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.     

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.     

Early Postnatal Changes in the Somatodendritic Morphology of Ankle Flexor Motoneurons in the Rat

The development of locomotor function in the rat spans the first 3 postnatal weeks. We have studied morphological features of the soma and dendrites of motoneurons innervating the physiological flexor muscles of the ankle, tibialis anterior and extensor digitorum longus, by intracellular injection in vitro between the first and ninth postnatal days. We obtained serial optical sections of 96 adequately filled motoneurons in whole-mounted hemisected spinal cords by confocal microscopy, projected them onto a single plane and analysed them morphometrically. On the day after birth, the somatodendritic surfaces of most such motoneurons were covered in growth-associated spiny, thorny or hair-like appendages. These had disappeared from the soma by the fourth postnatal day and from most proximal dendrites by day 7, but were still common distally on day 9. During this period there was little or no net growth of either the soma (which was still much smaller than in the adult) or the dendritic tree. A dorsal dendritic bias was present and 'sprays' of long, loosely bundled dorsal dendrites were often seen. The mean number of primary dendrites remained constant at about eight, and their combined diameter was already significantly correlated with mean soma diameter, as in the adult cat. Thus, the critical neonatal period during which these ankle flexor motoneurons are known to change their electrophysiological properties and to be particularly sensitive to interference with neuromuscular interaction is characterized by major changes in the neuronal surface, presumably linked to synaptogenesis.     

Induction of Leydig cell adenomas by ammonium perfluorooctanoate: a possible endocrine-related mechanism.

Ammonium perfluorooctanoate (C8) produced an increased incidence of Leydig cell adenomas in Crl:CD BR (CD) rats fed 300 ppm for 2 years. A hormonal (nongenotoxic) mechanism was examined since C8 was negative in short-term tests for genotoxicity. Adult male CD rats were gavaged with either 0, 1, 10, 25, or 50 mg/kg C8 for 14 days. In addition, a control group was pair-fed to the 50 mg/kg C8 group. A dose-dependent decrease in body and relative accessory sex organ (ASO) weights was seen, with the relative ASO weights of the 50 mg/kg group significantly less than those of the pair-fed control. Serum estradiol levels were elevated in the 10, 25, and 50 mg/kg C8-treated animals. Estradiol levels in the 50 mg/kg C8 group were 2.7-fold greater than those in the pair-fed control. The increase in serum estradiol levels occurred at the same dose levels as the increase in hepatic beta-oxidation activity. A statistically significant downward trend with dose was seen in serum testosterone levels when compared with the ad libitum control. However, when the 50 mg/kg C8-treated rats were compared with their pair-fed control, no significant differences were seen. Challenge experiments, which can identify the presence and location of a lesion in an endocrine axis, were undertaken to clarify the significance of this downward trend in serum testosterone following C8 exposure. In the challenge experiments, adult CD rats were gavaged with either 0 or 50 mg/kg C8 for 14 days. One hour before termination, rats received either a human chorionic gonadotropin (hCG), gonadotropin-releasing hormone (GnRH), or naloxone challenge. Following hCG challenge, serum testosterone levels in the 50 mg/kg C8 were significantly decreased (50%) from those in the ad libitum controls. Similar decreases, although not significant, were seen in serum testosterone following GnRH and naloxone challenge. The challenge experiments suggest that the decrease in serum testosterone following C8 exposure is due to a lesion at the level of the testis. In addition, progesterone, 17 alpha-hydroxyprogesterone, and androstenedione were examined in the 50 mg/kg C8-treated males following hCG challenge. A 60% decrease was observed in androstenedione levels in the C8-treated animals from those in the ad libitum controls; no other differences were seen. These data suggest that the decrease in serum testosterone following hCG challenge may be due to a decrease in the conversion of 17 alpha-hydroxyprogesterone to androstenedione. The observed effects described above can be attributed to the elevated serum estradiol levels.(ABSTRACT TRUNCATED AT 400 WORDS)     

Residents can be trained to detect abdominal aortic aneurysms using personal ultrasound imagers: a pilot study.

Our objective was to test the hypothesis that internal medicine residents can be trained to screen for abdominal aortic aneurysm (AAA) using personal ultrasound imagers. We trained 5 randomly chosen internal medicine residents to image the abdominal aorta for patients with risk factors for AAAs using personal ultrasound imagers. Residents were trained in 3 or 4 one-on-one sessions with an instructor. To be eligible, patients had to be older than 65 years and have hypertension. After training, each of the 5 residents studied 3 patients independently. In 12 of the residents' 15 unsupervised studies, their abdominal aorta measurements were within 5 mm of the instructor's measurements with standard echocardiography (mean difference 3 mm, range 0-6 mm). Residents detected 3 previously unknown AAAs measuring 5.2, 4.2, and 3.9 cm in diameter. We conclude residents can be trained to image the abdominal aorta with personal ultrasound imagers and to identify AAAs in patients at risk.