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Biomedical subjects

A J Cunningham

Publications and source records attributed to A J Cunningham.

At least 37 records · Page 2Linked to original sources

The effects of midazolam on pure tone audiometry, speech audiometry, and audiological reaction times in human volunteers.

UNLABELLED: Auditory evoked potentials are effected by benzodiazepines, as is cortical processing of auditory stimuli. The effect of benzodiazepines on auditory sensitivity has not, however, been studied. We designed the present study to investigate the effect of sedative doses of midazolam on pure tone and speech audiometry and on audiological reaction times in healthy volunteers. Thirty volunteers underwent baseline audiological assessment for pure tones and speech and had their audiological reaction times measured at 10 and 50 dB above their threshold hearing level at a frequency of 1 kHz. Subjects were then randomly assigned to one of two groups. Group A (n = 15) received midazolam (0.04 mg/kg) IV, and Group B (n = 15) received a similar volume of placebo IV. The audiological tests were repeated 5 min later, and performance was compared with baseline data. Scheffé post hoc tests were used to assess the significance of changes in each group. There was no pre- to posttest change in audiological performance in either the placebo group (P = 0.194) or the midazolam group (P = 0.957). Speech audiometry performance was likewise unaffected by midazolam (P = 0.154). Reaction time at the 10-dB and 50-dB sensation levels were both significantly prolonged after midazolam administration (P = 0.023 and P = 0.012, respectively). In this study, we demonstrate that sedation with midazolam (0.04 mg/kg) does not alter pure tone or speech audiometric thresholds, but it does significantly delay the reaction time to auditory stimuli. Medical practitioners should advise midazolam-sedated patients of their impaired reaction to auditory warning signals (e.g., traffic and car horns) as part of the day-ward discharge recommendations. IMPLICATIONS: In this study, we demonstrate that sedation of healthy volunteers with the benzodiazepine midazolam, in the common clinical dosage, does not affect their hearing capability as measured by pure tone and speech audiometry. However, one's ability to react to auditory signals is impaired after midazolam, which may have implications for patients after day-case procedures.

Adult↗

The effects of recombinant human growth hormone on cardiopulmonary function in elective abdominal aortic aneurysm repair.

OBJECTIVES: Cardiorespiratory complications are the predominant source of morbidity in patients undergoing major surgery. Recombinant human growth hormone (rhGH) has previously been shown to be effective in improving respiratory and cardiac function in compromised patients. DESIGN: The aim of this study was to assess the effects of perioperative rhGH on cardiac function in 33 patients undergoing elective infrarenal abdominal aortic aneurysm repair. METHODS: Patients were randomised to one of three groups: placebo for 6 days before and after surgery (control, n = 12); genotropin (GH) 0.3 units/kg/day for 6 days before and after surgery (pre and postop GH, n = 10) and placebo for 6 days before and GH (0.3 units/kg/day) for 6 days after surgery (postop EH, n = 11). Patients were assessed on days 7 and 1 before and days 7, 14 and 50 after operation. Intraoperative cardiac index (CI) was measured after induction of anaesthesia, before and after aortic cross-clamping, after aortic unclamping and at the end of surgery. RESULTS: Pretreatment with GH resulted in a significantly higher heart rate during surgery and was associated with a trend towards higher cardiac index (CI) (p < 0.067) at all stages of surgery. Mean arterial blood pressure at the stage of aortic unclamping was significantly higher in patients treated with GH preoperatively. CONCLUSIONS: Larger studies are required to evaluate the beneficial effects of GH in aortic surgery. However, data from this pilot study suggests that perioperative GH administration may result in improved cardiac performance during aortic surgery.

Aged↗

Flow cytometry using annexin V can detect early apoptosis in peripheral blood stem cell harvests from patients with leukaemia and lymphoma.

Quantifying progenitor cells in peripheral blood stem cell (PBSC) harvests by flow cytometric enumeration of CD34+ cells does not account for cell viability. Cell membrane asymmetry in early apoptosis exposes phosphatidylserine on the cell surface. This can be detected by staining with annexin V FITC. Apoptosis in 30 autologous PBSC harvests mobilised by cyclophosphamide + G-CSF or standard chemotherapy + G-CSF was analysed immediately after collection by dual-colour flow cytometry with CD34 PE and annexin V FITC. Harvests contained a median of 3.4 x 10(6)/kg (range 0.3-91.8) CD34+ cells. Of these 87.6% (range 30-96.5) were annexin V-. In 10% of harvests more than 50% of CD34+ cells were apoptotic. Differences in PBSC mobilisation or collection could not explain the variation in annexin V binding. Cyclophosphamide + G-CSF significantly increased the yield of CD34+ cells but did not increase apoptosis. Comparison of consecutive harvests showed no difference in the numbers of CD34+ cells collected but found a significant decrease in apoptotic CD34+ cells through multiple collections. Analysis of annexin V binding in PBSC harvests is a simple flow cytometry technique which gives additional information on the status of CD34+ progenitor cells.

