Biomedical subjects
J Davidson
Publications and source records attributed to J Davidson.
A 102-center prospective study of seizure in association with bupropion.
BACKGROUND: This trial was conducted to determine the incidence of seizures associated with the use of bupropion. METHOD: A total of 3341 depressed patients from 102 sites were enrolled in this 8-week, prospective, open trial. Following the 8-week treatment phase, patients could elect to enroll in a humanitarian continuation phase of unlimited duration. Dosing was initiated at 225 mg/day and increased to 450 mg/day as tolerated. Investigators carefully monitored seizure occurrences and rated their patients' response to and tolerance of bupropion. RESULTS: A total of 1986 patients (61%) completed the 8-week treatment phase, and 1616 (81%) of these elected to be maintained on bupropion treatment in the humanitarian continuation phase. The observed seizure rate was 0.24% for the treatment phase and 0.40% for the entire study. An 8-week survival analysis performed on patients with a dosing regimen of 300 to 450 mg/day yielded a cumulative rate of 0.36%. Patients, including those previously resistant to antidepressant treatment, responded to and tolerated bupropion well. CONCLUSION: These rates confirm earlier seizure estimates and fall within accepted parameters for antidepressant drugs. This trial enhances bupropion's position as a valuable alternative for the management of depression.
A-O plate mandibular reconstruction: a complication critique.
Immediate A-O plate mandibular reconstruction was used in 31 patients, following the excision of malignant disease. This five-year retrospective study shows that 48% (15/31) of the patients are living (one with recurrence), with a mean follow-up of 30 months (range nine to 60 months). The mean survival of the deceased patients was 11 months (range two weeks to 46 months). Postoperative complications are evaluated with respect to the mandibular defect, radiation status, dentition, adjuvant onlay bone grafting and T stage. Briefly, 11/31 patients (36%) enjoyed an uneventful recovery, 9/31 (29%) developed a minor wound complication, 6/31 (19%) developed a major wound complication and 5/31 (16%) had significant aspiration. Four plates were removed and an additional three plates were exposed. In general, those patients in whom the condylar head was removed, or in whom the mandibular resection crossed the midline, experienced more wound complications (67% vs. 37%). Simultaneous onlay bone grafting almost doubled the complication rate and this reconstructive technique has been abandoned. No significant contribution to complication rate was made by radiation status, T stage or dentition in our patient population. In addition, four plates have been uneventfully irradiated postoperatively, and five patients have been successfully fit with dentures over their reconstruction plates.
Treatment of posttraumatic stress disorder with amitriptyline and placebo.
Amitriptyline hydrochloride was compared with placebo in 46 veterans with chronic posttraumatic stress disorder. Treatment continued up to 8 weeks, and efficacy was measured by five observer and two self-rated scales. Percent recovery rates were higher for amitriptyline than placebo on two measures. In patients who completed 4 weeks (n = 40), better outcome with amitriptyline was noted on the Hamilton depression scale only. In the group completing 8 weeks of treatment (n = 33), the drug was superior to placebo on Hamilton depression, Hamilton anxiety, Clinical Global Impression severity, and Impact of Event scales. There was no evidence for drug effects on the structured interview for posttraumatic stress disorder. Drug-placebo differences were greater in the presence of comorbidity in general, although recovery rates were uniformly low in the presence of major depression, panic disorder, and alcoholism. At the end of treatment, 64% of the amitriptyline and 72% of the placebo samples still met diagnostic criteria for posttraumatic stress disorder.
The risk of developing subsequent nonmelanoma skin cancers.
Data from the Southeast Arizona Skin Cancer Registry collected during 1985 through June 1988 were used in this study. Patients who had a nonmelanoma skin cancer (basal cell or squamous cell carcinoma) removed in 1985 were observed until subsequent nonmelanoma skin cancers developed or until June 30, 1988. Twelve categories of nonmelanoma skin cancers were developed on the basis of the type of first nonmelanoma skin cancer and type of second, third, and fourth nonmelanoma skin cancers. Analyses showed the highest risk of a subsequent nonmelanoma skin cancer developing was within 1 year (36.39%), the rate of developing another nonmelanoma skin cancer depended on type (squamous cell carcinoma, 100%; basal cell carcinoma, 44.23% to 83.65%), and total risk decreased during the 1277 days of the study.
