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OBJECTIVES To characterize the epidemiology of children and adolescents admitted for deliberate self-harm to PICUs in the United States by examining patient demographics, diagnoses, modes of self-harm, and outcomes. DESIGN Descriptive analysis of a large, multicenter, quality-controlled database. SETTING The 137 PICUs participating in the Virtual Pediatric Systems database during the study period. PATIENTS Children between 6 and 18 years old admitted to a participating PICU from January 1, 2009, to December 31, 2017, with a diagnosis involving deliberate self-harm or a suicide attempt. INTERVENTIONS None. MEASUREMENTS AND MAIN RESULTS Of 9,197 admissions for self-harm, females accounted for 6,740 (73.3%), whereas males incurred 174 of the 284 deaths (61.3%). Admissions for self-harm doubled over the study period (0.56% in 2009 vs 1.13% in 2017), with an increase observed across every age group. After PICU care, most patients were transferred to a general care floor (51.1%) or to a psychiatric rehabilitation facility (31.8%). Intentional drug ingestion (84%) was the most common mode of self-harm but was associated with less than 1% of the fatalities. Asphyxia/hanging or firearms were a factor in 411 (4.5%) and 106 (1.2%) of the admissions but were associated with 117 (28.5%) and 55 (51.9%) of the deaths, respectively. CONCLUSIONS PICU admissions due to self-harm increased for all age groups during the study period. Females accounted for most of these admissions, whereas males accrued most of the in-hospital deaths. Intentional drug ingestion was the most common mode of self-harm and was rarely fatal, whereas asphyxia and firearms were the mechanisms associated with the highest mortality.

To prove drug-related crimes, it is important to estimate the date on which a specific drug was ingested. Previously, we developed a method, "micro-segmental hair analysis," to estimate the day of ingestion of a single-dose drug by segmenting a hair strand into 0.4-mm segments, which correspond to daily hair growth. In this study, the method was improved to estimate the days of continuous drug ingestion. The subjects ingested four hay-fever medicines (fexofenadine, epinastine, cetirizine, and loratadine) continuously (1-18 days) and chlorpheniramine as a single dose at intervals of several weeks as an internal temporal marker (ITM). The hair strands of the subjects were collected and subjected to a micro-segmental analysis. The distribution curves of each hay-fever medicine in a hair strand had broad peaks reflecting the number of days of drug ingestion. The positions on the curves corresponding to the first and final ingestion days of hay-fever medicines were identified using the ITM. The positions were near the hair segments on both ends of full width at half maximum (W2 ) of the broad peak. When the first and final days of continuous ingestion were estimated using W2 , independent of peak shape, the absolute average error from the actual ingestion days was approximately 2 days. Overall, we established a method to estimate the days of both single-dose and continuous drug ingestions. Furthermore, the method would be useful to investigate drug ingestion history in various scenes such as drug-related crimes and therapeutic drug monitoring.

Cerumen was found to be a promising alternative specimen for the detection of drugs. In a pilot study, drugs of abuse were identified at a higher detection rate and a longer detection window in cerumen than in urine. In this study, cerumen from subjects was analyzed after they ingested the designer stimulant 4-fluoroamphetamine (4-FA) in a controlled manner.METHODS: Twelve subjects ingested placebo and 100 mg of 4-FA. Five of them were also given 150 mg of 4-FA in 150 mL Royal Club bitter lemon drink at least after 7 days. Cerumen was sampled using cotton swabs at baseline, 1 h after the ingestion of the drug and at the end of the study day (12 h). After extraction with ethyl acetate followed by solid-phase extraction, the extracts were analyzed using liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS).RESULTS AND DISCUSSION: In the cerumen of all 12 subjects, 4-FA was detected 12 h after its ingestion; in most subjects, cerumen was detected after 1 h of ingestion, ranging from 0.06 to 13.90 (median 1.52) ng per swab. The detection of 4-FA in cerumen sampled 7 days or more after the first dose suggested a long detection window of cerumen.CONCLUSIONS: Cerumen can be successfully used to detect a single drug ingestion even immediately after the ingestion when a sufficient amount of cerumen is used.

