Search PubMed⌕ Search

Biomedical subjects

J M Dougherty

Publications and source records attributed to J M Dougherty.

At least 19 recordsLinked to original sources
PubMed1999

Evaluation of the patient with gastrointestinal bleeding: an evidence based approach.

Gastrointestinal bleeding is a common and potentially life-threatening problem. The incidence of upper gastrointestinal bleeding (UGIB) is 40 to 150 episodes per 100,000 population per year. Mortality in large series is 6% to 10% for UGIB and has remained unchanged over the past 30 to 60 years. The incidence of hospitalization for acute lower gastrointestinal bleeding is about 20 to 27 episodes per 100,000 population per year, with a 200-fold increase with advancing age from the third to ninth decades. The mortality rate is 4% to 10% or higher. The evaluation of overt or acute gastrointestinal bleeding in the ED is reviewed here from the perspective of evidence-based medicine.

Evidence-Based Medicine↗
PubMed1997

Transcutaneous pacing in a hypothermic-dog model.

STUDY OBJECTIVE: To evaluate the hemodynamic response to transcutaneous pacing (TCP) during rewarming from hypothermia. METHODS: We conducted a prospective, controlled laboratory investigation using 20 mongrel dogs. The animals were anesthetized, intubated, and mechanically ventilated. Arterial pressure, core temperature, and cardiac rhythm were continuously monitored. All dogs were cooled to a core temperature of 27 degrees C; experimental animals were then subjected to TCP with active rewarming, and control animals underwent sham transcutaneous pacing and rewarmed in the same manner. Serial hemodynamic measurements, time to rewarming, and cardiac isoenzyme concentrations were analyzed. RESULTS: Rewarming was accomplished significantly faster in the paced group (171.5 +/- 31.5 minutes) than in the control group (254 +/- 55.9 minutes, P < .05). After rewarming, the mean cardiac index in the paced dogs returned to 84% of baseline, compared with 63% of baseline in the nonpaced group (P < .05). None of the paced animals demonstrated significant hemodynamic deterioration, potentially lethal arrhythmias, or other evidence of myocardial injury. CONCLUSION: TCP is safe, effective and easily implemented in dogs. In this small series of dogs, TCP restored and maintained hemodynamic stability and allowed the hypothermic animals to rewarm in half the time required by their nonpaced counterparts.

Animals↗
PubMed1997

In vitro amoebicidal activity of propamidine and pentamidine isethionate against Acanthamoeba species and toxicity to corneal tissues.

Effective chemotherapy for Acanthamoeba keratitis has been hampered because of the marked resistance of the parasites to a variety of antimicrobial agents. In view of the fact that topical Brolene (propamidine isethionate) and neosporin are currently considered to be the medical treatment of choice in Europe, we sought to determine whether pentamidine may be equally effective, because the drug is more readily available to ophthalmologists in the United States. In this study, we compared the amoebicidal activity of the Brolene (commercial product), propamidine isethionate and pentamidine isethionate (Pentam) in vitro against three different species of Acanthamoeba, and the drugs' corresponding biocompatibility with rabbit corneal epithelial and endothelial cell cultures. The results indicated that there were significant species differences in drug sensitivity. Propamidine (> 1,000 micrograms/ml) was clearly less effective than pentamidine (> 125 micrograms/ml) against A. castellanii, although equivalent potency (> 250 micrograms/ml) was observed against A. polyphaga. On the other hand, propamidine (> 31.25 micrograms/ml) was slightly more effective than pentamidine (> 62.5 micrograms/ml) against A. hatchetti. Both drugs were also relatively nontoxic after short-term contact with cell cultures, even though the highest concentration of pentamidine caused low-grade injury to the superficial epithelium and reversible membrane damage to the endothelium. Steady-state levels of propamidine at effective amoebicidal concentrations, however, were much more toxic than pentamidine, which indicated that the drug has a much lower therapeutic index. Our data suggest that pentamidine may be an effective therapeutic option because of its potency and low toxicity.

Acanthamoeba↗
PubMed1996

Structure and practice of institutional review boards in the United States.

