Acute subdural haematoma in a boxer.

On the basis of the judgements of the Court of First Instance, and of the Court of Appeal, (Michael Alexander Watson versus British Board of Control Limited) the causation aspects of two sequential acute subdural haematomas sustained by a boxer, are critically examined. The beneficial effects in this case of 'resuscitation' at the ringside, and its feasibility, are very doubtful. So also are the practicability and benefit of direct transfer to a neurosurgical department, with the timing of operation being advanced by some 45 minutes, or more probably by only 15 minutes.

The realities of postoperative disability and the carer's burden.

Outcome after high-risk, complex neurosurgery for progressive skull base pathology, and its effect on carers, has been examined. Two different outcome measures were used. The Glasgow Outcome Score (GOS) assesses overall social capability and dependence of the patient, while the 36 item short-form health survey (SF-36), a generic quality of life measure, can be compared directly with the general population. Overall outcome using the GOS indicated a favourable outcome for 13 of the 17 patients studied. The SF-36 demonstrated that more than half the patients were functioning at a level below the accepted norm. The reasons for this discrepancy and the validity of outcome scales have been analysed. In addition, the effect upon carers, its relevance to assessment of outcome, and the need to involve potential carers in the process of informed consent was stated. Our conclusions are applicable throughout the surgical specialities, and especially to high-risk complex surgery.

Addition of sodium bicarbonate to lidocaine decreases the duration of peripheral nerve block in the rat.

BACKGROUND: Adding sodium bicarbonate to lidocaine to enhance its efficacy during peripheral nerve block is controversial. The authors studied the effect of adding sodium bicarbonate to lidocaine with and without epinephrine versus equivalent alkalinization by sodium hydroxide (NaOH) on onset, degree, and duration of peripheral nerve block. METHODS: Part I examined alkalinization by sodium bicarbonate versus NaOH to pH 7.8 on 0.5% lidocaine, with and without epinephrine (1:100,000), prepared from crystalline salt. Part II examined 0.5% and 1.0% commercial lidocaine solutions, with and without epinephrine, either unalkalinized or alkalinized with sodium bicarbonate or NaOH. With NaOH, pH was adjusted to 7.8, but with sodium bicarbonate, no pH adjustments were made to simulate clinical conditions. RESULTS: In part I, addition of either NaOH or sodium bicarbonate to 0.5% lidocaine without epinephrine produced a faster onset than did unalkalinized lidocaine, without effecting degree or duration of block. In solutions with epinephrine there were no differences in onset, degree, or duration between lidocaine alkalinized with sodium bicarbonate versus NaOH. In part II, addition of sodium bicarbonate or NaOH to 1.0% commercial lidocaine without epinephrine did not accelerate onset compared with the unalkalinized solution. However, adding sodium bicarbonate decreased the degree and duration of block by 25% and more than 50%, respectively, compared with lidocaine unalkalinized and alkalinized with NaOH. With epinephrine, sodium bicarbonate hastened onset without effecting degree and duration compared with the unalkalinized solution. CONCLUSIONS: With 1% commercial lidocaine without epinephrine, sodium bicarbonate decreases the degree and duration of block. However, in solutions with epinephrine, sodium bicarbonate hastens onset, without effecting degree or duration.

Clinical judgment and clinical practice guidelines.

Clinicians make judgments under conditions of uncertainty. Decision research has shown that in uncertain situations individuals do not always act rationally, coherently, or to maximize their expected utility. Advocates of clinical guidelines believe that these guidelines will eliminate some of the cognitive biases that the practitioner may introduce into the medical decision-making process in an attempt to reduce its uncertainty. Other physicians have grave doubts about guidelines' application in practice. Guideline implementation lags well behind their development. Studies of practicing physicians and a survey of clinicians in one specialty and setting indicate that experienced clinicians may be implementing guidelines selectively. Many clinicians are concerned that guidelines are based on randomized trials and do not reflect the complexity of the real world, in which a decision's context and framework are important. Their reluctance also may be due to the difficulty of applying general guidelines to specific clinical situations. The problem will only increase in the future. The patients of the 21st century will be older and have more complex disease states. Physicians will have more patient-specific therapies and need to exercise more sophisticated clinical judgment. They may be more willing to use guidelines in making those judgments if research can demonstrate guidelines' effectiveness in improving decision making for individual patients.

Outcome after complex neurosurgery: the caregiver's burden is forgotten.

