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Biomedical subjects

M S King

Publications and source records attributed to M S King.

At least 19 recordsLinked to original sources
PubMed1997

District level information systems: two cases from South Africa.

The health system in South Africa has to date been fragmented and centralised. The priority of the new government is to establish an integrated and decentralised district health system of which a key element is the development of district health and management information systems (H & MIS). This paper presents experiences from two projects in the Western Cape in which a process to establish a district-based H & MIS was initiated and a situation analysis of the information systems was done. The two projects applied different research methods but the results show with remarkable consistency that much time is used on data collection, but information is not used at local level. The projects have applied different approaches towards developing a district H & MIS but in both important pre-requisites for a successful, action-led H & MIS include local ownership and motivation, a process based around existing local management structures and the active involvement of the community.

Delivery of Health Care↗
PubMed1997

The influence of the full blood count on medical inpatient management.

AIM: This investigation studied the use of the full blood count (FBC) in a general medical inpatient ward at Groote Schuur Hospital. OBJECTIVES: To determine the relative frequency of the reasons for which FBCs were requested (clinically indicated v. routine) and how they influenced patient management. PATIENTS: One hundred and sixty-five consecutive general medical inpatients admitted to the ward between September and December 1993 were included. Each patient underwent an FBC and differential white cell count prior to entering the ward. DESIGN: After taking a history and examining the patient, the physician responsible for each of the 165 patients completed a questionnaire. OUTCOMES MEASURED: Physicians had to indicate whether the FBC was routine or clinically indicated and how the FBC result influenced their patient management. RESULTS: In 67.9% of cases the FBC was considered to be clinically indicated, while in 32.1% of cases it was routine. Although it was felt that 76.4% of the clinically indicated tests influenced patient care, patient management was changed in only 24.7% of cases. In the case of routine tests, care was influenced in only 2.0% of cases. CONCLUSION: Routine tests have a very low clinical yield. There is no substitute for good clinical judgement and the practice of routine tests must be reviewed, as much time, money and patient discomfort could be saved by the elimination of unnecessary investigations.

Blood Cell Count↗
PubMed1996

Demonstration of a bilateral projection from the rostral nucleus of the solitary tract to the medial parabrachial nucleus in rat.

This study examined the projection from the rostral nucleus of the solitary tract (rNST) to the medial parabrachial nucleus (mPBN) in male Wistar rats using DiI as a retrograde tracer and biotinylated dextran as an anterograde tracer. Following successful unilateral injection of DiI into the mPBN (n = 8), retrogradely labeled neurons were always found in the rNST both ipsilateral and contralateral to the pontine injection site. Significantly, approximately 25% of the total number of DiI-labeled neurons were located in the contralateral rNST. The labeled neurons were located throughout the rostral-caudal extent of the rNST with the most cells being located in the central portion of the nucleus, and the fewest located ventromedially and dorsolaterally. Supporting the findings of the retrograde labeling study, axons and terminals, anterogradely labeled by injecting biotinylated dextran unilaterally into the rNST (n = 4), were always found in both the ipsilateral and contralateral mPBN. Although the intensity of anterograde labeling was higher ipsilaterally, a mirror-image staining pattern consistently was present contralaterally. These results indicate that there is a substantial contralateral component of the projection from the rNST to the mPBN. This suggests that convergence of gustatory information from the two sides of the oral cavity may occur within the pons before processing in higher brain centers. These findings may have important implications as to where and how bilateral gustatory information is processed and integrated.

Animals↗
PubMed1996

Neurotransmitter and neuromodulator activity in the gustatory zone of the nucleus tractus solitarius.

The rostral nucleus of the solitary tract (rNST) is the first central relay in the gustatory pathway. While previous investigations have provided a wealth of information on the pattern of central terminations of gustatory afferent fibers, the morphology of synaptic connections of rNST neurons and responses of second order neurons to taste stimuli applied to the tongue, little is known regarding the neurophysiological characteristics of synaptic transmission in rNST. We have used an in vitro brain slice preparation of the rNST to study the intrinsic biophysical properties, neuropharmacology and synaptic responses of rNST neurons. These experiments have revealed that rNST neurons respond to the excitatory amino acid neurotransmitter glutamate, as well as the inhibitory amino acid neurotransmitter gamma amino butyric acid (GABA). By use of glutamate receptor agonists and antagonists we have shown that rNST neurons have AMPA/kainate and NMDA ionotropic glutamate receptors, as well as matabotropic glutamate receptors. In addition, rNST neurons respond to both GABAA and GABAB receptor agonists. The nature of the transmission at the synapse between primary afferent fibers and second order neurons in rNST has been examined by electrical stimulation of the solitary tract to elicit post-synaptic potentials (PSP). Three types of monosynaptic PSP result from stimulation of the solitary tract: excitatory post-synaptic potentials, inhibitory post-synaptic potentials, and a complex mixture of excitatory and inhibitory potentials. These new discoveries provide details about synaptic transmission in rNST and thereby clarify the underlying mechanism by which gustatory information is processed.

