Oral oxycodone offers equivalent analgesia to intravenous patient-controlled analgesia after total hip replacement: a randomized, single-centre, non-blinded, non-inferiority study.

BACKGROUND: To determine if oral oxycodone (OOXY) could provide equivalent postoperative analgesia and a similar side-effect profile to i.v. patient-controlled morphine in patients undergoing elective primary total hip replacement (THR) under spinal anaesthesia. METHODS: We studied 110 consecutive patients aged 60-85 yr. After operation, patients were randomly allocated to receive either oral controlled- and immediate-release OOXY or i.v. patient-controlled analgesia (IVPCA) with morphine. Both groups received regular co-analgesia and antiemetics. The primary outcome measures were: (i) postoperative pain at rest and movement and (ii) nausea score recorded 12 hourly. The secondary outcome measures were: (i) time to first mobilization, (ii) total amount of opioid consumed, (iii) number of additional antiemetic doses, and (iv) time to analgesic discontinuation. RESULTS: There were no statistically significant differences in the primary outcome measures of pain at rest and movement (P>0.05, 95% confidence intervals -0.41, +0.96) or nausea score (P>0.5). The secondary outcome measures showed no significant difference in the total amount of opioid consumed (102 vs 63 mg; P>0.05) or time to mobilization (24.45 vs 26.6 h, P=0.2). The number of antiemetic doses required in the first 24 h was significantly lower in the OOXY group (1.1 vs 1.4, P<0.05). The time to analgesic discontinuation was significantly shorter in the OOXY group (50.5 vs 56.6 h, P<0.05). Oral analgesia with OOXY was approximately GBP 10 less expensive per patient than IVPCA. CONCLUSIONS: Oral analgesia with OOXY after THR offers non-inferior analgesia to IVPCA and may offer some logistical and cost advantages.

Sepsis and the heart.

Septic shock, the most severe complication of sepsis, accounts for approximately 10% of all admissions to intensive care. Our understanding of its complex pathophysiology remains incomplete but clearly involves stimulation of the immune system with subsequent inflammation and microvascular dysfunction. Cardiovascular dysfunction is pronounced and characterized by elements of hypovolaemic, cytotoxic, and distributive shock. In addition, significant myocardial depression is commonly observed. This septic cardiomyopathy is characterized by biventricular impairment of intrinsic myocardial contractility, with a subsequent reduction in left ventricular (LV) ejection fraction and LV stroke work index. This review details the myocardial dysfunction observed in adult septic shock, and discusses the underlying pathophysiology. The utility of using the regulatory protein troponin for the detection of myocardial dysfunction is also considered. Finally, options for the management of sepsis-induced LV hypokinesia are discussed, including the use of levosimendan.

A survey of intensive care unit visiting policies in the United Kingdom.

Admission to an intensive care unit is a highly stressful event for both patients and their relatives. Feelings of anxiety, pain, fear and a sense of isolation are often reported by survivors of a critical illness, whilst the majority of relatives report symptoms of anxiety or depression while their relative was in the intensive care unit. Traditionally, infection control concerns and a belief that liberal visiting by patients' relatives interferes with the provision of patient care have led many units to impose restricted visiting policies. However, recent studies suggest that an open visiting policy with unrestricted visiting hours improve visitors' satisfaction and reduces anxiety. In order to determine current visiting practice and provision for relatives within intensive care units, a questionnaire was sent to the principal nurse in all units within the United Kingdom. A total of 206 hospitals out of 271 completed the survey (76%). We found that 165 (80.1%) of responding units still impose restricted visiting policies, with wide variations in the facilities available to patients' relatives.

Abdominal compartment syndrome: an under-diagnosed contributory factor to morbidity and mortality in the critically ill.

