Vinegaroon exposures reported to a Poison center.

BACKGROUND: Vinegaroons (Mastigoproctus giganteus), also known as whip scorpions, are arachnids commonly found in the southwestern United States, parts of Mexico, and southern Florida. They do not bite, but have special teeth on the inside of the trochanters of the front appendages, used to crush prey. They are best known for having pygidial gland secretions containing 83% acetic acid, which are sprayed upon potential predators. There are no published descriptions of injury to human related to vinegaroon exposures. Our primary aim was to characterize types of exposures and clinical effects reported to a poison center that serves an area indigenous to this animal. METHODS: The database from a regional poison center was searched for all cases from 1998 to 2022 regarding human exposures to the vinegaroon. Data captured included age, sex, exposure route, type and duration of symptoms, and part of the body affected. RESULTS: There were 50 exposures reported, with age range from 5 months to 54 years. Females represented 32 cases, males 17, and one unknown. Bites were more commonly described (36 cases), with 13 cases reported skin exposure to secretions, 3 ocular exposures, and 2 ingestions. Location of injury was upper extremities in 16 cases, lower in 11 cases, and torso in 3 cases. Symptoms were present in 88% and included pain, skin erythema, numbness or tingling, itching, and swelling. Ocular exposure were associated with pain in all 3 cases, with blurred vision in one case; effects lasted 1 h, 17 h, and more than 5 days. Four non-ocular exposures were followed to outcome, with duration of effects ranging from less than 1 h to more than 2 days. DISCUSSION/CONCLUSION: In a large series of vinegaroon exposures, females predominated, with most exposures occurring from skin contact with secretions. The most common symptoms were pain, erythema, numbness, itching, and swelling, which resolved in less than two days. Ocular exposures were associated with more symptoms and longer duration of effects.

Comparison of F(ab')2 and Fab antivenoms in rattlesnake envenomation: First year's post-marketing experience with F(ab')2 in New Mexico.

Two antivenoms are available for rattlesnake envenomations in the U.S., Fab (CroFab®, BTG, UK), and F(ab')2 (Anavip®, Bioclon, Mexico) antivenom (AV) with F(ab')2AV released in October 2018. The F(ab')2AV Phase 3 comparative clinical trial demonstrated similar efficacy in treating venom-caused hematologic toxicity, similar rates of Types I and III hypersensitivity reactions, and a lower rate of recurrent hematological effects than FabAV. We hypothesized that a post-marketing, comparative study of effectiveness and rates of hypersensitivity reactions in treating rattlesnake envenomations in New Mexico would demonstrate similar outcomes. Patients eligible for the study presented to a New Mexico healthcare facility between May and October 2019 and were known/suspected to have a rattlesnake bite. Exclusion criteria for antivenom comparison were those with a dry bite, lost to follow-up, or late presentation. All cases were included for patient/bite demographics, initial local control, hematological control, number of maintenance/control doses, development of persistent, recurrent or late-, new-onset hematologic effects, and hypersensitivity reactions. We used Fisher's exact tests for analysis and 0.05 cutoff to determine significance. There were 54 rattlesnake-bitten patients in New Mexico with 17 excluded for comparison of antivenom because of dry bites, loss to follow-up, and one case of late presentation. Thirty-seven patients remained for comparative analysis between F(ab')2AV (n = 11) and FabAV (n = 26). There were no significant demographic differences between F(ab')2 and Fab-treated patients. No patient had a Type I hypersensitivity reaction. No rescue doses were given. The rate of recurrent, persistent or late-, new-onset of hematologic effects was 0% with F(ab')2AV and 29% with FabAV. No patient was readmitted. No patient had bleeding complications. Type III hypersensitivity reactions were similar between F(ab')2AV (36%) and FabAV (25%). The results of our study are consistent with the Phase 3 clinical comparative trial and indicate no significant differences in safety or effectiveness between FabAV and F(ab')2AV. F(ab')2AV offers the advantages of not requiring maintenance doses and may have a lower rate of late hematologic effects in treating rattlesnake envenomations.

