Gastrointestinal Decontamination Research Articles

The Insidious Enemy of the Liver: The Situation in Childhood Acetaminophen Poisoning and Early N-AC Treatment.

This study was designed as a cross-sectional, observational, retrospective study. The variables of the study were paracetamol overdose, demographic information, poisoning mechanisms, clinical, laboratory findings, and clinical progression of the cases. The cases compared in whom treatment was initiated within the first 8 hours after poisoning and those in whom it was not. χ2, t test, and logistic regression analyses were conducted at appropriate facilities. Three hundred forty-eight cases were included in the study. N-AC treatment was initiated within the first 8 hours after poisoning in 322 cases (92.5%), and 26 cases received N-AC treatment after 8 hours after poisoning. Liver toxicity developed in 6 cases (1.7%), and indications for liver transplantation were met in 36 cases (10.3%). Among the 26 cases for which treatment was not initiated within the first 8 hours, 18 cases (69.2%) had indications for liver transplantation (P < 0.01). It was found that N-AC within the first 8 hours reduced the risk by 43 times (P = 0.02) and being older than 6 years, being admitted to the intensive care unit, and having alanine aminotransferase values above 1000 U/L increased the risk significantly (P = 0.009, P = 0.005, P < 0.001). When a receiver operating characteristic curve was plotted for the 4th-hour blood acetaminophen level to predict liver transplantation, a value of 684.5 μg/mL emerged with 89% sensitivity and 93% specificity (area under the curve, 0.951). As a result, this study demonstrates the protective effect of early-initiated N-AC therapy on liver toxicity in pediatric acetaminophen poisoning cases. It also highlights a significant impact of gastrointestinal decontamination methods.

An in vitro study of metformin adsorption to activated charcoal

Introduction Metformin is a biguanide used to manage patients with type 2 diabetes mellitus. However, metabolic acidosis with an elevated lactate concentration and death caused by metformin overdoses are toxicological concerns. Although activated charcoal has been widely used for gastrointestinal decontamination in cases of acute poisoning, there is no evidence regarding its efficacy in treating metformin overdoses. We therefore evaluated the adsorptive capacity of activated charcoal for metformin in vitro. Methods Activated charcoal (specific surface area: 1,080 m2/g) mixed with various concentrations of metformin solution was dissolved in simulated gastric and intestinal fluids at 37° Celsius. The suspension was then filtered and the metformin concentration in the filtrate was determined using high-performance liquid chromatography. The maximum adsorptive capacity for metformin was calculated using the Langmuir adsorption isotherm equation. Results The amount of metformin adsorbed per gram of activated charcoal ranged from 0.7 to 8.1 mg/g at pH 1.2, and from 8.4 to 48.2 mg/g at pH 6.8. The corresponding maximum adsorptive capacities were 10.6 mg/g and 55.9 mg/g respectively. Discussion The maximum adsorptive capacity of activated charcoal for metformin was similar to that of its capacity for other poorly adsorbed substances. This is likely because metformin is water-soluble and has high polarity—factors that correlate with poor adsorption on activated charcoal. Conclusions The maximum adsorption of metformin by activated charcoal was low. Therefore, activated charcoal may not be effective for treating patients with metformin overdose.

Does Mixing Activated Charcoal With Cola Improve Tolerability Without Affecting Pharmacokinetics? A Randomized Controlled Crossover Trial

IntroductionActivated charcoal is the most common form of gastrointestinal decontamination used for the poisoned patient. One limitation to its use is patient tolerability due to palatability. Some recommend mixing activated charcoal with cola to improve palatability. An important question is whether mixing activated charcoal with cola affects the ability of the activated charcoal to adsorb xenobiotic. MethodsThis was a prospective randomized controlled crossover trial. Five healthy adults aged 18 to 40 years were recruited. Participants received 45 mg/kg acetaminophen rounded down to the nearest whole tablet. One hour later, they were randomized to receive 50 g of an activated charcoal-water premixture alone or mixed with cola. Acetaminophen levels were collected. The area under the curve of acetaminophen concentrations over time was measured as a marker for degree of absorption. Participants also completed an appeal questionnaire in which they rated the activated charcoal preparations. Participants would then return after at least 7 days to repeat the study with the other activated charcoal preparation. ResultsFour male participants and 1 female participant were recruited. There was no statistical difference in preference score for activated charcoal alone versus the cola-activated charcoal mixture. There was no statistical difference in the area under the curve of acetaminophen concentrations over time between activated charcoal alone and the cola-activated charcoal mixture. Of note, the study is limited by the small sample size, limiting its statistical power. DiscussionThe absorption of acetaminophen in an overdose model is no different when participants received activated charcoal alone or a cola-activated charcoal mixture as suggested by area under the curve. In this small study, there was no difference in preference for activated charcoal alone or a cola-activated charcoal mixture across a range of palatability questions. On an individual level, some participants preferred the activated charcoal-cola mixture, and some preferred the activated charcoal alone.

