Biomedical subjects
Publications and source records attributed to R C Dart.
We report clinical improvement with the use of an ovine antibody (Fab fragment) to tricyclic antidepressants for the treatment of toxic effects of amitriptyline on the central nervous system and heart in a 48-year-old man.
BACKGROUND: Coagulation abnormalities following crotaline (pit viper) snakebite have traditionally been considered short-lived, but laboratory studies have rarely been reported beyond the first few days of treatment for envenomation. During the course of an antivenom clinical trial, we observed coagulation defects as late as 2 weeks following envenomation. OBJECTIVES: To document and characterize the recurrence or persistence of coagulopathy among patients envenomed by pit vipers and treated with a Fab antivenom. METHODS: Patients with moderate pit viper envenomation were enrolled in a multicenter, prospective clinical trial. A Fab-based antivenom preparation, antivenom polyvalent crotalid (ovine) Fab, was administered in all cases. Platelet count, fibrinogen level, presence of fibrin split products, prothrombin time, and partial thromboplastin time were determined before treatment and at standard intervals during the following 2 weeks. RESULTS: Of 38 patients completing the study, 20 (53%) had recurrent, persistent, or late coagulopathy 2 to 14 days after envenomation. Thrombocytopenia occurred in patients with prior thrombocytopenia; hypofibrinogenemia occurred only in those with prior hypofibrinogenemia or positive fibrin split products. No patient experienced significant spontaneous bleeding. One patient with coagulopathy developed minor bleeding following minor surgery 12 days after envenomation. CONCLUSIONS: Prolonged or recurrent coagulopathy may occur after envenomation by North American pit vipers. Patients treated with Fab-based antivenom may benefit from periodic rather than single-bolus dosing. Patients with coagulopathy should undergo close monitoring during the first 2 weeks after snakebite.
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We report significant central nervous system depression and the previously unreported phenomenon of pupillary constriction after acute overdose of olanzapine (Zyprexa) in 4 patients. Phase 2 trials describe a typically benign course in overdose, and published abstracts note a wide spectrum of clinical effects with supratherapeutic ingestion of olanzapine. Our patients demonstrated profound central nervous system depression, and 2 required advanced airway support. All 4 patients recovered with supportive care. Olanzapine should be added to opioid and alpha(2)-adrenergic agonist intoxication in the differential diagnosis of the patient with depressed mental status and miosis.
STUDY OBJECTIVE: The purpose of this study was to provide the first description of the effects of ingestion of low-concentration hydrofluoric acid in a population reported to a regional poison control center. METHODS: A retrospective analysis of data collected by trained personnel using a standardized data collection system was performed. All charts involving hydrofluoric acid exposures for a 2-year period from a certified regional poison control center were identified by a computerized search. Each chart was abstracted by trained and blinded personnel. RESULTS: There were 1,772 exposures to hydrofluoric acid; 135 involved ingestion. There were 99 cases of human hydrofluoric acid ingestion for analysis. All ingestions involved consumer products containing 6% to 8% hydrofluoric acid. Symptoms, most commonly mild gastrointestinal effects, were reported by 49 patients. Two patients with minimal effects during an observation period of 2 to 4 hours deteriorated suddenly and died. All other patients recovered completely. Of 29 cases in which calcium concentrations were recorded, 4 cases of hypocalcemia occurred. All patients who had major effects or died were adults who had ingested more than 3 ounces of hydrofluoric acid with suicidal intent. Death occurred precipitously in patients who had appeared well a few minutes earlier. CONCLUSION: Death occurred in 2 patients, both of whom were adults who had ingested more than 3 ounces with suicidal intent. Ingestion of a household product containing hydrofluoric acid is a potentially life-threatening condition that requires close monitoring and prompt therapy. The abrupt deterioration and lack of warning signs indicate the need for better diagnostic methods.
