Sirolimus enhances the magnitude and quality of viral-specific CD8+ T-cell responses to vaccinia virus vaccination in rhesus macaques.

Sirolimus is a potent antiproliferative agent used clinically to prevent renal allograft rejection. However, little is known about the effects of maintenance immunosuppressive agents on the immune response to potentially protective vaccines. Here we show that sirolimus paradoxically increases the magnitude and quality of the CD8+ T-cell response to vaccinia vaccination in nonhuman primates, fostering more robust recall responses compared to untreated and tacrolimus-treated controls. Enhancement of both the central and effector memory compartments of the vaccinia-specific CD8+ T-cell response was observed. These data elucidate new mechanistic characteristics of sirolimus and suggest immune applications extending beyond its role as an immunosuppressant.

A surgical approach to the upper thoracic spine.

We describe a surgical approach to the upper thoracic spine which allows an adequate exposure of the vertebral bodies from T1 to T3. The approach causes little functional disturbance and is especially useful in older patients with spinal tumours causing spinal cord compression.

Surgery for malignant extradural tumours of the spine.

We have reviewed 41 patients with malignant extradural tumours of the spine treated by anterior decompression for cord compression, or uncontrolled back pain or both. An anterior operation alone was performed in 37 cases, four had combined or staged anterior and posterior decompression. An anterior operation on its own achieved major neurological recovery in 18 of the 33 cases with neurological loss (56%); only four remained unchanged. Eleven had minor improvement but not enough to allow them to walk or to regain bladder function. No patient with complete paraplegia gained a useful neurological recovery. Back pain was improved in 30 of the 41 patients (73%), sound internal fixation being important in this respect. There were four early deaths and another 23 died from disseminated disease after a mean survival of 4.1 months. Fourteen patients are still alive with a mean survival of 14 months.

Circadian photoreception: ageing and the eye's important role in systemic health.

AIM: To analyse how age-related losses in crystalline lens transmittance and pupillary area affect circadian photoreception and compare the circadian performance of phakic and pseudophakic individuals of the same age. METHODS: The spectral sensitivity of circadian photoreception peaks in the blue part of the spectrum at approximately 460 nm. Photosensitive retinal ganglion cells send unconscious information about environmental illumination to non-visual brain centres including the human body's master biological clock in the suprachiasmatic nuclei. This information permits human physiology to be optimised and aligned with geophysical day-night cycles using neural and hormonal messengers including melatonin. Age-related transmittance spectra of crystalline lenses and photopic pupil diameter are used with the spectral sensitivity of melatonin suppression and the transmittance spectra of intraocular lenses (IOLs) to analyse how ageing and IOL chromophores affect circadian photoreception. RESULTS: Ageing increases crystalline lens light absorption and decreases pupil area resulting in progressive loss of circadian photoreception. A 10-year-old child has circadian photoreception 10-fold greater than a 95-year-old phakic adult. A 45-year-old adult retains only half the circadian photoreception of early youth. Pseudophakia improves circadian photoreception at all ages, particularly with UV-only blocking IOLs which transmit blue wavelengths optimal for non-visual photoreception. CONCLUSIONS: Non-visual retinal ganglion photoreceptor responses to bright, properly timed light exposures help assure effective circadian photoentrainment and optimal diurnal physiological processes. Circadian photoreception can persist in visually blind individuals if retinal ganglion cell photoreceptors and their suprachiasmatic connections are intact. Retinal illumination decreases with ageing due to pupillary miosis and reduced crystalline lens light transmission especially of short wavelengths. Inadequate environmental light and/or ganglion photoreception can cause circadian disruption, increasing the risk of insomnia, depression, numerous systemic disorders and possibly early mortality. Artificial lighting is dimmer and less blue-weighted than natural daylight, contributing to age-related losses in unconscious circadian photoreception. Optimal intraocular lens design should consider the spectral requirements of both conscious and unconscious retinal photoreception.

Strapping of curly toes in children.

This is a retrospective review of 49 children with curly toes treated by strapping; 24 children (44 toes) presented for review. The strapping produced improvement in 68% of toes while strapping was maintained, but there was a statistically significant loss of correction once strapping was stopped. There was some sustained improvement in the shape of the toes compared with the natural history, but not sufficient to warrant its use for this minor congenital deformity. Treatment should be reserved for the more severely deformed toe, as this may cause symptoms in later life, and the author recommends open flexor tenotomy.