Annexin A5↗

Pituitary apoplexy after spinal anaesthesia.

We report the case of a previously healthy 51-yr-old male who underwent an uneventful total hip replacement under spinal anaesthesia. His immediate postoperative course was complicated by the development of a severe frontal headache. Initial conservative treatment included oral analgesics and an epidural blood patch. The headache persisted and was followed by progressive vision loss and a right partial third nerve palsy. The patient was almost blind at the time of transfer to our neurosurgical unit. Relevant investigations revealed marked hyponatraemia (serum sodium concentration 122 mmol litre-1) and second-degree heart block (Mobitz I). A CT scan showed a pituitary tumour and confirmed the clinical diagnosis of pituitary apoplexy. Urgent craniotomy was scheduled and a large necrotic pituitary adenoma was excised. The postoperative course was uneventful with return of near normal vision at the time of discharge. Clinicians should consider this diagnosis when focal neurological deficits occur with post-dural puncture headache.

Adenoma↗

Interleukin-1 beta (IL-1 beta) and tumour necrosis factor (TNF) inhibit long-term potentiation in the rat dentate gyrus in vitro.

The effects of the cytokine, interleukin-1 beta (IL-1 beta), and its receptor antagonist IL-1ra, were studied on long-term potentiation in the dentate gyrus of rat hippocampal slices. Field excitatory postsynaptic potentials were recorded extracellularly in the molecular region of the dentate gyrus in response to stimulation of the medial perforant path. Low frequency synaptic transmission was unaffected by IL-1 beta (1 ng/ml), but pre-treatment with IL-1 beta completely blocked induction of long-term potentiation. Co-application of IL-1 beta and IL-1ra (100 ng/ml) attenuated the inhibitory effect of IL-1 beta. In parallel with these findings, we demonstrate that IL-1 beta also inhibited 45Ca influx into the slices. The inhibitory effect of IL-1 beta on induction was mimicked by tumour necrosis factor (TNF; 4.5 ng/ml) and lipopolysaccharide (LPS; 10 micrograms/ml). These results indicate a modulatory role for cytokines in hippocampus and suggest that the inhibitory effect of IL-1 beta on long-term potentiation may relate to its inhibitory effect on calcium channel activity.

Animals↗

Laparoscopic cholecystectomy: haemodynamic and neuroendocrine responses after pneumoperitoneum and changes in position.

We have assessed the potential for myocardial ischaemia during laparoscopic cholecystectomy in 16 otherwise healthy patients. Continuous ambulatory ECG monitoring was commenced 12 h before operation and continued for 24 h after operation. The neuroendocrine stress response was assessed by measuring plasma concentrations of adrenaline and noradrenaline, human growth hormone, cortisol, renin and aldosterone, and prolactin, at specified times during surgery. Acute ST segment changes in the ECG occurred in only two patients. These episodes were independent of creation of pneumoperitoneum and changes in position. Acute intraoperative increases in MAP were noted during insufflation of carbon dioxide and reverse Trendelenburg positioning (P < 0.05). A four-fold increase in plasma concentrations of renin and aldosterone was noted after pneumoperitoneum and reverse Trendelenburg positioning (P > 0.05). There was a linear correlation between changes in plasma renin and aldosterone concentrations and MAP (r = 0.97 and r = 0.85, respectively). Prolactin concentrations increased four-fold after induction of anaesthesia. Cortisol, HGH, adrenaline and noradrenaline concentrations increased after deflation of the pneumoperitoneum. The time profile-concentration changes of increased MAP and renin-aldosterone suggests a cause-effect relationship. Increased intra-abdominal pressure and reverse Trendelenburg positioning may reduce cardiac output and renal blood flow. The early increase in prolactin concentration was probably secondary to the effect of the opioid fentanyl.

Adult↗

Group psychological therapy for cancer patients: a point of view, and discussion of the hierarchy of options.

OBJECTIVE: We present here a point of view about the logical role of group psychological therapies in the care of cancer patients, and propose a comprehensive, four-stage program that could be implemented at any large cancer treatment center. METHOD: Our proposals rest on a review of the literature, and on our own experience with various kinds of psychological help for cancer patients, some of which is described. RESULTS: It is clear that group psychological therapies improve the quality of life of many participating cancer patients, and there is preliminary evidence that it may prolong life in some cases. We describe five main kinds of adjuvant psychological therapy, arranging them on a hierarchy of increasingly active participation by the recipient, and noting the status of evidence for their efficacy. They are: providing information, emotional support, behavioral training in coping skills, psychotherapy (of various kinds), and more speculatively, spiritual/existential therapy. CONCLUSIONS: We propose that it is time to consider psychological therapy as an adjuvant in cancer management, analogous to adjuvant chemotherapy. The main indication for advocating group psychological therapy to patients should, we argue, be an expert assessment that the patient is likely to benefit, and should not (as is usual at present) be restricted to either 1) those patients with overt psychopathology, or 2) those few who specifically request it.

Adaptation, Psychological↗

A randomised comparison of two forms of a brief, group, psychoeducational program for cancer patients: weekly sessions versus a "weekend intensive".