Sleeping aids are often abused in the commission of drug-facilitated crimes. Generally, there is little evidence that a victim ingested a spiked drink unknowingly because the unconscious victim cannot report the situation to the police immediately after the crime occurred. Although conventional segmental hair analysis can estimate the number of months since a targeted drug was ingested, this analysis cannot determine the specific day of ingestion. We recently developed a method of micro-segmental hair analysis using internal temporal markers (ITMs) to estimate the day of drug ingestion. This method was based on volunteer ingestion of ITMs to determine a timescale within individual hair strands, by segmenting a single hair strand at 0.4-mm intervals, corresponding to daily hair growth. This study assessed the ability of this method to estimate the day of ingestion of an over-the-counter sleeping aid, diphenhydramine, which can be easily abused. To model ingestion of a diphenhydramine-spiked drink unknowingly, each subject ingested a dose of diphenhydramine, followed by ingestion of two doses of the ITM, chlorpheniramine, 14days apart. Several hair strands were collected from each subject's scalp several weeks after the second ITM ingestion. Diphenhydramine and ITM were detected at specific regions within individual hair strands. The day of diphenhydramine ingestion was estimated from the distances between the regions and the days of ITM ingestion. The error between estimated and actual ingestion day ranged from -0.1 to 1.9days regardless of subjects and hair collection times. The total time required for micro-segmental analysis of 96 hair segments (hair length: 3.84cm) was approximately 2days and the cost was almost the same as in general drug analysis. This procedure may be applicable to the investigation of crimes facilitated by various drugs.

Heat stroke is a medical emergency which may lead to mortality unless diagnosed early and treated effectively. Heat stroke may manifest rapidly, hence making it difficult to differentiate it from other clinical causes in a collapsed victim.1 We are presenting a case report of twelve patients who were admitted to our emergency department from a music festival held on 13-15th of March 2014. They developed complications arising from a combination of severe adverse weather condition, prolonged outdoor physical exertion due to long hours of dancing and drug-use, resulting in heat stroke. Three of them died while the remaining patients survived. Their condition was initially misdiagnosed as a classical illicit drug overdose. This was based on the history of drug ingestion by some of the patients who attended the music festival on that day. The information in this case report aims, to create awareness amongst members of the medical team on duty in outdoor events, pre hospital responders and ED physicians when treating and managing similar cases in the future. In addition it is intended to warn the organizers of such events to take adequate precautions to avoid such tragedies in the future.

The authors investigated the role of poor drug adherence in treatment‐resistant hypertension following observed drug ingestion in 102 patients. Median blood pressures (BPs) were 170/91 mm Hg at referral, 153/84 mm Hg prior to, and 142/79 mm Hg during a 4‐ to 6‐hour period after drug ingestion. Median daytime ambulatory BP monitoring (ABPM) over the following 24 hours was 142/80 mm Hg. Median BP at a final follow‐up clinic visit was 147/79 mm Hg. The cumulative number of patients achieving a goal of

As transplantation has progressively become a more viable option for children with life-threatening illness, ensuring that adolescents do not lose their new organ secondary to medication non-adherence is paramount. The first step to addressing non-adherence is adequate assessment of this construct. In this investigation, we introduce the MACS. The MACS includes self-report and drug assay levels. Self-report is a subjective measure with a low false-positive rate, but is vulnerable to social desirability. Drug assays are an objective measure of drug ingestion, but values suggestive of non-adherence may be influenced by medical complications and timing. The MACS builds on the strengths of both methods and attempts to contain their weaknesses. The sample in this study consisted of 82 adolescent solid organ transplant recipients. The non-adherence rate using the MACS in this sample was 61%. Initial data to support this system are promising. The occurrence of rejection episodes and mortality were significantly related to membership in the Genuinely Non-adherent category. Beyond providing initial support for the MACS, we discuss the clinical implications of this adherence classification system.

A study of the characteristics before conception of 145 mothers and 135 fathers of Down's children compared to control parents has shown that the Down's mothers, even when controlled for age, had significantly more illnesses before conception, particularly psychological illness, and significantly more drug ingestion in the year before conception. There were no other differences in the mothers and the fathers did not demonstrate a similar tendency. Since morbidity and drug ingestion are both associated with increasing age, it is suggested that further investigation of the role of environmental factors such as illness or drug ingestion may elucidate further the aetiology of Down's syndrome.