OBJECTIVE: The institutional review board (IRB) is a critical element in the protection of patients' and subjects' rights with regard to their participation in research protocols. The purpose of this study was to describe the structure and current practices of IRBs in the United States. METHODS: A self-administered questionnaire was mailed to the IRB chair of each U.S. hospital with a capacity of at least 400 beds (n = 907). The survey contained 21 questions outlining committee size and structure, review of research proposals, and policies concerning scientific misconduct. Chairs also were asked what advice they would offer a young investigator preparing a proposal for submission. RESULTS: A total of 488 surveys (54%) were returned; 447 of the responding institutions had an IRB committee. Committees had an average of 14 members, representing 27 medical specialties. Orthopedics had the least IRB representation (10% of committees), followed by emergency medicine (12%) and ophthalmology (15%). The majority of research proposals go through 5 specific steps once submitted for review. Common reasons for proposal rejection were improperly designed consent form (54%), poor study design (44%), unacceptable risk to subjects (34%), ethical or legal reasons (24%), and scientific merit (14%). When a research proposal is rejected, 86% of the responding IRBs assist the investigator in making appropriate revisions. Although a number of IRBs (17%) have dealt with scientific misconduct allegations, only 58% have a written policy regarding research integrity. CONCLUSION: Despite variations in committee structure and representation, IRBs have similar procedures for governing research. Investigators should be familiar with these procedures and are encouraged to discuss their proposal with an IRB representative prior to formal review.

Ethics, Institutional↗
PubMed1994

Chlorpromazine protection against Ca(2+)-dependent and oxidative cell injury. Limitations due to depressed mitochondrial function.

Chlorpromazine (CPZ), a phenothiazine, demonstrated both cytoprotective and toxic effects on cardiomyocytes. CPZ markedly reduced cytotoxicity caused by two toxic challenges, each with a distinct cytotoxic mechanism. Lethal cell injury was induced in cultured neonatal cardiomyocytes by either: (1) ionomycin, a Ca2+ ionophore that caused Ca(2+)-dependent cell injury; or (2) ethacrynic acid (EA), a glutathione (GSH) depletor that killed cells primarily via peroxidative damage. Pretreatment with 50 microM CPZ reduced the extent of ionomycin-induced cell death, as measured by lactate dehydrogenase (LDH) leakage, but enhanced the loss of intracellular ATP and collapsed the mitochondrial transmembrane potential (delta psi). In EA-treated cultures, 50 microM CPZ also lowered LDH leakage and diminished the peroxidative damage responsible for the cytotoxicity, but again enhanced the loss of intracellular ATP and collapsed the delta psi. CPZ protection was incomplete and limited to a narrow concentration range that was essentially identical for both toxic challenges. Maximum protection was observed with 50 microM CPZ, yet the amount of residual damage was similar to the degree of injury caused by a mitochondrial uncoupler, carbonylcyanide-m-chlorophenylhydrazone alone. In the absence of either challenge, 50 microM CPZ did not affect cellular energy status or kill the cells, but a higher concentration of CPZ (150 microM) did deenergize unchallenged cardiomyocytes. These data demonstrate that CPZ can reduce cytotoxicity caused by either Ca(2+)-dependent events or oxidative stress. However, even at an optimally protective level, CPZ in combination with either ionomycin or EA deenergized the cells, although neither toxic challenge nor 50 microM CPZ alone seriously affected delta psi. It would appear that intracellular perturbations induced by either challenge promote a depression of mitochondrial function by CPZ, which limits the protective action of the drug. Since both of the challenges used contain toxicologic features exhibited by a wide variety of toxic insults, results of this study have both mechanistic and clinical implications.

Adenosine Triphosphate↗
PubMed1991

Effect of contact lens preservatives on Acanthamoeba.