Frequency of vascular injury with blunt trauma-induced extremity injury.
Vascular injury associated with select blunt trauma-induced orthopedic injuries is thought to occur frequently enough to require angiography in most cases. We sought to establish the actual frequency of such vascular injuries by reviewing all orthopedic and vascular patients seen during 4 years at one institution. A total of 569 at-risk parajoint fractures or dislocations were seen with a 1.5% incidence of vascular injury; all were recognized on clinical examination and vascular consultation then obtained. Vascular injury in this setting is uncommon, associated with particular clinical presentations, and recognized by the orthopedic surgeon, without need for routine angiography or vascular consultation.
A study of the pyrogenic actions of interleukin-1 alpha and interleukin-1 beta: interactions with a steroidal and a non-steroidal anti-inflammatory agent.
1. The pyrogenic effects of intravenously administered human recombinant interleukin-1 alpha (IL-1 alpha) and IL-1 beta were studied in the rabbit. 2. Both cytokines produced dose-related increases in body temperature. At all doses studied (100-5000 u kg-1) both cytokines elicited a monophasic increase in body temperature, beginning 15 min and reaching a maximum 45 min after administration. 3. A comparison of thermal response index (TRI2, the magnitude of febrile responses over 2 h obtained by integrating the change in temperature in degrees C against time in hours) values indicated that IL-1 beta (500 u kg-1, TRI2 = 0.69 +/- 0.04, n = 4) was approximately 5 fold more potent than IL-1 alpha (2500 u kg-1, TRI2 = 0.73 +/- 0.07, n = 4, all values are means +/- s.e.means) in elevating body temperature. delta Tmax values for the above doses of IL-1 beta and IL-1 alpha were 0.60 +/- 0.06 and 0.61 +/- 0.03 respectively. When IL-1 alpha and IL-1 beta were heated for 30 min at 60 degrees C prior to administration no biological activity was observed. 4. A cyclo-oxygenase inhibitor, ketoprofen (3 mg kg-1) administered 15 min before either cytokine completely abolished the fever induced by both IL-1 alpha (2500 u kg-1) and IL-1 beta (500 u kg-1). 5. Intravenous administration of the steroidal anti-inflammatory agent dexamethasone (3 mg kg-1) 1 h before either cytokine attenuated the fever induced by IL-1 alpha (2500 u kg-1) and IL-1 beta (500 u kg-1). 6. The effects of ketoprofen and dexamethasone on IL-I pyrogenicity indicate that prostanoids are almost certainly involved in the responses. The different potencies of IL-l alpha and IL-1 beta may be related to their relative ability to stimulate prostanoid biosynthesis.
The effect of continuous epidural analgesia on postoperative pain, rehabilitation, and duration of hospitalization in total knee arthroplasty.
Efficacies of three alternate methods of postoperative analgesia were studied in 156 patients who had total knee arthroplasty (TKA). Forty-two of these patients received parenteral meperidine hydrochloride or morphine (Group 1), 58 patients received periodic epidural injections of morphine (Group 2), and 56 patients received continuous epidural infusions of bupivacaine hydrochloride and Duramorph (Group 3). The postoperative course of all patients was documented in terms of the incidence and severity of pain, range of joint motion, duration of hospitalization, and occurrence of complications. Although epidural analgesia increased the cost and duration of the operation, good-to-excellent pain relief was attained in 86% (Group 2) and 88% (Group 3) of cases with epidural analgesia compared with 61% of patients (Group 1) receiving conventional analgesia. Moreover, 67% of patients in Group 1 experienced frequent episodes of moderate-to-severe postoperative pain in contrast to 40% of patients in Group 2 and only 10% of patients in Group 3. As a result of diminished pain, greater joint motion was obtained within the first 72 hours in Groups 2 and 3. They also had shorter hospitalization (9.6 days versus 11.2 days for Group 1 and 10.8 days for Group 2). However, the use of epidural analgesia did not reduce the incidence of complications, including nausea. Continuous infusion of epidural bupivacaine and Duramorph provided good-to-excellent control of postoperative pain after TKA. However, better analgesics are needed to reduce the high incidence of side effects associated with various treatment methods.
