Ultrastructural pathology and cytochemical investigations of l-2-chloropropionic acid-induced neurointoxication of the rat cerebellum

The objectives of the studies described were to assess the ultrastructural neuropathology, blood-brain barrier (BBB) integrity and calcium status of the cerebellum of rats following a single dose of 750 mg · kg^–1 l-2-chloropropionic acid (l-2-CPA). The first indications of intoxication appeared at 36 h when condensation of many granule cells associated with Purkinje cell degeneration and marked astroglial swelling were observed. Some electron-lucent granule cells were also noted lying amongst these condensed forms. Condensed granule cells had swollen, electron-lucent mitochondria, dilated Golgi apparatus and nuclear crenation. Occasionally, areas of granule cell necrosis were also present at this time. Granule cell condensation probably represents a preliminary and irreversible stage in an excitotoxic process that leads to necrosis. At 48 and 72 h, most granule cells were necrotic, and occasionally, extravasation of both erythrocytes and leucocytes into the expanded extravascular space was observed. Evaluation of the BBB by ultrastructural cytochemical visualisation of horseradish peroxidase injected i.v. 2 min before killing by perfusion fixation showed substantial leakage. At 36 h post-dose, ultrastructural calcium localisation using oxalate/pyroantimonate precipitation demonstrated a substantial increase in calcium pyroantimonate precipitate in mitochondria and other membranous cytoplasmic organelles (especially the Golgi apparatus) in condensed granule cells, but with little in their nuclei. However, their immediate neighbours (of ostensibly normal ultrastructural appearances) contained greater amounts of intranuclear precipitate. Swollen astroglial cells (especially the Bergmann glia) contained considerable quantities of precipitate. A possible excitotoxic mechanism via l-2-CPA-induced NMDA receptor agonism leading to overwhelming calcium influx and disruption of cellular calcium homeostasis is proposed. Received: 8 May 1996 / Revised: 1 September 1996 / Accepted: 11 September 1996     

Technical and biological factors in disease-free survival after hepatic resection for colorectal cancer metastases.

Careful patient selection for hepatic resection of colorectal cancer metastases is essential to improve current poor results. Carcinoembryonic antigen level and number of metastases were significant preoperative prognostic indicators of 5-year disease-free survival in patients selected clinically for hepatic surgery. Surgical margin, weight of hepatic tissue resected, carcinoembryonic antigen level, and flow cytometry were significant postoperative prognostic indicators. Patients with a carcinoembryonic antigen level less than 200 ng/mL, 1-cm surgical margins, and less than 1,000 g of liver tissue removed had a greater than 50% estimated 5-year disease-free survival rate. If the metastases were diploid on flow cytometry, an additional survival advantage may have been gained. Inadequate surgical margins led to high rates of liver-only recurrence. Nonhepatic recurrence was unrelated to surgical margins. Intraoperative liver examination by ultrasound during primary colon cancer resection and adjuvant chemotherapy may offer earlier selection of biologically appropriate patients and improved outcome; both recommendations require clinical trials.     

Subclavian revascularization. A quarter century experience.

OBJECTIVE: Twenty-five years of experience with subclavian revascularizations were reviewed to determine the long-term patency rates of different extrathoracic approaches. SUMMARY BACKGROUND DATA: Although it is generally agreed that proximal subclavian stenosis should be treated by an extrathoracic route whenever possible, the optimum procedure is debated. Alternatives include subclavian carotid bypass, subclavian-to-subclavian or axillo-axillary bypasses, and the authors' preferred technique of subclavian carotid transposition (SCT). METHODS: Records were researched for the past 25 years in a single specialty surgical clinic for extrathoracic subclavian revascularizations. One hundred ninety such procedures were identified, and hospital charts and office medical records were reviewed for procedure, preoperative symptoms, blood pressure differentials, and postoperative complications. Patency was determined by physical examination, differential blood pressures, Doppler spectral analysis, duplex examinations, and arteriography. RESULTS: Bypass procedures were used infrequently, and although the results are reported, they are excluded from any analysis. Subclavian carotid transposition was used in 178 procedures. All anastomoses were found to be patient at follow-up, except for one, which failed at 26 months. Mean follow-up was 46 months, with five patients lost to follow-up. Overall mortality rate was 2.2%, with the mortality falling to 1.1% if only subclavian carotid transposition patients are included. CONCLUSIONS: Subclavian carotid transposition should be the treatment of choice for routine subclavian carotid occlusive disease because of its exceptional long-term patency and low morbidity.     