Papillary adenocarcinoma arising in a thyroglossal cyst.

Carcinoma arising in a thyroglossal cyst is a rare but well-recognized condition. In this paper we present a further case of papillary adenocarcinoma arising in a thyroglossal cyst, and review the published experience of this condition.

A serine protease inhibitor, protease nexin I, rescues motoneurons from naturally occurring and axotomy-induced cell death.

Protease nexin I (PNI) is a member of the family of serine protease inhibitors (serpins) that have been shown to promote neurite outgrowth in vitro from different neuronal cell types. These include neuroblastoma cells, hippocampal neurons, and sympathetic neurons. Free PNI protein is markedly decreased in various anatomical brain regions, including hippocampus, of patients with Alzheimer disease. Here, we report that PNI rescued spinal motoneurons during the period of naturally occurring (programmed) cell death in the chicken in a dose-dependent fashion. Furthermore, PNI prevented axotomy-induced spinal motoneuron death in the neonatal mouse. The survival effect of PNI on motoneurons during the period of programmed cell death was not associated with increased intramuscular nerve branching. PNI also significantly increased the nuclear size of motoneurons during the period of programmed cell death and prevented axotomy-induced atrophy of surviving motoneurons. These results are consistent with the possible role of PNI as a neurotrophic agent. They also support the idea that serine proteases or, more precisely, the balance of proteases and serpins may be involved in regulating the fate of neuronal cells during development.

Outpatient treatment of upper extremity injuries in childhood using intravenous regional anaesthesia.

Intravenous (i.v.) regional anaesthesia was used in outpatient treatment of 400 upper extremity fractures and dislocations in children ranging in age from 3 to 16 years. All reductions were performed in the emergency department. Good analgesia was achieved in 90% of the patients, and only nine children (2.3%) had unacceptable reductions that required further treatment under general anaesthesia. Intravenous regional anaesthesia is a safe and effective procedure that facilitates outpatient treatment of upper extremity injuries in children.

Intravenous regional anaesthesia for the treatment of upper limb injuries in childhood.

A prospective study was made of the use of intravenous regional anaesthesia for the treatment of upper limb fractures and dislocations in 200 children aged from 3 to 15 years. An aqueous solution containing 5 mg/ml of lignocaine (0.5%) was administered in a dosage of 3 mg/kgm body weight, but dosages of 2 mg/kgm were used in each arm of a child with bilateral injuries. Intravenous regional anaesthesia was well tolerated and was a safe and effective method of treating these injuries in a casualty department with adequate resuscitation facilities and staff trained in the management of local anaesthetic toxicity.

Colorectal resection in Victoria:a comparison of hospital based and individual audit.

BACKGROUND: The results of personal audit have not been tested against a hospital-based audit previously and the results of two such audits of colorectal resection in the State of Victoria have provided this opportunity. In addition, data reflecting the results of colorectal resection across a range of hospitals and surgeons in the Victorian community have been obtained. METHODS: A total of 535 patients undergoing a colorectal resection, with an anastomosis performed, were studied in two serially conducted prospective audits arranged by the Standards Sub-Committee of the Victorian State Committee. One study was public hospital-based and the second was based on voluntary reporting by individual surgeons. RESULTS: Similar results were obtained in each study, demonstrating the accuracy of individual reporting. The combined results (wound infection rate 12.3%, anastomotic leak rate 3.7% and mortality 4.5%) are compared to previously published data. CONCLUSIONS: In the State of Victoria the results of audit by individual surgeons performing colorectal resection were similar to the hospital-based audit. The results obtained compare favourably with previously published data.

Clinical indicators in colorectal surgery.

Two studies conducted in the state of Victoria have tested potential clinical indicators and the suggested thresholds for resection of colorectal carcinoma where an anastomosis has been performed. These studies involving 535 patients were independent of one another: one hospital based and one surgeon based. Threshold figures for these draft indicators have been compared with the study figures and found to be similar. It is suggested that wound infection (elective operation without formation of a stoma), anastomotic leak (clinically recognized) and mortality (elective operations in patients under the age of 80 years) are the most appropriate clinical indicators of colorectal resection for carcinoma.