Aromatic polypeptide amphiphiles for drug adsorption: a new approach for drug overdose treatment

This work represents a new application of aromatic polypeptide amphiphiles as a gastrointestinal decontamination technology.

Late-onset non-obstructive mesenteric ischemia (NOMI) resulting from delayed absorption of overdosed antihypertensive drugs: An autopsy case report.

Non-obstructive mesenteric ischemia (NOMI) is caused by reduced blood flow to the intestines without physical occlusion in the mesenteric artery. Previous reports show that drug overdose occasionally induces late-onset NOMI; however, in most cases, the reason for the delayed onset is unclear. Here, we present an autopsy case of late-onset NOMI that was induced by a drug overdose. An 80-year-old man was admitted to the intensive care unit because of severe hypotension after an overdose of antihypertensive drugs. He received vasopressor therapy and continuous hemodiafiltration dialysis; however, gastrointestinal decontamination was not performed. He began to recover but developed acute mesenteric ischemia on the evening of day 4 and died on day 5. Autopsy showed discontinuous submucosal bleeding from the duodenum to the colon; there was no thrombus in the mesenteric artery, which led to a diagnosis of NOMI. In the stomach, there was 250mL of reddish-brown fluid with a muddy brown substance. Histologic examination revealed ischemic necrosis in the small intestine. Quantitative analysis of serum collected during hospitalization revealed that nifedipine and cilostazol levels had peaked on day 3 of hospitalization. The formulation of nifedipine was a controlled-release tablet, and the low water solubility of cilostazol may have caused the tablets to adhere and remain in the stomach. Therefore, the drugs had been released into the blood stream several days after hospitalization, leading to delayed-onset NOMI. In cases of overdose, it is crucial to consider the formulation and properties of the involved drugs when determining medical treatment.

Strychnine Poisoning: Literature Review

Strychnine poisoning is an quite unusual but a serious poisoning in which convulsions are the major threat to life. Convulsions are predominantly noted at the spinal level, and the key to recognizing this poison is observation of convulsive activity in the awake patient without a postictal phase. Successful treatment requires aggressive airway control and treatment of seizures with benzodiazepines or barbiturates. Neuromuscular blockade may be required. Gastrointestinal decontamination is usually indicated in recent acute ingestions but may precipitate convulsions. Recovery from strychnine poisoning is usually complete and rapid if treatment is aggressive.

Two Patients of 113 and 77 Years Old of Atropa Belladonna Poisoning Case Report

Atropa belladonna is a deadly poisonous plant. Its roots, leaves and fruits contain alkaloids: atropine, hyosciamine and scopolamine. Atropa belladonna poisoning is a serious condition and should be considered in the presence of anticholinergic toxidroma. Treatment is mainly symptomatic, including gastrointestinal decontamination with activated charcoal. In severe cases, physostigmine can be used as an antidote. Atropa Belladonna poisoning should be considered in a patient with symptoms of anticholinergic poisoning.

Physicians' perspectives on different therapeutic approaches for aluminum phosphide poisoning and their relevant outcomes.