This case study documents the nearly complete consumption of adult human remains by two domestic dogs (Canis familiaris) inside a residence. While scavenging behavior has been observed for coyotes, wolves, hyenas and other canines in natural outdoor environments, little information is available concerning canine scavenging of human remains in an indoor setting. In this case, the dogs were confined with the body inside a residence for approximately 1 month. The impact of intrinsic and extrinsic factors on canine scavenging behavior and the postmortem interval are examined, such as clothing on the body, perimortem trauma, drug ingestion and the availability of alternative food sources. While cases of canine scavenging of their owners are scant in the literature, this phenomenon is probably not uncommon, particularly among the elderly and indigent who live alone with pets and are socially isolated.

Syncope is a common condition that may lead to serious injuries including burns and head injury. To date, here has been no specific discussion of syncope and burns in the literature. A retrospective case-note review of consecutive patients admitted to a Tertiary Burns Centre over a 3.5-year-period was conducted. Five hundred and fifty nine patients were admitted during the study period. Six of these had burns related to alterations of consciousness that excluded alcohol/drug ingestion and epilepsy. The mean percentage body surface area burnt was 9.7%, the mean length of hospital stay was 28.5 days and the mean length of stay per percentage surface area burnt was 4.0 days per percent body surface burnt. The mean size of the injury in syncopal patients is slightly larger than the general burns patients (8.4%) but the length of stay is doubled. This is partly related to surgery being delayed due to investigation of the syncope episode. Focused investigations should reduce both the overall length of hospital stay and the number of investigations.

The most important cause of hypoglycaemia in the presence of high insulin and C-peptide concentrations is insulinoma. However, a similar picture arises from use of sulphonylureas, which is sometimes covert. All specimens received in two years by a supraregional assay service laboratory from adults with low glucose and inappropriately high insulin and C-peptide concentrations were tested for sulphonylureas by a radioimmunoassay that employed antibodies to glibenclamide. In sulphonylurea-positive cases a questionnaire was sent to the consultant responsible for the patient, to elicit further information. Samples from 93 adult patients met the criteria, and 34 (37%) of these gave a positive result on screening for sulphonylureas. The consultants provided further information on 31 of the 34, and in 20 the presence of a sulphonylurea was unexpected. In 10 the features were such as to raise the possibility of factitious drug ingestion. A simple screening technique applied to specimens from patients with hyperinsulinaemic hypoglycaemia indicated that, in a substantial proportion of cases, the patient was taking a sulphonylurea.

The recent American Academy of Clinical Toxicology/European Association of Poisons Centres and Clinical Toxicologists position statement on activated charcoal stated "there are insufficient data to support or exclude its use after 1 hour of ingestion.'' The purpose of this study was to determine the effectiveness of activated charcoal administered 1, 2, and 3 hours after drug ingestion.This was a human volunteer, randomized crossover study. Ten volunteers ingested 4 g of acetaminophen on four occasions at least 1 week apart. One ingestion served as a control and the other three as experimental ingestions with charcoal being administered at 1, 2, and 3 hours after acetaminophen dosing. Eight blood specimens were obtained over the initial 8 hours for serum acetaminophen concentrations that were used for calculation of routine pharmacokinetic parameters. Repeated measures of ANOVA and Tukey's HSD test were used for statistical analysis.Pharmacokinetic parameters for acetaminophen in our volunteers were consistent with literature values. The mean area under the curve (AUC+/-SD) for the control and the 1-, 2-, and 3-hour groups were 221 +/- 54, 154 +/- 71, 206 +/- 67 and 204 +/- 58 mg/L/h, respectively. The 1-hour group was the only one differing from control (p0.01). The decrease of bioavailability at 1 hour was 30.3%, which is similar to previous studies.Our data do not support the administration of activated charcoal as a gastrointestinal decontamination strategy beyond 1 hour after drug overdose.

Background The diagnosis of fixed ‘drug’ eruption is not difficult for dermatologists, but it is difficult to identify the causative agent when the patient denies ingestion of any drugs. There have been some reported cases of fixed ‘food’ eruption. Case Summary A 71-year-old woman experienced repeated erythema and tense bulla with a burning sensation and pruritus on the right ankle. The eruption remitted leaving pigmentation. The patient denied previous ingestion of any drug. We suspected cashew nut as the causative agent. Oral challenge and patch tests with cashew nut were positive. Discussion A fixed eruption without any antecedent drug ingestion should alert us to think of food as a causative agent.

