Metabolite profiles evaluated, according to sex, do not predict resting energy expenditure and lean body mass in healthy non-obese subjects.

PURPOSE: Differences in resting energy expenditure (REE) between men and women mainly result from sex-related differences in lean body mass (LBM). So far, a little is known about whether REE and LBM are reflected by a distinct human metabolite profile. Therefore, we aimed to identify plasma and urine metabolite patterns that are associated with REE and LBM of healthy subjects. METHODS: We investigated 301 healthy male and female subjects (18-80 years) under standardized conditions in the cross-sectional KarMeN (Karlsruhe Metabolomics and Nutrition) study. REE was determined by indirect calorimetry and LBM by dual X-ray absorptiometry. Fasting blood and 24 h urine samples were analyzed by targeted and non-targeted metabolomics methods using GC × GC-MS, GC-MS, LC-MS, and NMR. Data were evaluated by predictive modeling of combined data using different machine learning algorithms, namely SVM, glmnet, and PLS. RESULTS: When evaluating data of men and women combined, we were able to predict REE and LBM with high accuracy (> 90%). This, however, was a clear effect of sex, which is supported by the high degree of overlap in identified important metabolites for LBM, REE, and sex, respectively. The applied machine learning algorithms did not reveal a metabolite pattern predictive of REE or LBM, when analyzing data for men and women, separately. CONCLUSIONS: We could not identify a sex independent predictive metabolite pattern for REE or LBM. REE and LBM have no impact on plasma and urine metabolite profiles in the KarMeN Study participants. Studies applying metabolomics in healthy humans need to consider sex specific data evaluation.

Using serosurveys to optimize surveillance for zoonotic pathogens.

Zoonotic pathogens pose a significant risk to human health, with spillover into human populations contributing to chronic disease, sporadic epidemics, and occasional pandemics. Despite the widely recognized burden of zoonotic spillover, our ability to identify which animal populations serve as primary reservoirs for these pathogens remains incomplete. This challenge is compounded when prevalence reaches detectable levels only at specific times of year. In these cases, statistical models designed to predict the timing of peak prevalence could guide field sampling for active infections. Here we develop a general model that leverages routinely collected serosurveillance data to optimize sampling for elusive pathogens. Using simulated data sets we show that our methodology reliably identifies times when pathogen prevalence is expected to peak. We then apply our method to two putative Ebolavirus reservoirs, straw-colored fruit bats (Eidolon helvum) and hammer-headed bats (Hypsignathus monstrosus) to predict when these species should be sampled to maximize the probability of detecting active infections. In addition to guiding future sampling of these species, our method yields predictions for the times of year that are most likely to produce future spillover events. The generality and simplicity of our methodology make it broadly applicable to a wide range of putative reservoir species where seasonal patterns of birth lead to predictable, but potentially short-lived, pulses of pathogen prevalence.

MEK inhibition induces expression of differentiation marker Keratin 10 in human keratinocytes.

BRAF mutant metastatic melanoma was regularly treated in the past with a BRAF inhibitor (BRAFi) alone or in combination with inhibitors of the mitogen-activated protein kinase kinase (MEKi), which is still a common treatment. This combination therapy strongly reduced the occurrence of keratoacanthomas and squamous cell carcinoma, which was frequently seen when BRAFi was used as monotherapy. Here we addressed the question whether MEK inhibition counteracts squamous cell carcinoma development in part by promoting keratinocyte differentiation. Exposure of human immortalized keratinocytes to different concentrations of MEKi revealed a significant increase in the expression of differentiation-associated keratins K10 and K1 as determined by qRT-PCR and immunofluorescence staining. Taken together, the present study suggests that in a combined treatment of melanoma with BRAFi/MEKi, MEKi reduces the incidence of squamous cell carcinomas by promoting keratinocyte differentiation under combined BRAFi/MEKi treatment in melanoma. This might open further treatment perspectives for skin cancer treatment.

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.

