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Biomedical subjects

M J Kelly

Publications and source records attributed to M J Kelly.

At least 91 records · Page 5Linked to original sources

Yttrium synovectomy in haemophilic arthropathy.

Between 1987 and 1991 we performed Yttrium-90 (Y-90) silicate radionuclide synovectomies on 40 joints of 20 haemophiliac patients with haemophilic arthropathy. All were male, their mean age was 31 yr and 15 of the 20 (75%) were HIV antibody positive. The number of joint bleeds and amount of factor (VIII and IX) replacement given in the 6 months pre- and 6 and 12 months post-radionuclide synovectomy was compared. Y-90 silicate synovectomy was shown significantly to reduce both the number of joint bleeds (P < 0.001) and factor usage (P < 0.001) in the 6 months after the procedure, a result maintained up to 12 months. Depot methyl prednisolone was co-administered with Y-90 but thought unlikely to contribute to joint response beyond 6 months. The reduction of joint bleeds and factor usage was even more dramatic in the 6- to 12-month period post-synovectomy although this was not reflected by the P value (P < 0.001). The reduction of joint bleeds and factor consumption post-synovectomy was most obvious in elbow joints, although the other joints as a group showed a significant reduction. Patients who were HIV antibody positive showed considerable improvement up to 12 months post-treatment, both in reduction of joint bleeds and as a consequence factor consumption. This improvement was seen to a lesser extent in the smaller HIV-negative group.

Adolescent↗

Cholecystokinin (CCK)-HIDA scintigraphy in patients with suspected gall-bladder dysfunction.

Cholecystokinin hepatobiliary (CCK-HIDA) scintigraphy is used to triage patients with chronic abdominal pain and suspected gall-bladder dysfunction. This study evaluates the predictive value of CCK-HIDA for clinical outcome after surgical and medical therapy. Fifty-six patients (45 females), mean age 43 +/- 9 years, with otherwise normal investigations, including normal ultrasound, fasted for more than 8h and then had 70MBq technetium-99m-EHIDA injected. One and a half hours later 15 ng/kg CCK was infused over 45 min. Seventy minutes dynamic imaging commenced 5 min prior to infusion. An abnormal gall-bladder ejection fraction (GBEF) was defined as < 50%. Patients were treated medically, or by cholecystectomy, depending on the surgeon's overall assessment, including results of the CCK-HIDA study. Patient status was then obtained in 51/56 patients at least 3 months after the scan or at least 1 month after surgery. All surgical specimens were reviewed independently for pathological changes of chronic acalculous cholecystitis. Of the 11 patients with an abnormal gall-bladder ejection fraction, nine (82%) underwent cholecystectomy, all of whom achieved total symptomatic cure, while two patients underwent other therapy, both of whom remained symptomatically unchanged. Of the 40 patients whose gall-bladder ejection fraction was normal, only five (12.5%) underwent cholecystectomy, of whom four were cured and one partially improved at follow up. Of the 35 patients with a normal gall-bladder ejection fraction and who underwent forms of therapy other than cholecystectomy, nine were cured symptomatically, 13 improved, 10 remained unchanged and three were symptomatically worse at follow up.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Corticosteroids and peptic ulceration.

The relationship between corticosteroids and peptic ulceration, together with the major complications of gastrointestinal haemorrhage and perforation, remains an area of clinical concern. This paper reviews the literature regarding peptic ulceration and corticosteroids. Risk factors related to an increased incidence of peptic ulceration in patients prescribed corticosteroids are discussed. These include: total dose of corticosteroid, previous history of peptic ulceration, advanced malignant disease and concurrent prescribing of nonsteroidal anti-inflammatory drugs (NSAIDs). It is suggested that prophylaxis should be considered for those patients with two or more risk factors. Choice and efficacy of prophylaxis is also considered.

Adrenal Cortex Hormones↗

Monoaminergic neuronal activity in subcortical brain regions in essential hypertension.