Aluminum phosphide is a highly toxic pesticide that results in high mortality. To date, there is neither a definitive antidote nor a unified protocol for managing acute aluminum phosphide poisoning. This cross-sectional questionnaire-based study aims to explore different management approaches and rely on the expertise of Egyptian medical professionals to enhance the prognosis for acute aluminum phosphide poisoning. A self-administered questionnaire was formulated and electronically distributed according to published literature and experience of senior physicians. Responses were received from 151 physicians from 10 governorates. Management modalities were variable among respondents. Noradrenaline was used by 90.7% of respondents with no fixed-dose regimen. In all, 84.1% of participants utilized oil in gastrointestinal decontamination; paraffin oil was the most used solution. Overall, 92.1, 61.6, 46.4, and 34.4% of participants used sodium bicarbonate, proton pump inhibitors, IV magnesium sulfate, and antioxidants, respectively. Regarding the frequency of acute aluminum phosphide poisoning, 47% of participants managed these cases daily or a few times a week. Participants' responses denoted a poor prognosis of acute aluminum phosphide poisoning, and high percentages attributed the prognosis to exposure factors rather than treatment modalities. Statistical analysis revealed that using oil in gastrointestinal decontamination improved the outcome by 4.62-fold. Clinical toxicologists were more likely to rescue≥30% of the cases about 3-fold (2.97) than other specialties. Clinical toxicologists used oil in gastrointestinal decontamination, magnesium sulfate, and antioxidant therapy and calculated base deficit before administration of sodium bicarbonate by 7.70-, 5.30-, 3.26-, and 2.08-fold than other specialties.

Three cases of acute chlorfenapyr poisoning

This paper reported 3 cases of poisoning caused by chlorfenagyr. Chlorfenapyr poisoning has gradually increased in clinical practice. The early stage after poisoning is digestive tract symptoms, followed by sweating, high fever, changes in consciousness, changes in myocardial enzymology, etc. Its main mechanism of intoxication is uncoupling oxidative phosphorylation. Since there is no specific antidote after poisoning, the fatality rate of chlorfenapyr poisoning remains high. The therapeutic measures are early gastrointestinal decontamination, symptomatic and supportive treatments, and early blood purification may be an effective treatment.

Awareness raising and dealing with methanol poisoning based on effective strategies

Intoxication with methanol most commonly occurs as a consequence of ingesting, inhaling, or coming into contact with formulations that include methanol as a base. Clinical manifestations of methanol poisoning include suppression of the central nervous system, gastrointestinal symptoms, and decompensated metabolic acidosis, which is associated with impaired vision and either early or late blindness within 0.5–4 h after ingestion. After ingestion, methanol concentrations in the blood that are greater than 50 mg/dl should raise some concern. Ingested methanol is typically digested by alcohol dehydrogenase (ADH), and it is subsequently redistributed to the body's water to attain a volume distribution that is about equivalent to 0.77 L/kg. Moreover, it is removed from the body as its natural, unchanged parent molecules. Due to the fact that methanol poisoning is relatively uncommon but frequently involves a large number of victims at the same time, this type of incident occupies a special position in the field of clinical toxicology. The beginning of the COVID-19 pandemic has resulted in an increase in erroneous assumptions regarding the preventative capability of methanol in comparison to viral infection. More than 1000 Iranians fell ill, and more than 300 of them passed away in March of this year after they consumed methanol in the expectation that it would protect them from a new coronavirus. The Atlanta epidemic, which involved 323 individuals and resulted in the deaths of 41, is one example of mass poisoning. Another example is the Kristiansand outbreak, which involved 70 people and resulted in the deaths of three. In 2003, the AAPCC received reports of more than one thousand pediatric exposures. Since methanol poisoning is associated with high mortality rates, it is vital that the condition be addressed seriously and managed as quickly as feasible. The objective of this review was to raise awareness about the mechanism and metabolism of methanol toxicity, the introduction of therapeutic interventions such as gastrointestinal decontamination and methanol metabolism inhibition, the correction of metabolic disturbances, and the establishment of novel diagnostic/screening nanoparticle-based strategies for methanol poisoning such as the discovery of ADH inhibitors as well as the detection of the adulteration of alcoholic drinks by nanoparticles in order to prevent methanol poisoning. In conclusion, increasing warnings and knowledge about clinical manifestations, medical interventions, and novel strategies for methanol poisoning probably results in a decrease in the death load.

Management of Poisonings and Intoxications.