A case of accidental ingestion of cannabis by a toddler is reported. Details of her presentation, investigations performed management and her recovery are outlined. Included is a discussion of alternative differential diagnoses and a summary of similar cases reported previously in journals. The management of the toddler and her family is also addressed. The case illustrates the need to consider drug ingestion in a toddler or child with reduced conscious levels and with or without abnormal neurological findings.

Analysis of drugs in hair is often used as a routine method to obtain detailed information about drug ingestion. However, few studies have been conducted on deposition of synthetic cannabinoids and metabolites in hair. The first purpose of this study was to establish and validate an analytical method for detection of JWH-018, JWH-073, and their metabolites in hair, by use of UHPLC–MS–MS, for forensic application. The second purpose was to investigate the distribution of synthetic cannabinoids metabolites in hair and the effect of hair pigmentation, by use of an animal model. For this, JWH-073 was chosen as a representative synthetic cannabinoid. Finally, the developed method was applied to hair samples from 18 individuals suspected of synthetic cannabinoids use. JWH-018, JWH-073, and their metabolites were extracted from hair with methanol. The extract was then filtered and analyzed by UHPLC–MS–MS with an electrospray ion source in positive-ionization mode. Validation proved the method was selective, sensitive, accurate, and precise, with acceptable linearity within the calibration ranges. No significant variations were observed when different sources of both human and rat hair were used. The animal study demonstrated that JWH-073 N-COOH M was the major metabolite of JWH-073 in rat hair, and hair pigmentation did not have a significant effect on incorporation of JWH-073 and its metabolites into hair. In the analysis of 18 authentic hair samples, only JWH-018, JWH-018 N-5-OH M, and JWH-073 were detected, with wide variation in concentrations.

Anaesthetists require a good knowledge of the excretion of drugs in breast milk and the potential hazards to suckling infants of drug ingestion via breast milk. A brief account of the physiology of lactation is given. The mechanisms of drug passage into breast milk are discussed followed by a review of the excretion in breast milk of drugs used in anaesthetic practice. Suggestions for the management of anaesthesia in breast feeding mothers are offered.

Summary Background Post-sclerotherapy pigmentation, usually overlying the treated veins and independent of any drug ingestion, is common. This pigmentation is brown and represents haemosiderin and sometimes melanin as well. It usually slowly fades over a period of months, only uncommonly persisting for years. Cutaneous pigmentation due to minocycline ingestion is a known but rare adverse effect. It usually appears as a round or irregular shaped patch that is dark blue to black, representing minocycline moieties and iron complexes. Its persistence for years is common. Clinically and histopathologically, these two causes of pigmentation are quite distinct. In the absence of ulceration, minocycline pigmentation koebnerised by sclerotherapy has not previously been reported. Aims To determine the nature of the pigmentation appearing in three patients who had been taking minocycline at the time, or shortly after, they had received sclerotherapy. Clinically, although this pigmentation had the usual distribution observed after sclerotherapy, it was persistent and appeared dark blue to black. Results The persistent post-sclerotherapy linear pigmentation observed in all three patients had the characteistics of minocycline pigmentation. Conclusions This is the first report of such minocycline-aggravated post-sclerotherapy pigmentation. Persistent post-sclerotherapy pigmentation caused by minocycline is a risk associated with ingestion of this drug. Patients need to be warned of this risk because, unlike post-sclerotherapy pigmentation that develops in the absence of drug ingestion, minocycline-aggravated post-sclerotherapy pigmentation may persist for years.

Epidemiologic and experimental reports suggest that female hormones protect against the development of colorectal cancer, but studies are limited. We describe a patient in the placebo arm of a 4-year primary chemoprevention trial who developed adenomatous polyps and then had eradication of polyps after the administration of oral contraceptives. No change in the prostaglandin levels in the colonic mucosa was noted after polyp elimination, making nonsteroidal anti-inflammatory drug ingestion unlikely as a cause. This report represents the regression of colorectal adenomas with the use of estrogen/progesterone compounds.