As the abdomen is a closed cavity, it follows that any increase in abdominal contents will inexorably lead to a rise in the intra-abdominal pressure. Normally this is less than 7 mm Hg, but when it persistently exceeds 12 mm Hg, renal, intestinal, pulmonary, cardiovascular and central nervous system dysfunction arises. A wide range of conditions encountered in both medical and surgical intensive care units are associated with a rise in intra-abdominal pressure. When this pressure is continually above 20 mm Hg, organ system failure can occur, a condition known as abdominal compartment syndrome. Failure to recognise and treat this syndrome is associated with a high morbidity and mortality.

Ventilator associated pneumonia.

Hospital acquired or nosocomial infections continue to be an important cause of morbidity and mortality. The critically ill patient is at particular risk of developing intensive care unit acquired infection, with the lungs being especially vulnerable. Nosocomial bacterial pneumonia occurring after two days of mechanical ventilation is referred to as ventilator associated pneumonia, and is the most common nosocomial infection seen in the intensive care unit. Intubation of the trachea and mechanical ventilation is associated with a 7-fold to 21-fold increase in the incidence of pneumonia and up to 28% of patients receiving mechanical ventilation will develop this complication. Its development is associated with an attributable increase in morbidity and mortality. The establishment of an accurate diagnosis of ventilator associated pneumonia remains problematic and as yet there is still no accepted "gold standard" for diagnosis. The responsible pathogens vary according to case mix, local resistance patterns, and methodology of sampling. However, there is general agreement that rapid initiation of appropriate antimicrobial therapy improves outcome.

Embryonic Testicular Regression Syndrome Presenting as Primary Amenorrhea: A Case Report and Review of Disorders of Sexual Development.

BACKGROUND: Sex development depends on the synchronous interaction of complicated genetic and hormonal events. Sex differentiation begins with sex determination, which is the assignment of the embryonic bipotential gonads as either testes or ovaries on the basis of transcriptional regulation. Hormonal regulation then directs the development of the male or female phenotype. Disruptions of this intricate cascade of events result in disorders of sexual development. CASE: A 16-year-old female adolescent presented with primary amenorrhea. Evaluation revealed female external genitalia, XY karyotype, absent gonadal tissue, and rudimentary Müllerian structures. On the basis of her constellation of findings, the most logical diagnosis was the rare embryonic testicular regression syndrome. SUMMARY AND CONCLUSION: A careful understanding of embryonic sexual development is critical to the evaluation of patients with disorders of sexual development.

Synaptic heterogeneity and stimulus-induced modulation of depression in central synapses.

Short-term plasticity is a pervasive feature of synapses. Synapses exhibit many forms of plasticity operating over a range of time scales. We develop an optimization method that allows rapid characterization of synapses with multiple time scales of facilitation and depression. Investigation of paired neurons that are postsynaptic to the same identified interneuron in the buccal ganglion of Aplysia reveals that the responses of the two neurons differ in the magnitude of synaptic depression. Also, for single neurons, prolonged stimulation of the presynaptic neuron causes stimulus-induced increases in the early phase of synaptic depression. These observations can be described by a model that incorporates two availability factors, e.g., depletable vesicle pools or desensitizing receptor populations, with different time courses of recovery, and a single facilitation component. This model accurately predicts the responses to novel stimuli. The source of synaptic heterogeneity is identified with variations in the relative sizes of the two availability factors, and the stimulus-induced decrement in the early synaptic response is explained by a slowing of the recovery rate of one of the availability factors. The synaptic heterogeneity and stimulus-induced modifications in synaptic depression observed here emphasize that synaptic efficacy depends on both the individual properties of synapses and their past history.

Autoimmune neutropenia in Hodgkin's disease.

A patient was profoundly neutropenic at the time of diagnosis of stage IIIB Hodgkin's disease. The neutropenia was not due to infection or bone marrow involvement by tumor. It did not respond to discontinuation of medication or to splenectomy, done for pathologic staging of Hodgkin's disease. The patient's serum contained abnormally increased granulocyte-binding antibody, which reacted with his own cells. The neutropenia resolved with high-dose prednisone therapy, and has not recurred after chemotherapy. Thus, immune neutropenia--as well as autoimmune hemolytic anemia and immune thrombocytopenic purpura--can be associated with Hodgkin's disease. Recognition and treatment of such immune processes assume major importance in planning cytotoxic therapy for the underlying malignancy.