Poisoning occurs after exposure to any of a number of substances, including medicines, which can result in severe toxicity including death. The nephrologist may be involved in poisonings that cause kidney disease and for targeted treatments. The overall approach to the poisoned patient involves the initial acute resuscitation and performing a risk assessment, whereby the exposure is considered in terms of the anticipated severity and in the context of the patient's status and treatments that may be required. Time-critical interventions such as gastrointestinal decontamination ( e.g. , activated charcoal) and antidotes are administered when indicated. The nephrologist is usually involved when elimination enhancement techniques are required, such as urine alkalinization or extracorporeal treatments. There is increasing data to guide decision making for the use of extracorporeal treatments in the poisoned patient. Principles to consider are clinical indications such as whether severe toxicity is present, anticipated, and/or will persist and whether the poison will be significantly removed by the extracorporeal treatment. Extracorporeal clearance is maximized for low-molecular weight drugs that are water soluble with minimal protein binding (<80%) and low endogenous clearance and volume of distribution. The dosage of some antidotes ( e.g. , N-acetylcysteine, ethanol, fomepizole) should be increased to maintain therapeutic concentrations once the extracorporeal treatment is initiated. To maximize the effect of an extracorporeal treatment, blood and effluent flows should be optimized, the filter with the largest surface area selected, and duration tailored to remove enough poison to reduce toxicity. Intermittent hemodialysis is recommended in most cases when an extracorporeal treatment is required because it is the most efficient, and continuous kidney replacement therapy is prescribed in some circumstances, particularly if intermittent hemodialysis is not readily available.

The role of whole bowel irrigation in the treatment of toxic ingestions.

There is no high-quality evidence regarding the benefit of any gastrointestinal decontamination procedure in the overdose patient. The original and twice reaffirmed position of the AACT and EAPCCT is based upon the best evidence and practical considerations. WBI was recommended as a treatment for the ingestion of modified release pharmaceuticals, iron salts and other substances not adsorbed by activated charcoal. This is a best evidence recommendation.

Compliance to whole bowel irrigation recommendations: a single poison center study

Introduction: Whole Bowel Irrigation (WBI) is used as a method of gastrointestinal decontamination for poisoned patients and may have low compliance when recommended by poison centers (PC). We set out to determine WBI compliance and analyze trends and possible associations between WBI compliance and clinical outcomes. Methods: We conducted a single-center retrospective chart review of PC data from 1/1/2011 to 12/31/2019 and included cases in which WBI was recommended. We collected demographic data, exposure history, therapies recommended and performed, and clinical outcomes. Compliance rate was calculated. Chi-squared and Mann-Whitney U tests were performed to look for differences in compliance based on case characteristics such as compliance rate by year, compliance based medication ingested and presence of intubation. We also looked for a possible association between WBI compliance and clinical outcome. Results: Four hundred and eighty-three cases met inclusion criteria. Fifty-five percent of patients were male and the median age was 32.5 years. Compliance to WBI recommendations was 58.2%. There was no significant difference in compliance when comparing by age, gender, medication ingested, or year. There was no association between compliance to WBI and clinical outcomes. Conclusions: We calculated a compliance rate of 58% when WBI was recommended. Compliance to WBI does not appear to be associated with changes in clinical outcome.

Availability of Antidotes for Management of Acute Toxicity Cases at Emergency Departments in Qassim Hospitals: A Retrospective Study.

Background: Drug overdose is a medico-social issue worldwide that may occur intentionally or unintentionally. It is one of the most common reasons for emergency department visits, and it is also a frequent cause of morbidity and mortality globally. This study aims to determine the occurrence of acute toxicity cases and their management outcomes at the emergency departments in Qassim Province hospitals in Saudi Arabia. In addition, the study aims to investigate the antidote availabilities at those medical centers.Methods: A retrospective hospital record-based study of acute toxicity cases admitted to the emergency department in hospitals in Qassim during the period from January 1, 2020, to December 31, 2020, was conducted. Data were collected based on hospital resources such as gastrointestinal decontamination, stabilization, elimination enhancement resources, and antidotes from Qassim hospitals, and the availability of antidotes as well as the clinical data of the patients with the management outcome.Results: A total of 264 patients with acute toxicity were admitted to the emergency departments of 14 hospitals in Qassim Province in 2020. Of the 264 cases, 179 (68%) were males, and 85 (32%) cases were females. Ninety-five percent of the cases were admitted to public hospitals, whereas 5% were admitted to private hospitals. The largest group by age of admitted cases were aged 11-20 years (19.3%). This study showed that 99% received appropriate treatment for their cause of toxicity, whereas 1% did not. The most common causes of toxicity in Qassim were found to be food poisoning (20.5%), followed by intentional suicide attempts with warfarin/enoxaparin/aspirin overdoses (15.9%) and acetaminophen (paracetamol) overdosage seen in 15.5% of admitted cases. Flagyl, in addition to fluids, was used in the management of 16.7% of cases, N-acetyl cysteine was used for 16.3%, and vitamins K and B6 were used for 14.0% of cases. Activated charcoal, atropine, calcium chloride, calcium gluconate, flumazenil, insulin, magnesium, sodium bicarbonate, and vitamin K were available at all the studied hospitals. However, all the hospitals lacked both ethylenediaminetetraacetic acid (EDTA) and a cyanide kit. Methylene blue and leucovorin were available in only one of the studied hospitals.

