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Biomedical subjects

J Dougherty

Publications and source records attributed to J Dougherty.

At least 19 recordsLinked to original sources
PubMed1991

A phase III comparison trial of streptozotocin, mitomycin, and 5-fluorouracil with cisplatin, cytosine arabinoside, and caffeine in patients with advanced pancreatic carcinoma.

Conventional chemotherapy for unresectable or metastatic adenocarcinoma of the pancreas has had little effect on palliation or survival. Almost all studies of systemic therapy have involved empiric use of a variety of Phase II or conventional agents alone or in combination. On the basis of recent studies using a human tumor pancreatic cancer (PC) xenograft in nude mice, a Phase I clinical trial of cisplatin, high-dose cytosine arabinoside (Ara-C), and caffeine (CAC) was performed in patients with advanced incurable PC. A tolerable dose and schedule of the three agents were developed. Seven of 18 patients with measurable disease in this Phase I trial had partial responses to CAC. A Phase III comparison of CAC versus standard treatment using streptozotocin, mitomycin, and 5-fluorouracil (SMF) was performed. Eighty-two patients with advanced PC were entered into this random assignment trial. The two treatment arms were well balanced for the usual prognostic factors. Although the acute (e.g., nausea and vomiting) toxicities of CAC were greater than those of SMF, both groups of patients tolerated treatment resonably well. Ninety percent of patients were evaluable for response. Two patients (5.5%) on the CAC treatment arm (95% confidence interval [CI], 0% to 15%) and four patients (10.2%) on the SMF treatment arm (95% CI, 1% to 22%) had objective responses (partial response in measurable disease or improvement in evaluable disease). No complete remissions were observed. The 95% confidence limits of response for CAC and SMF overlapped. The median duration of survival for all patients on the SMF treatment arm was 10 months, although it was 5 months on the CAC treatment arm (P = 0.008). In this Phase III comparison, CAC was not superior to conventional therapy with SMF in terms of response and was inferior for survival. Neither regimen is effective treatment for advanced PC.

Adenocarcinoma↗
PubMed1991

Tumorigenicity of adenovirus-transformed cells and their sensitivity to tumor necrosis factor alpha and NK/LAK cell cytolysis.

Sensitivity of a library of cloned adenovirus-transformed rat cell lines of varying tumorigenicity to cytotoxic action of tumor necrosis factor alpha (TNF alpha) was studied and correlated with their sensitivity to NK/LAK cell cytolysis. Our data confirm earlier reports that expression of the E1A oncogene of Ad2 or Ad5 is associated with sensitivity of transformed cells to TNF alpha and also NK/LAK cytotoxicity. Ad2-transformed cell line which expresses the E3 early region in addition to the E1 gene block is resistant to TNF alpha, but remains sensitive to NK/LAK cells. All cell lines which express the E1A oncogene of highly oncogenic Ad12 are resistant to NK but not LAK cells. Their sensitivity to TNF alpha, however, varies over a broad range and does not correlate with either their susceptibility to NK/LAK cytolysis or their tumorigenic potential.

Adenovirus Early Proteins↗
PubMed1990

Phase II study of CHIP chemotherapy in advanced adenocarcinomas of the upper gastrointestinal tract.

Iproplatin (CHIP) is a second generation cisplatin analogue which has completed its Phase I trials. We studied the efficacy and toxicity of CHIP in 36 previously untreated patients with advanced upper gastrointestinal tract adenocarcinomas (GE junction, cardia, antrum and body of the stomach). The starting dose was 275 mg/m2; course were repeated on an every four week schedule. Thirty-five patients were evaluable for response. Three partial remissions (8.5%) [95% confidence limits 2.5-15%] were seen. Toxicity was tolerable and included mild myelosuppression and mild nausea and vomiting. Although well tolerated, in patients with gastric and GE junction adenocarcinomas, CHIP chemotherapy was not more and probably slightly less, effective than the parent analogue cisplatin.

Adenocarcinoma↗
PubMed1990

Pathological laughter.

A man experienced one hour and 40 minutes of continual, inappropriate, uncontrollable laughter. The onset was preceded by a single-inhalation exposure to an insecticide of very low toxicity. The episode was terminated by a single dose of IV diazepam. A discussion of pathological laughter, including its proposed pathophysiology, differential diagnosis, clinical relevance, and management, is presented.

Adult↗
PubMed1990

In vivo and in vitro collagenolytic activity of Acanthamoeba castellanii.