Unpredicted late-, new-onset thrombocytopenia and hypofibrinogenemia in Fab antivenom-treated rattlesnake envenomation.

The use of Fab antivenom (Crotalidae Polyvalent Immune Fab (Ovine) (CroFab); Boston Scientific) against North American Crotalidae envenomation is associated with the development of late- (≥4 days post-envenomation), new-onset of hematological abnormalities. Although attempts have been made to identify predictive indicators during the acute phase of an envenomation, of patients who are not at-risk of late-, new-onset of hematological abnormalities, there has been at least one prior report of a patient who developed thrombocytopenia that was unpredicted by current indicators. We add three cases of unpredicted, late-, new-onset of hematological abnormalities in patients with Fab-treated rattlesnake bite.

Envenomations during pregnancy reported to the national poison data system, 2009-2018.

Envenomations during pregnancy have consequences affecting both maternal and fetal outcomes. U.S. poison center data on envenomations offers a comparative view of envenomations in pregnant and non-pregnant women. The National Poison Data System of the American Association of Poison Control Centers was searched for cases of envenomation during pregnancy between January 1, 2009 and December 31, 2018 and compared with exposures to non-pregnant females of childbearing age. Odds ratios and descriptive statistics were used where appropriate. There were a total of 3,555 venomous animal exposures in pregnant women during this 10-year period, most commonly with scorpion stings. These were compared with 87,553 envenomations in non-pregnant women of childbearing age during that time period. Overall, drug treatment was administered in 350 (9.9%) cases of envenomation in pregnant women compared with 21,381 (24.4%) of non-pregnant patients. Antihistamines were less likely to be used in pregnant patients with scorpion (1.8% v. 9.2%), hymenoptera (bee, wasp, or hornet) (12.4% v. 37.1%), black widow spider (2.8% v. 8.1%), and caterpillar (10.4% v. 37.7%) exposures. There was an increased likelihood of antivenom use during pregnancy with rattlesnake envenomations (85.0% v. 58.9%) and black widow spider bites (4.8% v. 2.2%). There were no maternal deaths, and most maternal outcomes were coded as having no (1.0%) or minor (87.6%) effects. Three fetal deaths occurred, all following snakebites and all before 20 weeks gestation. Two were attributed as related, and one as of uncertain relationship to the exposure, by the managing poison centers. Most envenomations caused no or minor effects to pregnant women.

Recurrent and persistent coagulopathy following pit viper envenomation.

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.

A randomized multicenter trial of crotalinae polyvalent immune Fab (ovine) antivenom for the treatment for crotaline snakebite in the United States.

BACKGROUND: Current therapy for crotaline snakebite includes antivenin (Crotalidae) polyvalent, an antivenom with numerous adverse effects. We compared the efficacy and safety of 2 dosing regimens with a new antivenom, Crotalinae polyvalent immune Fab (Fab AV). METHODS: A single dose of Fab AV alone (as-needed [PRN] group) was compared with an initial dose plus repeated treatments during 18 hours (scheduled group) in a multicenter randomized trial. The study included patients with minimal or moderate envenomation by a crotaline snake within the preceding 6 hours, aged 10 years or older, in whom worsening of the envenomation syndrome was observed before Fab AV treatment. After treatment with Fab AV to achieve initial control, patients were randomized to the scheduled or PRN treatment group. Scheduled group patients received additional doses of Fab AV every 6 hours for 3 doses. The PRN group received no planned additional doses of antivenom. RESULTS: The mean severity score of the 31 patients decreased from 4.35 to 2.39 points (P<.001); there was no difference between scheduled and PRN groups. No patient in the scheduled group received unplanned Fab AV doses, but 8 of 16 patients in the PRN group received unplanned doses (P =.002). Acute reactions occurred in 6 patients (19%), and serum sickness occurred in 6 (23%) of 26 patients who returned for follow-up. CONCLUSIONS: In the first randomized trial of antivenom in the United States, Fab AV effectively terminated venom effects. Since the unplanned use of Fab AV in the PRN group was common, the treatment regimen may require more than 1 initial dose.