OBJECT: The goals of this study were twofold: 1) to determine outcome, including quality of life, in patients who have undergone surgery for petroclival meningioma in which a standard skull base approach was used; and 2) to assess the impact of the patients' surgical treatment on their caregivers. METHODS: Seventeen patients (13 women and four men ranging in age from 29 to 63 years) who underwent a transpetrosal approach for a petroclival meningioma during a 5-year period were prospectively included in this study. Pre- and postoperative data including adverse events were noted. The patients were assessed at 3, 6, and 12 months postoperatively, and annually thereafter, and they completed a postoperative SF-36 questionnaire. In addition, each patient's caregiver was interviewed to determine the effect of the patient's illness on the caregiver's life and responsibilities. Twenty-two operations were performed. A new permanent neurological deficit developed in five patients and in eight a temporary deficit or exacerbation of existing deficits occurred. Two patients underwent surgery to create a facial-hypoglossal nerve communication; five required a temporary percutaneous gastrostomy and/or tracheostomy; three required a shunt; and one underwent successful squint surgery. At 1 year postoperatively 13 patients had made a good or moderate recovery, three were severely disabled, and one had died--outcomes in keeping with other studies. By contrast, responses to the SF-36 questionnaire showed that, in all eight of its categories, between 43% and 75% of surviving patients were functioning below accepted norms. Fifty-six percent of caregivers experienced a major change in lifestyle and 38% experienced a major change with respect to their work. CONCLUSIONS: After transpetrosal excision of a petroclival meningioma, the quality of life for the patient is worse than that indicated in surgeons' reported results. The impact on the patient's caregiver is profound-a burden perhaps not fully appreciated by the surgeon.

Retrovirus-mediated transduction of porcine keratinocytes in organ culture.

Direct transfer of new genetic information to keratinocytes in epidermis may prove effective in treating certain genodermatoses; however, current methods for in vivo gene transfer to skin do not lead to persistence of the transgene. The goal of this study was to explore direct gene transfer using retrovirus-mediated transduction. Retroviral vectors integrate a DNA copy of their genome into the host chromosome and therefore have the potential to effect a permanent gene therapy. To facilitate development of methods for in vivo transduction with retroviral vectors, a porcine skin organ culture model was constructed in which the denuded surface was repopulated with replicating keratinocytes from hair follicles and epidermal remnants. In situ transduction was carried out by topical application of two retrovirus vectors, MFGlacZ (10(7) blue forming units per ml) and LZRN pseudotyped with the G protein of vesicular stomatitis virus (VSV) (10(9) colony forming units per ml), each encoding the beta-galactosidase reporter gene and the latter encoding the neomycin phosphotransferase selectable gene. Beta-galactosidase expressing cells were observed more frequently with LZRN than with MFGlacZ; however, transduction efficiency remained low in both instances. At equivalent titers, the VSV-G pseudotyped retroviral vector was shown to transduce porcine keratinocytes more efficiently than a similar vector with the amphotropic envelope. The number of beta-gal+ cells in organ culture could be increased by selection of LZRN-transduced cells in situ with G418. To achieve transduction of epidermis in vivo, these studies point out the importance of high titer retroviral vectors, pseudotyping with VSV-G protein, and in situ selection.

Propofol and ethanol produce additive hypnotic and anesthetic effects in the mouse.

The sedative and anesthetic effects of ethanol and propofol when these drugs are coadministered are not known. Accordingly, we investigated the nature of the pharmacological interaction between ethanol and propofol during hypnosis and anesthesia in the mouse. Propofol, ethanol, and mixtures of the two were administered through the tail vein in male CD-1 mice (n = 162). The loss of righting response occurring 10 s after injection and persisting at least 10 s thereafter was defined as hypnosis, and lack of a motor response to tail clamping 60 s after injection was defined as anesthesia. The 50% effective dose (ED50) values for the hypnotic and anesthetic actions of the drugs were determined with quantal dose-response curves, using probit analysis. The pharmacological interactions were identified by the locations of ED50 values on their corresponding hypnosis and anesthesia isoboles. For each drug alone, the hypnotic and anesthetic ED50 values with 0.95 confidence intervals were 16.70 (11.98, 23.20) mg/kg and 25.02 (20.27, 31.29) mg/kg for propofol and 0.88 (0.81, 0.95) g/kg and 1.80 (1.45, 2.23) g/kg for ethanol, respectively. For the drugs in combination, the ED50 values for hypnosis with 0.95 confidence intervals were 6.98 (6.50, 7.49) mg/kg propofol with 0.61 (0.57, 0.66) g/kg ethanol, and for anesthesia were 10.55 (9.76, 11.42) mg/kg propofol with 0.93 (0.86, 1.05) g/kg ethanol, respectively. When plotted isobolographically, we found these combinations to be behaviorally additive both for hypnosis and anesthesia. Although a finding of synergism would have excluded the possibility of an identical mechanism of action for the drugs, elucidation of the molecular basis of the additivity must await further studies.