[CT urography in women with primary or recurrent pelvic tumors : background and initial experiences]. / CT-Urographie bei Frauen mit primären oder rezidivierenden Beckentumoren : Hintergrund und erste Erfahrungen.

Malignant tumors of the female pelvis account for 12-13% of newly diagnosed solid neoplasms among women in the USA and Germany. German guidelines advocate diagnostic imaging for local recurrence and metastasis while there are no recommendations for primary tumors. As excretory urography has been replaced by the excretory phase of computed tomography urography (CTU) in many institutions, two independent observers retrospectively evaluated CTUs of primary or recurrent female pelvic tumors to rule out associations between CTU findings and subsequent urologic measures. Among 31 CTUs of 27 women (age 29-84 years, mean 57 years) with 15 primary and 13 recurrent tumors, 83-100% of unremarkable proximal, middle and distal ureter segments were completely delineated in the excretory phase (delay 6-29 min, mean 16 min). The most common pathological findings included distal ureter obstruction (n=19, 61%), bladder compression (n=13, 42%) and bladder invasion (n=8, 26%). Out of 20 pathologically altered urinary tracts 8 were subsequently subjected to urologic measures (2-tailed Fisher exact test, p=0.0215) but none of the 10 unremarkable urinary tracts were treated. It appears that CTU is a sensible pre-therapeutic test for the urinary tract for primary and recurrent female pelvic tumors.

Modulation of innate and adaptive immunity by the probiotic Bifidobacterium longum PCB133 in turkeys.

The use of protective, probiotic cultures in poultry farming may serve as a useful strategy to improve food product safety from the beginning of the food chain and thus to protect consumer health. The objective of this study was to investigate the effect of the probiotic strain Bifidobacterium longum PCB133 on innate and adaptive immune responses in turkeys beginning at 2 wk of age, under farming conditions. The vaccination efficiency against Newcastle disease virus served as the primary endpoint. At 2 wk of age, male turkeys (British United Turkey Big 6 strain) were randomly assigned to the control (n = 25) or probiotic group (n = 25). Turkeys in the probiotic group received the probiotic B. longum PCB133 (at least 3 × 10(7) cfu/d) incorporated into the daily feed ration for 5 wk, until slaughter at 7 wk of age. At the beginning of the probiotic intervention, birds in both groups were vaccinated against Newcastle disease. Birds were weighed weekly throughout the intervention period, and finally blood sera and heparinized blood were collected for immune function tests (lymphocyte proliferation, phagocytosis, respiratory burst), and for the determination of Newcastle disease virus antibody titers. No effects on BW gain and on the proliferation of blood lymphocytes were elicited by the 5-wk intervention with the probiotic. Concerning the primary endpoint of the study (i.e., specific antibody production as a response to vaccination against Newcastle disease), no adjuvant effect of the probiotic could be determined. In addition, innate immune functions tested were not significantly affected. In conclusion, first scientific evidence on the application of the probiotic strain B. longum PCB133 in turkeys beginning at 2 wk of age does not support an improvement in live performance, humoral immunity, or innate immunity.

COUP-TFII is regulated by high glucose in endothelial cells.

Diabetes mellitus is an important risk factor for cardiovascular diseases. Clinical evidence supports a link between hyperglycemia, endothelial dysfunction, and vascular disorders. However, the precise molecular mechanisms causing endothelial dysfunction in diabetic patients remain unclear. An interesting novel mediator could be chicken ovalbumin upstream promoter-transcription factor II (COUP-TFII), which plays an essential role in glucose metabolism. COUP-TFII is known to be expressed in venous endothelial cells. In this study, we show COUP-TFII expression in human umbilical vein endothelial cells (HUVECs) and human coronary artery endothelial cells. HUVECs express glucose transporters 1, 3, 6, and 10, and the insulin receptor. Insulin in combination with glucose activates protein kinase B (PKB or Akt) phosphorylation via phosphoinositide 3-kinase (PI3-kinase). Short-term (60-240 min) stimulation of HUVECs with high glucose increased COUP-TFII expression independent of insulin. Long-term (48 h) stimulation of HUVECs with high glucose augmented expression of the insulin receptor and E-selectin, but downregulated COUP-TFII protein expression. Downregulation of COUP-TFII by shRNA leads to downregulation of E-selectin and upregulation of eNOS and glucose transporters. Our data suggest that COUP-TFII is regulated by glucose in a time- and dose-dependent manner in endothelial cells. COUP-TFII might affect endothelial function in a diabetic background.