In this study we aimed to elucidate the role of central noradrenergic, dopaminergic, adrenergic and serotonergic neuronal systems in the development of essential hypertension. Fifteen untreated essential hypertensive subjects (aged 44 +/- 3 years) and 32 healthy volunteers (aged 38 +/- 3 years) participated in this study. By combining direct blood sampling techniques with cerebral blood flow scans we were able to differentiate between cortical and subcortical venous drainage of the brain. Veno-arterial MHPG, HVA and 5-HIAA plasma concentration gradients combined with internal jugular vein plasma flows were used, according to the Fick Principle, to derive metabolite spillovers which in turn were used as indicators of central noradrenergic, dopaminergic and serotonergic neuronal activity, respectively. These amine systems, in both the brainstem and forebrain, have been implicated in the regulation of sympathetic outflow and blood pressure. Total body noradrenaline spillover to plasma was concurrently measured to assess the relationship between central monoamine turnover and sympathetic activity. Compared to their healthy counterparts the hypertensive subjects had an elevated release of MHPG from subcortical brain regions (1.4 +/- 0.3 v 0.5 +/- 0.2 nmol/min, p < 0.05). An inverse relationship between blood pressure and subcortical HVA overflow existed, with the HVA overflow being significantly lower in the hypertensives (0.5 +/- 0.2 v 2.1 +/- 0.5 nmol/min, p < 0.05). Subcortical 5-HUAA overflow did not differ between the two groups, and adrenaline spillover from the brain was not detected in either group. Subcortical MHPG overflow was significantly correlated with total body NA spillover to plasma (p < 0.05). These results indicate that reciprocal aberrations in subcortical noradrenaline and dopamine turnover exist in essential hypertension. Although the physiological significance of this remains to be unequivocally elucidated we postulate that elevated subcortical noradrenergic activity, presumably in the forebrain where noradrenergic neurons are pressor, may cause sympathoexcitation and play a role in the development of essential hypertension.

3,4-Dihydroxyphenylacetic Acid↗

The potency of mu-opioid hyperpolarization of hypothalamic arcuate neurons is rapidly attenuated by 17 beta-estradiol.

The mu-opioid agonist DAMGO (Tyr-D-Ala-Gly-MePhe-Gly-ol) hyperpolarizes the majority of arcuate hypothalamic (ARC) neurons by opening an inwardly rectifying potassium conductance. The EC50 for the DAMGO-induced hyperpolarization was 60 +/- 3 nM in ARC neurons from ovariectomized guinea pigs. Superfusion of 17 beta-estradiol (E2; 100 nM) for 20 min in vitro resulted in a significant decrease in DAMGO potency (EC50 = 212 +/- 16 nM) in 40% of the neurons that were tested. This rapid effect of E2 on the mu-opioid response was not mimicked by the biologically inactive isomer 17 alpha-estradiol. Multiple concentrations of E2 were used to generate an E2 concentration-response curve, with an EC50 of 9 nM and a maximal increase in the DAMGO EX50 of 411% of controls. The membrane properties and firing rate of E2-sensitive and E2-insensitive neurons were not different. Streptavidin-FITC labeling did not reveal any significant morphological differences between the groups, but a higher number of E2-sensitive cells was found in the lateral ARC and cell-poor zone. Moreover, immunocytochemical staining of the recorded cells revealed that beta-endorphin neurons were among those sensitive to E2. Therefore, E2 could increase beta-endorphin release by decreasing the potency of beta-endorphinergic autoinhibition, thus increasing the tonic opioid inhibition of E2-insensitive cells. Furthermore, the diffuse projections of hypothalamic beta-endorphin neurons would allow E2 to alter processes throughout the brain, as well as having local effects in the hypothalamus.

Animals↗

Endoscopic transanal resection (ETAR) of colorectal strictures in stapled anastomoses.

Anastomotic strictures complicating colorectal anastomoses can be difficult to treat. Endoscopic transanal resection (ETAR) using cutting electrocautery has been described for benign and malignant polypoid rectal lesions, but is not a well-recognised method of treating anastomotic strictures. There are possible theoretical risks to limit the effectiveness of this method in stapled anastomoses. We report five patients with stapled colorectal anastomotic strictures all treated successfully without complication by ETAR, and recommend this treatment option.

Anastomosis, Surgical↗

Simple and rapid method for the determination of the diastereomers of difenacoum in blood and liver using high-performance liquid chromatography with fluorescence detection.