Prophylactic oral naltrexone with epidural morphine: effect on adverse reactions and ventilatory responses to carbon dioxide.
The influence of two different doses of oral naltrexone on the adverse effects and the analgesia of epidural morphine were compared in a double-blind, placebo-controlled study. Forty-five patients undergoing cesarean section were provided postoperative analgesia with 4 mg epidural morphine. Five minutes later they received 6 mg naltrexone, 9 mg naltrexone, or placebo as an oral solution. Pain relief was assessed by the Visual Analog Scale (VAS) and by direct questioning of the patients. Requirement for additional analgesics and side effects were noted. Respiratory effects of epidural morphine and naltrexone were assessed using the ventilatory responses to CO2 and by monitoring O2 saturation (Spo2) using pulse oximetry. All patients in the placebo group had adequate analgesia. One of the 15 patients who received naltrexone 6 mg had inadequate analgesia versus five of the 15 patients who received naltrexone 9 mg (P less than 0.05), 9 mg versus placebo. Ten patients (67%) in the placebo group had pruritus while no patient in the 6 mg naltrexone group and one patient in the 9 mg group experienced mild pruritus (P less than 0.05), placebo versus other two groups. The CO2 response slopes were depressed compared to control values from 6-16 h in the placebo group, from 6-12 h in the 6 mg naltrexone group. No significant depression was noted in the 9 mg naltrexone group. The authors conclude that oral naltrexone 6 mg significantly reduces the incidence of pruritus associated with epidural morphine without affecting analgesia and that 9 mg naltrexone is associated with shorter duration of analgesia than 6 mg naltrexone.
Regional cerebral blood flow imaging: a quantitative comparison of technetium-99m-HMPAO SPECT with C15O2 PET.
The aim of this study was to compare technetium-99m-hexamethylpropyleneamineoxime (99mTc-HMPAO) single-photon emission computed tomography (SPECT) with regional cerebral blood flow (rCBF) imaging using positron emission tomography (PET). As investigation of dementia is likely to be one of the main uses of routine rCBF imaging, 18 demented patients were imaged with both techniques. The PET data were compared quantitatively with three versions of the SPECT data. These were, first, data normalized to the SPECT cerebellar uptake, second, data linearly corrected using the PET cerebellar value and, finally, data Lassen corrected for washout from the high flow areas. Both the linearly-corrected (r = 0.81) and the Lassen-corrected (r = 0.79) HMPAO SPECT data showed good correlation with the PET rCBF data. The relationship between the normalized HMPAO SPECT data and the PET data was nonlinear. It is not yet possible to obtain rCBF values in absolute units from HMPAO SPECT without knowledge of the true rCBF in one reference region for each patient.
Zygomatic fractures: comparison of methods of internal fixation.
We have analyzed different methods of internal fixation of simple displaced fractures of the zygoma in an attempt to define the simplest method(s) of achieving postreduction stability. Twenty-five combinations of interfragmentary wiring and miniplate and screw fixation of fractured zygomas on human skulls were compared for postreduction rotational stability against stresses simulating the muscular forces that act to displace the zygoma once it has been reduced. Analysis of the data suggests that while three-point fixation using either miniplates or interosseous wires allows for virtually no displacement, two-point fixation and in some cases one-point fixation provide acceptable stability. In general, stable fixation is achieved by methods that involve the use of at least one miniplate and incorporate the frontozygomatic suture line as one of the points of fixation.
Isatin and tribulin concentrations are increased in rabbit brain but not liver following pentylenetetrazole administration.
Isatin has recently been identified in rat tissues and normal human urine where it constitutes the major part of the endogenous monoamine oxidase inhibitor, tribulin. In this study, we have measured both isatin (by gas chromatography/mass spectrometry) and tribulin (inhibition of a standard rat liver monoamine oxidase preparation) in extracts of rabbit brains and livers after intravenous administration of the anxiogenic, proconvulsant agent pentylenetetrazole. There were increased levels of both isatin and tribulin in rabbit brains, but not in livers, after pentylenetetrazole, compared with saline treated controls. This finding supports the hypothesis that isatin is a component of tribulin activity and may have a role in anxiety or epilepsy.