Single-strand nuclease action on heat-denatured spermiogenic chromatin.

The aim of this study was to compare the sensitivity of chromatin from representative cellular stages of spermiogenesis to a single-strandeded nuclease after heat denaturation. Thermal denaturation of chromatin was assayed in situ in fixed round, elongating and elongated spermatids and in testicular sperm from mice. Production of single-stranded deoxyribonucleic acid (DNA) at elevated temperatures was monitored by digesting chromatin with endonuclease specific for single-stranded DNA (S1 nuclease), staining the residual DNA with gallocyanin-chrome alum (GAC) and measuring the stain content by absorption cytophotometry. Changes in GCA staining were minimal over the temperature range of 22-90 degrees C in each cell type not exposed to nuclease. Staining of undigested cells decreased progressively with advancing cell maturity. Nuclease had no effect on the GCA content of round spermatids below 60 degrees C, but above this temperature there was a progressive decrease in GCA-stainable chromatin. Both round and elongating spermatid stages showed a significantly greater sensitivity to nuclease digestion than did more mature stages; sperm showed no effects of nuclease action below 80 degrees C. Progressive chromatin condensation and a concomitant decrease in the number of available DNA phosphate groups during spermiogenic cell maturation may be responsible for the observed decline in sensitivity to nuclease and decreased GCA staining. Thermal denaturation of round spermatids labeled with 3H-thymidine produced no change in autoradiographic mean nuclear grain counts, indicating no loss of thymidine-labeled DNA from the slides during denaturation. When round spermatids and sperm were hydrolyzed with hot tricholoroacetic acid before staining, both nuclear GCA content and autoradiograph grain count were partially reduced, indicating incomplete DNA removal. Almost complete loss of Feulgen-stainable material occurred in these cells and may be due to depurination and elimination of Feulgren-reactant aldehyde groups.

Spontaneous fluctuations in pupil size are not triggered by lens accommodation.

Fluctuations in pupil size and lens accommodation are measured concurrently under open loop conditions, constant illumination and far fixation. In 12/17 trials no correlation was measured between the fluctuations in pupil size and lens accommodation. For the remaining 5/17 trials no lag was observed between the changes in pupil size and lens accommodation indicating that this correlation does not arise as a consequence of a near response. These observations suggest that under conditions of constant illumination and far fixation, the supranuclear centers controlling the near response are not active.

Circadian variation in alloxan sensitivity of mice as indicated by mortality and blood glucose alteration.

The objective of this study was to determine in mice if a time-dependent pancreatic beta-cell susceptibility to alloxan could be correlated to daily changes in blood glucose levels and to monitor the pattern of blood glucose at various times of day as mice became diabetic. Food was removed from mice standardized to a 12-h light:dark cycle (lights on at 0600 h CST, during the month of June) at 12 h before subcutaneous injection with 0.27 mg/g of alloxan. Six groups of 30 fasted mice were injected at 4-h intervals. Blood glucose levels were measured from each group immediately prior to injection, and at 2, 4, 8, 12, 24, 48, and 216 h after treatment. Animals receiving alloxan during the early- to middark period had an increase in blood glucose after 2 h, followed by a decline to hypoglycemic levels between 4 and 8 h, and recovery to hyperglycemic levels 48 h after alloxan exposure. Three and 30% of these animals were dead at 8 and 48 h, respectively. Mice treated during the midlight span had decreased blood glucose levels 2 h after alloxan treatment followed by an increase to diabetic hyperglycemia within 48 h. Twenty-three and 70% of the animals treated at 1430 h were dead at 8 and 48 h, respectively. At 216 h, total mortality was 45.6% and 81 of the 98 surviving mice were hyperglycemic. These data suggest a greater sensitivity to alloxan during the midlight resting period of the mice. This may be the result of increased sensitivity to the insulin released from the beta cells when alloxan was given during the light span.