Paraquat poisoning

Paraquat (10-dimethyl-4, 40-bipyridylium dichloride) is the most common herbicide used worldwide. Due to its inherent toxicity and lack of effective treatment, it has high case fatality of more than 50%. Paraquat exposure through ingestion or inhalation leads to multi-organ involvement including lungs, CNS, heart, kidneys and liver. Treatment is mainly supportive including initial resuscitation, gastrointestinal decontamination, anti-inflammatory, antioxidant and immunosuppressive therapy. We are reporting two cases of paraquat poisoning and their management in intensive care unit, of which one was successfully treated and discharged from ICU while other one expired.

Whole-bowel irrigation in cases of poisoning: A retrospective multicentre study of feasibility, tolerability, and effectiveness

BackgroundWhole-bowel irrigation (WBI) is a strategy of gastrointestinal decontamination, recommended by several European and American learned societies, which may be used in the management of the poisoned patients. ObjectivesThe objectives of this study were to describe the feasibility and tolerability of this technique and to compare the clinical outcome of a group of poisoned patients treated with WBI versus that of an untreated group. MethodsThis was a retrospective and observational study of data recorded by the Angers Poison Control Centre (PCC) between 2012 and 2018. All cases for which the PCC advised WBI were included. The association between outcomes (clinical deterioration after WBI advised by a PCC, length of hospitalisation), WBI treatment, and relevant associated risk factors was determined using univariate and multivariate logistic regression. ResultsA total of 257 patients were included. One hundred forty-one patients were treated with WBI with clearly successful induction of diarrhoea in 47 cases (31%). WBI was not initiated in 89 patients. WBI was initiated but unsuccessful (no diarrhoea) in nine cases. The median age is 46 years (interquartile range: 32-55 years), with a sex ratio (M/F) of 1.3. A total of 27 of 150 patients (18%) who underwent WBI had adverse effects possibly linked to WBI, mainly vomiting (n=23). The patients with clinical deterioration (n=49) were irrigated significantly less often (95% confidence interval: 0.13-0.52; p<0.001). After adjustment for sex, age, time to implementation of WBI, type of substance ingested, and admission to intensive care, patients who were treated with WBI were less likely to deteriorate clinically than patients who were not treated with WBI (p<0.001). ConclusionDespite a low rate of completion of this procedure, WBI appeared to provide clinical benefits in patients treated in comparison of an untreated group and is associated with an acceptably low risk of direct complications.

Mushroom ( Amanita phalloides) Poisoning: Mechanisms, Pathogenesis, Prognosis and Strategies of Treatment

Poisoning due to mushroom consumption is uncommon, but it causes death by causing acute liver failure (ALF). The ingestion of Amanita phalloides, is one of the ultimate frequent causes of mushroom poisoning globally. This type has three main categories of toxins: amatoxins, phallotoxins, and virotoxins. From these toxins amatoxins and its metabolite α-amanitin, is the main cause of toxicity in population which cause deterioration in synthesis of protein and consequent cell necrosis and inhibition of RNA polymerase II ,so finally cause cell death. Liver is the chief organ involved in toxicity, kidneys and central nervous system also involved. Latent period has been proceeds the poisoning symptoms, which includes gastrointestinal symptoms followed by liver failure symptoms, coma and ultimately death. Management including supportive cares, gastrointestinal decontamination, special medications (Benzyl penicillin, N-acetyl cyctien, cimetidine, silibinin and others) and, finally liver transplantation if clinical condition deteriorated.&#x0D;

Analytical toxicology service model at the subregional center level for severe acute poisoning