Background: In the fight against the global tuberculosis epidemic, it is essential to ensure that patients adhere to the treatment prescribed. As the treatment is given for a minimum of 6 months it is common for patients not to take their drugs regularly. Strategies are therefore needed to assess adherence to treatment. One established method is to examine the patient's urine for the presence of drug metabolites. A rapid point-of-care test would overcome some of the drawbacks associated with currently available methods. Method: A rapid, safe point-of-care test for isoniazid metabolites (IsoScreen, Surescreen Diagnostics Limited, Derby, UK) has been developed and used to help assess adherence to treatment in a busy clinic for tuberculosis patients in South London. Results: Urine samples were examined from 191 patients receiving isoniazid, usually in combination with rifampicin and other anti-tuberculous drugs. Isoscreen was positive in 93.2% of patients, suggesting that 6.8% might be poorly adhering to treatment. By contrast, examining the same urine samples for evidence of rifampicin ingestion gave positive results in only 43.5%, due to the fact that this test is only positive for a few hours after drug ingestion. Conclusion: IsoScreen has been shown to provide a rapid and safe point-of-care test, which contributes to the detection of non-adherence in patients with tuberculosis.

Zaleplon ("Sonata") is a pyrazolopyrimidine derivative approved for use in the United States for the treatment of insomnia. To date, there has been little data in the toxicological literature where zaleplon has been implicated as causing a fatal intoxication, either alone or in combination with other drugs. This report documents a case where zaleplon was identified in a suicide by multiple drug ingestion. The following zaleplon concentrations were found: heart blood 2.2mg/l; bile 8.6mg/l and urine 1.4mg/l. Zaleplon was also detected but not quantitated in the kidney and liver.

This patient presented with clinical features consistent with acute cervical myelopathy or Guillain–Barré syndrome but ventricular arrhythmias on the electrocardiogram alerted the authors to a possible toxic cause. The history of drug ingestion was then elucidated, indicating aconitine poisoning from herbal medicine. Aconitine-containing plants are the most frequently encountered herbal agents that cause serious toxicity in Hong Kong (Chan et al, 1993).

The topic of drug ingestion related to pregnancy, and the peri-pregnant period including lactation has always been important but under-studied. It is therefore gratifying to see that in this issue there are 4 papers devoted to this topic, covering the period from 3 months prior to conception to early post-partum, including lactation.

Drug exposure during pregnancy is a common occurence (Doering and Stewart 1978; Hogan and Todd 2001). During pregnancy, drug ingestion may not only affect the mother, it may cross the plancenta als...

To determine the decrease of drug absorption when syrup of ipecac is administered at various times within one hour of drug ingestion.Ten healthy human volunteers were recruited for a four-limbed randomized crossover study. The three experimental limbs consisted of administration of 30 mL syrup of ipecac, at 5, 30, or 60 minutes after ingestion of 3900 mg acetaminophen as 12 x 325 mg tablets with 250 mL room temperature water. The fourth limb served as control. Blood samples were drawn at 0, 0.5, 1.0, 2.0, 3.0, 4.0, 6.0, and 8.0 hours after analgesic ingestion for serum acetaminophen concentration determination by high-performance liquid chromatography. Repeated measures ANOVA and Tukey's HSD tests were used for group comparisons.The area under the serum concentration vs time curve was (mean +/- SD) 206 +/- 48, 67 +/- 37, 183 +/- 78, and 162 +/- 47 mg/L for control, 5, 30, and 60 minutes, respectively. This corresponds to decreases in bioavailability of 67, 11, and 21%. Only the 5-minute group differed significantly from control (p0.05). Sedation was observed as a significant adverse effect of ipecac administration.Our data do not support benefit from ipecac administration at 30 minutes and beyond. Our data suggest that benefit is lost at some point between 5 and 30 minutes. The sedative effect of ipecac may confound the observation of patients who have ingested sedative hypnotic agents.