Pre-operative fasting: a nationwide survey of German anaesthesia departments.

BACKGROUND: Shorter pre-operative fasting improves clinical outcome without an increased risk. Since October 2004, German Anaesthesiology Societies have officially recommended a fast of 2 h for clear fluids and 6 h for solid food before elective surgery. We conducted a nationwide survey to evaluate the current clinical practice in Germany. METHODS: Between July 2006 and January 2007, standardized questionnaires were mailed to 3751 Anaesthesiology Society members in leading positions requesting anonymous response. RESULTS: The overall response rate was 66% (n=2418). Of those, 2148 (92%) claimed familiarity with the new guidelines. About a third (n=806, 34%) reported full adherence to the new recommendations, whereas 1043 (45%) reported an eased fasting practice. Traditional Nil per os after midnight was still recommended by 157 (7%). Commonest reasons reported for adopting the new guidelines were: 'improved pre-operative comfort' (84%), and 'increased patient satisfaction' (83%); reasons against were: 'low flexibility in operation room management' (19%), and 'increased risk of aspiration' (13%). CONCLUSION: Despite the apparent understanding of the benefits from reduced pre-operative fasting, full implementation of the guidelines remains poor in German anaesthesiology departments.

[Reduced preoperative fasting periods. Current status after a survey of patients and colleagues]. / Verkürzte präoperative Nüchternheit. Erhebung eines Istzustands nach Analyse von Patienten- und Mitarbeiteraussagen.

BACKGROUND: Since October 2004 German Anaesthesiology Societies have officially recommended a decreased fasting period of 2 h for clear fluids and 6 h for solid food before elective surgery. A survey of patients and health care workers was carried out in our university clinic to assess the implementation of the new fasting recommendations. METHODS: Surgical patients (n=865) as well as physicians and nurses specialized in anaesthesia and surgery (n=2,355) were invited to complete a written questionnaire. The survey inquired about prescribed and practiced duration of fasting, attitudes towards reduced preoperative fasting and knowledge of the new guidelines. RESULTS: Data from 784 patients (91%) and 557 health care workers (24%) were analysed. Patients reported mean fasting times of 10+/-5 h for fluids and 15+/-4 h for solid food. Of the patients 52% and 16% would have preferred to drink and eat before surgery, respectively and 10% were informed about the new recommendations of shorter preoperative fluid and solid fasting. Such patients reported significantly reduced fasting times for fluids compared with those who were recommended to fast for the traditional longer periods (8+/-6 versus 12+/-4 h, p<0.001). Preoperative fasting advice remembered by the patients significantly differed from the prescribed recommendations (2 h fluid fasting, 22 versus 53%, p<0.001). Anaesthesiologists were significantly more knowledgeable of the new guidelines (90 versus 32-42%, p<0.001) and significantly more willing to recommend the new short preoperative fasting times (75 versus 15-19%, p<0.001) than other health care workers. Of all health care workers 82% and 32% reported patients' frequent desire to drink and eat before surgery, respectively, 92% considered reduced preoperative fasting to be positive, 76% feared increased risks for patients and 42% expected a decreased flexibility in their daily work. CONCLUSION: The current guidelines for preoperative fasting have not been widely implemented. Besides a knowledge discrepancy, remarkable concerns remain regarding higher risk for patients which may be important barriers to implementation. Nevertheless, health care workers are aware of patients' desire for shorter preoperative fasting. If the new guidelines are recommended patients will make use of them. Further training of staff and adequate implementation tools are needed.