Afferent Pathways↗
PubMed1994

Relationship between structure and function of neurons in the rat rostral nucleus tractus solitarii.

To investigate the relationship between the structure and function of neurons in the rostral (gustatory) nucleus tractus solitarii (rNTS), we analyzed the morphological and biophysical properties of rNTS neurons by performing whole-cell recordings in a brain slice preparation. Overall, neurons (n = 58) had a mean somal diameter of 16 microns, an average dendritic length of 598 microns, an average dendritic thickness of 0.91 microns, and a spine density of 0.037 spines/microns. Neurons were separated into three groups (elongate, multipolar, and ovoid) on the basis of previously established morphological criteria. The highest percentage (49%) of neurons were classified as ovoid, while 35% were multipolar and only 16% were elongate. The most frequently observed firing pattern, in all three cell types, elicited by a 1,200 ms, 100 pA depolarizing current pulse was a regularly firing spike train. However, the intrinsic firing properties of the remaining neurons were different. Thirty-one percent of the ovoid neurons responded with a short burst of action potentials and 44% of the elongate neurons showed a delay in the onset of the spike train following a hyperpolarizing prepulse. Less than 16% of the multipolar neurons demonstrated either of these firing characteristics. Therefore, rNTS neurons with similar morphology do not have unique biophysical properties. However, the data suggest that there may be subpopulations of the three morphological types, each of which displays a different firing pattern. Since the structure and function of the three morphological groups were not strictly correlated, these subpopulations may represent functional groups.

Action Potentials↗
PubMed1994

Preventing deep venous thrombosis in hospitalized patients.

Deep venous thrombosis with subsequent pulmonary embolism remains a significant cause of morbidity and mortality in hospitalized patients. Although prophylactic treatment may reduce the incidence of deep venous thrombosis by up to 70 percent, it is estimated that only 32 percent of hospitalized patients at high risk receive adequate prophylaxis. Older patients, obese patients and patients undergoing orthopedic procedures of the lower limbs are at particularly high risk of developing deep venous thrombosis. Both mechanical and pharmacologic measures provide effective prophylaxis. Newer treatment protocols have greatly reduced the incidence of drug side effects, particularly bleeding.

Hospitalization↗
PubMed1993

Substance P excites neurons in the gustatory zone of the rat nucleus tractus solitarius.

Whole-cell patch recordings of neurons in the rostral (gustatory) nucleus tractus solitarius (rNTS) were performed in a brain slice preparation from rat medulla. Neural responses to brief applications (10-45 s) of substance P (SP), via a constant superfusion apparatus, were recorded. SP transiently depolarized 80 of 117 (68%) rNTS neurons in a dose-dependent manner. Sub-micromolar concentrations of SP had potent excitatory effects, and the half maximal response occurred at 0.6 microM. The depolarizing effect of SP was accompanied by an increase in input resistance in 81% of the responsive neurons. The excitatory effects of SP persisted in low Ca2+ (0.2 mM) and high Mg2+ (12 mM) saline as well as in the presence of 2 microM TTX (n = 5 for each), suggesting direct postsynaptic action on the recorded neurons. SP also hyperpolarized 4 neurons (4%) and had no effect on 33 neurons (28%). Each of the 4 neurons which were hyperpolarized by SP showed a decrease in input resistance. A more detailed assessment of the types of neurons in the rNTS which respond to SP was also conducted. Neurons were separated into 4 electrophysiological groups on the basis of their repetitive firing pattern induced by a hyperpolarizing and depolarizing current injection paradigm. Neurons belonging to each of the 4 electrophysiological groups responded to SP. Eighteen neurons, which were filled with 1% biocytin during recording, were categorized as ovoid, multipolar or fusiform based on their morphological characteristics. SP excited all 3 morphological types of neurons in similar proportion. These results suggest that SP is an excitatory neurotransmitter in the rNTS. The effects of SP are not restricted to a particular neuron type defined either biophysically or morphologically. The implications of these results on the possible role of SP in processing gustatory and somatosensory information within the rNTS are discussed.

Animals↗
PubMed1992

Ventral pontine catecholaminergic pathway mediates the vasopressin response to splanchnic osmostimulation in conscious rats.