A rapid and sensitive high-performance liquid chromatographic method for the analysis of cis and trans diastereomers of the anticoagulant rodenticide difenacoum has been described. The methodology demonstrates potential for the analysis of diastereomers of related 4-hydroxycoumarin anticoagulants. Separations were achieved by reversed-phase chromatography on a Zorbax ODS column with gradient elution using acetonitrile-water, modified with 0.1% acetic acid, as the mobile phase. Detection of the analytes was effected by fluorescence at excitation and emission wavelengths of 310 and 390 nm, respectively. Sample preparation from both plasma and liver has been simplified to reduce preparation time and manipulation. The minimum detectable concentration of each diastereomer was 5 ng/ml. Recoveries of 100% were obtained from plasma and 93% from liver tissue. This method has been used for the investigation of the pharmacokinetics of difenacoum diastereomers in rats, and for investigation of unexplained hypoprothrombinaemic events encountered clinically.

4-Hydroxycoumarins↗

Endoscopic transanal resection in the management of patients with sessile rectal adenomas, anastomotic stricture and rectal cancer.

Forty patients underwent 61 endoscopic transanal resections using a urological resectoscope. Preoperative diagnoses were adenoma in 28 patients, carcinoma in seven and benign anastomotic stricture in five. Four patients with adenomas were found to have frank carcinoma. Ablation of 22 of 23 adenomas was achieved, 11 with a single transanal resection. Open operation was required for one patient. Locally advanced rectal malignancy was palliated in five of seven patients. All those with benign anastomotic stricture were cured by a single resection. The median operating time was 25 min, with 11 procedures exceeding 30 min. There were complications in seven cases (six bleeding, one septicaemia). The median hospital stay for the procedure alone was 3.5 days. There were no deaths within 30 days of operation. Endoscopic transanal resection is minimally invasive, quick, safe and effective. Histological surveillance is a major advantage and appears reliable. Low complication rates can be achieved by opting for several 'easy' resections and by restricting use of the procedure to lesions within 15 cm of the anal verge.

Adenoma↗

Torque history of electrically stimulated human quadriceps: implications for stimulation therapy.

The time course of knee extension torque was measured in human quadriceps muscles during 30 min of transcutaneous neuromuscular electrical stimulation (NMES). Ninety subjects were divided into six experimental groups (n = 15 per group), which received stimulation at one of the following frequency/duty cycle combinations: 10 Hz/50%, 30 Hz/50%, 50 Hz/50%, 10 Hz/70%, 30 Hz/70%, and 50 Hz/70%. Two-way analysis of variance revealed that the magnitude of the relative torque decrease (the percentage of decrease in torque relative to the initial value) was significantly different between frequencies (p < 0.005) and duty cycles (p < 0.02), with no significant interaction (p > 0.6). Increasing either frequency or duty cycle caused a greater decrease in torque. In spite of this result, there was no significant difference between groups in the total activity (torque-time integral) achieved during the 30 min treatment session. The magnitude of this activity corresponded to only about 7-14 maximum voluntary contractions. Finally, the average torque during the treatment session was significantly different among groups (p < 0.001), being greatest for the 50 Hz/50% group and least for the 10 Hz/70% group. Taken together, these data suggest that a smaller number of longer duration contractions produces the greatest muscle tension. They also suggest that the absolute torque levels achieved with NMES are relatively low compared with voluntary muscular activity.

Adult↗

Electrophysiology of guinea-pig supraoptic neurones: role of a hyperpolarization-activated cation current in phasic firing.