Acetaminophen/diphenhydramine overdose in profound hypothermia.

BACKGROUND: There are few reports of acetaminophen overdose in hypothermic patients and even fewer reports describing profound hypothermia. The kinetics, risk of hepatotoxicity, and the possible dose adjustments to N-acetylcysteine (NAC) therapy are not known in this setting. CASE REPORT: A 37-year-old female was found unconscious outside in December and was brought by ambulance to a tertiary care Emergency Department (ED) following a presumed overdose of acetaminophen and diphenhydramine. She later confirmed the ingestion and reported the ingestion had occurred approximately 18 hours prior to being found. On arrival, she was profoundly hypothermic, with a core rectal temperature of 17°C. Her initial serum acetaminophen concentration was 232 mcg/mL 19 hours post ingestion of a reported dose of approximately 50 grams of acetaminophen and 2.5 grams of diphenhydramine. Active rewarming was started immediately and IV NAC was initiated using the standard treatment protocol. The patient did not develop serious signs of hepatic injury or NAC toxicity. The patient's AST and ALT peaked 12 hours after admission at 84 IU/L (ref 10-37 U/L) and 104 IU/L (ref 12-78 U/L), respectively. Her INR peaked 2 hours after admission at 1.46 (ref < 1.2). DISCUSSION: Despite the significant ingestion of acetaminophen, delayed presentation, prolonged period of decreased responsiveness, and profound hypothermia, the patient did not develop any signs/symptoms of liver injury. NAC was administered in a standard dose during her rewarming period without apparent toxicity. The patient's absorption and/or metabolism of acetaminophen were likely slowed by her hypothermia and possibly by the anticholinergic coingestant. Initiation of IV NAC at a standard dose was apparently safe and effective in preventing hepatotoxicity as the patient was rewarmed. CONCLUSIONS: Profound hypothermia may be protective of hepatic injury in acetaminophen overdose. Delayed absorption from the coingestant, diphenhydramine, may also have played a role. IV NAC was given in a standard dose without apparent toxicity in the setting of profound hypothermia. Lastly, IV NAC, in standard dosing, appeared to be effective in preventing hepatotoxicity during rewarming in a patient with a potentially hepatotoxic concentration of acetaminophen with a coingestion of the anticholinergic agent, diphenhydramine.

Management of envenomations during pregnancy.

CONTEXT: Envenomations during pregnancy pose all the problems of envenomation in the nonpregnant state with additional complexity related to maternal physiologic changes, medication use during pregnancy, and the well-being of the fetus. OBJECTIVE: We review the obstetric literature and management options available to prevent maternal morbidity and mortality while limiting adverse obstetric outcomes after envenomation in pregnancy. METHODS: In January 2012, we searched the U.S. National Library of Medicine Medline/PubMed, Toxline, Reprotox, Google Scholar and Micromedex databases, core surgery and internal medicine textbooks, and references of retrieved articles for the years 1966 through 2011. Search terms included "envenomation in pregnancy," "stings in pregnancy," "antivenom use in pregnancy," "anaphylaxis in pregnancy," and variants of these with known venomous animals. Reference lists generated further case reports and articles. We included English language articles and abstracts. Levels of Evidence (LOE) for the reports cited and Grades of Recommendations (GOR) based on LOE for our recommendations use the National Guidelines Clearinghouse metric of the US DHHS. RESULTS: Recommendations for the management of envenomation in pregnancy are guided primarily by studies on nonpregnant persons and case reports of pregnancy. Clinically significant envenomations in pregnancy are reported for snakes, spiders, scorpions, jellyfish, and hymenoptera (bees, wasps, hornets, and ants). Adverse obstetric outcomes including miscarriage, preterm birth, placental abruption, and stillbirth are associated with envenomation in pregnancy. The limited available literature suggests that adverse outcomes are primarily related to venom effects on the mother. Optimization of maternal health such as management of anaphylaxis and antivenom administration is likely the best approach to improve fetal outcomes despite potential risks to the fetus of medication administration during pregnancy. Obstetric evaluation and fetal monitoring are imperative in cases of severe envenomation. CONCLUSION: The medical literature regarding envenomation in pregnancy includes primarily retrospective reviews and case series. The limited available evidence suggests that optimal management includes a venom-specific approach, including supportive care, antivenom administration in appropriate cases, treatment of anaphylaxis if present, and fetal assessment. The current available evidence suggests that antivenom use is safe in pregnancy and that what is good for the mother is good for the fetus. Further research is needed to clarify the optimal management schema for envenomation in pregnancy.

