GABA(A) alpha 1 subunit knock-out mice do not show a hyperlocomotor response following amphetamine or cocaine treatment.

The GABA(A) receptor system provides the major inhibitory control in the CNS, with the alpha 1 beta 2 gamma 2 subunit combination being the most abundant and widely distributed form of the receptor. The alpha1 subunit knock-out (alpha1 KO) mice had a surprisingly mild overt phenotype, despite having lost approximately 60% of all GABA(A) receptors. The alpha1 KO mice had normal spontaneous locomotor activity, but were more sensitive to the sedating/ataxic effects of diazepam than wildtype (WT) mice. Pharmacological modulation of dopamine and N-methyl-D-aspartate (NMDA) receptors also produced altered responses in alpha1 KO mice compared with WT mice. As expected, the NMDA receptor antagonist MK801, amphetamine and cocaine increased locomotor activity in WT mice. Although MK801 increased locomotor activity in alpha1 KO mice, amphetamine and cocaine induced stereotypy not hyperlocomotion. Binding studies showed no gross changes in the total number of D1, D2 or NMDA receptors. Furthermore, pre-pulse inhibition of acoustic startle and the effects of cocaine in conditioned place preference were similar in both alpha1 KO and WT mice, indicating selective rather that global changes in response to dopaminergic agents. These data demonstrate subtle changes in behaviours mediated by neurotransmitters other than GABA in alpha1 KO mice and suggest that compensation may have occurred beyond the GABAergic system.

The myotoxicity of bupivacaine, a 31P n.m.r. investigation.

Phosphorus nuclear magnetic resonance (n.m.r.) spectroscopy is a recently introduced method for the non-invasive study of muscle biochemistry. It was shown in the rat that an intramuscular injection of the drug resulted in degeneration that was reflected spectroscopically in a progressive decrease in the intracellular concentrations of phosphocreatine and adenosine triphosphate without a corresponding rise in that of inorganic phosphate. Furthermore, ATP was depleted in the presence of significant levels of phosphocreatine. As regeneration occurred spectra returned to normal and this was complete by day 10. No such spectroscopic effects were demonstrated in man following the use of bupivacaine in an intravenous regional anaesthetic. It is suggested that further studies in man are required before this drug can be administered intramuscularly with confidence.

An in vivo study of muscle phosphate metabolism in Becker's dystrophy by 31P NMR spectroscopy.

The forearm flexor muscles of five patients with Becker's dystrophy were examined by the painless and noninvasive technique of high resolution phosphorus nuclear magnetic resonance spectroscopy. In the mildly affected cases, the ratios of the signals of phosphocreatine to ATP and to inorganic phosphate were normal but they were reduced in the patients with advanced disease. Absolute quantitation under the conditions of the study was not feasible, but it was probable that whereas in advanced Becker's dystrophy the intramyocellular concentration of phosphocreatine was reduced, that of ATP was unchanged. The intramyocellular pH was normal in three of the four patients in whom this could be measured and an additional unidentified signal between those of phosphocreatine and inorganic phosphate was recorded in two patients. This study emphasizes some metabolic similarities between Becker's and Duchenne type muscular dystrophy and suggests that nuclear magnetic resonance spectroscopy may be a useful and objective technique with which to investigate the biochemistry of these and other muscle diseases.

Thyrotropin-releasing hormone action in the preoptic/anterior hypothalamus decreases thermoregulatory set point in ground squirrels.

