Biomedical subjects
Publications and source records attributed to H Rees.
Glomerular filtration rates (GFR) were estimated in 168 children (227 estimates) before treatment for haematological malignancies with high dose, intravenous methotrexate. Clinical management was altered on the basis of GFR in only two cases, both of whom had tumour lysis syndrome. Routine estimations of GFR do not contribute to management.
Substance P, acting through neurokinin I receptors, is involved in the processing of nociceptive information in the spinal cord. Sensitization of spinothalamic tract neurons occurs to low-intensity stimuli following capsaicin injection. The current study tested the effects of the novel neurokinin I receptor antagonist, SDZ NKT 343, on the sensitization of spinothalamic tract cells by capsaicin in monkeys. Spinothalamic tract cells from the lumbar enlargement with receptive fields in the hindpaw were isolated and recorded before and after intradermal injection of capsaicin. The background activity and responses to brushing, pressing and pinching the skin were assessed. Thirty minutes after capsaicin injection there was an increase in background activity and responses to brush and pressure applied to the receptive field. Infusion of SDZ NKT 343 (for 30-45 min) significantly reversed the increased response to brushing without affecting the increased background activity or the increased response to pressure. Thus, blockade of neurokinin 1 receptors reduces the sensitized responses to innocuous mechanical stimuli but not to noxious mechanical stimuli.
Several lines of evidence indicate that N-methyl-D-aspartate (NMDA) receptors play an important role in nociception in general and in pathological pain in particular. It has been previously demonstrated in behavioral studies that NMDA receptor antagonists attenuate pathological pain in humans and nociceptive behaviors in animals. In the present study, we investigated the effect of the NMDA receptor antagonist memantine (MEM) on the responses of spinothalamic tract (STT) cells in normal and neuropathic monkeys. Memantine was delivered into the spinal cord through a microdialysis fiber acutely implanted into the dorsal horn. Responses of STT cells to peripheral stimulation within their receptive fields were recorded before and after MEM infusion. In normal animals (n = 7), 10 mm MEM did not affect STT cell (n = 7) baseline activity or responses to mechanical stimuli (brush, press or pinch). In neuropathic animals (n = 6), 1.0, 3.0, 10.0 and 100 mm MEM did not affect baseline activity of STT cells (n = 7); however, in a dose-dependent fashion, it significantly reduced responses of these cells to all cutaneous stimuli. The data suggest that MEM can have a direct effect on STT cells, blocking NMDA receptors known to be present on this cell population and, furthermore, may be a therapeutic agent for chronic pain.
BACKGROUND: After resection of advanced abdominal neuroblastoma, children may have persistent postoperative diarrhea. Until recently, the magnitude of this problem had not been appreciated. METHODS: To assess the incidence, severity, and management of chronic postoperative diarrhea in these patients, we reviewed the case notes of all children with stage III or IV abdominal and pelvic neuroblastoma who underwent tumor resection in our hospital between January 1985 and September 1996. We classified the severity of diarrhea as follows: mild, less than 3 loose stools per day; moderate, 3 to 5 loose stools per day; and severe, more than 5 loose stools per day and/or urgency, incontinence, or nocturnal diarrhea. RESULTS: Seventy-seven children underwent resection during this period, and 23 (30%) had postoperative diarrhea, classified as mild in 11 patients, moderate in 7, and severe in 5. Dissection around the superior mesenteric and celiac arteries was associated with a significantly higher incidence of diarrhea. Fifteen children (65%) received treatment with loperamide, which reduced but did not abolish symptoms. Twelve children subsequently died of progressive neuroblastoma. Of the 11 surviving children (mean duration of follow-up, 8.4 years), 8 have persistent loose stools. CONCLUSIONS: Diarrhea, probably resulting from disruption of the autonomic nerve supply to the gut during clearance of tumor from the major vessels of the retroperitoneum, is common after resection of advanced abdominal neuroblastoma. Many children require long-term treatment to slow intestinal peristalsis, and a few have severe and unremitting diarrhea. More effective medical management of this complication is needed.
