralateral dorsolateral funiculus. Identical APTN stimulation also inhibited multireceptive spinal neurones which lay deep in the dorsal horn. These particular cells were shown to project to the brain in the ventrolateral funiculus. 4. It is proposed that noxious stimuli excite spinal lamina I projection neurones which send excitatory axons to the brain, including the APTN. The APTN inhibits deep multireceptive neurones, to reduce the perception of noxious stimuli. The discharge of spinal lamina I neurones, however, will be sustained by the noxious stimulus and by facilitation from the APTN. A sustained descending inhibition of this nature would reduce responses to prolonged injury. 5. The involvement of the APTN in responses to a chronic pain state was examined by comparing the behaviour of animals with bilateral lesions of the APTN with normal controls. Lesions of the APTN strongly enhanced the autotomy behaviour triggered by sectioning of the dorsal roots. 6. These observations support the suggestion that the APTN reduces the debilitating effects of prolonged injury.
Afferent Pathways↗
The role of glutamate and GABA receptors in the generation of dorsal root reflexes by acute arthritis in the anaesthetized rat.
1. In rats anaesthetized with pentobarbitone sodium, a unilateral acute arthritis was produced by the injection of kaolin and carrageenan into one knee-joint cavity. Four hours after injection, the medial articular nerve (MAN) was sectioned distally and recordings obtained from the proximal stump of the nerve. 2. Centrifugally conducted action potentials were recorded from the cut MAN following the development of arthritis. Acute dorsal rhizotomy, but not sympathectomy, prevented the action potentials, and so it is concluded that the action potentials represent dorsal root reflexes. 3. Central administration of either the GABAA receptor antagonist, bicuculline, or the non-NMDA receptor antagonist, CNQX, also prevented dorsal root reflexes in the MAN. 4. Neither the GABAB receptor antagonist, CGP35348, nor the NMDA receptor antagonist, AP7, altered the dorsal root reflexes in the MAN. 5. It is concluded that arthritis causes excess primary afferent depolarization in the dorsal horn of the spinal cord leading to dorsal root reflexes. It is proposed that these dorsal root reflexes contribute to the inflammation.
6-Cyano-7-nitroquinoxaline-2,3-dione↗
Fiber types contributing to dorsal root reflexes induced by joint inflammation in cats and monkeys.
1. Injection of kaolin and carrageenan into the knee joint of cats or monkeys resulted in an acute inflammation. Four hours after injection of the knee joint, efferent activity could be evoked in articular afferent fibers and in dorsal root filaments. We interpret this efferent activity to be dorsal root reflexes (DRRs). Under our experimental conditions, the DRRs were generally synchronized compound action potentials, although in some cases single-unit activity was also observed. 2. DRRs were not produced in animals with uninflamed knee joints and normal body temperatures. 3. Recordings from two different sites on cut dorsal root filaments ipsilateral to the inflamed knee joint allowed the determination of the conduction velocities of groups of afferent fibers carrying DRRs. The DRRs occurred in A beta-, A delta-, and C fibers. However, in these experiments the peripheral destination of the afferent fibers was unknown. 4. To prove that DRRs occurred in joint afferents, recordings were made from two different sites on the proximal stump of the medial articular nerve that innervated the inflamed knee. The DRRs were again found in all fiber types, i.e., group II, III, and IV (A beta, A delta, and C) articular afferent fibers. 5. Compound DRRs were recorded from the central end of a cut dorsal root filament after electrical stimulation at C fiber intensity of a dorsal root adjacent to the filament. This DRR activity was eliminated by extensive dorsal rhizotomies of the L2-S1 roots.(ABSTRACT TRUNCATED AT 250 WORDS)
Action Potentials↗
Association of infantile neuroaxonal dystrophy and osteopetrosis: a rare autosomal recessive disorder.
The association of neuroaxonal dystrophy and osteopetrosis is reported in 2 siblings born to non-consanguineous parents. The 1st child was diagnosed as having infantile osteopetrosis shortly after delivery. A computed tomography scan of the head revealed agenesis of the corpus callosum. She died at the age of 9 months. Post-mortem examination showed pneumonia and bony sclerosis. Neuropathological examination revealed cerebral atrophy, ventricular dilation, absence of the corpus callosum, and a small hippocampus. Neuroaxonal spheroids were found in hippocampus, basal ganglia, pons, medulla, spinal cord, cranial nerves, cerebellum, and peripheral nerves. Ultrastructural examination revealed membranous cytoplasmic bodies and electron-dense granular deposits within the neuroaxonal spheroids as well as the soma of neurons. The 2nd child was delivered at 36 weeks of gestation because of intrauterine fetal distress. The diagnosis of osteopetrosis and partial agenesis of the corpus callosum was made shortly after delivery. The child died at 1 month without an autopsy. There are rare cases reported previously with the association of neuroaxonal dystrophy and osteopetrosis. We review these cases and compare them with ours.