Earlier work has shown that thyrotropin releasing hormone (TRH) produces dose-dependent decreases in body temperature (Tb) and metabolic rate when microinjected into the dorsal hippocampus (HPC) or preoptic/anterior hypothalamus (PO/AH) of awake ground squirrels. This study employed a behavioral paradigm to investigate the possibility that TRH-induced hypothermia is associated with a decrease in thermoregulatory set point. Six animals were successfully trained to press a bar for radiant heat escape and cool air reinforcement in order to obtain a cooler ambient temperature (Ta). During experimental testing, the animals were microinjected remotely with TRH (10-1000 ng/microliters) or a control solution (sterile saline or TRH-OH) into the PO/AH. The micro-injections were delivered via bilateral injection cannulae inserted through chronic bilateral cannula guides that had been stereotaxically implanted under pentobarbital anesthesia. Cumulative and time-integrated bar presses were obtained on a computer generated display. Tb, measured in the brain via a bead-type thermistor, and chamber Ta were recorded continuously. Following TRH administration, a significant increase in mean bar-press rate was observed during the period in which Tb was falling, when compared to a comparable time period just prior to the microinjection. These findings complement results obtained from four animals that were trained to press a bar for heat reinforcement in a cold (- 10 degrees C) environment. In this alternative behavioral paradigm, microinjection of TRH into the PO/AH or HPC induced a decrease in mean bar-press rate as Tb was falling. The results support the hypothesis that TRH-induced hypothermia in golden-mantled ground squirrels is achieved by lowering thermoregulatory set point.

Medial and lateral wall decompression for thyroid ophthalmopathy.

A two-wall decompression of the orbit, consisting of removal of the medial and lateral walls, was successful in eight patients with thyroid ophthalmopathy. The lateral wall was by removed by using the standard orbitotomy technique in addition to enlarging the space with a pneumatic burr, and the medial wall was removed through a direct medial canthal incision. Two patients had optic neuropathy, one had intermittent subluxation of the globe, and five had symptoms of exposure or increased pressure in the orbital area. In our eight patients, the two with optic neuropathy improved, the patient with subluxation of the globe became asymptomatic, and the other five had less exposure and were more comfortable. The amount of decompression ranged between 4 and 7 mm. The lacrimal sac was injured in one patient; temporary silicone intubation avoided any permanent sequela.

Measuring the relationship between income and NHEs (national health expenditures).

This article uses recently published time series data for the Organization for Economic Cooperation and Development countries to estimate income elasticities for health care expenditures. Several different models and alternative specifications are examined to determine the sensitivity and robustness of the estimated relationships. Income is the dominant-determinant of health care spending and longrun income elasticity for health care is significantly greater than unity. This implies that health care is a luxury good, and expenditures will tend to rise with the level of national income. There is little evidence that the degree of public finance reduces the level of health care expenditures.

US Medicaid drug formularies: do they work?

Does the use of a restricted drug formulary achieve cost savings within state Medicaid programmes? Restricted formularies are often justified by putting forth the attributes of a perfectly operating and implicitly costless policy. Analysis suggests, however, that the operation of 'actual' restricted formularies produce realised effects that are substantially at odds with the desired effects. Although the implementation of a restricted formulary can reduce a state's drug expenditures, service substitution causes expenditures to increase elsewhere in the system. Furthermore, direct savings in the drug budget are completely offset by these spillover effects.

Synovial fluid lactate and the diagnosis of septic arthritis.

To assess the value of synovial fluid lactate estimation in the diagnosis of septic arthritis, 238 specimens received for routine culture and 75 reference samples were examined using a rapid enzyme technique. Samples were collected without special treatment and the effect of delay in transport to the laboratory investigated. Raised levels were found in all cases of untreated septic arthritis, in six out of ten partially treated patients and in 19 out of 219 non-septic fluids. Special treatment of the sample was unnecessary if it was examined within six hours of aspiration. The predictive value of a negative result was 98 per cent and the value of the test appeared to be in the rapid exclusion of sepsis in untreated patients.

Complications of intra- and peri-articular steroid injections.

A prospective study was conducted to investigate the possible complications associated with intra- and peri-articular steroid injections. Data are presented on 1147 injections performed on 672 patients out of a total of 688 consecutive patients attending an orthopaedic outpatient setting. It was found to be a safe procedure, with a very low complication rate, if performed while taking adequate precautions. This should encourage general practitioners to offer these injections in their surgeries.

Primary tumors of the axial skeleton. Experience of the Leeds Regional Bone Tumor Registry.

