The safety of patient-controlled sedation

We have investigated the safety of a previously described method of patient-controlled sedation in 100 healthy patients presenting for elective surgery. The device used 0.33-ml boluses of propofol (10 mg.ml⁻¹) infused over 6 s with no lockout. All patients attempted to put themselves to sleep by pressing a button on the hand-held device. The oxygen saturation, heart rate, sedation score and airway patency were noted every minute. When the patient stopped pressing the button, the anaesthetist took over the handset and continued pressing the button until the patient became unresponsive. The system allowed rapid sedation. Only five patients were still anxious after 2 min. After 3 min, no patient was still anxious and more than 70 patients had slurred speech. When they stopped pressing the button, 11 patients were judged oversedated, of whom two were unresponsive. One patient's oxygen saturation decreased transiently to 84%: no other patient's oxygen saturation decreased below 90%. There were no other significant changes. We conclude that the system studied works well but carries too high a risk of oversedation for unsupervised use.     

The relationship of the extrinsic blood supply to regeneration in graft reconstructed peripheral nerves

Median nerves of rats were reconstructed with conventional or vascular nerve grafts. After 2, 3 and 4 weeks, Allen Video-Enhanced Contrast, Differential Interference Contrast (AVEC-DIC) microscopy revealed axonal transport in most preparations, with varying degrees of myelination. Radio-isotope tracer was measured in the nerve. Two and 4 week measurements revealed no difference between the graft types. At 3 weeks the vascular graft group exhibited transport along the entire length of the nerve in contrast to a relatively abbreviated path length in the conventional graft group. Nerve conduction velocities (NCV) were measured proximal to, within and distal to the grafts. Three week NCV showed no difference between the graft types. The 4 week NCV revealed normal values in the vascular graft group at points distal to and within the graft. Significant slowing was seen in the conventional grafts at both points.     

The management of injuries--a review of deaths in hospital

A prospective review was undertaken of the management of 111 consecutive patients who died in hospital after admission for treatment of injuries. A standard set of data relating to each patient was reviewed by each member of a trauma death audit committee and then by the whole committee. Autopsy reports were available on all patients. Conclusions were drawn concerning defective aspects of patient management and possible avoidance of each death. Injury severity was assessed using the Trauma Score (TS) and Injury Severity Score (ISS). The possibly avoidable death (PAD) rate was 17%. The most common defects in management were related to inadequate fluid resuscitation and delays in definitive management. The greatest contributions to the PAD rate were from inadequate fluid resuscitation, delays and inadequate perception of the severity of injuries or significance of clinical deterioration. Increasing age was related to a higher frequency of PAD. PAD rate in the presence of severe head injury was 8%, but was 63% in the absence of a severe head injury. It is concluded that review of all trauma deaths is an achievable, beneficial and essential part of a hospital-based integrated trauma service. TS and ISS are not sufficiently sensitive to justify their use in selecting deaths for review. Improved blood volume replacement, earlier and more direct management and supervision by senior specialist staff, and elimination of causes of delay in patient management should all decrease the death rate from injuries particularly in patients without severe head injury.     

An evaluation of the mechanical failure modalities of a rotating hinge knee prosthesis

The clinical and metallurgical performance of 12 retrieved Noiles total knee prostheses was investigated. Clinical histories and serial roentgenograms were used in conjunction with the American Society for Testing and Materials (ASTM) standard implant retrieval and analysis techniques to assess device performance. All of the devices were removed because of implant loosening with pain, while two devices also had a late infection. The average time in situ for all devices was four years. Roentgenographically, all of the devices showed signs of progressive radiolucencies. Ten (83%) of the devices migrated proximally within the femur. A marked varus drift was observed in eight (67%) of the retrieved prostheses. Hypertrophy of the femoral cortex was observed in eight (67%) of the cases. Seventy-three percent of the polyethylene tibial stems exhibited extensive wear on the anterior and medial aspects of the articulating surface. Extensive wear was also seen on the anterior and extreme posterior aspects in 92% of the polyethylene tibial plateau bearings. This wear was a consequence of the migration of the femoral component leading to buttressing of the plastic components against bone or bone cement. This study indicates serious design flaws in the Noiles knee prosthesis that unless corrected would question the use of the device in either primary or revision knee surgery.     

Mesial temporal sclerosis and volumetric investigations

Volumetric MRI data acquisition permits reliable and accurate measurement of mesial temporal lobe structures. In normal subjects, these structures are very symmetric. A high degree of pathological specificity is associated with the finding of even minor volume asymmetries. Definition in this manner allows precise estimation of both absolute and relative volume differences, and precise anatomical localisation of volume loss within the hippocampus. There are good EEG and clinical correlates with the distribution of volume loss defined on MRI studies. Volumetric assessment is fast, reliable, non-invasive, and a relatively inexpensive component of the pre-operative work-up. It is the method of choice when imaging patients with clinical temporal lobe epilepsy undergoing pre-surgical evaluation. The finding of significant hippocampal volume asymmetry in a patient with clinical temporal lobe seizures being evaluated for epilepsy surgery may obviate the need for alternative sophisticated, invasive, or expensive investigative procedures. At our centre, such MRI allows "fast track" cases to proceed to surgery without further invasive investigations, and is likely to have a dramatic effect on pre-operative evaluation in most centres practising epilepsy surgery.     