A Comparative Study of the Percutaneous versus Intraoral Technique for Mental Nerve Block

Objective: Mental nerve block is frequently used to aid repair of facial lacerations; both percutaneous and intraoral approaches to blocking this nerve are used, but have never been compared. The authors compared the two techniques for pain of administration and effectiveness of anesthesia. Methods: A prospective, randomized, single-blind, crossover study was conducted using ten healthy volunteers aged 22 to 33 years. Patients having prior experience with mental nerve blocks, lidocaine allergy, active oral/facial infection, or previous facial fractures were excluded. Bilateral mental nerve blocks were done using intraoral technique on one side and percutaneous technique on the other. Both techniques were used by the same investigator and were carried out with 27-gauge needles and 2.5 mL of 2% buffered lidocaine at room temperature injected over 20 seconds. The oral mucosa was topically anesthetized with viscous lidocaine for 1 minute prior to intraoral injection. The orders of the blocks and sides of the face anesthetized were randomized. Subjective and objective pain (visual-analog scale), efficacy (anesthesia of lower lip), time to onset, and duration of anesthesia were evaluated. Results: The intraoral technique was subjectively less painful than the percutaneous approach in nine of ten subjects (p = 0.02). Scores on the visual-analog pain scale were significantly lower for the intraoral technique (p = 0.03). Intraoral injection produced lower-lip anesthesia in 10/10 subjects versus 7/10 for percutaneous (p = 0.25). Times to onset (approximately 1–2 minutes) and durations of anesthesia (approximately one hour) were similar for the two techniques. Conclusion: The intraoral approach to the mental nerve block with adjunctive topical anesthesia was subjectively and objectively less painful than the percutaneous approach without adjunctive anesthesia. While the intraoral approach had a greater efficacy of lower-lip anesthesia and a longer duration of action, these differences were not statistically significant.     

‘You have to learn to live with it’: a qualitative and quantitative study of older people with asthma

Introduction: Asthma mortality has declined overall because of a range of public health initiatives. In western countries, the majority of asthma deaths now occur in people over the age of 50. The reasons for the poorer response of older age groups to public health asthma initiatives are not known. Objectives: We undertook a study to investigate the disease perspectives of older people with asthma and barriers which may exist and prevent optimal asthma care. Methods: Fifty‐five participants (16 male and 39 female) aged over 50 from an inner city, suburban area and a rural region were recruited. Lung function was measured, and questionnaire data on asthma symptoms, knowledge and control, medication use and respiratory health were collected. Participants were also interviewed in‐depth, and the quantitative and qualitative data were triangulated. Results: Participants with a duration of asthma for >30 years reported significantly fewer symptoms and better quality of life irrespective of asthma severity, indicating less appreciation of symptoms in those with a long asthma duration. Interviews revealed this was related to previous asthma management strategies when treatment options were limited. Participants with a recent diagnosis sought understanding of asthma and the reason for their illness. Initiatives to improve asthma care in older people need to reflect these findings. Conclusions: Self‐management strategies for older people need to be tailored according to the time of disease onset and the duration of disease. Please cite this paper as: Goeman DP, O’Hehir RE, Jenkins C, Scharf SL and Douglass JA. ‘You have to learn to live with it’: a qualitative and quantitative study of older people with asthma. The Clinical Respiratory Journal 2007; 1:99–105.     

Muscle metabolism during sprint exercise in man: influence of sprint training.

In order to examine the influence of sprint training on metabolism and exercise performance during sprint exercise, 16 recreationally-active, untrained, men (VO2peak= 3.8+/-0.1 l.min(-1)) were randomly assigned to either a training (n= 8) or control group (n= 8). Each subject performed a 30-sec cycle sprint and a test to measure VO2peak before and after eight weeks of sprint training. The training group completed a series of sprints three times per week which progressed from three 30-sec cycle sprints in weeks 1 and 2, to six 30-sec sprints in weeks 7 and 8. Three mins of passive recovery separated each sprint throughout the training period. Muscle samples were obtained at rest and immediately following the pre- and post-training sprints and analysed for high energy phosphagens, glycogen and lactate; the activities of both phosphofructokinase (PFK) and citrate synthase (CS) were also measured and muscle fibre types were quantified. Training resulted in a 7.1% increase in mean power output (p<0.05), an 8% increase in VO2peak (p< 0.001), a 42% increase (p< 0.01) in CS activity and a 17% increase (p< 0.05) in resting intramuscular glycogen content. In contrast, neither PFK activity nor fibre type distribution changed with training. An increase (p< 0.05) in mean power output and attenuated (p< 0.01) ATP degradation were observed during sprint exercise following training. Glycogen degradation during sprint exercise was unaffected by sprint training. These data demonstrate that sprint training may have enhanced muscle oxidative but not glycolytic capacity.     