This study examines the role of catecholamines, cell bodies and fibers of passage within the subcoeruleus area (subLC) in the arginine vasopressin (AVP) response to splanchnic osmotic stimulation and hemorrhage. Bilateral chemical lesions were induced into the subLC, approximately 1 mm ventral to the locus coeruleus (LC), using 6-hydroxydopamine (6-OHDA) and ibotenic acid to selectively destroy catecholaminergic components and cell bodies, respectively. Vehicle and 5,7-dihydroxytryptamine (5,7-DHT) injections into the subLC area, 6-OHDA injections into the LC, as well as systemic desipramine pretreatment, were performed as controls for the possible non-specific effects of the lesions. Seven and 8 days later, plasma AVP level, plasma osmolality, mean arterial pressure and heart rate were measured following either gastric infusion of hypertonic (598 mOsm/kg; 2 ml/4 min) or isotonic (290 mOsm/kg) saline or a mild hemorrhage (2.5 ml/300 g) in conscious rats with indwelling tail artery catheters and naso-gastric tubes. 6-OHDA injections into subLC reduced the AVP response to the osmotic stimulation by 62.3% (P less than 0.01), as compared to vehicle-injected controls. These same rats demonstrated a normal AVP response to hemorrhage implying a specificity of the disrupted pathway. All controls confirmed that the effects of the 6-OHDA were due to specific action on noradrenergic components within the subLC area. Ibotenic acid lesions in the subLC did not significantly decrease the AVP response, demonstrating that mainly fibers and not cell bodies in this region are part of the pathway. 6-OHDA injections just anterior to the LC, where the dorsal noradrenergic bundle (DNAB) forms, reduced the AVP secretion due to hemorrhage by 77.0% (P less than 0.05), but had minor effects on the response to osmotic stimulation. These results indicate that catecholaminergic fibers travelling primarily within the subLC, in the ventral noradrenergic bundle (VNAB), carry splanchnic osmotic input to the hypothalamus, whereas the DNAB may mediate the AVP response to hemorrhage.

5,7-Dihydroxytryptamine↗
PubMed1992

Transthyretin is an inhibitor of monocyte and endothelial cell interleukin-1 production.

Human serum was found to contain an inhibitor of constitutive interleukin-1 (IL-1) production by human umbilical vein endothelial cells (ECs). Purification of the serum activity by anion exchange chromatography, molecular sieve HPLC, and hydroxyl apatite chromatography yielded material 82% pure with a molecular weight of 17 kDa by SDS-PAGE. Amino acid sequencing revealed the purified inhibitor to be transthyretin (TTR), a liver-derived protein. There was a 42.6% reduction in the production of spontaneous IL-1 activity in EC supernatants after coculture with 10 micrograms/ml TTR. TTR was subsequently found by ELISA to inhibit LPS-stimulated IL-1 production by cells of the human monocytic leukemia line THP-1 by 47.1 +/- 9.4%, whereas a less striking but still significant inhibition of monocyte-derived IL-1 beta production was also observed. Inhibition of IL-1 secretion correlated with increased IL-1 mRNA synthesis in both THP-1 cells and monocytes. Furthermore, TTR was associated with increased intracellular concentrations of IL-1 beta. These data suggest that TTR functions by inhibiting processing of newly synthesized peptide for secretion. This novel inhibitory effect of TTR on the production of IL-1 activity suggests a previously unrecognized endogenous antiinflammatory mediator.

Amino Acid Sequence↗
PubMed1991

Central neural pathway mediating splanchnic osmosensation.

To determine the central neural pathway which carries splanchnic osmosensory information to vasopressin (AVP) neurons in the hypothalamus, bilateral electrolytic lesions were placed in the ascending catecholaminergic fiber bundle, the locus coeruleus (LC), the locus subcoeruleus (subLC), the lateral parabrachial nucleus (LPB), the caudal periaqueductal gray (PAG) and the median preoptic nucleus (MPO). Six and seven days later, plasma AVP levels, plasma osmolality, mean arterial pressure and heart rate were measured following gastric infusion of hypertonic (598 mosm/kg; 2 ml/4 min) or isotonic (290 mosm/kg) saline in conscious rats with indwelling tail artery catheters and nasogastric tubes. The most effective pontine lesions, which were located in the ventral locus subcoeruleus (vsubLC) approximately 1.0 mm below the LC, decreased the AVP response to hypertonic gastric infusion by 59.7% (P less than 0.05) as compared to sham-lesioned controls. In addition, unilateral vsubLC lesions dramatically reduced the catecholamine innervation of the ipsilateral paraventricular nucleus (PVN), as qualitatively determined with dopamine beta-hydroxylase immunocytochemistry, suggesting that a pathway ascending with catecholaminergic fibers was disrupted. Lesions of the MPO were also very effective, decreasing the AVP response to hypertonic saline infusion by 60.3% (P less than 0.05), suggesting that the MPO is an integral relay center in this pathway. On the other hand, LC, LPB and PAG lesions were ineffective. Systemic plasma osmolality or cardiovascular factors did not mediate the AVP response. These results demonstrate, for the first time, that splanchnic osmotic information is transmitted to the hypothalamus via pathways within the ascending catecholaminergic fiber bundles, the MPO is a relay center where peripheral and central osmotic information may be integrated, and the LC, LPB, and PAG are not part of the splanchnic osmotic pathway.

