Biomechanics in orthopaedics: considerations of the hip and knee

This paper outlines concepts of mechanics used in orthopaedics. These concepts are then demonstrated (assuming only a basic understanding of physics) with relevance to the hip and knee, and used to explain some common conditions. Some equations are used in this article for completeness; they are not essential to understanding the core principles.     

Acetabular protrusion and the Monk Duopleet prosthesis in subcapital femoral neck fractures

A total of 166 patients with acute, displaced subcapital fractures of the femoral neck were treated over a 5-year period with the Monk Duopleet bi-articular prosthesis. The average age at operation was 77.8 years. 81 patients were available for review at an average of 37.1 months after surgery. Radiographic evidence of acetabular protrusion was found in 3 patients (3.7 per cent). This incidence of protrusion is considerably lower than that normally reported for one-piece prostheses such as the Austin Moore or Thompson. The causes of acetabular protrusion are discussed.     

ABC transporters of pathogenic fungi: recent advances in functional analyses]

ABC (ATP binding cassette) transporters consist of transmembrane domains which confer specificity, and structurally conserved nucleotide binding domains that contain highly conserved amino acid motifs. They act not only as transporters but also as receptors or channels that use energy generated by ATP hydrolysis. ABC transporters are widely dispersed in nature. They are found in cells ranging from prokaryotes (bacteria) to eukaryotes (including humans) and several are considered to play crucial roles in cellular homeostasis. Defects in ABC transporters in humans are associated with severe diseases such as type 2 diabetes and cystic fibrosis. Some ABC transporters extrude xenobiotics and confer resistance to chemotherapeutics on microbial pathogens and cancer cells. Thus ABC transporters are of considerable medical importance. Structure-function analysis of ABC transporters has begun to elucidate their mechanisms of substrate recognition, the functional regulation of ATP-binding and hydrolysis and to identify intrinsic physiological functions. In pathogenic fungi, ABC transporters contribute to the clinical problem of drug resistance. The application of new technologies to the examination of fungal ABC transporter function is providing new insights into the use of antifungal drugs in medical mycology and contributing to a better understanding of these important membrane proteins.     

Spontaneous regression of subcutaneous in‐transit malignant melanoma deposits of the lower leg after treatment with the carbon dioxide laser

Primary malignant melanoma (MM) is one of the few cancers that can show spontaneous regression, and although this is well described, the mechanisms behind this are unclear. Spontaneous regression of secondary metastatic deposits of melanoma is rare and there are only a handful of case reports supporting this phenomenon. We report a patient with in‐transit MM metastatic disease of the leg, who underwent carbon dioxide (CO₂) laser ablation, and subsequently developed remission of untreated deposits. We discuss the possible immunological mechanism for this phenomenon.     

Anisoylated plasminogen streptokinase activator complex (APSAC). A review of its mechanism of action, clinical pharmacology and therapeutic use in acute myocardial infarction

APSAC is a new thrombolytic agent with advantages over conventional therapy such as streptokinase. In particular, it is suitable for intravenous administration over 4 to 5 minutes, in contrast with the prolonged infusion required with intravenous streptokinase, thus facilitating treatment of acute myocardial infarction outside a coronary care unit. Additionally, its fibrinolytic action is theoretically selective for fibrin associated with thrombi, which should minimise systemic fibrinolysis. However, in practice, systemic fibrinolysis does occur to some extent in most patients, but clinically significant haemorrhagic complications are rare. At the recommended dose of 30U injected intravenously over a period of 4 to 5 minutes in patients with acute myocardial infarction of less than 6 hours' duration, reperfusion of occluded coronary arteries occurs in about 72% of patients (range 53 to 91% in individual studies). Subsequent reocclusion has been reported in 0 to 20% of patients in most studies, with an average reocclusion rate of around 10%. The reperfusion rate compares favourably with that reported for intracoronary streptokinase and has tended to be superior to that with intravenous streptokinase. Thus, APSAC is an important advance in thrombolytic therapy for patients with acute myocardial infarction. Of particular importance is its relative ease of administration, reducing the dependence on coronary care units with catheterisation facilities, and the associated costs and delays in implementing treatment. APSAC should result in effective thrombolytic therapy being rapidly introduced after acute myocardial infarction in a wider proportion of patients than was previously feasible.     