Agenesis of Corpus Callosum↗
Increase in enkephalin-like immunoreactivity in hippocampi of adults with generalized epilepsy.
The changes of opioid peptide reactivity in seizure activity have been well studied in animals. Increased enkephalin and dynorphin immunoreactivity in the hippocampi of animals are interpreted as the result of seizure induced mossy fibre sprouting. We studied the hippocampi of six patients with a history of long-standing grand mal seizures and six age-matched control patients with no history of epilepsy or neurologic disease, using frozen sections which were immunostained with antibodies against Leu-enkephalin and Met-enkephalin. The staining intensity in the CA3, CA4 and internal molecular layer of the dentate fascia in each case was quantified using optical densitometry image analysis. The CA3 and CA4 of the epileptic hippocampi showed highly significant increase in Leu-enkephalin-like immunoreactivity compared to the controls (P < 0.005) while the inner molecular layer showed only significant increase (P < 0.05). Met-Enkephalin-like immunoreactivity was only significantly increased in CA4 of the epileptic hippocampi (P < 0.05).
Adult↗
Do dorsal root reflexes augment peripheral inflammation?
Efferent activity was recorded in knee joint afferents in response to mechanical stimulation of the hindlimb following induction of acute arthritis. The activity was abolished by application of lidocaine or crushing the nerve proximally and by dorsal rhizotomy but not by sympathectomy. It was concluded that this activity represents dorsal root reflexes in response to natural stimulation of the hindlimb. We propose that increased activity of articular afferents and of dorsal horn neurons during arthritis results in the pathological activation of the central terminals of primary afferents by enhancing primary afferent depolarization. Dorsal root reflexes could then release substances in the knee joint and thus contribute to the acute inflammatory response.
Action Potentials↗
Proposed protocol for a multi-centre study to compare clinical and trade tests of colour vision in firefighters.
Fire-brigade recruits in the UK have their colour vision screened using the Ishihara test. This is unsatisfactory because it rejects subjects with minor deficiencies in colour vision and does not test for blue defects. The Home Office is currently reviewing its recommendations on visual standards. This paper summarizes defects in colour vision, discusses alternative clinical and trade tests for the fire-brigade, and proposes a multi-centre study to collect data on the performance of fire-brigade recruits in clinical and trade tests.
Clinical Protocols↗
Achondrogenesis type 2 diagnosed by transvaginal ultrasound at 12 weeks' gestation.
Ultrasound examination at 12 weeks' gestation revealed severe generalised subcutaneous oedema in a pregnancy at risk for achondrogenesis type II. Transvaginal scanning confirmed the oedema and suggested abnormal limb development. The prenatal diagnosis was confirmed by X-ray examination after transvaginal termination.
Abnormalities, Multiple↗
The anterior pretectal nucleus: a proposed role in sensory processing.
Four nuclei of the pretectal complex, the olivary pretectal nucleus, the medial pretectal nucleus, the nucleus of the optic tract and the posterior pretectal nucleus, all have a demonstrated role in visual function. In contrast, the anterior pretectal nucleus (APtN) has no inputs from retina and has few outputs to visual accessory nuclei. The APtN has connections with areas associated with sensory functions and it has been suggested that this nucleus may have a role to play in somatosensory processing. An increasing number of behavioural and electrophysiological studies support this view. Brief low-intensity electrical or chemical stimulation of the APtN causes antinociception in the tail flick test in both unanaesthetised and anaesthetised animals. This inhibition of the tail flick response is attenuated by naloxone, alpha-adrenoceptor antagonists and muscarinic cholinergic receptor antagonists. Electrical stimulation of the APtN is similarly effective in the paw pressure and formalin tests. APtN stimulation also causes a brief inhibition of the tooth pulp-evoked jaw opening reflex. studies with [C14]2-deoxyglucose indicate that peripheral noxious stimuli will cause an increase in metabolic activity within the APtN. Animals with electrodes placed in the APtN will self-administer electrical stimulation and this can reduce the aversive and autonomic effects of stimulating the ventromedial hypothalamus. Part of the antinociceptive effects of stimulating the APtN are due to a descending inhibition of spinal dorsal horn projection neurones. Multireceptive neurones deep in the dorsal horn are inhibited by APtN stimulation. In contrast, superficial projection neurones that respond to intense cutaneous stimuli are excited by APtN stimulation. The APtN receives an excitatory input from low-threshold afferents via the dorsal column pathway and a high-threshold excitatory drive from superficial cells projecting through the dorsolateral funiculus. The excitatory input from the dorsal columns may well participate in the long-term inhibition of spinal projection neurones evoked by dorsal column stimulation. These ascending excitatory pathways may also be important to the long-term activation of descending inhibition from the APtN.