OBJECTIVE: To test the application of a clinical definition of severe acute maternal morbidity. DESIGN: A one-year prospective descriptive multi-centre study. SETTING: Kalafong and Pretoria Academic hospitals, catering for the delivery of indigent women in the Pretoria Health Region. METHODS: A 'near-miss' describes a patient with an acute organ system dysfunction, which if not treated appropriately, could result in death. The case notes of women fitting this definition and all maternal deaths were analysed and compared. OUTCOME MEASURE: Determine the primary obstetric factors and the organ systems that failed. Identification of episodes of sub-standard care and missed opportunities. Results One hundred and forty-seven near misses and 30 maternal deaths were identified. The commonest reasons for a near-miss were: emergency hysterectomy in 42 women (29%); severe hypotension in 40 (27%); and pulmonary oedema in 24 (16%). The most common initiating obstetric conditions were hypertension in 38 women (26%); haemorrhage in 38 (26%); and abortion or puerperal sepsis in 29 (20%). The primary obstetric factors amongst the maternal deaths were: hypertension (33%); sepsis (27%); and maternal medical diseases (17%) in 10, 8 and 5 women respectively. Sub-standard care was identified in 82 cases. Breakdown in the health care administration was identified in 33, and patient-orientated missed opportunities on 34 occasions. CONCLUSION: The definition of severe acute maternal morbidity identified nearly five times as many cases as maternal death. This definition allows for an effective audit system of maternal care because it is clinically based, the definition is robust and the cases identified reflect the pattern of maternal death.
Antibodies to muscarinic cholinergic receptor proteins m1 to m4 were used in striate cortex tissue of normal rhesus monkeys to determine the laminar distribution of these proteins with special attention to geniculorecipient layers. The normal patterns were compared to those of monkeys whose ocular dominance system had been altered by visual deprivation. In normal monkeys, immunoreactivity of all four proteins was localized in complex laminar patterns; m1 was densest in layers 2, 3, and 6, followed by layer 5. In contrast, m2 reactivity was densest in lower layer 4C and in 4A; the latter exhibited a honeycomb pattern. Layers 2 and 3 displayed alternating dense and light regions; this pattern was complementary to that of cytochrome oxidase (CytOx). Laminar immunoreactivity for the m3 receptor was similar to the CytOx pattern, including a honeycomb in 4A and a pattern of alternating darker and lighter patches in layers 2/3. Antibody to m4 reacted most densely with layers 1, 2, 3, and 5, layers 2 and 3 exhibited alternating dark and light regions, and layer 4A had a faint honeycomb. Layer 4C was the lightest band. The differential distribution of these four muscarinic receptor subtypes suggests distinct roles in cholinergic modulation of visual processing in the primate striate cortex. Furthermore, all four muscarinic receptors appear to be insensitive to elimination of visual input via monocular occlusion from birth, to deprivation of pattern vision in one eye during a specific time period in adulthood, and to long-term retinal injury.
Protein kinase C (PKC) has been shown to be involved in nociceptive transmission in the spinal cord. This study tested the hypothesis that induction of central sensitization in the dorsal horn by an intradermal capsaicin injection involves activation of PKC. A PKC inhibitor (NPC15437) was infused through a microdialysis fiber into the spinal cord prior to capsaicin injection. The responses of spinothalamic tract (STT) cells were recorded before and after infusion of NPC15437, and after injection of capsaicin. STT cells show an increased background activity and increased responses to innocuous stimuli following capsaicin injection while responses to heat are decreased. Spinal infusion of the PKC inhibitor, NPC15437, had no effect on background activity or responses to peripherally applied stimuli prior to capsaicin injection. However, NPC15437 prevented the sensitization of cells to weak mechanical stimuli (brush and pressure) that occurs following capsaicin injection. NPC15437 had no effect on the increased background activity or decreased responses to heat stimuli induced by capsaicin injection, suggesting alternative mechanisms for these responses. These data suggest that PKC is important for the development of central sensitization to peripheral mechanical stimuli.
Spinal cord N-methyl-D-aspartate (NMDA) receptors play an important role in the transmission of acute and chronic pain. The present study investigated the ability of dextrorphan (DEX), a metabolite of dextromethorphan and a clinically safe NMDA antagonist, to attenuate the responses of nociceptive spinothalamic tract (STT) neurons in anesthetized monkeys. The STT cells were recorded extracellularly in the lumbosacral enlargement and were identified by antidromic activation from the ventral posterior lateral thalamic nucleus. DEX administered through a microdialysis fiber inserted into the dorsal horn inhibited the responses of STT cells in normal animals to noxious pinch and heat stimuli. In monkeys made neuropathic by tight ligation of the L7 or S1 spinal nerve, DEX significantly attenuated the responses of STT cells to noxious pinch and heat, as well as to innocuous brushing, pressure and von Frey filament stimuli. These findings strongly suggest that DEX should be considered a potentially useful therapeutic agent for the treatment of neuropathic pain in humans.