Mobility of injection drug users and transmission of HIV.
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Mandibulotomy in the irradiated patient.
Though the "mandibular swing," as an approach to certain upper aerodigestive tract malignancies, has been gaining popularity in recent years, there has been little reported as to the feasibility of this procedure in subjects who have received radical preoperative radiotherapy. We have recently reported the results of 23 such patients, and we now present an update. The results presented are of a retrospective analysis of 44 patients, 50% of whom received radical preoperative radiotherapy to fields including the osteotomy site. As in the previous study, there were no statistically significant differences between the complication rates in the irradiated and nonirradiated patient populations. All the patients were orally rehabilitated.
The corticotropin-releasing hormone test in patients with posttraumatic stress disorder.
To evaluate the hypothalamic-pituitary-adrenal (HPA) axis in patients with posttraumatic stress disorder (PTSD), we measured adrenocorticotropin hormone (ACTH) and cortisol responses following administration of corticotropin-releasing hormone (CRH) in 8 combat veterans with chronic PTSD. The PTSD patients had a significantly lower ACTH response to CRH compared to a control group of normal volunteers. Blunted ACTH responses occurred in patients with PTSD alone, as well as those PTSD patients who also had major depression. The cortisol response, although reduced, was not significantly different from normal. The blunted ACTH response to CRH in PTSD patients is similar to that seen in other psychiatric disorders, such as depression, panic disorder, and anorexia nervosa.
Cerebral blood flow measured by SPECT as a diagnostic tool in the study of dementia.
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Epidemiologic patterns in childhood hearing loss: a review.
In an attempt to clarify international epidemiologic trends, a review of the published literature pertaining to childhood hearing loss is presented. Inconsistencies of methodology and classification, which complicate the interpretation of data and make difficult the quantification of the influence of genuine population differences, are discussed. Selective review of the literature allows certain crude statements to be made regarding childhood hearing loss. In developed countries, serous otitis media is the most common cause of hearing loss in children, affecting up to two thirds of preschool children. In addition, 1.0-2.0/1000 children have bilateral SNHL of at least 50 dB. In underdeveloped countries, suppurative middle ear disease is common and is still frequently associated with either an intratemporal or intracranial complication. SNHL appears to occur almost twice as often as in developed countries, with a greater proportion being of infectious etiology. In specific populations, the Inuits, Amerindians and Aboriginals, acute and chronic suppurative otitis media are almost endemic, yet both cholesteatoma and serous otitis media are uncommon.
Lipopolysaccharide, muramyl dipeptide and polyinosinic: polycytidylic acid induce the accumulation of inositol phosphates in blood monocytes and lymphocytes.
Rabbit macrophages (Mø) and lymphocytes (Ly) incubated with three structurally dissimilar immunomodulators, lipopolysaccharide (bacterial endotoxin, LPS), polyinosinic: polycytidylic acid (poly-I:C) and muramyl dipeptide (MDP), were found to accumulate inositol phosphates (IPs) in a concentration- and time-dependent manner. The threshold concentration of LPS necessary for an increase in IPs in both cell types was less than 1 ng/ml and a maximum effect was observed between 1 and 10 micrograms/ml. The threshold concentrations for poly-I:C and MDP were between 0.1 and 1 microgram/ml for both cell types. Significant increases in the concentration of inositol phosphates occurred between 30 and 60 min after challenge of either cell type with any of the three agents studied. In addition, all three immunomodulators produced a greater accumulation of IPs in macrophages than in mixed lymphocytes and after 2 h appeared to approach a maximum in macrophages, whereas the IPs level in lymphocytes appeared to be still rising after 2 h. In Mø and Ly the IPs level was increased within 10 min of incubation in the presence of either PGE2 or medium previously obtained from cells incubated with LPS. In addition, anisomycin (a protein synthesis inhibitor) and ketoprofen (a cyclo-oxygenase inhibitor) inhibited the LPS-stimulated increase of IPs accumulation in both cell types. These two observations suggest that the LPS-stimulated increase in IPs in macrophages and lymphocytes is mediated by a protein intermediate and possibly a prostanoid.