Primary tumors of the axial skeleton are rare and a survey of the Leeds Regional Bone Tumor Registry found them to constitute only 55 of the 1950 cases (2.8%). Chordoma was the most frequent tumor in the cervical and sacral regions as well as the most common diagnosis overall and osteosarcoma ranked second. Pain was the most frequent presenting symptom but over half the patients developed some neurological abnormality. In spite of treatment survival was poor in patients with malignant lesions or neurological involvement. The establishment of Bone Tumor Registries is the only way that sufficient data on large numbers of these rare tumours can be amassed to provide a valuable and otherwise unavailable source of information for research, education and service.

The effect of macrophage conditioned media on Leydig cell function.

Primary gonadal failure frequently occurs in male patients with serious illness. This has suggested that activation of the immune system may affect the endocrine function of the testis. Most previous studies have evaluated the effects of individual cytokines on testosterone (T) production but with conflicting results. The present study was performed to compare the effects on Leydig cell function of a mixture of cytokines found in macrophage conditioned media (MCM), with that of individual recombinant cytokines. The MCM was found to contain an acid stable, heat labile, 16.5 kD factor(s) which significantly decreased the production of testosterone (T), dihydrotestosterone (dHT), adenosine 3':5'-cyclic monophosphate (cAMP), and guanosine 3':5'-cyclic monophosphate (cGMP). The MCM had no effect on the specific binding of human chorionic gonadotropin (hCG) but decreased the activity of 3-beta-hydroxysteroid dehydrogenase (3-beta-HSD) (a regulated Leydig cell enzyme). Neither tumor necrosis factor alpha (TNF alpha) interleukin 1 alpha (IL1 alpha), interleukin 1 beta (IL1 beta), interleukin 2 (IL2), interleukin 6 (IL6), or human interferon alpha,beta (IFN alpha,beta) had a similar effect. These results show that the cytokines or other factor(s) contained in MCM are potent regulators of T production, which could be important in understanding the low serum T levels associated with serious illness.

Excision of the distal ulna in patients with rheumatoid arthritis.

The results of excision of the distal ulna in 34 wrists of 25 patients with chronic rheumatoid arthritis of the distal radio-ulnar joint were reviewed. Rest pain had been cured or relieved in 77%, pain on pronation-supination in 86%, and limitation of pronation-supination in 90%, while 88% of the patients graded the result as excellent or fair. Despite this marked relief of symptoms, function of the upper limb was improved in only 25% of patients and remained unchanged in 60%. Ulnar subluxation of the carpus had occurred in 24% but seemed to be related to the destructive disease process rather than to the operation itself. The length of ulna resected was not related to the outcome of the operation.

Metabolic effects of tourniquet ischaemia studied by nuclear magnetic resonance spectroscopy.

A model of tourniquet ischaemia was developed in the hind limb of the rat, and the metabolic changes that occurred in the calf muscles were monitored by the non-invasive technique of phosphorus-31 nuclear magnetic resonance spectroscopy. During ischaemia the intramyocellular pH became acidic as the level of phosphocreatine declined and that of inorganic phosphate rose. Phosphocreatine was no longer detectable after approximately 2 hours and ATP was depleted after approximately 3.5 hours. Metabolic recovery was rapid (1 hour) if ATP was present when the tourniquet was released but was prolonged (3 or more hours) if ATP was depleted. Hourly release of the tourniquet for 10 minutes ensured the maintenance of ATP and rapid metabolic recovery. Release for intervals of only 5 minutes did not have the same protective effect and in fact worsened tissue pH during the period of tourniquet ischaemia. Heparin and corticosteroids were without effect during and after periods of tourniquet ischaemia.

A safe and effective low pressure tourniquet. A prospective evaluation.

An unusually wide pneumatic tourniquet has recently become available; we provide a simple formula for its use with a low but effective inflation pressure. A prospective, randomised and controlled trial in 600 lower limb and 150 upper limb operations is reported. The wide tourniquet (12.5 cm) was as effective at low pressure as was a conventional tourniquet (9 cm) inflated to significantly higher pressures. Fewer patients suffered from painful paraesthesiae after operation using the broad, low-pressure tourniquet.