Single preservatives used in contact lens solutions were evaluated for their effectiveness in killing Acanthamoeba castellanii and Acanthamoeba polyphaga trophozoites and cysts. Preservatives were tested against amoebae at intervals varying from 30 minutes to 24 hours. The preservatives were tested with axenically and nonaxenically grown organisms. Chlorhexidine (0.001% and 0.005%), polyaminopropyl biguanide (0.0015%), benzalkonium chloride (0.001% and 0.004%), and hydrogen peroxide (3%) were very effective preservatives. Lower concentrations of these same preservatives were less effective. Thimerosal (0.001% and 0.004%), sorbic acid (0.1%), potassium sorbate (0.13%), EDTA (0.1%), polyaminopropyl biguanide (0.00005%), and polyquaternium-1 (0.001%) were not effective as tested. However, thimerosal 0.004% when combined in solution with EDTA was effective. Preservatives were more effective when tested against axenically prepared organisms than when tested against co-cultured organisms.

Acanthamoeba↗
PubMed1991

In vitro penetration of human corneal epithelium by Acanthamoeba castellanii: a scanning and transmission electron microscopy study.

Human corneal buttons were exposed to Acanthamoeba castellanii trophozoites and cysts for 12 hours at 35 degrees C. The buttons examined by light microscopy and scanning and transmission electron microscopy had severe epithelial ulceration and penetration by trophozoites. Observations on trophozoites below the surface suggest that penetration is accomplished by both secreted cytolytic enzymes and phagocytosis. It is likely that the secretion of one or more enzymes constitutes the initial step in preparing the host tissue for endocytosis or that the secretory mechanism is used by the amebas to move through the outer squamous layer to the basement epithelium where phagocytosis occurs. Based on this study and a previous study, it appears that entry into the cornea is a two-step process involving adherence and penetration by trophozoites.

Acanthamoeba↗
PubMed1991

In vitro intercellular adherence of Acanthamoeba castellanii: a scanning and transmission electron microscopy study.

Human corneal buttons were exposed to trophozoites and cysts of Acanthamoeba castellanii for 12 hours. Examination of the buttons by scanning electron microscopy showed numerous trophozoites on the surface of the epithelium. Trophozoites examined by transmission electron microscopy had limited regions of attachment to the epithelium but extensive regions of attachment to each other. Attachment regions were characterized as plaque-like maculae of an incomplete desmosome junction. Firm attachment mechanisms may explain how penetration of the human cornea occurs.

Acanthamoeba↗
PubMed1991

The role of tetracycline in chronic blepharitis. Inhibition of lipase production in staphylococci.

Tetracycline administered in low doses can be effective in the long-term management of patients with meibomian keratoconjunctivitis (MKC). However, the mechanism of action does not appear to be a reduction of bacteria. Seventy-five percent of the ocular staphylococci in such patients are resistant to tetracycline. An alternative mechanism of action could be the inhibition of production of extracellular enzymes by the ocular flora. Inhibition of lipase production could result in lowered levels of toxic hydrolysis products (free fatty acids), which may exacerbate the disease process. The authors tested this hypothesis by examining the differential effect of tetracycline on growth and lipase production in a tetracycline-resistant and tetracycline-sensitive strain of Staphylococcus epidermidis and S. aureus isolated from patients with MKC and Staphylococcal blepharitis. Tetracycline caused significant decreases in the production of lipase in the sensitive and resistant strains of S. epidermidis without concominant decreases in growth. In contrast, S. aureus strains showed parallel decreases in both lipase production and inhibition of growth. The authors propose that the sensitivity of lipase production to tetracycline, in tetracycline-resistant S. epidermidis, may partially explain the clinical improvement observed in MKC patients.

Blepharitis↗
PubMed1991

The role of wax and sterol ester fatty acids in chronic blepharitis.

The authors analyzed the long-chain fatty acids derived from the wax and sterol ester fractions of meibomian secretions from patients with chronic blepharitis and normal individuals. Meibomian secretions were partitioned into separate lipid classes by thin-layer chromatography (TLC). Wax and sterol esters were eluted and transesterified. The liberated fatty acid methyl esters (FAME) were analyzed by gas liquid chromatography. Equivalent chain lengths (ECL) were determined for the 58 peaks found. Thirty-three peaks were positively identified by standards. Peaks were quantified by area normalization. Percentage compositions were computed for each individual and tabulated by group; each fatty acid was analyzed by analysis of variance, and each clinical group was compared with normal subjects. The authors found increases in the series of monounsaturated fatty acids from patient wax/sterol esters compared with normal subjects (P less than 0.05). The authors also found differences in some members of the series of normal, straight, and branched saturated moieties. These differences between normal groups and the blepharitic groups represent a biologically significant pattern that may relate to the disease process. Discriminant analysis provided a 73% probability of correct classification into clinical groups based strictly on FAME analysis (P less than 0.05).