Magnetic resonance imaging in macromelia and macrodactyly.

We report five cases presenting with soft tissue and bone overgrowth that demonstrate the ability of MRI to establish a diagnosis in the absence of specific clinical features. Disorders included macrodystrophia lipomatosa, angiolipomatosis, Klippel-Trenaunay-Weber syndrome, blue rubber bleb naevus syndrome and one case of segmental limited hypertrophy. The MRI appearances, and other radiological features of these conditions are discussed. MRI is recommended in all cases of macrodystrophy when the clinical features and plain film findings are indeterminate.

The radiological appearances of small cell (oat cell) carcinoma of the oesophagus.

We present three patients with primary small cell (oat cell) carcinoma of the oesophagus from a clinical and radiological point of view and review the radiological appearances of previously reported cases. The features of this rate neoplasm are variable, but extensive circumferential oesophageal wall thickening associated with luminal widening should raise the possibility of this diagnosis.

Spinal cord injury in youth.

To identify special characteristics of the pediatric spinal cord-injured (SCI) population, we analyzed a database of 1,770 traumatic SCI patients; 88 (5%) fell into the two pediatric subgroups: 0-12 years (n = 26) and 13-15 years (n = 62) at time of injury. Differences between age groups were identified with regard to demographics, neurologic characteristics, associated injuries and complications, and management. Mode level of bony injury was C2 in preteens, C4 in teens, and C4-C5 in adults. Scoliosis developed far more frequently in children, particularly preteens (23%), than in adults (5%). Violent etiologies, predominantly gunshots, accounted for a disproportionate share of injuries to preteens (19%) and African-Americans (28%), as compared with adults (12%) and Caucasians (7%). This last finding underscores the urgent need to mount a response to the nationwide proliferation of gunshot-related SCI in children and minorities.

Minor morbidity after day-case surgery.

The number of patients and procedures considered suitable for day-case anaesthesia and surgery continues to grow and it is hoped that 50-60% of all operations in the UK will eventually be performed on a day-patient basis. However, minor but troublesome post-operative side effects remain common. We have examined the incidence of the most common causes of minor morbidity, namely headache, nausea/vomiting and pain occurring after a wide variety of day-case surgical and diagnostic procedures. Patient satisfaction with treatment and the impact of day case surgery on the workload of the general practitioner was also assessed. The anaesthetic records of the patients involved were reviewed in an attempt to determine if there was any association between the anaesthetic technique and an adverse outcome. A simple postal questionnaire completed on the morning after surgery was returned by 553 patients (response rate over 87%). More than 50% of respondents complained of some morbidity, with 40% complaining of pain, 19% of headache and 9% of nausea and vomiting. One third self-medicated to modify their symptoms, and in most cases (81%) this was effective. However, 6% of patients called their GP for advice and 2% received a home visit. No patient required readmission. A total of 92 patients (17%) would have preferred treatment as an in-patient. Analysis of the anaesthetic drugs and techniques suggested that the commonly used anti-emetics droperidol and metoclopramide had little effect on the incidence of postoperative nausea and vomiting. Intubation was associated with a significantly higher incidence of minor morbidity although this may be related to surgical factors.

Effects of anaesthesia on the human immune system.

The ability of certain anaesthetic agents to influence the immune response has been recognized for almost 30 years. The purpose of this review is to briefly describe the different components of the immune system and examine the way in which surgery and anaesthesia influence these.

Anaesthetic management of the morbidly obese patient.

Morbidly obese patients are prone to many clinical conditions that can effect anaesthesia. Of major concern to the anaesthetist are difficulties with airway management and abnormalities of cardiorespiratory function. Safe anaesthesia requires an appreciation of potential problems and a thorough understanding of the pathophysiological changes that accompany morbid obesity.