Envenomations are an important cause of injury in the Americas. While supportive care alone may result in an acceptable outcome, antivenom offers a specific therapy that can significantly reduce the injury and symptoms of the envenomation. Antivenoms are hyperimmune sera collected from animals immunised with venom. The antibodies contained in the serum bind and inactive venom components. This leads to cessation or reversal of the toxic effects of the venom. The serum is often processed to increase the level of antibodies directed against venom components and decrease the amount of inactive proteins that may cause allergic reactions. The processing may include precipitation of inactive proteins, chromatographic methods and cleavage of the immunoglobulins to form antibody fragments known as Fab or F(ab)2. In the Americas, antivenoms are produced to treat crotalid and Micrurus snake envenomations. Latrodectus and Loxosceles spider envenomations and Centruroides and Tityus scorpion envenomations. The indications, method of administration and incidence of adverse reactions differ greatly for each antivenom. The adverse effects encountered when using antivenoms are primarily allergic in nature. Anaphylaxis, which may be life threatening, is a major concern. Preparations to treat anaphylaxis must be made before initiating antivenom therapy. Serum sickness is also common with many of the antivenom preparations.
This study was conducted to test the hypothesis that a Fab-based crotalid antivenin (FabAV) in commercially packaged vials will remain effective under more extreme heat and motion conditions than would be expected in field settings. Vials containing FabAV were subjected to heat or motion. The effect of heat or motion on the ED50 of FabAV was determined using a mouse model of crotalid snake envenomation. The ED50 for the heat stability groups (expressed as a ratio of mg antivenin to mg venom) were as follows: 4 degrees C x 60 days (control) = 26.5, 70 degrees C x 60 days = 66.3, 70 degrees C x 30 days = 52.4, 50 degrees C x 60 days = 25.8, 50 degrees C x 30 days = 34.0. The ED50 for the two motion stability groups were similar: 4 degrees C x 60 days = 40.3 and 70 degrees C x 60 days = 48.3. These results indicate that FabAV is heat stable at 50 degrees C for 60 days, but had less potency when heated to 70 degrees C for 30 days. FabAV appears less potent after agitation, but remains effective in the mouse model. We conclude that FabAV can be safely stored for at least 60 days without refrigeration under most field conditions where snake envenomation may occur.
OBJECTIVE: To report the indications and adverse events associated with administration of the oral N-acetylcysteine preparation by the intravenous route. DESIGN: Retrospective consecutive case series analysis of 226,720 Toxic Exposure Surveillance System data sheets from a certified regional poison center during the period January 1, 1992 through December 31, 1993. SETTING: A regional poison center certified by the American Association of Poison Control Centers. PATIENTS: Seventy-six patients treated with the oral N-acetylcysteine solution by the intravenous route. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We report the indications and adverse events associated with the intravenous administration of the oral N-acetylcysteine preparation. Four (4/76, 5.3%) patients developed adverse events attributable to N-acetylcysteine. None of these events involved hemodynamic, cardiovascular, or pulmonary effects. All reactions occurred during infusion of the initial N-acetylcysteine dose. There were three (3/76, 3.9%) deaths overall; however, they were not attributable to the intravenous administration of the oral N-acetylcysteine preparation. CONCLUSIONS: Intravenous administration of the oral N-acetylcysteine preparation appears to have limited adverse effects and offers another mechanism of delivery of the potentially lifesaving N-acetylcysteine when oral administration is not possible.
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STUDY OBJECTIVE: To examine the incidence of abnormal urinalyses after rattlesnake envenomations and its association with bite severity and antivenom administration. METHODS: A retrospective review of data collected in a prospective manner for an experimental crotalid antivenom trial. Subjects were individuals with minimal to moderate North American crotalid envenomations. Incidence and characterization of abnormal urinalysis after crotalid envenomation is presented. Additionally, the relationship of abnormal urinalysis to bite severity is examined. A preliminary test of antivenom protein urinalysis interference was also conducted. RESULTS: Forty-three percent of the urinalyses reported prior to antivenom treatment had abnormalities. Thirty-three of 41 subjects (80%) had an abnormal urinalysis, defined as the presence of cells, blood, glucose, or protein, at some time during the 2-week period following envenomation. All but 3 of these subjects had urinalyses which returned to normal by 2 weeks postenvenomation. Fifteen of 22 subjects (68%) with minimal envenomations had an abnormal urinalysis at some time following envenomation, while 18 of 19 subjects (95%) with moderate envenomations had abnormal urinalyses (p < 0.05). In addition, high concentrations of antivenom added to urine were found to produce a positive urine dipstick test for protein. CONCLUSION: In our study of patients with minimal to moderate North American crotalid envenomations, there was a high incidence of abnormal urinalyses. The urine abnormalities tended to be more common with increased bite severity and more frequent during the first few hours following envenomation. Antivenom appearance in the urine could be responsible for some of our findings.