The Gotfried percutaneous compression plate compared with the conventional classic hip screw for the fixation of intertrochanteric fractures of the hip.

We performed a randomised, prospective trial in 111 patients with intertrochanteric fractures of the hip comparing the use of the Gotfried percutaneous compression plate (PCCP) with that of the classic hip screw (CHS). Blood loss and transfusion requirement were less in the PCCP group but the operating time was significantly longer. The complication rate after operation was similar in both groups, and at a minimum follow-up of six months there was no difference in the rates of fracture healing or implant failure. The PCCP gives results which are similar to those obtained with a conventional device. Its suggested advantages seem to be theoretical rather than practical and, being a fixed-angle implant, it is not universally applicable.

The three-dimensional anatomy of the proximal femur in Perthes' disease.

A new method of recording the three-dimensional anatomy of the proximal femur from a single anteroposterior radiograph is described. This technique shows that in Perthes' disease the femoral head and neck are in significant anteversion and true varus. This anatomical configuration may be important in the pathogenesis and treatment of this disorder.

Leukergy--a new diagnostic test for bone infection.

This new blood test for infection is based on the phenomenon of leukergy in which white cells agglomerate in the peripheral blood of patients with inflammatory diseases. It was used in 26 patients with proven bone or joint infection and was positive in 25. The leukergy test was more accurate than the ESR, white cell count or blood culture. The percentage of cells agglomerated correlated with the clinical severity of the infection and the test detected reactivation of the septic process better than the other haematological tests. It is a rapid and inexpensive method which is useful in the diagnosis and management of bone and joint infections.

Brachial plexus anaesthesia for upper limb surgery: a review of eight years' experience.

1248 supraclavicular brachial plexus blocks and 665 axillary plexus blocks were administered to 1913 patients undergoing upper limb surgery. Plexus block alone was successful in 83.5%. In a further 11.4% of cases, adequate anaesthesia was obtained following augmentation by other regional or local techniques. This resulted in an overall success rate of 94.9% and general anaesthesia was required in only 5.1%. The two percutaneous approaches to the brachial plexus did not differ in their success-rates but clinically apparent pneumothorax occurred in 0.8% of supraclavicular blocks. Brachial plexus block anaesthesia is recommended as a safe and satisfactory alternative to general anaesthesia for upper limb surgery.

Repair of acute rupture of the Achilles tendon: a new technique using polyester tape without external splintage.

INTRODUCTION: A new method of treating acute rupture of the Achilles tendon using polyester tape is reported. This requires no postoperative splintage, allows earlier mobilisation and prompt return to work and sport. PATIENTS AND METHODS: Thirty patients were reviewed prospectively and at a mean of 3 years from surgery. RESULTS: The average time of return to work, full weight-bearing and to driving was 40 days, 45 days and 49 days, respectively. The average time for return to sport was 122 days. Three patients required further surgery, two for infected wounds and one for scar release. There was one sural nerve injury. Twenty-two patients regained a normal range of ankle and subtalar movement, with the mean power of plantar flexion 84% of the opposite side. Of the 22 patients who played sport, 14 were still performing at the same or a higher level. There were no re-ruptures over this period. CONCLUSIONS: The technique is straightforward and avoids splintage. It also conveys other short- and long-term advantages over more established methods.

Prospective randomised study of an orthopaedic geriatric inpatient service.

A randomised controlled trial of two management regimens was carried out in women patients over 65 years of age with hip fractures. Ninety seven patients were admitted to a designated orthopaedic geriatric unit and 125 to orthopaedic wards. No difference was observed in mortality, length of stay, or placement of patients between the two groups. More medical conditions were recognised and treated in patients in the orthopaedic geriatric unit group. It is concluded that designated orthopaedic geriatric units can provide medical care to these patients and should be administered without additional cost.