Macronutrient intake of dogs, self-selecting diets varying in composition offered ad libitum.

The diet of the domestic dog has changed significantly from that of its wolf ancestor, with to date only two studies having examined macronutrient self-selection in dogs. Whilst the first focused solely on protein intake, determining an intake of 30% metabolisable energy (ME), the second investigated dietary protein, fat and carbohydrate (PFC), indicating an intake ratio of 30:63:7% by energy. This study's aim was to further elucidate macronutrient intake by providing greater macronutrient range, energy content, and to investigate over a longer duration than previous studies. Fifteen adult dogs were given access to three wet diets providing 500% of daily ME, twice daily over 10 days. The diets were nutritionally complete and formulated using the same four ingredients in different proportions to supply high levels of protein (58% ME), fat (86% ME) or carbohydrate (54% ME). Overall fat and carbohydrate consumption significantly declined from 6,382 to 917 kcals per day (p < 0.001) and 553 to 214 kcals day-1 (p < .01) respectively. Protein intake, however, remained constant over the study and ranged from 4,786 to 4,156 kcals day-1 . Such results impacted on percentage total energy intake, with fat decreasing from 68% to 52% (p < .001) and protein increasing from 29% to 44% (p < .01). Our findings suggest that dogs still possess a "feast or famine" mentality, wherein energy dense fat is prioritised over protein initially. With continued feeding over 10 days, a transition to a more balanced energy contribution from both macronutrients is evident. The study also shows that given the option, dogs do not select carbohydrate to be a significant portion of the diet. The health implications of such dietary selection are of interest.

Aeromonas veronii biovar sobria bacteraemia with septic arthritis confirmed by 16S rDNA PCR in an immunocompetent adult.

An 81-year-old man developed septic arthritis and bacteraemia with Aeromonas veronii biovar sobria. Cultures of the joint wash-out fluid were negative; however, DNA matching that of Aeromonas veronii was identified by 16S rDNA PCR. The patient was successfully treated with a 4 week course of ciprofloxacin. No recognized risk factors were found.

Current understandings on the immunology of leishmaniasis and recent developments in prevention and treatment.

Leishmaniasis is a major tropical disease with a wide clinical spectrum of cutaneous, mucocutaneous and visceral involvement. Presentation is often varied and diagnosis can be challenging. The outcome of infection is determined by the parasite species and the host's immunological response. The CD4+ T helper cell is critical with animal models demonstrating that cure is associated with strong IFN-gamma, interleukin (IL)-2 and IL-12 responses in the absence of classical Th2 cytokines or IL-10. Prevention has focussed on vector control, control of animal reservoirs and efforts to develop a protective vaccine. Treatment options historically have relied on antimonials though agents with better tolerability and efficacy have been developed including amphotericin and the oral agent miltefosine. Drug resistance, human immunodeficiency virus and changes in vector epidemiology threaten recent advances. Renewed impetus led by the WHO is required to co-ordinate future international effort to develop new drugs and ultimately a vaccine.

The use of thalidomide in the treatment of intracranial tuberculomas in adults: two case reports.

We present two cases of tuberculous meningitis (TBM) in adults complicated by focal neurological deficits which showed progression whilst on steroids. In case 1 an MRI demonstrated multiple ring-enhancing lesions compressing the optic chiasm leading to a bitemporal hemianopia. After the introduction of thalidomide serial imaging and field perimetry at 6, 9, 12 and 24 months into treatment showed progressive improvement. In case 2, two months into anti-tuberculous treatment with steroids, the patient developed fluctuating right sided paralysis with the MRI demonstrating a large ring-enhancing mass encasing the left internal carotid and middle cerebral arteries. Thalidomide was introduced as an immunomodulatory adjunct and subsequently the patient made a complete neurological recovery. The immunomodulatory effects of thalidomide may have a role in the acute and chronic management of TBM complicated by intracranial tuberculomas.

Prolonged survival in AIDS-related progressive multifocal leucoencephalopathy following anti-retroviral therapy and cidofovir.