Hematuria in the burned child

Hematuria is a frequent complication in burn patients, but its clinical significance has not been reported. The incidence, etiologies, treatment, and outcome of hematuria in 1,785 burn patients treated from 1964 to 1983, have been reviewed. Ninety-one patients had hematuria (greater than 15 RBC/HPF with unspun urine). There were five main causes: urinary infections (UTI), 50 cases; renal calculi (RC), 14 cases, including 3% and 5% total body surface area burn patients; catheter trauma, 7 cases; renal vein thrombosis (RVT), 5 cases; and acute renal failure (ATN), 4 cases. Ten patients died in the UTI group, five with Candida as the infecting organism. No RC patients died, but two required surgical extraction of their stones. This incidence of RC may be due to large intake of dairy products and antacids and to prolonged immobilization. The catheter trauma group had no deaths and was the youngest group. One RVT patient was diagnosed clinically and successfully treated surgically. The other three were diagnosed at necropsy. The ATN patients all developed renal failure late as part of multiple organ system failure and all died. We conclude hematuria is a serious finding in burn patients and prompt diagnosis of its etiology and treatment are essential for maintaining renal function and patient survival.     

Traumatic intratemporal facial nerve injury: management rationale for preservation of function

A retrospective review of 29 cases of intratemporal facial nerve injuries included 18 temporal bone fractures, 7 gunshot wounds, and 4 iatrogenic complications. Surgical exploration confirmed involvement of the fallopian canal in the perigeniculate region in 14 longitudinal and 3 transverse or mixed fractures of the petrous pyramid. Gunshot and iatrogenic injuries usually occurred within the tympanic and vertical segments of the facial canal and at the stylomastoid foramen. When hearing is salvageable, the middle fossa approach provides the best access to the perigeniculate region of the facial nerve. In the presence of severe sensorineural hearing loss, the transmastoid-translabyrinthine approach is the most appropriate for total facial nerve exploration. Grade I to III results can be anticipated in timely decompression of lesions caused by edema or intraneural hemorrhage. Undetectable at the time of surgery, stretch and compression injuries with disruption of the endoneural tubules often lead to suboptimal results. Moderate-to-severe dysfunction (Grade IV), with slight weakness and synkinesis, is the outcome to be expected from the use of interpositional grafts.     

Liver transplantation: MR angiography with surgical validation

Thirty patients (mean age, 45 years) were evaluated with magnetic resonance (MR) angiography before liver transplantation to assess the accuracy of MR angiography. A series of breath-hold, two-dimensional images were acquired and subsequently processed to form three-dimensional projection angiograms. Graphic information on blood flow in the portal vein was acquired by using presaturation bolus tracking. Correlative duplex ultrasound (US) was performed in 28 patients, and surgical or autopsy correlation was available in all cases. MR angiography demonstrated patency of the portal vein in 26 (96%) of 27 patients, made possible the diagnosis of portal venous occlusion in three of three patients, depicted reversed portal flow in one patient, and provided clear delineation of the extent of varices and specific portosystemic collateral vessels. When duplex US was successful, there was full agreement with MR angiographic results in assessing portal vein patency and flow direction. All of the MR findings were corroborated at surgical exploration or autopsy. The authors conclude that MR angiography is very accurate in the portal system and is valuable in preoperative assessment for liver transplantation.     

Variability in hand surface representations in areas 3b and 1 in adult owl and squirrel monkeys

Detailed microelectrode maps of the hand representation were derived in cortical areas 3b and 1 from a series of normal adult owl and squirrel monkeys. While overlap relationships were maintained, and all maps were internally topographic, many map features varied significantly when examined in detail. Variable features of the hand representations among different monkeys included a) the overall shapes and sizes of hand surface representations; b) the actual and proportional areas of representations of different skin surfaces and the cortical magnifications of representations of specific skin surfaces, which commonly varied severalfold in area 3b and manyfold in area 1; c) the topographic relationships among skin surface representations, with skin surfaces that were represented adjacently in some monkeys represented in locations many hundreds of microns apart in others; d) the internal orderliness of representations; e) the completeness of representations of the dorsal hand surfaces; and f) the skin surfaces represented along the borders of the hand representation. Owl monkey maps were, in general, internally more strictly topographic than squirrel monkey maps. In both species, area 3b was more strictly topographic and less variable than was area 1. The degree of individual variability revealed in these experiments is difficult to reconcile with the hypothesis that details of cortical maps are ontogenetically specified during a period in early life. Instead, we propose that differences in the details of cortical map structure are the consequence of individual differences in lifelong use of the hands. This conclusion is consistent with earlier studies of the consequences of peripheral nerve transection and digital amputation, which revealed that cortical maps are dynamically maintained and are alterable as a function of use or nerve injury in these monkeys (Merzenich et al., '83a,b, '84a; Merzenich, '86; Jenkins et al., '84; Jenkins and Merzenich, '87).