Animals↗
Delivering at the right price--the costs of primary maternity care at the Diepkloof Community Health Centre, Soweto.
This paper reports on a study of the costs of primary maternity care services at the Diepkloof Community Health Centre (DK) in Soweto. DK, the Soweto community health centre system as a whole and numerous other non-hospital settings provide a wide range of maternal health services to substantial numbers of women, and relieve hospitals of a major potential clinical burden. However, no research has been done in South Africa on the relative costs of the provision of these services in different settings and by different types of health worker. The cost structure of these services at DK is presented and the costs of antenatal care, deliveries in midwife-run labour wards, postnatal care (at the health centre and at home) and family planning services detailed. Some comparisons are made with existing data for another community health centre and with Baragwanath Hospital. These results are relevant to policy and planning of maternal health services. They are also shown to be of relevance to management and several areas of potential improvement of these services are noted.
Cost-Benefit Analysis↗
What does primary health care cost and can we afford to find out? Rationale and methodology for a cost analysis of the Diepkloof Community Health Centre, Soweto.
Accurate information on the costs of providing primary health care (PHC) services is now an urgent priority for health policy makers and planners, if the Government's stated commitment to an adequate PHC system is to be realised. Cost information is also a critical management tool for both public and private sector providers. In this context, the inability of public sector PHC providers to generate accurate cost accounting information is a serious shortcoming. In an attempt to address this lack of local PHC cost data, a detailed analysis of the costs of PHC services was undertaken at the Diepkloof Community Health Centre (DK) in Soweto during 1990. The study aimed to assess the cost of each service provided at DK and where possible, to identify areas of inefficiency. This paper is the first of two that report the findings of this study. It briefly describes the methodology employed and presents the major results. These raise several important management issues. Most importantly, the study suggests that there is excess capacity in the administrative and in several of the clinical areas of this community health centre; this implies that the average cost per service could be reduced in several areas. Certain services, such as home visits, are particularly expensive and require careful evaluation. The policy implications of this analysis are also examined. The high cost of several services implies that extension of this type of PHC service to all urban and rural areas is likely to be unaffordable.(ABSTRACT TRUNCATED AT 250 WORDS)
Community Health Services↗
The pontine parabrachial region mediates some of the descending inhibitory effects of stimulating the anterior pretectal nucleus.
Electrical stimulation of the anterior pretectal nucleus (APtN) elicits antinociception by inhibiting the responses of spinal multireceptive neurones to noxious stimuli. This descending inhibition is mediated, in part, by activating cells in the ventrolateral medulla. Neuronal tract tracing has previously shown that the APtN also projects directly to the pontine parabrachial region (PPR). The PPR, investigated by Katayama et al. (Brain Res., 296 (1984) 263-283), corresponds to the cholinergic cell group Ch5 of Mesulam et al. (Neuroscience, 10 (1983) 1185-1201). In this study, the pathway from APtN to PPR was investigated using urethane anaesthetised rats. Electrical stimulation (single square wave 0.2 ms pulses, 1-10 V, 5 Hz) of the APtN potently excites 40% of the cells recorded in the PPR. In the reverse experiment, stimulation of the PPR at the same parameters excited 36% of the cells recorded in the APtN. The contribution of this pathway to the spinal inhibitory effects of APtN stimulation was then examined. Unanaesthetised animals received electrical stimulation to the APtN (35 microA r.m.s., 15 s) and the increase in tail-flick latencies was measured. Bilateral electrolytic lesions of the PPR caused a 67% reduction of the antinociceptive effect of APtN stimulation. In urethane anaesthetised rats, microinjection of tetracaine into the PPR blocked the inhibition of multireceptive dorsal horn neurones caused by APtN stimulation (20 s train of 50 microA square wave 0.1 ms pulses, 100 Hz). In conclusion, these experiments strongly sugget that the PPR may be an important part of a descending antinociceptive pathway originating in the APtN.
Animals↗