Formed visual hallucinations are commonly associated with seizures, drug ingestion, and psychiatric disorders, or they can occur as release phenomena in the setting of visual loss. [1] Although a picture within a picture is a desirable feature in many new televisions, we report a patient who developed this unusual release hallucination within a visual field defect. ### Case report. A 51-year-old woman complained of seeing "a picture within a picture - like the new kind of television sets" in her lower left visual field. She described a rectangular scene with a red …

To pregnant or breast feeding women drugs should be given with caution. We report the case of a 5-week-old breast-fed infant whose mother was taking 300 mg allopurinol/day for 4 weeks. Allopurinol and oxypurinol were detected by HPLC in maternal plasma and breast milk with a method first described here. In infant's plasma taken 2 h after breast feeding oxypurinol was found; allopurinol was below the limit of detection. The milk/plasma ratio in the mother 2 h (4 h) after drug ingestion was 0.9 (1.4) for allopurinol and 3.9 (2.4) for oxypurinol. The average daily dose for the baby of allopurinol was 0.14–0.20 mg/kg and that of oxypurinol 7.2–8.0 mg/kg by ingestion of breast milk after oral intake of allopurinol by the mother.

Maternal drug intake before delivery may influence the clinical behavior of the newborn. The effects of anesthetic agents and narcotics may cause symptoms of depression in the infant. Infants of substance-abusing mothers may also have altered clinical states. This is a case report of a newborn, very depressed at birth, who apparently was sedated by diphenhydramine (Benadryl) ingested by the mother before delivery. The importance of complete history of drug ingestion by mother before delivery is important in evaluating the behavior of a neonate.

A 40-year-old man developed multiple longitudinal pigmented streaks in his nails. His sister was also found to have a single streak on a fingernail. Neither had any history of drug ingestion or recent illness and examination failed to reveal any other signs in the skin or mucosal surfaces. A biopsy of the nail matrix at the base of one streak showed no evidence of a naevus or lentigo, the principal finding being pigmentary incontinence and excess macrophages.

Nine cases of ‘basilar artery migraine’ (BAM) have been recorded. In 8 cases, excess of beta activity was observed during the attacks and disappeared in less than 3 days. The inter-ictal EEGs were normal. Drug ingestion was excluded each time. These EEG patterns are different from those which have been reported in the literature, i.e., transitory posterior abnormal slow waves. However, case no. 1 is in agreement with the literature. The expression ‘BAM’ probably covers different syndromes which are further discussed.

After several months of treatment, Cebus apella, Cebus albifrons, and Saimiri sciurea monkeys maintained on haloperidol, in doses of 0.5 or 1.0 mg/kg orally 5 days per week, began to display severe movement disorders, typically 1-6 h post-drug. Cebus monkeys exhibited violent, uncontrolled movements that flung the animals about the cage. Such episodes usually lasted only a few minutes, recurring several times during the period following drug ingestion. Writhing and bizarre postures dominated the response in S. sciurea. Cessation of drug treatment produced no distinctive after-effects. When tested as long as 508 days after the last administration, however, Cebus monkeys responded to haloperidol with several episodes of hyperkinesis, even at challenge doses considerably lower than those in the original treatment.

This paper describes the distribution of new cases of aplastic anaemia in parts of the UK in 1985. The age, sex and spatial pattern are described. Special attention is given to the investigation of five childhood cases which occurred close in space and time. The results are contrasted with similar data from elsewhere.

It has been claimed that gastric and duodenal ulcer (GU and DU) symptoms decrease in frequency with time, indicating 'burn out' of ulcer. The present study was undertaken to investigate further this phenomenon in GU. The prevalence of symptom experience during 1 year was examined in 447 medically treated patients with GU diagnosed 2-20 or more years previously. When ulcer history length was measured from either first symptom onset or first ulcer diagnosis, reporting of symptoms did not become less frequent as history length increased. This remained true after adjustment for GU location, sex, age, smoking, and analgesic and non-steroidal anti-inflammatory drug ingestion. It is concluded that GU symptoms do not decrease in frequency with time.

Summary The ingestion of non-steroidal anti-inflammatory drugs (NSAID) in 272 patients with bleeding or perforated peptic ulcer was compared with 272 age/sex matched controls. A significantly higher proportion of patients with gastric ulcers had received NSAID than those with duodenal ulcers. Twelve of 90 (13%) patients admitted with bleeding duodenal ulcers had received NSAID compared with 11 of 26 (42%) patients with bleeding gastric ulcers (P = 0.003). Sixteen of 132 (12%) patients with perforated duodenal ulcer were taking NSAID compared with 8 of 24 (33%) patients with perforated gastric ulcer. Thirty eight percent of patients with both bleeding and perforated gastric ulcers had received NSAID compared with 13% bleeding and perforated duodenal ulcers (P less than 0.002). This study confirms the association of NSAID and complicated peptic ulcer in patients of over 65 years and highlights the particular susceptibility of the gastric mucosa to their injurious effect.