OBJECTIVES: To describe a case of fat embolus syndrome with lipoid pneumonia resulting from intravenous infusion of lipid and to illustrate the potential for accidental intravenous administration of vegetable oil-based progesterone preparations in the treatment of oncology patients. CASE REPORT: A patient with recurrent ovarian carcinoma accidentally received approximately 20 mL (0.29 mL/kg) of a peanut oil-based methylprogesterone product intravenously via infusion pump over 24 hours. The patient developed a lipoid pneumonia with dyspnea, cough, hypoxia, radiographic infiltrates, and a pleural effusion. She was hospitalized for 4 days, and signs and symptoms resolved over 2 weeks following steroids and supportive care. DISCUSSION: Experience with accidental or intentional intravenous lipid overdose in humans is limited. Typical findings of fat embolus syndrome are similar to lipid aspiration, with respiratory distress, hypoxia, and pulmonary infiltrates. In contrast to aspiration, however, fat embolus syndrome results in lipogranulomas surrounding blood vessels, rather than air passages, and potentially produces cerebrovascular, accident-like symptoms. Management of fat embolus syndrome is similar to that for lipid aspiration. However, as seen in this case, fat embolus syndrome typically resolves over several weeks as opposed to the 3-month to 1-year period seen with aspiration lipoid pneumonias. CONCLUSIONS: Accidental intravenous infusion of vegetable oil-based products is a potential complication of the increased use of intravenous progesterones.
DMPS (2,3-dimercaptopropane-1-sulfonate, Na salt), when used as a challenge test for mercury in workers involved in the production of a calomel skin-bleaching lotion and in direct contact with mercurous chloride, elevated urine levels of mercury. A DMPS treatment regimen was devised and initiated. Three days after the challenge test, DMPS was administered p.o. (400 mg per day) for 8 days, followed by a no-treatment period of five days. A new cycle of DMPS treatment for 7 days was initiated and followed by 5 days without treatment. A third period of treatment was begun for 6 days, followed by a 5-day no-treatment period. The urinary mercury greatly increased during those periods when DMPS was administered (1754, 314, and 173 microgram/24 h for the periods 1, 2 and 3, compared with 106, 48 and 53 microgram/24 h on the corresponding no-treatment periods). One of the workers presented signs of drug intolerance and was discharged after receiving the first cycle of treatment. DMPS treatment was effective in lowering the body burden of mercury and in decreasing the urinary mercury concentration to normal levels.
STUDY OBJECTIVE: To investigate the effect of an orally administered premixed slurry of deferoxamine mesylate (DFO) and activated charcoal (AC) on the gastrointestinal (GI) absorption of ferrous sulfate under physiologic conditions. METHODS: This was a prospective, crossover, controlled human volunteer study. Participants were healthy adult subjects aged 25 to 38 years. Volunteers ingested either 5 mg/kg ferrous sulfate alone, 5 mg/kg ferrous sulfate added to 25 g of 20% (weight/ volume) AC, or 5 mg/kg ferrous sulfate added to a premixed slurry consisting of 8 g of DFO and 25 g of 20% (weight/volume) AC. The same group of volunteers was used in each limb of the study. Serum iron concentrations were measured at baseline and at 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, and 24 hours after ingestion for all subjects. Urinary iron was determined over the first 12 hours after ingestion for each limb. The maximum iron concentration (Cmax), the time to maximum iron concentration (Tmax), and the area under the curve (AUC) were compared for all three limbs. RESULTS: The AUC (P = .042) and Cmax (P = .017) were significantly lower in all subjects in the DFO/AC limb compared with the two control limbs. There was no significant difference in the Tmax iron concentration (P = .77). In the ferrous sulfate control limb, female volunteers had a significantly higher mean Cmax (P = .008) and AUC (P = .014) than males. Iron was undetectable in all baseline and 12-hour urine collections. CONCLUSION: In this model, a premixed 1:3 (weight/weight) DFO/ AC slurry reduced the GI absorption of ferrous sulfate in adult volunteers under physiologic conditions.