Pulmonary mucormycosis with extensive bronchial necrosis and bronchomediastinal fistula: A case report and review.

Mucormycosis is a life-threatening infection caused by fungi in the Mucorales species. It most often affects immunocompromised hosts, including diabetics patients. It can affect a variety of organ systems with pulmonary manifestations being the second most common. In severe cases, significant bronchial necrosis and angioinvasion can be seen. Due to its rarity, such extensive cases are not often reported in literature. We present a case of a 32-year-old man who presented with severe bronchial necrosis, including bronchomediastinal fistula, due to Rhizopus. Despite prompt treatment, he developed massive hemoptysis from invasion of the pulmonary vasculature and died. We also provide a brief review of mucormycosis.

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.

Inhibition of myoblast differentiation in vitro by a protein isolated from liver cell medium.

We have recently discovered that cells of Coon's Buffalo rat liver (BRL) line secrete a protein which is a potent inhibitor of skeletal myoblast differentiation in vitro. Using ion exchange and molecular exclusion chromatography, we have prepared this protein, which we designate "differentiation inhibitor" (DI), from the materials secreted by BRL cells maintained in serum-free medium. It is a relatively heat-stable protein which is inactivated by treatment with trypsin and mercaptoethanol and has an apparent molecular weight in the range 30,000--36,000. It exhibits no detectable mitogenic or lectin activity and differs from previously reported inhibitors of myoblast differentiation in several respects. It is active in all skeletal myoblast systems tested (Yaffe's L6 line as well as primary cultures of rat, chick, and Japanese quail myoblasts), and it blocks fusion, elevation of creatine kinase, and increased binding of alpha-bungarotoxin. Parallel fractionation of fetal bovine serum (FBS) and chick embryo extract (CEE) yields a peak of activity which similarly inhibits myoblast differentiation. We suggest that the differentiation inhibitor from BRL cells may correspond to the differentiation-inhibiting component(s) of FBS and CEE, and we call attention to the possibility that such a substance could play a role in embryonic growth of myoblasts and in satellite cell formation.

Unusual dynamical arrest in polymer grafted nanoparticles.

We present results of temperature dependent measurements of dynamics of polymer grafted nanoparticles with high grafting density with star polymerlike morphology. We observed for the low grafting density and hence low functionality sample, a dynamically arrested state with lowering of temperature, similar to what was conjectured earlier. However the high grafting density sample shows liquidlike relaxation at all measured temperatures. Possible origin of dynamical arrest in the two grafting density sample is discussed.

THE GERMAN DOSE RATE MONITORING NETWORK AND IMPLEMENTED DATA HARMONIZATION TECHNIQUES.

Environmental radiation monitoring networks have been established in Europe and world-wide for the purpose of protecting population and environment against ionizing radiation. Some of these networks had been established during the cold war period and were improved after the Chernobyl accident in 1986. Today, the German Federal Office for Radiation Protection (BfS) operates an early warning network with roughly 1800 ambient dose equivalent rate (ADER) stations equally distributed over the German territory. The hardware and software of all network components are developed in-house allowing the continuous optimization of all relevant components. A probe characterization and quality assurance and control program are in place. Operational and technical aspects of the network and data harmonization techniques are described. The latter allows for calculating of the terrestrial and net ADER combined with uncertainties mainly from site specific effects. Harmonized data are finally used as input to the German emergency management system and the European radiological data exchange platform.

Very stable 188Re-S4 chelates for labelling biomolecules: preparation with highly concentrated perrhenate eluates.