Indicators for serious kidney complications associated with toxic exposures: an analysis of the National Poison Data System.

CONTEXT: Over two million poisoning exposures are reported to U.S. poison control centers annually. A broad population-based survey of toxic exposures and the correlated patterns of reported kidney injury (acute or chronic) have not been systematically characterized. OBJECTIVE: Our objective was to study the demographic and exposure patterns associated with indicators for serious kidney complications (ISKC), as defined by the variables in the NPDS. MATERIALS AND METHODS: This was a retrospective, case-control study using the data elements available in the NPDS. We assessed data related to patient characteristics, substance exposure, and management. Cases and controls were derived from adult and pediatric exposures documented in NPDS (2001-2007) as having "renal effects." For substance-specific analyses, cases were restricted to those involving single substances or single entity pharmaceutical preparations. ISKC cases presented with one or more of the following NPDS codes: increased creatinine, and/or oliguria/anuria, and/or renal failure. Controls were subjects with "renal effects" but did not have increased creatinine, nor anuria/oliguria, nor renal failure. Univariate and multivariate logistic regression analyses identified factors associated with ISKC and determined the relationship between these factors. RESULTS: From the approximate 16.8 million exposures reported to the NPDS within the study timeframe, there were 16,444 single substance exposures with renal effects of which 9,074 cases experienced ISKC (55.2%) compared to 7,370 controls without ISKC. Cases with ISKC tended to be males, adults, and reported to involve intentional exposures. Cases with ISKC had higher rates of reported hemodialysis/hemofiltration (27.7%; N = 2,517) and death (10.9%; N = 990) compared to controls, respectively, (2.1%; N = 155) and (0.8%; N = 60), p < 0.001. Substances considered a priori to be nephrotoxic were associated with a higher risk of ISKC. DISCUSSION AND CONCLUSION: The NPDS provided insight into the subjects and types of exposures that associate with ISKC. Subjects with ISKC experienced higher rates of morbidity and mortality compared to subjects without ISKC. We identified subject characteristics and classes of compounds associated with ISKC. We hope that the hypotheses generated from this study of the NPDS will raise awareness of the possible risk factors and complications associated with ISKC.

Linking pharmacology to clinical reports: cyclobenzaprine and its possible association with serotonin syndrome.

The link between cyclobenzaprine (Flexeril) administration and serotonin syndrome (SS) is subject to debate. Establishing such a connection is difficult because of the limited number of case reports available and the almost complete ignorance of its preclinical pharmacology. In this context, evidence is provided here that cyclobenzaprine blocks the serotonin and norepinephrine transporters and binds to another set of five serotonin receptors. SS should be considered when indicative signs occur in the context of cyclobenzaprine use.

Substance use and sexual assault.

The charts of 234 consecutive sexual assault victims age 12 years or greater were reviewed. Substance use by victims and assailants is prevalent. Victims reported substance use immediately preassault in 51% of cases, and substance use by their assailants in 44%. Victim substance use was associated with a trend toward impaired memory for key elements of the assault. Victim knowledge of assailant substance use was associated with acquaintance assaults. Adult and adolescent substance use rates were not significantly different. Adolescents had a higher rate of acquaintance assaults and nongenital injury. Adults had increased rates of memory impairment and weapon involvement.