SUBJECT OBJECTIVE: To test the efficacy and safety of a new antivenom, affinity-purified, mixed monospecific crotalid antivenom ovine Fab, in human subjects with minimal or moderate crotalid envenomation. METHODS: We conducted a prospective multicenter clinical trial of 11 patients 10 years or older with progressive manifestations after mild to moderate crotalid snakebite. After giving their consent, subjects received four to eight vials of study drug and were then repeatedly examined over 48 hours and at 7 and 14 days after discharge. Each patient's clinical condition was evaluated serially with the use of a validated severity score, as well as on the basis of the investigator's assessment. RESULTS: In all 11 subjects to the antivenom was judged by the investigator to have had a beneficial response. The severity score for each patient remained the same or decreased over the first 4 hours. However, two subjects demonstrated worsened condition 12 to 15 hours after antivenom administration. In no subject did an allergic reaction develop. CONCLUSION: In this patient group, affinity-purified, mixed monospecific crotalid antivenom ovine Fab was associated with a halt of progressive crotalid venom poisoning. Initial safety data are promising but must be addressed further in subsequent studies.
STUDY OBJECTIVE: To describe the association among venom antigenemia, serum antivenom concentrations, and venom effects in a 53-year-old woman who was bitten by a Western Diamondback rattlesnake (Crotalus atrox). METHODS: The patient was enrolled in a multicenter trial of an investigational Fab antivenom. Her clinical condition and coagulation parameters were monitored for 2 weeks after the bite. RESULTS: After antivenom administration, the progression of the venom's effects was arrested. The antivenom reversed some local venom effects, caused venom antigens to disappear from the blood, and resolved the patient's profound thrombocytopenia (before antivenom, 12,000/mm3; 1 hour after antivenom, 227,000/mm3). Local venom effects recurred twice in the 24 hours after antivenom administration but were easily managed with additional Fab antivenom. Venom antigenemia was detected on days 5 and 8 after the initial treatment and was accompanied in one instance by the new onset of hypofibrinogenemia (119 mg/L) that resolved spontaneously and in both instances by renewed profound thrombocytopenia. Repeat Fab antivenom does no days 6 and 9 were followed by increases in platelet count (from 16,000 to 40,000/mm3 and from 11,000 to 20,000/mm3, respectively) and by the reduction or disappearance of venom antigenemia. The patient sustained no significant bleeding complications, and all laboratory values had returned to normal 2 weeks after the bite. CONCLUSION: Initial control of local symptoms and coagulopathy was prompt after the administration of Fab antivenom. Repeat doses during the 24 to 36 hours after a bite may be necessary for local control. Recrudescence of coagulopathy was likely due in part to renewed venom antigenemia after clearance of Fab antivenom. The role of Fab antivenom in the treatment of recurrent coagulopathy requires further study.
STUDY OBJECTIVE: To examine an association between bite location in cases of North American crotalid envenomation and the severity of clinical manifestations. METHODS: We conducted a retrospective review of prospectively collected data for an experimental trial of crotalid antivenom. Our subjects were otherwise healthy individuals with minimal to moderate North American crotalid envenomation. We compared the severity of envenomation for patients with digit bites distal to the proximal interphalangeal joint and bites more proximal using a previously developed and validated snakebite severity score. RESULTS: Thirteen subjects were classified as having distal bites and 24 as having proximal bites. At baseline (before antivenom administration), the distal group had a mean severity score of 2.9 +/- 1.1, whereas the proximal group had a mean severity score of 5.0 +/- 2.2 (P = .0024). Patients in the proximal group tended to demonstrate a more rapid initial decline in severity score after receiving antivenom than did the distal group. CONCLUSION: In minimal to moderate North America crotalid envenomation, patients who sustained bites on distal aspects the digits tended to experience less severe clinical manifestations of envenomation. It is possible that an isolated bite to the distal aspect of a finger is an early marker of minimal envenomation.