Afferent Pathways↗
PubMed1990

The role of intracellular messengers in adrenocorticotropin secretion in vitro.

Adrenocorticotropin (ACTH), an opiomelanocortin peptide, is secreted from anterior pituitary corticotrophs upon stimulation with corticotropin-releasing hormone (CRH), arginine vasopressin (AVP) and several other neuropeptides. CRH, the most potent secretagogue of ACTH, stimulates ACTH secretion and biosynthesis by increasing the production of cyclic adenosine 3',5'-monophosphate (cAMP) within corticotrophs. AVP, which is a weak secretagogue of ACTH but strongly potentiates CRH-stimulated ACTH secretion, operates through the phosphatidylinositol (PI) transduction pathway. Both CRH and AVP increase cytosolic free [Ca2+] within normal corticotrophs indicating a role for Ca2+ in ACTH secretion. Glucocorticoids inhibit ACTH synthesis by suppressing transcription of the proopiomelanocortin (POMC) gene and attenuate ACTH release by decreasing cAMP accumulation stimulated by CRH. This review focuses on the roles of these intracellular messengers in ACTH secretion from normal anterior pituitary cells in vitro, and discusses the possible interactions between the cAMP, calcium and PI transduction pathways. Future areas of research are suggested such as identification of protein substrates of cAMP-dependent and Ca2(+)-dependent kinases within normal corticotrophs and evaluation of their role in ACTH biosynthesis and secretion.

Adrenocorticotropic Hormone↗
PubMed1989

Physiological concentrations of atrial natriuretic factors with intact N-terminal sequences inhibit corticotropin-releasing factor-stimulated adrenocorticotropin secretion from cultured anterior pituitary cells.

The effectiveness of atrial natriuretic factors (ANFs) as inhibitors of CRF-stimulated ACTH secretion was examined in cultured rat anterior pituitary cells. alpha ANF-(1-28) significantly inhibited ACTH release stimulated by 1-5 nM CRF. At the most effective concentration of 100 pM, alpha ANF-(1-28) inhibited ACTH release by 40.1% (P less than 0.001). This effect was manifested after 3 h, but not after 0.5 or 1 h, of incubation, suggesting that ACTH synthesis may have been reduced. Conversely, alpha ANF-(5-28), at concentrations of 10 pM to 10 nM, had no effect on ACTH secretion after 0.5, 1, or 3 h. alpha ANF-(1-11) weakly inhibited ACTH secretion at concentrations of 100 and 1000 pM. Again, these effects were observed after 3 h, but not after 0.5 or 1 h, of incubation. These results suggest that ANF-induced inhibition of CRF-stimulated ACTH release requires 1) an intact N-terminal sequence of the ANF peptide, 2) low concentrations, and 3) more than 1 h of incubation. The results explain previous negative evidence and suggest that alpha ANF-(1-28) may be a physiological inhibitor of ACTH secretion.

Adrenocorticotropic Hormone↗
PubMed1987

Acetylcholine activates cerebral interneurons and feeding motor program in Limax maximus.

The cellular and network effects of acetylcholine (ACh) on the control system for feeding in Limax maximus were measured by intracellular recordings from feeding command-like interneurons and whole nerve recordings from buccal ganglion motor nerve roots that normally innervate the ingestive feeding muscles. The buccal ganglion motor nerve root discharge pattern that causes rhythmic feeding movements, termed the feeding motor program (FMP), was elicited either by attractive taste solutions applied to the lip chemoreceptors or by ACh applied to the cerebral ganglia. The ability of exogenous ACh applied to the cerebral ganglia to trigger FMP was blocked by the cholinergic antagonists curare and atropine. If the strength of the lip-applied taste stimulus was in the range of 1-2 times threshold, cerebral application of the cholinergic antagonists blocked or greatly decreased the ability of lip-applied taste solutions to trigger FMP (5 of 8 trials). The cerebral feeding interneurons, some of which activate FMP when stimulated intracellularly, are excited by small pulses of ACh applied directly to the cell body from an ACh-filled micropipette. A pulse of ACh that activates several of the feeding interneurons simultaneously triggers FMP. The data suggest that under certain stimulus conditions an obligatory set of cholinergic synapses onto the feedininterneurons must be activated for taste inputs to trigger ingestion. The determination of ACh's action within the feeding control system is necessary for understanding how enhanced cholinergic transmission leads to prolonged associative memory retention (Sahley, et al., 1986).

Acetylcholine↗