Hemodynamic effects of infusions of the emulsion formulation of propofol during nitrous oxide anesthesia in humans

The hemodynamic response to anesthesia with the aqueous emulsion formulation of propofol was studied in healthy patients (ASA I or II), aged 39-57 yr, premedicated with morphine, 0.15 mg/kg. Anesthesia was induced in all patients with propofol, 2 mg/kg. Subsequently, patients were randomly assigned to two groups and maintained by a continuous intravenous infusion (group 1 received 54 micrograms X kg-1 X min-1, group 2 received 108 micrograms X kg-1 X min-1) to supplement 67% nitrous oxide. Three minutes after induction, systolic arterial pressure (SAP) decreased 28% (P less than 0.01) and was associated with decreased (-12%) cardiac output (Q70) and decreased (-15%) systemic vascular resistance (SVR). The hemodynamic response to tracheal intubation was not obtunded, but peak values of arterial pressures and heart rate did not exceed those recorded awake. Thirty minutes elapsed before repeating measurements prior to the first surgical incision. In group 1, SAP and Q70 decreased to 65% and 68% of awake values and in group 2 to 55% and 74% (P less than 0.05). Mild ventilatory depression persisted for the duration of spontaneous ventilation and was not reduced by the stimulus of surgery, which caused no significant hemodynamic responses in either group. Decreasing arterial PCO2 to the awake value by controlled ventilation increased SVR (P less than 0.05), but the associated increased SAP and decreased Q70 did not reach statistical significance. No patient reported awareness. The infusion of the emulsion formulation of propofol was associated with satisfactory anesthesia and recovery and with hemodynamic effects similar to those recorded with other intravenous anesthetics.     

Functional magnetic resonance imaging neuroactivation studies in normal subjects and subjects with the narcoleptic syndrome. Actions of modafinil

Functional magnetic resonance imaging (fMRI) can be used to detect regional brain responses to changes in sensory stimuli. We have used fMRI to determine the amount of visual and auditory cortical activation in 12 normal subjects and 12 subjects with the narcoleptic syndrome, using a multiplexed visual and auditory stimulation paradigm. In both normal and narcoleptic subjects, mean cortical activation levels during the presentation of periodic visual and auditory stimulation showed no appreciable differences with either age or sex. Normal subjects showed higher levels of visual activation at 10:00 hours than 15:00 hours, with a reverse pattern in narcoleptic subjects (P = 0.007). The group differences in spatial extent of cortical activation between control and narcoleptic subjects were small and statistically insignificant. The alerting action, and imaging response, to a single oral dose of the sleep-preventing drug modafinil 400 mg were then determined and compared with placebo in both the 12 normal (8 given modafinil, 4 placebo) and 12 narcoleptic subjects (8 modafinil, 4 placebo). Modafinil caused an increase in self-reported levels of alertness in 7 of 8 narcoleptic subjects, but there was no significant difference between mean pretreatment and post-treatment activation levels as determined by fMRI for either normal or narcoleptic syndrome subjects given modafinil. However, in the modafinil-treated group of 8 normal and 8 narcoleptic subjects, there was a clock time independent correlation between the initial level of activation as determined by the pretreatment scan and the post-treatment change in activation (visual, P = 0.002; and auditory, P = 0.001). No correlation was observed in placebo-treated subjects (P = 0.99 and 0.77, respectively). Although limited by the small number of subjects, and the lack of an objective measure of alertness, the findings of this study suggest that low cortical activation levels in both normal and narcoleptic subjects are increased following the administration of modafinil. Functional magnetic resonance imaging may be a valuable addition to established studies of attention.