Blepharitis↗
PubMed1990

The effect of currently available contact lens disinfection systems on Acanthamoeba castellanii and Acanthamoeba polyphaga.

Contact lens disinfection systems were evaluated for their effectiveness in killing Acanthamoeba castellanii and Acanthamoeba polyphaga trophozoites and cysts. Amoebae were inoculated into commercially available contact lens cleaning and soaking solutions. At intervals varying from 30 minutes to 24 hours, solutions were filtered. The filters were removed and cultured for Acanthamoeba organisms. Striking differences were observed in the abilities of the different disinfecting solutions to kill the organisms. Solutions containing chlorhexidine were effective at very short exposure times. Solutions containing benzalkonium chloride required slightly longer exposure times but were faster than solutions containing only thimerosal. Solutions containing sorbate, polyaminopropyl biguanide, or polyquaternium-1 were not effective at killing Acanthamoeba organisms in the time allotted for the experiment. Solutions containing hydrogen peroxide were quite effective if the agent was not prematurely catalyzed. A. polyphaga generally required longer exposure to disinfectants than did A. castellanii for complete inhibition to occur.

Acanthamoeba↗
PubMed1990

Ilionguinal-iliohypogastric nerve entrapment.

Ilionguinal-iliohypogastric nerve entrapment was described as early as 1942 as a rare but proven cause of chronic inguinal pain in patients with previous lower abdominal surgery. We describe two cases of patients who presented to the emergency care unit with complaints of chronic lower abdominal pain. Surgical histories revealed known risk factors for ilioinguinal-iliohypogastric nerve entrapment. After application of a simple bedside procedure, the diagnoses were confirmed.

Abdomen↗
PubMed1990

Hyperacute T-wave criteria using computer ECG analysis.

Hyperacute T waves (HATWs) have been described as tall-amplitude, primary T-wave abnormalities sometimes seen in the early phases of transmural myocardial infarction. Despite numerous human and animal studies addressing the presence and significance of HATWs, there are no widely held, reliable ECG criteria for their accurate identification. Using a specially designed computer program on a Hewlett-Packard Realm ECG analysis system, we screened 13,393 adult ECGs to identify those having T-wave amplitudes greater than accepted standards (limb leads, greater than 0.5 mV; precordial leads, greater than 1.0 mV). Patients with other known causes of primary and secondary tall T waves were excluded from the study sample. Patients with tall-amplitude T-waves who then developed clinically verifiable myocardial infarction were labeled the HATW group. The HATW group (21) represented 4.1% of the tall T wave group (513) and 0.16% of the entire sample. The remaining patients, who did not meet HATW criteria, were called the early repolarization variant (ERV) group (51). Both groups underwent comparative computer morphology analysis. Nine parameters were statistically significant in discriminating HATWs from early repolarization variants. A combination of J-point position/T-wave amplitude of more than 25%, T-wave amplitude/QRS amplitude of more than 75%, J-point position of more than 0.30 mV, and age of more than 45 years predicted HATWs from a control group with a specificity of 98.0% and a sensitivity of 61.9% and with positive and negative predictive values of 92.9% and 86.2%, respectively. We conclude that HATWs have characterizable discriminating ECG morphology as determined by computer ECG analysis compared with a control group.

Electrocardiography↗
PubMed1989

Use of rib belts in acute rib fractures.