Axenic cultures of Acanthamoeba castellanii contained a collagenolytic enzyme that digested collagen shields and purified collagen in vitro. Specificity of biologic activity was determined by the addition of selected enzyme inhibitors to the assays and revealed that the parasite-conditioned medium contained both collagenase and lower concentrations of other proteolytic enzymes. However, most of the collagenolytic and pathogenic activity was directly attributable to specific collagenase. Intrastromal injection of sterile, Acanthamoeba-conditioned culture medium into naive Lewis rats produced corneal lesions clinically similar to and closely resembling those found in biopsy specimens of human patients diagnosed with acanthamoebic keratitis. Histopathologic analysis revealed moderate-to-severe neutrophil infiltration, disruption of stromal lamellae, and edema. Identical pathologic sequelae were produced by intrastromal injection of purified collagenase (25 units/ml). The pathogenicity of the soluble parasite-derived product was removed by passage over affinity columns armed with antibody specific for collagenase. These results indicated that soluble parasite-derived factors were capable of producing lesions characteristic of acanthamoebic keratitis and that the pathogenicity of these factors was either directly or indirectly attributable to specific collagenase activity.

Acanthamoeba↗
PubMed1990

Combined utility of gene rearrangement analysis and flow cytometry in the diagnosis of lymphoproliferative disease in the bone marrow.

The diagnosis of lymphoma involving bone marrow is often complicated by the presence of nonspecific lymphoid aggregates. Morphologic criteria may not permit the distinction of benign from malignant lymphoid aggregates with certainty in all cases. We combined morphology with immunophenotypic and immunogenotypic analyses of aspirated marrow cells to develop more reliable criteria for the diagnosis of marrow involvement by lymphoma. The presence of morphologically recognizable lymphoma cells in the bone marrow aspirate was always confirmed by immunogenotypic analysis. The yield of either immunophenotypic or immunogenotypic analyses on morphologically negative marrows was very low. Focal paratrabecular involvement by lymphoma was not always confirmed by immunophenotypic or immunogenotypic analyses, probably due to sampling error and factors interfering with aspiration of the lymphoid aggregates. Thus, the immunologic and molecular studies supported, but did not substantially improve upon the morphologic criteria that are in common usage for distinguishing benign from malignant lymphoid aggregates in the bone marrow. Finally, evidence of B-lymphocyte clonality was obtained in four of five cases in which there were nonspecific lymphoid aggregates in the bone marrow in the absence of otherwise clinically definable malignancy.

Aged↗
PubMed1990

The incidence of bacteremia associated with emergent intubation: relevance to prophylaxis against bacterial endocarditis.

STUDY OBJECTIVE: To examine the incidence of bacteremia associated with emergent nasotracheal intubation. STUDY DESIGN: Non-randomized, controlled cohort trial during 30 minutes post-intubation with limited in-hospital follow-up. SETTING: Emergency care unit and inpatient setting of a tertiary care facility. PATIENTS: Emergency care unit patients with acute respiratory distress necessitating non-elective emergency airway placement. MEASUREMENTS AND MAIN RESULTS: We studied 84 blood cultures obtained from 21 patients intubated emergently. Fourteen patients were intubated by the nasotracheal (NT) route and seven patients were intubated orotracheally (OT) for comparison. Pre-intubation and post-intubation blood cultures were obtained at two to five, 10 to 15 and 30 minutes after intubation. Patients were excluded if they had strong clinical evidence of pre-existing bacterial infection, had received antibiotics within 48 hours of presentation or were less than 16 years of age. Of the patients that were NT intubated, 29% (4/14) of patients became bacteremic after intubation. All had negative pre-intubation cultures. Organisms isolated were nasopharyngeal florae and included: Streptococcus viridans, Veillonellae sp., aerobic diphtheroids, and other mouth florae. Of the seven patients with OT intubation, six were culture negative. One was excluded because of positive preintubation cultures secondary to urosepsis. No patients in our study developed complications that could be directly attributed to these organisms or to intubation alone. CONCLUSIONS: The risk of bacteremia associated with emergency nasotracheal intubation is substantial and is accompanied by organisms that may produce serious morbidity in the patient with valvular heart disease or compromised immunity. Our findings suggest that, whenever possible, the nasotracheal route should be avoided for emergency intubation in patients with valvular heart disease and if used, prophylactic antibiotics should be strongly considered.

Aged↗
PubMed1989

Prevalence of HIV infection among intravenous drug users in the United States.