AIM: The preparation and stability of a new (188)Re-S(4)-complex [S(4) = (1-aza-18-crown-6)(O)C-C(SH)-C(SH)-C(O)NH-(CH(2))(3)-NH-(CH(2))(3)-NHC(O)-C(SH)-C(SH)-C(O)(1-aza-18-crown-6] was studied at therapeutic relevant radioactive concentrations. The results were compared with (188)Re-MAG(3) (MAG(3): mercaptoacetyltriglycine) and (188)Re-DMSA preparations (DMSA: dimercaptosuccinic acid) performed with the same highly concentrated [(188)Re]perrhenate solution (12-15 GBq/ml). METHODS: The (188)Re complexes were prepared by direct reduction of perrhenate ((188)Re-S(4)-complex) as well as via the (188)Re-EDTA precursor complex ((188)Re-MAG(3), (188)Re-DMSA). The preparations were stabilised with 15 mg of ascorbic acid and analysed after 1, 2, and 24 hours by TLC and HPLC. Additionally, in vitro and in vivo stability studies were performed with the purified complexes. RESULTS: After stabilisation with 15 mg of ascorbic acid, all of the complexes were nearly stable under nitrogen for hours, and only 2-8% of perrhenate was observed after 24 h. In contrast, only the (188)Re-S(4) complex was completely stable in vitro and in all investigated in vivo samples after separation of ligand excess and reducing agent by HPLC. CONCLUSION: The bridging amine group or free carboxylic groups of the S(4)-ligand framework make available reactive positions for coupling biomolecules to the chelate. Thus it appears that the new (188)Re-S(4) complexes offer the possibility of stable and high specific activity labelling of biomolecules for therapeutic application.

The 188Re(III)-EDTA complex--a multipurpose starting material for the preparation of relevant 188Re complexes under mild conditions.

An easy and gentle method for the preparation of 188Re(V) complexes with bidentate and tetradentate ligands is described starting from the precursor complex 188Re(III)-EDTA. That complex is prepared at room temperature in acidic solution and reacts by a combined re-oxidation/ligand exchange reaction with appropriate ligands like DMSA or ECD (DMSA = dimercapto succinic acid, ECD = L,L-ethylene dicysteine diethyl ester) or en, tau, and cyclam (en = ethylene diamine, tau = 1,4,8,11-tetraazaundecane, cyclam = 1,4,8,11-tetraazacyclo-tetradecane) to the 188Re(V)-oxo- and dioxocomplexes, respectively. The chelates were unambiguously identified by chromatographic comparison with spectroscopically characterised samples or known 99mTc-kit reconstitutions. The reaction succeeds under mild conditions (room temperature, short time, neutral or weak basic solutions) with high yields and has potential for labelling of sensitive biomolecules with 188Re.

Incorporation of mevalonate into dolichol and other isoprenoids during estrogen-induced chick oviduct differentiation.

Incorporation of [14C]mevalonate into dolichol and other isoprenoid compounds by chick oviduct explants has been studied. A reliable assay of dolichol biosynthesis employing several chromatographic procedures, including two-dimentional TLC, was developed. Incorporation of [14C]mevalonate into dolichol by oviduct explants was linear for at least 6 h. The effect of estrogen-induced differentiation was studied by incubation of explants obtained from chicks treated for various periods of time with diethylstilbestrol. Mevalonate incorporation into dolichol, when expressed as cpm per g of tissue, was not affected by estrogen treatment, but since the oviduct increased about 100-fold in mass during differentiation, each oviduct synthesizes about 100-fold more dolichol. In most tissues, the major product of mevalonate incorporation is cholesterol. However, although approx. 90% of the non-saponifiable 14C-labeled compounds were in the so-called 'cholesterol fraction', oviduct explants from estrogenized chicks synthesized little, if any, cholesterol. A number of cholesterol biosynthetic intermediates were observed, with compounds comigrating with squalene and lanosterol accounting for about 50% of the total. Since the estrogenized chick has serum cholesterol levels in the range of 800-900 mg/dl, these results suggest that oviduct has secondary control points which allow it to inhibit cholesterol synthesis when mevalonate is used as the precursor. In support of this hypothesis is the observation that explants from untreated chicks can incorporate mevalonate into cholesterol.

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.