The current treatment for uncomplicated rib fractures is the exclusion of associated injuries followed by symptomatic treatment with analgesics. Encouragement of deep breathing is also recommended to avoid secondary or delayed pulmonary complications. The use of circumferential rib belts in treating patients with acute rib fractures has been discouraged because of possible complications from restricted ventilation. A review of the literature revealed no previous clinical studies to support this view. We designed and conducted a controlled, prospective, randomized pilot study to determine if there was any increased morbidity associated with the use of rib belts in the treatment of patients with acute rib fractures. Twenty-five adult patients with radiographically proven acute rib fractures were randomized into two groups. The first group was treated with analgesics and a standard circumferential rib belt (Zimmer Universal Rib Belt). The second group was treated with oral analgesics alone. Patients were contacted by telephone three days after the initial injury and then reexamined 14 days postinjury. Rates of pain resolution, compliance, and delayed complications were determined. Rib belts were not found to significantly reduce the severity of pain. Four complications (one case of bloody pleural effusion requiring hospitalization, two cases of asymptomatic discoid atelectasis, and one case of allergic contact dermatitis) were identified, all occurring in the group of patients receiving rib belts. This pilot study indicates that while rib belts are widely accepted by patients for control of pain, they appear to be associated with an increased incidence of complications. Clinical studies with larger sample sizes will be needed to confirm these findings.

Acetaminophen↗
PubMed1989

Radial artery cannulation guided by Doppler ultrasound.

A technique to enhance difficult percutaneous radial artery cannulations using Doppler ultrasound is described. A series of 12 patients (nine hypotensive and three normotensive patients with poorly palpable or absent radial pulses) was assembled and the radial arteries were cannulated using standard intravenous catheters and a hand-held Doppler ultrasound device. Localization and cannulation of the arteries was facilitated by noting the characteristic sounds using the Doppler. Eleven of the 12 patients had successful cannulation of the radial artery. In one case the artery was localized but the catheter could not be advanced. No complications were encountered. It was concluded that the use of a common Doppler ultrasound on selected patients with poor peripheral pulses may facilitate percutaneous radial artery cannulations and minimize the number of catheter punctures before successful placement.

Arteries↗
PubMed1989

The role of wax and sterol esters of meibomian secretions in chronic blepharitis.

We analyzed the fatty wax esters and sterol esters found in the expressed lipid secretions of six patients from each of six clinical groups of chronic blepharitis, plus eight normal controls. Using gas liquid chromatography (GLC), 12 peaks corresponding to equivalent chain lengths (ECL) of 33.6, 35.4, 36.1, 37.3, 38.2, 39.2, 40.1, 41.2, 42.1, 43.2, 44.9 and 45.7 were found in the fatty wax esters and five peaks corresponding to ECL 19.1, 20.0, 21.1, 22.0 and 23.2 were found in the sterol esters. The clinical groups showed significant differences in several of these components. Sterol and wax esters represent the largest fraction of the total meibomian lipid secretion. The finding that the blepharitic groups exhibit biochemical differences in the distribution of these esters indicates that the esters may play a role in the disease process, perhaps by providing a preferential substrate for normal flora which we have shown to have lipolytic capabilities. The resultant de-esterification could alter the tear film and contribute to ocular irritation. In addition, the differences seen in the composition of the ester fraction of the meibomian secretion could lead to differences in melting point, which, in turn, could affect viscosity and surface tension of the tear film, leading to changes in breakup time and to secretion stagnation within glands.

Blepharitis↗
PubMed1987

Magnesium levels in cardiac arrest victims: relationship between magnesium levels and successful resuscitation.

Multivariate analysis was performed to evaluate significant differences between electrolytes, serum magnesium, and successful resuscitation in cardiac arrest victims in a prospective controlled study. Twenty-two cardiac arrest victims having ventricular fibrillation or tachycardia, electromechanical dissociation, or asystole were compared with 19 matched controls with no ventricular arrhythmias. Of the control group, one was hypermagnesemic (5%), 17 normomagnesemic (90%), and one hypomagnesemic (5%). In the arrest group, eight were hypermagnesemic (36%), nine normomagnesemic (41%), and five hypomagnesemic (23%). Thirteen of 22 cardiac arrest victims (59%) had an abnormal serum magnesium level. All hypermagnesemic and hypomagnesemic patients expired (100%). In the normomagnesemic group, four out of nine (44%) were successfully resuscitated. A positive correlation was identified between normomagnesemia and successful resuscitation (P less than .01). There was no correlation between other electrolytes and successful resuscitation (P greater than .05).

Arrhythmias, Cardiac↗