We reviewed 92 published and unpublished studies of the prevalence of infection with the human immunodeficiency virus (HIV) among intravenous drug users (IVDUs) in the United States. Human immunodeficiency virus seroprevalence among IVDUs in drug treatment programs in the United States ranged from 0% to 65%. Seroprevalence was highest in the Northeast (10% to 65%) and Puerto Rico (45% to 59%); lower in the South Atlantic (7% to 29%) and in the metropolitan areas of Atlanta, Ga (10%), Detroit, Mich (7% to 13%), and San Francisco, Calif (7% to 13%); and 5% or less in other areas of the West, the Midwest, and the South. Among IVDUs seen in drug treatment programs, risk of infection was not associated with gender or age but was associated with black and Hispanic ethnicity, male homosexual orientation, and certain intravenous drug-use practices. Cross-sectional and cohort studies indicated increases in seroprevalence of between 0% and 14% per year among IVDUs in treatment. We estimated that between 61,000 and 398,000 IVDUs in the United States were infected with human immunodeficiency virus, or 5% to 33% of the IVDU population. High rates of infection among IVDUs in treatment in the Northeast indicate the potential for rapid spread in regions where rates are currently low. An urgent need exists to monitor human immunodeficiency virus infection levels and trends more widely and to develop effective programs to reduce the further spread of human immunodeficiency virus infection among IVDUs.

Black or African American↗
PubMed1989

Randomized double-blind trial of intravenous prochlorperazine for the treatment of acute headache.

In a prospective, randomized, double-blind clinical trial, intravenous prochlorperazine edisylate (Compazine Edisylate) was compared with a placebo in the treatment of severe headaches. Eighty-two adult patients with vascular or tension-type headaches were identified at the time of presentation to one of three participating emergency departments. After the patient gave informed consent, a 2-mL intravenous injection of sterile saline solution or prochlorperazine edisylate (10 mg) was given to each patient at the time of randomization. The treatment groups were similar with regard to age, sex, and type and duration of headache. Within 60 minutes after injection, 74% (31/42) of those who received prochlorperazine had complete relief; 14% (6/42) of the patients had partial relief. Overall, there was complete or partial relief of pain in 88% (37/42) of the drug group and in 45% (18/40) of the placebo group. This difference was statistically significant using chi 2 analysis. Adverse effects were minimal; one patient experienced asymptomatic orthostatic hypotension. These results suggest that intravenous prochlorperazine is an effective treatment for patients with severe vascular or tension headaches who present to the emergency department.

Acute Disease↗
PubMed1988

Emergency department protocol for the diagnosis and evaluation of geriatric abuse.

As the number of elderly persons in the United States continues to increase, geriatric abuse has become the most recent manifestation of domestic violence seen in the emergency department. Recent data suggest that 1 million elderly persons are battered, neglected, or exploited each year by family members or caretakers. This maltreatment may be more difficult to identify than child or spouse abuse because of the relative isolation of the victims and their reluctance to report abuse. Many of these cases involve only subtle signs and have a great potential to pass undetected. We summarize the current literature on geriatric abuse and describe an ED protocol for identifying and reporting suspected victims. We retrospectively reviewed the medical records of 36 elderly patients hospitalized with documented abuse or neglect. Physical maltreatment was evident in 29 patients (80%), and 16 of the cases (44%) involved psychological abuse. Key points in the history, physical examination, and psychosocial evaluation were analyzed to identify specific criteria used in the development of the protocol. This framework will aid the emergency physician in the crucial first steps of identifying abuse, obtaining evidence, and providing immediate treatment and crisis intervention. Awareness that the problem exists and improved detection and intervention procedures are needed to prevent abuse of elderly persons from becoming more widespread.

Aged↗
PubMed1988

Detomidine: a preliminary analysis of its duration of action in the horse by variable interval responding.

Variable interval (VI) reinforcement scheduling is a specific type of operant conditioning that is sensitive to drug effects even when overt clinical signs of the drug have diminished. Six horses were conditioned to break a light beam with a head-bobbing movement and this behaviour was reinforced with a reward of clean oats (approximately 30 mg/reinforcement). Initial training procedures included familiarisation with the behavioural equipment and fixed-ratio reinforced scheduling. To establish baseline rates of behaviour, the horses were converted to a variable interval (60 secs) reinforcement schedule and kept on this schedule for the remainder of the study. A within subjects cross-over design was used with three treatments counterbalanced with the six horses. Detomidine (40 micrograms/kg bodyweight, xylazine (1.1 mg/kg bodyweight) and saline (10 ml) were administered intravenously on Monday mornings with VI responding rates measured during a routine 30 min session each day from Monday to Friday. Responses and reinforcements were recorded and dispensed by use of an electromechanical relay system wired to an electric eye, an automatic feeder and a programming and recording system. Xylazine produced a small decrease in responding rates at 1 h post dose, while detomidine treated horses showed a dramatic decrease in responding rates after 1 h and a lingering effect at 24 h. No long range effects were seen with either treatment and all horses returned to baseline responding rates by 48 h post dose.