The effect of operative technique and uterine size on blood loss during myomectomy: a prospective randomized study.

OBJECTIVES: To compare operative blood loss between two accepted blood loss-reducing techniques used during myomectomy and to evaluate the effect of preoperatively determined uterine volume on blood loss. DESIGN: Subjects were stratified by ultrasound-determined uterine volume < 600 cm3 (n = 11) and > or = 600 cm3 (n = 10) and then randomized into treatment groups. The same radiologist, surgeons, and anesthetic induction technique were involved in every case. In the pharmacologic technique, diluted vasopressin (20 U in 20 mL normal saline) was injected into the serosa and/or myometrium overlying the fibroid(s) before the uterine incision(s). In the mechanical technique, a penrose drain tourniquet was passed through defects created in the broad ligaments at the level of the internal os and secured posteriorly, occluding the uterine vessels. In addition, vascular clamps were placed on the infundibulopelvic ligaments, occluding anastomotic blood flow through the ovarian vessels. RESULTS: There was no difference in operative blood loss, operating time, preoperative and intraoperative mean arterial blood pressures, postoperative febrile morbidity, preoperative and postoperative hematocrits, transfusion rates, and length of hospital stay between groups. Blood loss was significantly greater for uteri with ultrasound-determined volumes > or 600 cm3 (627 +/- 175 mL, mean +/- SEM) than for those < 600 cm3 (228 +/- 49 mL). For all subjects, blood lost while operating on the uterus (mean, 379 mL; range, 35 to 1,968 mL) was positively correlated with the total weight of the fibroids resected and with time spent operating on the uterus. Total blood loss (mean, 418 mL; range, 42 to 1,968 mL) was also positively correlated with the time spent operating on the uterus and with total operating time. CONCLUSIONS: There were no demonstrable differences in blood loss, morbidity, or transfusion requirements between subjects undergoing myomectomy using pharmacologic vasoconstriction and mechanical vascular occlusion techniques. Blood loss during myomectomy is primarily incurred while operating on the uterus and is correlated with preoperative uterine size, total weight of fibroids removed, and operating time.

Polypropylene small-diameter vascular grafts.

Polypropylene's physical properties (e.g., high tensile strength) and relatively inert behavior suggest that fabrication into an arterial substitute may result in an efficacious prosthesis. Grafts were woven from polypropylene yarn into conduits 4 mm I.D. x 50 mm in length. Control grafts were Dacron and ePTFE. Baseline platelet aggregometry on all dogs was performed with 10(-5) M ADP. Aspirin and dipyridamole were given for three days preoperatively and maintained for 2 weeks after surgery. Fifty-four grafts were placed into the aortoiliac position, two different graft materials per dog. The grafts were explanted at intervals of 2 weeks through 16 months; photographed for thrombus-free surface area determinations; and preserved for light, scanning, and transmission electron microscopy. Late (4-16 month) patency was 81% (13/16) for polypropylene, 69% (9/13) for Dacron, and 20% (1/5) for ePTFE. These data include one year patencies of 11/12 (92%) for polypropylene and 7/10 (70%) for Dacron. Late patency for polypropylene grafts was better than for PTFE (p less than 0.05). Platelet aggregation status did not predict graft patency. Light microscopy of 2-week polypropylene explants showed inner capsules composed of myofibroblasts and macrophages, with patchy areas of endothelial cells lining the lumen. By 1 month, a confluent endothelialized surface was seen in all polypropylene explants. Progressive thickening of inner capsules with myofibroblasts and collagen continued through 4 months, reaching a mean thickness of 142 +/- 50 microns (compared to 150 +/- 30 microns for Dacron). These findings suggest potential clinical efficacy for polypropylene as an arterial substitute.

Enhanced endothelialization of expanded polytetrafluoroethylene grafts by fibroblast growth factor type 1 pretreatment.