Peribursal fat plane of the shoulder: anatomic study and clinical experience

A comprehensive anatomic and radiographic analysis of the peribursal fat plane in 12 cadavers confirmed that the fat plane seen on radiographs represents extrasynovial fat lining the subacromial bursa and documented the anatomic relations of the bursa. A three-part retrospective clinical evaluation of rotator cuff tears, calcific tendinitis, and rheumatoid arthritis was performed. Two osteoradiologists blindly graded the appearance of the peribursal fat plane with the shoulder in external versus internal rotation in 21 patients with arthrographically intact rotator cuffs and 21 patients with disrupted rotator cuffs. The peribursal fat plane was seen better with disrupted rotator cuffs. The peribursal fat plane was seen better with the shoulder in internal rotation and was seen in 60% of control subjects but only 21% of patients with rotator cuff tears. Partial or complete obliteration of this fat plane is a sensitive (79%) but less specific (60%) indicator of rotator cuff tears. Obliteration of the peribursal fat plane by inflammatory processes in adjacent tissues, including calcific tendinitis and rheumatoid arthritis, occurred with a high frequency.     

Evaluating food fortification options: general principles revisited with folic acid.

OBJECTIVES. This article uses folic acid as an example to illustrate some of the complex issues and general principles that emerge when evaluating fortification of the food supply as one possible means to address a public health recommendation. METHODS. Distributions of current daily folate intakes from conventional foods and dietary supplements were estimated. Intakes that might result from fortification of cereal-grain products and ready-to-eat cereals at various levels for eight age-gender groups were also estimated by using the US Department of Agriculture's 1987-1988 Nationwide Food Consumption Survey. RESULTS. The results illustrate that fortification of the US food supply tends to increase folate intakes of consumers at the high end of the intake distribution curves in the general population to a greater extent than it affects consumers at the low end of the intake distribution curves in the target population. CONCLUSIONS. The effectiveness of food fortification options for a target population and the safety for the general population impose conflicting challenges that must be considered concurrently when making decisions about fortifying the US food supply.     

Tumor targeting by an aptamer.

Aptamers are small oligonucleotides that are selected to bind tightly and specifically to a target molecule. We sought to determine whether aptamers have potential for in vivo delivery of radioisotopes or cytotoxic agents. METHODS: TTA1, an aptamer to the extracellular matrix protein tenascin-C, was prepared in fluorescent and radiolabeled forms. After in vivo administration, uptake and tumor distribution of Rhodamine Red-X-labeled aptamer was studied by fluorescence microscopy. In glioblastoma (U251) and breast cancer (MDA-MB-435) tumor xenografts, biodistribution and imaging studies were performed using TTA1 radiolabeled with (99m)Tc. Tenascin-C levels and tumor uptake were studied in a variety of additional human tumor xenografts. To assess the effect of radiometal chelate on biodistribution, mercapto-acetyl diglycine (MAG(2)) was compared with diethylenetriaminepentaacetic acid and with MAG(2)-3,400-molecular-weight PEG (PEG(3,400)). RESULTS: Intravenous injection of fluorescent aptamer TTA1 produced bright perivascular fluorescence in a xenografted human tumor within 10 min. In the ensuing 3 h, fluorescence diffused throughout the tumor. Labeled with (99m)Tc, TTA1 displayed rapid blood clearance, a half-life of less than 2 min, and rapid tumor penetration: 6% injected dose (%ID)/g at 10 min. Tumor retention was durable, with 2.7 %ID/g at 60 min and a long-lived phase that stabilized at 1 %ID/g. Rapid tumor uptake and blood clearance yielded a tumor-to-blood ratio of 50 within 3 h. Both renal and hepatic clearance pathways were observed. Using the (99m)Tc-labeled aptamer, images of glioblastoma and breast tumors were obtained by planar scintigraphy. Aptamer uptake, seen in several different human tumors, required the presence of the target protein, human tenascin-C. Modification of the MAG(2) radiometal chelator dramatically altered the uptake and clearance patterns. CONCLUSION: TTA1 is taken up by a variety of solid tumors including breast, glioblastoma, lung, and colon. Rapid uptake by tumors and rapid clearance from the blood and other nontarget tissues enables clear tumor imaging. As synthetic molecules, aptamers are readily modified in a site-specific manner. A variety of aptamer conjugates accumulate in tumors, suggesting imaging and potentially therapeutic applications.