We describe the case of a 44-year-old man who developed sub-acute cerebellar ataxia due to AIDS-related progressive multifocal leucoencephalopathy (PML) caused by JC virus. Following treatment with highly active anti-retroviral therapy (HAART) and cidofovir, he made a marked neurological improvement and is leading an independent life 18 months after the diagnosis of PML. Early recognition of AIDS-related PML and treatment with HAART improves prognosis. Cidofovir, an inhibitor of viral DNA polymerase, appears to have an additive beneficial effect and should be considered especially in patients who fail to improve despite treatment with HAART and in patients who have a high JC virus load in CSF.

An analysis of imported infections over a 5-year period at a teaching hospital in the United Kingdom.

Background. Imported infections are an important cause of morbidity and mortality in the United Kingdom. Methods. A 5-year analysis of cases seen in a large teaching and district general hospital in the Eastern Region of the UK was performed using ward records correlated with Hospital coding data and Hospital Episode Statistics from the Department of Health. Results. A surprising number (301) and diversity of imported infections was diagnosed. Prophylactic measures were, where assessable, generally inadequate. Conclusions. These data warrant renewed efforts to educate travellers of the risks of infection acquired abroad. The continued rise in global travel along with emergence of new infectious diseases emphasises further the need for expanded infectious diseases services incorporating accessible travel advice services in the UK which are currently underprovided.

Modulation of recombinant small-conductance Ca(2+)-activated K(+) channels by the muscle relaxant chlorzoxazone and structurally related compounds.

Using the patch clamp technique we investigated the effects of the centrally acting muscle relaxant chlorzoxazone and three structurally related compounds, 1-ethyl-2-benzimidazolinone (1-EBIO), zoxazolamine, and 1,3-dihydro-1-[2-hydroxy-5-(triflu oromethyl)phenyl]-5-(trifluoromethyl)-2H-benzimidazol-2-one (NS 1619) on recombinant rat brain SK2 channels (rSK2 channels) expressed in HEK293 mammalian cells. SK channels are small conductance K(+) channels normally activated by a rise in intracellular Ca(2+) concentration; they modulate the electrical excitability in neurons and neuroendocrine cells. When applied externally, chlorzoxazone, 1-EBIO, and zoxazolamine activated rSK2 channel currents in cells dialyzed with a nominally Ca(2+)-free intracellular solution. The activation was reversible, reproducible, and depended on the chemical structure and concentration. The order of potency was 1-EBIO > chlorzoxazone > zoxazolamine. Activation of rSK2 channels by chlorzoxazone, 1-EBIO, and zoxazolamine declined at higher drug concentrations. Zoxazolamine, when applied in combination with chlorzoxazone or 1-EBIO, partially inhibited the rSK2 channel current responses, suggesting a partial-agonist mode of action. 1-EBIO failed to activate rSK2 channel currents when applied to excised inside-out membrane patches exposed to a Ca(2+)-free intracellular solution. In contrast, 1-EBIO activated rSK2 currents in a concentration-dependent manner when coapplied to the patches with a solution containing 20 nM free Ca(2+). NS 1619 did not activate rSK2 channel currents; it inhibited rSK2 channel currents activated by the other three test compounds or by high intracellular Ca(2+). We conclude that chlorzoxazone and its derivatives act through a common mechanism to modulate rSK2 channels, and SK channel modulation in the brain may partly underlie the clinical effects of chlorzoxazone.

Block of rat brain recombinant SK channels by tricyclic antidepressants and related compounds.

SK channels are small conductance, Ca(2+)-activated K(+) channels that underlie neuronal slow afterhyperpolarization and mediate spike frequency adaptation. Using the patch clamp technique, we tested the effects of eight clinically relevant psychoactive compounds structurally related to the tricyclic antidepressants, on SK2 subtype channels cloned from rat brain and functionally expressed in the human embryonic kidney cell line, HEK293. Amitriptyline, carbamazepine, chlorpromazine, cyproheptadine, imipramine, tacrine and trifluperazine blocked SK2 channel currents with micromolar affinity. The block was reversible and concentration-dependent. The potency differed according to chemical structure. In contrast, the cognitive enhancer linopirdine was ineffective at blocking these channels. Our results point to a distinct pharmacological profile for SK channels.

Localisation of bone-forming cells during fracture healing by osteocalcin immunocytochemistry: an experimental study of the rabbit tibia.