UNLABELLED: There is considerable evidence that brief group psychoeducational programs for cancer patients, offering support and some training in coping skills, may have lasting beneficial effects on mood and quality of life. OBJECTIVE: To compare two different formats of a brief, group psychoeducational program for cancer patients; a standard format of six weekly two-hour sessions or a "weekend intensive," involving the same content and contact time compressed into two days. METHOD: Cancer patients were randomly assigned to either the standard weekly intervention (n = 77) or the weekend program (n = 79). Two assessment measures were used: Profile of Mood States (POMS) and Functional Living Index for Cancer (FLIC). Assessments were made before and after each intervention and at a nineteen-week follow-up. RESULTS: While the two formats were found to be equivalent in their overall effects on mood and quality of life, there were some differences. There was a sudden, large improvement in mood by the end of the weekend version of the course (2-day time point) but this did not persist, and by the six-week point and again at nineteen-weeks, mood improvement was the same for both groups. Quality of life improvement seemed to be marginally greater with the six-weekly sessions (reaching statistical significance at the 6-week point). CONCLUSIONS: The two formats produced similar improvements in both mood and quality of life. We discuss the need for further studies to find optimal ways of presenting such help for different patient groups.

Activities of Daily Living↗

Group psychological therapy for cancer patients. A brief discussion of indications for its use, and the range of interventions available.

The growing evidence for the efficacy of psychological therapy in improving quality of life in cancer patients suggests that we should now consider it an adjuvant treatment in cancer management, analogous to adjuvant chemotherapy. If this is accepted, it follows that the main indication for advocating such adjuvant psychological therapy to patients should be an expert assessment that the patient is likely to benefit; it should not (as is usual at present) be restricted to either those patients with overt psychopathology, or those few who specifically request it. We describe five main kinds of therapy, arranging them on a hierarchy of increasingly active participation by the recipient, and noting the status of evidence for their efficacy. These five types are: providing information, emotional support, behavioral training in coping skills, psychotherapy (of various kinds), and, more speculatively, spiritual/existential therapy.

Adaptation, Psychological↗

A simple method for isolating alpha 2 macroglobulin-cytokine complexes.

There is the need for a simple, effective procedure for separating alpha 2 macroglobulin-cytokine complexes from free cytokine in order that the nature and possible immunological significance of cytokine-binding by alpha 2 macroglobulin (alpha 2-M) might be further investigated. This presentation describes a method which exploits the presence of zinc-binding sites on alpha 2-M which permit the isolation of complexes from other proteins by zinc-affinity chromatography. Furthermore the method may be used in either a column or batch format.

Chromatography, Affinity↗

Laparoscopic surgery--anesthetic implications.

Laparoscopic cholecystectomy is a relatively new surgical procedure which is enjoying ever-increasing popularity and presenting new anesthetic challenges. The advantages of shorter hospital stay and more rapid return to normal activities are combined with less pain associated with the small limited incisions and less postoperative ileus compared with the traditional open cholecystectomy. The efficacy of laparoscopic appendectomy and hemicolectomy has been recently evaluated. However, there have been no prospective randomized studies to date comparing laparoscopic with traditional laparotomy techniques. The physiological effects of prolonged pneumoperitoneum and the longer duration of surgery with the laparoscopic techniques are of concern. The application of laparoscopic inguinal hernia repair may be limited because, unlike traditional surgical hepair, general anesthesia is required and concerns have been expressed about the duration of surgery and the possibility of hernia recurrence. Notwithstanding case reports and series describing successful diaphragmatic and hiatus hernia repair using a laparoscopic surgical technique, the frequently encountered complications of cervical surgical emphysema, pneumothorax, and pneumomediastinum, attributed to passage of insufflating gas through weak points or defects in the diaphragm, must be of major concern. Anesthesiologists must maintain a high index of suspicion for these potential complication and must undertake appropriate monitoring. If there is clinical evidence of a tension pneumothorax, immediate chest tube decompression is indicated. Intraoperative complications of laparoscopic surgery are mostly due to traumatic injuries sustained during blind trocar insertion and physiological changes associated with patient positioning and pneumoperitoneum creation. The choice of anesthetic technique for upper abdominal laparoscopic procedures is most frequently limited to general anesthesia. Controlled ventilation avoids hypercarbia, and an anesthetic technique incorporating antiemetics and nonsteroidal anti-inflammatory agents has reduced postoperative nausea and vomiting following laparoscopic cholecystectomy. The use of nitrous oxide during laparoscopic procedures remains controversial. Laparoscopic cholecystectomy is a major advance in the management of patients with symptomatic gall-bladder disease. However, in the present era of cost containment, older and sicker patients may present for this procedure on the day of surgery without adequate preoperative evaluation. Anesthesiologists should thus be prepared to recommend deflation of the pneumoperitoneum and possibly conversion to an open procedure if hemodynamic, oxygenation, or ventilation difficulties arise during the procedure.

Anesthesia↗