BACKGROUND: Biomaterial pretreatment with endothelial cell mitogens may enhance endothelialization. METHODS: Modified fibrin glue (FG) containing 1 ng/cm2 recombinant 125I-labeled fibroblast growth factor type 1 (125I-FGF-1), 20 micrograms/cm2 heparin, 2.86 mg/cm2 fibrinogen, and 2.86 x 10(-2) units/cm2 thrombin was pressure perfused into expanded polytetrafluoroethylene (ePTFE) grafts. Grafts were interposed into infrarenal aortas of 24 New Zealand white rabbits and explanted after 0, 5, 30, and 60 minutes and 1, 7, 14, and 30 days. Residual radioactivity was determined by gamma-counting. Remaining 125I-FGF-1 is expressed as percent of value at time 0. To determine the effect of the FG/FGF-1 on graft healing, three groups of 50 x 4 mm 60 microns internodal-distance nonreinforced ePTFE grafts were implanted in the aortoiliac position of 12 dogs. Group I (n = 12) contained the complete modified FG, group II (n = 6) contained FG with heparin but no FGF-1, and group III (n = 6) contained untreated identical ePTFE. Tritiated thymidine (0.5 microCi/kg) was injected intramuscularly 10 hours before explantation after 7 and 28 days for light and electron microscopy and en face autoradiography. RESULTS: Retention of 125I-FGF-1 showed rapid initial loss (delta %/delta min = -24.1) followed by slow loss after 1 hour (delta %/delta min = -0.03), with 13.4% +/- 6.9% remaining at 1 week and 3.8% +/- 1.1% at 30 days. Every FG/FGF-1 graft at 28 days showed extensive capillary ingrowth and confluent endothelialized luminal surfaces, not seen in any specimen of the other two groups. Autoradiography revealed a significant increase (p less than 0.05) in 3H-thymidine incorporation in the FG/FGF-1 grafts at 28 days versus all groups as a function of time and graft treatment. CONCLUSIONS: Pressure perfusion of an FGF-1/FG suspension into 60 microns internodal-distance ePTFE grafts promotes endothelialization through capillary ingrowth and increased endothelial cell proliferation.

Albumin impregnated vascular grafts: albumin resorption and tissue reactions.

This study aimed to determine the kinetics of albumin resorption from and the healing of two types of albumin impregnated Vasculour II (Bard Cardiovascular) Dacron grafts (ACG-A and ACG-B) using whole blood preclotted Vasculour II Dacron grafts (without albumin) as controls (PCC). Prostheses measuring 4 mm ID x 50 mm length were implanted in the aortoiliac position in 24 dogs (ACG-A n = 12, ACG-B n = 24, PCC n = 12) and explanted after 1, 2 4, and 6 months. Platelet count, platelet aggregometry to 10(-5) M ADP, prothrombin time (PT), and partial thromboplastin time (PTT) were determined preoperatively and at explantation. Sections of the explanted grafts were assayed for human albumin by immunohistochemical techniques utilizing a rabbit polyclonal mono-specific antibody for human albumin followed by the addition of a biotinylated goat anti-rabbit IgG. Immunoperoxidase staining was then performed using Avidin D horse-radish peroxidase. Histology of the grafts (light microscopy, scanning electron microscopy, and transmission electron microscopy) as well as percent thrombus free surface area (TFSA) by computerized planimetry were also determined. Seven of 48 grafts were occluded (85.4% patency) with no difference among the three groups. Platelet aggregometry was not predictive of graft patency. No change in PT or PTT occurred nor was there any difference among the three groups. Retained albumin was detected in every one-month explant but not beyond that time, with the sensitivity for detecting human albumin in this assay being 20 mg albumin per gram of Dacron. All ACG explants at one month revealed inner capsular fibrin coagula not present in PCC specimens.(ABSTRACT TRUNCATED AT 250 WORDS)

Partially bioresorbable vascular grafts in dogs.