Recurrence phenomena after immunoglobulin therapy for snake envenomations: Part 1. Pharmacokinetics and pharmacodynamics of immunoglobulin antivenoms and related antibodies.

The production of immunoglobulin antivenoms has evolved over the past 50 years, resulting in a choice of source animals and highly purified, target-specific immunoglobulin fragments (IgG, Fab2, and Fab). Differences in pharmacokinetic and pharmacodynamic properties of these fragments may affect clinical efficacy. For example, both local and systemic recurrences (worsening after initial improvement) with intact or fragmented immunoglobulin antivenoms have been observed. Local recurrence may result in greater tissue injury, and coagulopathic recurrence may result in the risk of hemorrhage. The latter is of particular concern because coagulopathic recurrence usually occurs after patient discharge. Similar phenomena of symptom recurrence have been observed with ovine, digoxin-specific Fab, and with Fab2 and IgG antivenoms from a variety of source animals as well. Recurrence of venom effects in Fab-treated patients appears to be the result of a pharmacokinetic and pharmacodynamic mismatch between the antivenom and target venom components. That is, tissue penetration and venom neutralization is incomplete, and clearance of unbound antivenom (antivenom that has not bound its venom target) is significantly faster than the clearance of some venom components, allowing signs and symptoms of envenomation to recur. Understanding the relative kinetics and dynamics of immunoglobulins and their targets may allow the physician to anticipate their clinical implications and may suggest modifications of the drug or dose to produce better clinical results.

Recurrence phenomena after immunoglobulin therapy for snake envenomations: Part 2. Guidelines for clinical management with crotaline Fab antivenom.

Recurrent local and coagulopathic effects (worsening after clinical improvement) have been described after treatment with Fab antivenom for envenomation by North American crotaline snakes. Although similar phenomena have been described previously in snakebite, few studies have examined recurrence or its management. Recurrence is consistent with known venom and antivenom kinetics and dynamics. The clinical significance of late coagulopathy after snakebite is uncertain, but clinically significant bleeding is a possibility. Prevention and treatment of recurrence with Fab antivenom require repeated dosing for at least 18 hours, with close monitoring of at-risk patients in the follow-up period. Duration of therapy depends on individual risk factors and coagulation response.

Massive ibuprofen ingestion with survival.

OBJECTIVE: To report a massive, 100 g ibuprofen ingestion in an adolescent, with survival. CASE REPORT: The patient developed coma, metabolic acidosis, and mild thrombocytopenia, but improved rapidly with supportive care. Renal function remained normal and no gastrointestinal bleeding occurred. CONCLUSIONS: Massive ingestion of ibuprofen may result in a variable picture with some elements of significant toxicity, but supportive care usually results in survival without sequelae.

Accidental, intravenous infusion of a peanut oil-based medication.

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.

Oxidant-induced alterations in glucose and phosphate transport in LLC-PK1 cells: mechanisms of injury.

To determine the effects of oxidant injury on specialized functions of proximal tubular epithelial cells, we determined sodium-dependent uptake of glucose ([alpha-14C]methylglucoside) and phosphate (32Pi) in LLC-PK1 cells after exposure to 0-500 microM hydrogen peroxide. Oxidant stress resulted in significant (P < 0.01) inhibition of glucose and phosphate transport. Decreased transport of glucose and phosphate was associated with marked ATP depletion, decreased activity of the sodium pump as determined by 86Rb uptake, direct inhibition of Na(+)-K(+)-adenosinetriphosphatase (Na(+)-K(+)-ATPase) activity, and an increase in intracellular sodium content, whereas intracellular potassium content declined. Decreased glucose and phosphate transport, inhibition of 86Rb uptake and Na(+)-K(+)-ATPase activity, and altered intracellular ion content were prevented by catalase and partially prevented by the membrane-permeable iron chelator phenathroline, whereas the slowly membrane-permeable iron chelator deferoxamine had little or no effect. To determine whether oxidant injury could also inhibit transporter function at the membrane level, plasma membrane vesicles were isolated from LLC-PK1 cells exposed to 500 microM hydrogen peroxide. Such membrane vesicles exhibited decreased sodium-dependent glucose transport, whereas sodium-dependent phosphate transport was not altered. We conclude that oxidant injury results in ATP depletion and inactivation of Na(+)-K(+)-ATPase which leads to disruption of the normal ion gradients sufficient to interfere with glucose and phosphate transport. Glucose transport is also inhibited by disruption of transporter activity within the plasma membrane. These alterations are mediated in part by the intracellular generation of an iron-dependent radical.