Eighty patients took part in this double-blind, single-dose group-comparative study, comparing the analgesic efficacy of tiaramide hydrochloride 100 mg and 200 mg, paracetamol 1000 mg, and placebo for pain after orthopedic operations. The four treatment groups were similar on entry to the trial. Pain relief was assessed up to 6 h after treatment, using a visual analogue pain scale and a pain score, both giving similar results. Statistically significant pain relief (mean pain intensity differences and sum of pain intensity differences) was seen in the group receiving paracetamol compared to those receiving placebo or tiaramide from 1 h to 6 h after drug ingestion. There was no significant difference between placebo and tiaramide 100 or 200 mg. No adverse reactions were reported.

Cannabis has been cultivated and used in the Far East for several thousand years. Its introduction and widespread abuse in the West, however, has been a more recent phenomenon. The detection of cannabis abuse through the analysis of body fluids has been relatively difficult. Methods, however, have been developed which allow the routine analysis of blood and urine. Radioimmunoassay (RIA) is used to screen samples and a combination of RIA and high-performance liquid chromatography (HPLC) is used to confirm the initial finding. These techniques have been successfully applied to the analysis of samples submitted for forensic analysis. In certain instances, some limited interpretation in regard to time since drug ingestion has been possible. Although most of the analytical problems have been resolved, difficulties still exist in relation to the law concerning cannabis, especially in regard to charges of cannabis possession, based on the presence of cannabinoids in body fluids.

The patient who presents only the signs and symptoms of microcytic anemia due to bleeding from the alimentary tract must be subjected to a very careful search for all information which might lead to a diagnosis, with special emphasis on history of drug ingestion and on those diagnostic procedures available for direct and indirect visualization of the tract. Surgical exploration will be the ultimate diagnostic procedure for many such patients but should be postponed until all other diagnostic methods have been employed and until there has been ample opportunity to make certain that the bleeding persists despite withdrawal of all drugs which might be causative. Because it is easier to recognize a known cause of bleeding, we have presented examples of unusual causes from our own experience.

SUMMARY Two cases of “toxic epidermal necrolysis” with a fatal outcome are reported. The histological features have been assessed and it is believed that in this condition bullae form as a result of coalescence of intra-epidermal vesicles which themselves have formed from the rupture of numerous intracellular vacuoles. Acantholysis did not occur. Although there was a history of drug ingestion in both cases the etiological role of these, or of intercurrent disease, was unhelpful in elucidating the pathogenesis of the syndrome.

Barotrauma related to drug ingestion is an uncommon entity. We present the cases of two young women who sustained barotrauma associated with the use of alkaloidal cocaine.

• A mother and daughter had benign familial acanthosis nigricans. Familial acanthosis nigricans begins in early childhood and may be accentuated at puberty. The eruption is not associated with underlying illness. Forms of acanthosis nigricans are associated with obesity, endocrinologic abnormalities, drug ingestion, and malignant neoplasms. ( Arch Dermatol 1984;120:1351-1354)

The clinical details of four fair-skinned women with recurrent blistering and skin fragility are presented. All had considerable sun-exposure and had used sunbeds for years. Specific causes of bullous dermatoses including drug ingestion, porphyria, cutaneous amyloidosis and epidermolysis bullosa acquisita were excluded. Long-term recurrent exposure to high doses of sunbed radiation in chronically sun-damaged skin appears to be a further cause of pseudoporphyria.

An 18-year-old woman developed Stevens-Johnson syndrome six days after the onset of an adenovirus conjunctivitis. Adenovirus serum antibody titers increased from 1:16 to 1:64 during a four-week period, and there was no history of drug ingestion or other infection.

True cyclopia is a rare anomaly in which the organogenetic development of the two separate eyes is suppressed. A case of true cyclopia with normal karyotype is presented. There was a history of the use of an intrauterine device for contraception and of drug ingestion during early pregnancy. An anatomicopathological study of the monster with detailed presentation of the cyclopean eye is reported. The possible causes of cyclopia with particular relation to this case are discussed.