Intradermal injection of capsaicin results in sensitization of spinothalamic tract cells to brushing and pressure applied to the cutaneous receptive field in anesthetized monkeys. A significant increase in background activity also occurs immediately after capsaicin injection that lasts for at least 2 h. A 40-50% decrease in the response to noxious heat stimuli is also observed following capsaicin injection. This study investigated the spinal role of second messengers by extracellularly recording from spinothalamic tract cells and delivering inhibitors of second messenger pathways to the spinal cord by microdialysis. Blockade of protein kinases with the general protein kinase inhibitor, H7 (5.0 mM, n = 6), reduced the sensitization of the cells to brush and pressure. Blockade of protein kinase C with NPC15437 (10.0 mM, n = 10) reduced the increased background activity and the increased responses to brush. Blockade of protein kinase A with H89 (0.01 mM, n = 9) was most effective. H89 reduced the background activity, the increased responses to brush and press, and reversed the decreased response to noxious heat stimuli. Blockade of G-proteins with the general G-protein inhibitor, GDP-beta-S (1.0 mM, n = 9), reduced the background activity and the responses to brush and pressure without affecting the decreased response to heat. Thus, multiple intracellular messengers appear to be involved in the processing of central sensitization induced by activation of C-fibers following intradermal injection of capsaicin.
OBJECTIVE: To describe the epidemiology of incomplete abortion (spontaneous miscarriage and illegally induced) in South Africa. DESIGN: Multicentre, prospective, descriptive study. SETTING: Fifty-six public hospitals in nine provinces (a stratified, random sample of all hospitals treating gynaecological emergencies). PATIENTS: All women of gestation under 22 weeks who presented with incomplete abortion during the 2-week study period. MAIN OUTCOME MEASURES: Incidence of, morbidity associated with and mortality from incomplete abortion. MAIN RESULTS: An estimated 44686 (95% CI 35633-53709) women per year were admitted to South Africa's public hospitals with incomplete abortion. An estimated 425 (95% CI 78-735) women die in public hospitals from complications of abortion. Fifteen per cent (95% CI 13-18) of patients have severe morbidity while a further 19% (95% CI 16-22) have moderate morbidity, as assessed by categories designed for the study which largely reflect infection. There were marked inter-provincial differences and inter-age group differences in trimester of presentation and proportion of patients with appreciable morbidity. CONCLUSIONS: Incomplete abortions and, in particular, unsafe abortions are an important cause of mortality and morbidity in South Africa. The methods used in this study underestimate the true incidence for reasons that are discussed. A high priority should be given to the prevention of unsafe abortion.
OBJECTIVE: The objective of this report was to review and describe the management of incomplete abortion by public sector hospitals. DESIGN: A descriptive study in which data were collected prospectively from routine hospital records on all women admitted with incomplete abortion to a stratified random sample of hospitals between 14 and 28 September 1994. SETTING: Public sector hospitals in South Africa. PATIENTS: Women with incomplete abortions. MAIN OUTCOME MEASURES: Length of hospital stay, details of medical management, details of surgical management, determinants of the above. MAIN RESULTS: Data were collected on 803 patients from the 56 participating hospitals. Of these, 767 (95.9%) were in hospital for 1 day or more, and 753 (95.3%) women underwent evacuation of the uterus. Sharp curettage was the method employed in 726 (96.9%) and general anaesthesia was used for 601 (68%) of the women requiring uterine evacuation. Antibiotics were prescribed for 396 (49.5%) and blood transfusions were administered to 125 (17%) women. Statistical analysis showed length of stay to be longer in small hospitals (under 500 beds) and when the medical condition was more severe. Antibiotic usage and blood transfusion were more common with increasing severity and a low haemoglobin level on admission. However, some inappropriate management was identified with regard to both. MAIN CONCLUSIONS: It is suggested that uncomplicated incomplete abortion can be more effectively and safely managed using the manual vacuum aspiration technique with sedation/analgesia as an outpatient procedure. Attention should be directed at the introduction of this management routine at all types of hospital and to the ensuring of appropriate management of women with complicated abortion.
In 1994, a national hospital-based study was undertaken of cases of incomplete abortion presenting to public hospitals in South Africa. Data were collected for all women admitted to a random sample of hospitals with incomplete abortion during a two-week period. The WHO protocol for such studies was used as a basis for developing the methods to describe the epidemiology of incomplete abortion and hospital management of cases. Attempts were made to estimate the proportion of cases that might have been induced. This report focuses on methodological issues arising from the study that have implications for future research. The findings demonstrate that only a small proportion of the women acknowledged having had an induced abortion and that only a few of those who did showed evidence of interference with pregnancy. Clinical opinion of sepsis and the likelihood of induction were found to be highly unreliable. These findings considerably reduce the usefulness of the WHO-protocol method of estimating the likely origin of incomplete abortions. Results presented in terms of three partially overlapping descriptive categories are judged to better reflect the limitations of the data collected.
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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.
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.
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.
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.