Animals↗
PubMed1988

Repair of Achilles tendon ruptures with Dacron vascular graft.

A technique has been developed for the repair of Achilles tendon ruptures that allows for early mobilization of the patient. A Dacron vascular graft is woven from distal to proximal and across the site of the rupture in a Bunnell-type fashion. The patients are immobilized in a short-leg cast for two weeks and are then fitted for a posterior fiberglass splint. Seven patients with acute ruptures who were treated with repair with the Dacron graft were followed for a period ranging from ten to 38 months. They were allowed to return to their normal level of activity approximately five months after surgery. There have been no reruptures. This technique also holds particular promise for the late reconstruction of an Achilles tendon rupture as well as for the treatment of partial tears in the severely degenerated tendon.

Achilles Tendon↗
PubMed1987

Basal forebrain infusion of HC-3 in rats: maze learning deficits and neuropathology.

Ten adult male Sprague-Dawley rats were infused with hemicholinium (HC-3) using mini-osmotic pumps over a 14 day period through bilateral, chronically implanted cannulae in the nucleus basalis magnocellularis (nbm). Ten matched controls were infused in the same fashion with saline. HC-3 rats receiving implants demonstrated a significant deficit in maze-learning ability compared with individual and group performances before receiving the implants. In saline rats there was no significant difference in maze-learning ability before and after receiving implants. The HC-3 group receiving implants demonstrated a significant deficit in maze-learning ability compared with the saline control group. Serial sections through nbm from control and HC-3 rats indicated that all cannulae were located within infusion range of nbm. In HC-3 subjects, cholinergic cell bodies were destroyed with concurrent degeneration of terminal fields in cortex. Except for cannula insertion damage, the cholinergic neurotransmitter system appeared unharmed in controls. Stains for neuritic plaques and neurofibrillary damage were negative in both groups. The memory deficit in experimental subjects supported by the demonstrated destruction of nbm cholinergic neurons suggests that HC-3 may be useful in the development of an animal model for Alzheimer's Disease.

Animals↗
PubMed1987

Repetitive doses of activated charcoal in the treatment of poisoning.

Activated charcoal has found a renewed role in the management of overdosed patients. Routinely administered to reduce the gastrointestinal (GI) absorption of many drugs, growing evidence indicates that repeated doses of charcoal also may enhance drug elimination. Some drugs are excreted into the bile or gastric fluids (phencyclidine, digoxin) and are reabsorbed. Other drugs (theophylline, phenobarbital) can diffuse from the plasma into the lumen of the GI tract. Activated charcoal is administered at regular intervals to sequester these toxins in the GI tract, eventually causing their excretion in feces. This article reviews the evidence for the safety and efficacy of repetitive charcoal therapy. While supportive management remains the mainstay of therapy in poisoned patients, activated charcoal is inexpensive, effective, simple to administer, and may obviate the need for more invasive methods of toxin removal.

Acute Disease↗
PubMed1987

Toxic smoke inhalation: cyanide poisoning in fire victims.

The most common cause of death in fires is the inhalation of noxious gases rather than thermal injury. Hydrogen cyanide gas, the most toxic product of combustion, seldom is recognized as a significant hazard in smoke inhalation. During the first four months of 1986, toxic amounts of cyanide were found in four of the six fatalities from house fires in Akron, Ohio. These cases illustrate the increasing frequency of cyanide poisoning in household fires. Sources of cyanide toxicity include the increased use of synthetic polymers in building materials and furnishings. Prompt recognition of and therapy for cyanide intoxication may reduce the morbidity and number of delayed deaths in fire victims. The key point in the diagnosis of cyanide poisoning is a high index of suspicion. The clinical presentation of cyanide intoxication, its diagnosis, and subsequent treatment are discussed. Finally, a prehospital protocol for treating smoke-inhalation victims who may have been exposed to cyanide gas is suggested.

Aged↗