Relationship of venom effects to venom antigen and antivenom serum concentrations in a patient with Crotalus atrox envenomation treated with a Fab antivenom.

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.

Renal endosomal phosphate (Pi) transport in normal and diabetic rats and response to chronic Pi deprivation.

Chronic renal adaptation to dietary deprivation of Pi is accompanied by increased Na+/Pi co-transport across the brush border membrane of the renal proximal tubule. The increased activity of this co-transport system depends on de novo protein synthesis and insulin. The present study used normal and diabetic rats to determine if the endosomal pool of Na+/Pi co-transporters was altered by Pi deprivation and the possible role of insulin. In response to 5 days of dietary Pi deprivation there was a significant increase in endosomal Na+/Pi co-transport in control rats but there was no change in diabetic rats. The increase in endosomal Pi uptake was restored in diabetic rats treated with exogenous insulin. Na(+)-independent Pi uptake and proline uptake remained unchanged in all groups. The changes in endosomal Na+/Pi co-transport correlated with the abundance of the specific Na+/Pi co-transporter protein, as determined by Western blots. The pattern of endosomal changes paralleled that observed in brush border membranes. One possibility consistent with these findings is that the endosomal fraction contains newly synthesized Na+/Pi co-transporters targeted for delivery to the apical brush border membrane. Increased synthesis and delivery is required to maintain the adaptation to chronic Pi deprivation.

Vanadate action on renal phosphate transport.

Insulin stimulates reabsorption of phosphate (Pi) in the renal proximal tubule. Previous studies have shown that vanadate can mimic the action of insulin on various tissues. In the present study, we tested the action of vanadate on renal Pi transport both in control rats and in rats made diabetic by injection of streptozotocin. Vanadate was administered orally for 4 days by inclusion in drinking water (0.7 mg/ml). By the 4th day, vanadate treatment of control rats did not change acid-base status, plasma glucose or the filtered load of Pi, but the urinary excretion of Pi was reduced to 2.5 +/- 0.9 compared with 17.6 +/- 3.5 mumol/mg creatine (P < 0.02) in untreated control rats. However, Na+/Pi cotransport by isolated brush border membrane vesicles was not different between the two groups. Findings in parathyroidectomized rats were similar. By the 4th day of vanadate treatment of diabetic rats, there was reversal of polyuria, polydipsia and hyperglycemia with no change in acid-base status. The filtered load of Pi was decreased by vanadate, and urinary Pi excretion also tended to decrease but not significantly. The values for Pi excretion were 21.4 +/- 7.6 in vanadate treated diabetics and 36.1 +/- 4.5 mumol/mg creatinine in untreated diabetics. In contrast to vanadate, daily injections of insulin did not change the filtered load of Pi but reduced urinary Pi excretion in diabetic rats to 15.6 +/- 2.2 mumol/mg creatinine (P < 0.02). These findings suggest that vanadate stimulated tubular Pi reabsorption in control rats but not in diabetic rats. Vanadate treatment of diabetic rats may tend to decrease tubular Pi reabsorption in contrast to the action of insulin.

Affinity-purified, mixed monospecific crotalid antivenom ovine Fab for the treatment of crotalid venom poisoning.

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.