Previous studies have shown the effectiveness of partially resorbable arterial prostheses in the rabbit. This study compares these same compound prostheses with commercial graft materials in the dog. Conduits 4 mm inner diameter X 50 mm in length were woven from composite yarns containing 69% polyglactin 910 (PG910)/31% polypropylene or containing 70% polydioxanone/30% polypropylene. Nonresorbable controls were woven Dacron and expanded polytetrafluoroethylene (ePTFE). Baseline platelet aggregometry to 10(-5) mol/L adenosine diphosphate was performed. Seventy prostheses were implanted into the aorto-ilac positions, and the prosthesis/tissue complexes were harvested serially from 2 weeks to 1 year. Explanted specimens were photographed and fixed for light microscopy and for scanning and transmission electron microscopy. Results showed no aneurysms or perigraft hematomas. Overall patency for the PG910/polypropylene grafts was 18 of 20 (90%) and for polydioxanone/polypropylene was 19 of 22 (86%). For Dacron and ePTFE, 13 of 19 (68%) and 6 of 11 (54%) remained patent at time of explantation. The partially resorbable grafts, as a group, had significantly greater patency than the control grafts (p less than 0.03). Platelet aggregometry was not predictive of graft patency. Histologic analysis of the partially bioresorbable groups showed inner capsules (IC) composed of myofibroblasts and collagen beneath confluent endothelialized surfaces by 1 month. Kinetics of IC formation paralleled the rates of resorption of the resorbable components. IC cellularity and thickness were greater than those within Dacron or ePTFE. This study suggests an enhanced transinterstitial endothelial cell and myofibroblast ingrowth into the ICs of partially resorbable grafts and shows the effectiveness of these prostheses in the dog.

Effects of hypercholesterolemia on healing of vascular grafts.

Small-diameter vascular grafts woven from bioresorbable lactide/glycolide copolymers have been successfully interposed into aortas of normal NZW rabbits. The current study examines the histologic and functional reactions to these bioresorbable grafts in severely hypercholesterolemic rabbits, a standard animal model of atherosclerosis. Sixty rabbits were placed on a 2% cholesterol, 6% peanut oil atherogenic diet. Baseline serum cholesterols and triglycerides were measured and repeated at operation 3 months later. Woven polyglactin 910 (PG910) grafts were interposed into infrarenal aortas. Fifty-two rabbits died on the diet or within 3 days of surgery and eight survived operation (normal NZW rabbit operative mortality is less than 10%). Cholesterol levels rose from 63 to 1989, p less than .001. Of the eight survivors, five died after 3 weeks, and one died after 2 1/2 months. Two were sacrificed at 2 and 4 months. Four aortic disruptions with retroperitoneal hematomas, one pseudoaneurysm, and one diffuse aneurysm were observed, greater than in normal rabbits, p less than .001. Inspection revealed severe atherosclerosis. Histologically, 3-week explants showed only small areas of neointima with myofibroblasts and endothelial cells; the outer capsules were infiltrated by lipid-laden macrophages. Graft material in 2- to 4-month explants was replaced by tissue with histologic atherosclerosis. More severe atherosclerosis was observed in native aortas at the perianastomotic areas than the more distant aortic segments. Abundant intracellular lipid was seen also in splenic histiocytes and hepatic cells with evidence of micronodular cirrhosis. Macrophages phagocytizing bioresorbable prostheses may release growth factors mediating the formation of a cellular tissue conduit. Severe hypercholesterolemia may alter monokine release from macrophages resulting in a weakened prosthesis/tissue complex.

Steps towards cost-benefit analysis of regional neurosurgical care.

OBJECTIVE: To determine the cost of averting death or severe disability by neurosurgical intervention. DESIGN: Retrospective analysis of one year's admissions for neurosurgery; comparison of outcome with expected outcome in the absence of neurosurgical intervention and with the cost of neurosurgery. SETTING: Wessex Neurological Centre. PATIENTS: 1026 Patients were admitted to the neurosurgical service in 1984. Of 1185 admissions, 978 case records were available and outcome was known in 919. MAIN OUTCOME MEASURES: Outcome was assessed with the Glasgow outcome scale, modified as necessary, from the case notes, or by letter follow up to the general practitioner. Expected outcomes for each of the 54 diagnoses were derived from both published reports where available and an expert panel of 18 consultant neurosurgeons. The cost of the neurosurgical service for 1983-4 was known from a separate study and the cost per patient was calculated using the length of stay. RESULTS: The cost of neurosurgery in 1983-4 was 1.8 million pounds. In all, 243 deaths or severe disabilities were estimated to have been averted at an average cost of 7325 pounds (range 5000 pounds to 70,000 pounds). The overall cost per quality adjusted life year (QALY) was 350 pounds (range 34 pounds to greater than 400,000 pounds). The cost of long term care for severely disabled survivors is at least 18-fold greater than the cost of neurosurgical intervention to avert such disability. CONCLUSIONS: In Britain neurosurgery is not expensive in comparison with the costs and benefits of other areas of medicine, and the cost per QALY is unexpectedly low except for severe diffuse head injury, malignant brain tumors, and cerebral metastases. The neurosurgical budget should be assessed in the context of managing a patient in hospital and subsequently in the community.