Acute poisoning may necessitate identification of the toxic agent; however, several acutely poisoned patients are treated with minimal laboratory assistance. We investigated whether focused reference to laboratory toxicology tests conducted during a pilot project for a subregional analytical toxicology service influences treatment decisions. Patients with acute poisoning presented to the level 1 regional emergency medical center from May 2018 to April 2019 were initially reviewed. Poison samples were referred to the subregional toxicological analytical service. In total, 253 substance samples were tested among 111 patients during the study. According to the reported drug levels, 3 (1.2%) samples contained lethal doses, 49 (19%) had toxic levels, and 28 (11%) contained detectable levels of a lethal toxin or pesticide. Disagreement between the clinical assessment and laboratory analyses was found for 62 patients (fair kappa = 0.24, 56%), and they often had lower Glasgow Coma Scale, higher severity scores, older age, and less likelihood of receiving gastrointestinal decontamination. The regional analytical toxicology services were helpful for diagnostic planning and therapeutic management of acute poisoning. For seriously poisoned patients with inconsistent histories, it is necessary to reevaluate the classic therapeutic process based on the medical history.

Actions that should not be taken with a paediatric patient who has been exposed to a potentially toxic substance

ObjectiveTo show the preparation process by the Poisoning Working Group of the Spanish Society of Paediatric Emergencies (GTI-SEUP), of the list of things “not to do” for a paediatric patient who has been exposed to a potentially toxic substance. MethodThe preparation process of the list was carried out in three phases. First: “Brainstorming” that was open to all members of the GTI-SEUP. Second: Recommendations were selected by following modified-Delphi methodology. All participants were asked to rate the proposals (from 1 = strongly disagree to 9 = strongly agree). Those with an average score greater than 8 were accepted (provided that at least two-thirds of the participants had given them a score ≥ 7), and a second consultation was made for the recommendations with an average score between 6 and 8. Third: Writing and creating a consensus of the final document was done. ResultA total of 11 proposals were initially obtained. Thirty-two of the 57 GTI-SEUP participants completed the scoring questionnaire. In the first consultation, seven “not to do” recommendations were accepted, and four obtained a doubtful average score (between 6 and 8). After the second consultation, the list was made up of eight recommendations. Two refer to general management, four to gastrointestinal decontamination techniques, and two to the administration of antidotes. ConclusionThe list of actions that should not be taken with a child that has been exposed to a possible poison is a consensus tool, within the GTI-SEUP, to promote improvement in the quality of care offered to these patients. This improvement is based on avoiding unnecessary measures, which can sometimes be harmful to the child.

Management of Poisoning and Drug Overdose

Drug overdose and poisoning are leading causes of emergency department visits and hospital admissions in the United States, accounting for more than 500,000 emergency department visits and 11,000 deaths each year. This chapter discusses the approach to the patient with poisoning or drug overdose, beginning with the initial stabilization period in which the physician proceeds through the ABCDs (airway, breathing, circulation, dextrose, decontamination) of stabilization. The management of some of the more common complications of poisoning and drug overdose are summarized and include coma, hypotension and cardiac dysrhythmias, hypertension, seizures, hyperthermia, hypothermia, and rhabdomyolysis. The physician should also perform a careful diagnostic evaluation that includes a directed history, physical examination, and the appropriate laboratory tests. The next step is to prevent further absorption of the drug or poison by decontaminating the skin or gastrointestinal tract and, possibly, by administering antidotes and performing other measures that enhance elimination of the drug from the body. The diagnosis and treatment of overdoses of a number of specific drugs and poisons that a physician may encounter, as well as food poisoning and smoke inhalation, are discussed. Tables present the ABCDs of initial stabilization of the poisoned patient; mechanisms of drug-induced hypotension; causes of cardiac disturbances; drug-induced seizures; drug-induced hyperthermia; autonomic syndromes induced by drugs or poison; the use of the clinical laboratory in the initial diagnosis of poisoning; methods of gastrointestinal decontamination; methods of and indications for enhanced drug removal; toxicity of common beta blockers; common stimulant drugs; corrosive agents; dosing of digoxin-specific antibodies; poisoning with ethylene glycol or methanol; manifestations of excessive acetylcholine activity; common tricyclic and other antidepressants; seafood poisonings; drugs or classes that require activated charcoal treatment; and special circumstances for use of activated charcoal. This review contains 3 figures, 22 tables, and 198 references.