1. Immunocytochemically identified magnocellular neurosecretory cells (MNCs) in the guinea-pig supraoptic nucleus (SON) were studied using the in vitro intracellular recording technique. Cells were identified as containing arginine vasopressin (AVP) or oxytocin (OT) following recordings made with biocytin-filled electrodes. Both AVP and OT MNCs demonstrated a fusiform or pyramidal shape (15-20 microns by 26-39 microns), with two to three processes. There were no significant differences in the proportion of AVP and OT cells in the retrochiasmatic (caudal) versus the rostral slices. 2. No significant differences in passive membrane properties were observed between AVP and OT cells, except that AVP cells exhibited a significantly broader action potential width (1.51 +/- 0.1 ms, n = 11) than did OT cells (1.01 +/- 0.08 ms, n = 7). 3. Firing patterns were recorded for 100 MNCs, 41% of which fired in a phasic manner (repeated clustering of action potentials into bursts). Of the seventy-seven cells which were immunocytochemically identified, only AVP-containing MNCs displayed phasic firing. Phasic firing occurred only in MNCs demonstrating a depolarizing potential which followed hyperpolarizing after-potentials (HAPs). The presence of the depolarizing potential was not always associated with phasic firing, however, as both OT cells and non-phasic AVP cells sometimes exhibited a depolarizing potential. 4. In 160 MNCs examined for the presence of the time-dependent inward rectification (TDR in current clamp, or Ih in voltage clamp), a significant difference in the proportion of cells expressing the Ih was observed in the two cell types. The Ih was expressed in forty-five of fifty-four AVP MNCs (83%) and in six of fifteen OT MNCs (40%). No significant association was found with firing pattern. 5. The Ih exhibited properties similar to those found in other CNS and peripheral tissues. It appeared on steps to potentials more hyperpolarized than -65 mV. It was augmented by raising the extracellular potassium concentration, blocked by 2 mM CsCl, and insensitive to 100-500 microM BaCl2. Activation followed a single exponential, and the time constant of activation was voltage dependent. 6. The adenylate cyclase activator forskolin increased the Ih and shifted its activation curve to more depolarized levels. In cells recorded for several hours, the Ih varied in amplitude, suggesting intrinsic modulation, possibly by intracellular second messenger systems. The Ih in guinea-pig SON MNCs appears to serve an excitatory role, bringing cells closer to firing threshold.

Action Potentials↗

Role of a T-type calcium current in supporting a depolarizing potential, damped oscillations, and phasic firing in vasopressinergic guinea pig supraoptic neurons.

Guinea pig magnocellular neurosecretory cells (MNCs) of the supraoptic nucleus (SON) were studied using the in vitro slice preparation. Intracellular recordings were made with biocytin-filled electrodes, permitting immunocytochemical identification of the recorded cells as arginine vasopressin- (AVP) versus oxytocin- (OT) containing. Only AVP cells displaying a depolarizing potential (DP) fired phasically. The DP was associated with a transient inward current measured in voltage clamp, which exhibited a number of properties of the T-type calcium current: activation threshold of -64 mV, time course of up to 250 ms, blockade by nickel and augmentation by barium chloride. This current has not been reported previously in SON neurons. The T-type current (IT) was always associated with a damped oscillation of the membrane following the offset from hyperpolarizing steps. In all cells tested, an apamin-sensitive afterhyperpolarization (AHP) was observed, similar to the calcium-dependent potassium current (IK, Ca) described in rat SON and other CNS regions. Therefore, as with other CNS regions displaying damped oscillations, guinea pig SON cells possess both an IT and an IK, Ca. We have previously described an Ih activating at hyperpolarized potentials in these cells, which depolarizes the membrane to a range in which the IT and IK, Ca can interactively support oscillations. In summary, the IT and associated depolarizing potential appears to be a requisite feature for phasic firing in AVP cells of guinea pig SON.

Animals↗

Disruption caused by the house officer's bleep: a simple solution.

For a 'control' week, all bleep calls a surgical house officer received were charted without the nurses' knowledge and graded according to an arbitrary scale of usefulness. Also recorded were time of day, the person bleeping and whether the house officer was involved in patient care. A system was then tried in a later 'test' week, whereby only the nurse in charge would bleep the house officer and a board was placed on the house officer's own two wards where tasks could be written. Again all calls were recorded. This led to a decrease in inappropriate bleep calls from the nurses (58 per cent falling to 15 per cent p < 0.01) and a fall in numbers of nurses' bleep calls by two-thirds before 5 pm (p < 0.01). There was also a decrease in the number of bleeps when the house officer was directly involved in patient care (46 per cent falling to 28 per cent). The nurses in charge were agreeable to the changes. The entire study was repeated by another house officer with similar results. There has been little research on the disruption caused by the bleep and we believe that by this simple policy the house officers' day can be disrupted far less.

Medical Staff, Hospital↗

Chiropractic.

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Aged↗