An immunocytochemical method was used to localise osteocalcin-producing cells during fracture healing in a rabbit model. In preliminary studies, tibial growth plates from young rabbits were used as a source of new bone formation, in order to determine the optimal tissue preparatory techniques. In the present study, a tibial shaft fracture was created in adult rabbits to study closed fracture healing. An indirect peroxidase method was used to stain paraffin-embedded tissue sections for osteocalcin. Osteocalcin-producing cells were positively identified at the periosteal and endosteal surfaces near the fracture site. Osteocalcin staining was not demonstrated in the surrounding soft tissues. At the interface between newly formed bone trabeculae and the cartilage layer within the callus, chondrocytic cells consistently showed localisation of osteocalcin. Within cartilaginous areas of the callus, some chondrocytes showed positive staining for osteocalcin. These cells were often seen in the proximity of blood vessels. The findings suggest that during fracture healing, under certain conditions, chondrocytes are capable of producing osteocalcin and thus could be considered capable of possible transformation into osteoblasts.

Prospective, multi-centre trial of mortality following general or spinal anaesthesia for hip fracture surgery in the elderly.

In a prospective randomized multi-centre study, the mortality following internal fixation surgery for fracture of the upper femur was investigated in 538 elderly patients allocated to receive subarachnoid blockade or general (narcotic-relaxant) anaesthesia. The 28-day mortality was 6.6% with subarachnoid, and 5.9% with general, anaesthesia. The difference was not significant (95% confidence limits: -3.5 to +4.8). At 1 year following surgery, the mortality was 20.4%. Increasing age, ischaemic heart disease, cardiac failure, preoperative arrhythmias and poor ASA status were all associated with increases in early and long term mortality. A delay to surgery of more than 24 h from admission was also associated with an increased 28-day mortality. Senile dementia and admission other than from the patient's own home, were factors associated with a poorer long term outcome. From the point of view of mortality, subarachnoid anaesthesia did not appear to confer any advantages over general anaesthesia in non-prosthetic surgery for hip fracture in the elderly.

Pituitary fossa injection with alcohol for widespread cancer pain.

Trans-sphenoidal injection of 95 percent dehydrated alcohol into the pituitary fossa was attempted in 10 patients to control pain associated with widely disseminated metastatic cancer. Significant pain relief was obtained in eight patients, some of whom had tumours not recognised as being hormone sensitive. Effects of pituitary destruction were easily managed, and there were few complications. There was no mortality directly attributable to the injection.

Responses of motoneurones to electrophoretically applied dopamine.

1. The effect of electrophoretically applied dopamine upon motoneurone excitability has been investigated. Field potentials originating from antidromically activated motoneurones were recorded from the ventral horn of the rat lumbar spinal cord. 2. Field potentials showed an increase in amplitude following electrophoretic application of dopamine. Dopamine was shown to be less potent than noradrenaline and 5-hydroxytryptamine in producing these changes. 3. Measurement of the transport number of dopamine suggest that the relatively low potency of dopamine cannot be attributed to differences in ionic mobilities between the amines. 4. Electrophoretic application of alpha-flupenthixol was shown to discriminate between dopamine and 5-hydroxytryptamine responses. Dopamine responses were profoundly reduced. 5. Electrophoretically applied alpha-flupenthixol also discriminated between dopamine and noradrenaline. Noradrenaline responses were consistently potentiated by alpha-flupenthixol. The possibility is discussed that dopamine may not merely be a precursor for noradrenaline in the rat spinal cord.

The value of anaesthesia training in the first two postgraduate years.

The value of an anaesthetic attachment during the first two postgraduate years is considered under three major headings, the value to the recent graduate, the value to the specialty, and the value to the community. The anaesthetic attachment offers all recent graduates an opportunity to perfect practical skills which should from part of the armamentarium of all doctors, and for some there is the option to acquire the ability to administer a safe anaesthetic. Exposure to the specialty at this time is important for recruitment to the specialist ranks.

Constant negative pressure: an adjunct in the treatment of gastroschisis.

Three cases of gastroschisis are described, managed surgically in the neonatal period by staged reduction employing a dacron reinforced silastic sac. All three cases were treated during the postoperative period with the application of constant negative pressure around the thorax and abdomen. Reduction of the eviscerated mass appeared to be accelerated and all three cases survived. The possible benefits of constant negative pressure around the thorax and abdomen in the treatment of gastroschisis are discussed.