A 23-year old woman developed headache and papilledema due to benign intracranial hypertension (BIH) while taking lithium carbonate for only seven months because of manic-depressive disease. Having discarded other causes, drug ingestion was the most likely etiology of the syndrome since it was observed that symptoms improved upon lithium withdrawal and worsened when the treatment was restarted. This report shows that BIH may appear as a side-effect of relatively short-term therapy with lithium and, therefore, funduscopic exams should be performed in every patient receiving this drug.

Sixty-eight patients who had attempted suicide were matched with non-suicidal patients with similar diagnoses to assess the extent to which excessive drug ingestion by the suicidal group might have contributed to their behaviour. It was found that the suicidal patients were consuming more drugs, particularly those of a potentially depressing kind. The implications of this finding are discussed. Language: en

Misonidazole, a potent new antitumor agent that selectively increases the effect of ionizing radiations on poorly oxygenated tumor tumor cells, was given to 21 patients at New York University-Bellevue Medical Center. In 11 of the 21 patients, hearing loss developed secondary to drug ingestion. In all cases the hearing loss was sensorineural, of cochlear origin, and at least partially reversible. There did not seem to be a relationship between degree of hearing loss and age, sex, dose, anatomic site of lesion, or prior hearing loss.

This study evaluated laboratory sleep and performance after placebo, after 5, 10 and 20 mg of midazolam and after 30 mg of flurazepam. EEG recordings showed that 20 mg of midazolam significantly decreased sleep latency and stage 1 sleep, increased stage 2 sleep, and delayed the onset of the first REM period when compared with placebo. Subjective reports from the patients showed that the dose decreased the frequency of awakenings. In the morning, 9 h after drug ingestion, performance on most tests was affected very little by 20 mg of midazolam. However, performance on two psychomotor tests was slightly impaired after 20 mg of midazolam, while a test of free recall was slightly improved. On most variables, 5 mg of midazolam acted like placebo, while 10 mg of midazolam was intermediate between placebo and 20 mg of midazolam. Preliminary data suggest that 20 mg of midazolam may be as efficacious in inducing sleep as 30 mg of flurazepam, but may show fewer performance decrements in the morning.

The importance of teratology to obstetrician and patient has been demonstrated by the occurrence of a number of "mini-epidemics" of anomalies caused by drug ingestion during pregnancy. The scope of the problem is discussed, and drugs are reviewed by therapeutic classification for their teratologic potential.

p-Chloroamphetamine (PCA) given in a single oral dose to rats lowered brain serotonin acutely almost as effectively as after ip injection. Likewise, PCA depleted brain serotonin when mixed with the diet, though the amount of food intake was reduced from that normally consumed due to the anorexic action of PCA. In one study in rats fed diets containing PCA for 125 days, the degree of brain serotonin and 5-hydroxyindoleacetic acid depletion was maximal at about 1–4 weeks and diminished during further drug ingestion by rats. In another study in rats fed diets containing PCA for 90 days, brain serotonin concentration was slightly but significantly reduced 2 weeks after drug administration was stopped. Brain serotonin concentration was decreased in dogs at the end of 90 days of oral drug administration and had not returned to control values 2 weeks after drug was discontinued. These results suggest that long-lasting (presumably neurotoxic) effects on brain serotonin neurons are less likely to occur when PCA is given orally than when it is injected ip.

The placenta has been considered a protective barrier between the mother and fetus. Because many drugs pass relatively freely between mother and fetus, the possible causal relationship between drug ingestion and the incidence of birth defects in humans demands critical examination. A brief review of background information about this interaction and an overview of the effects of commonly used drugs are presented.

• At the Massachusetts General Hospital between 1964 and 1972, there was an estimated 118% increase in emergency ward admissions for drug overdose suicide attempts and an estimated 257% increase in such attempts by individuals in the 20- to 29-year age range. Approximately 67% of overdoses seen in 1972 and 1974 occurred in individuals under age 30. An increase in drug overdose suicide attempts by males was noted. By 1972, males were making approximately as many attempts as females. Based on extrapolations from the Massachusetts General Hospital drug overdose data, and not including an estimate of non-hospital-treated suicide attempts, an estimated annual (1972) suicide attempt rate of 337/100,000 (0.38%) was obtained for Boston. The estimated suicide attempt-completed suicide ratio for the Boston area was 39:1. These estimates should be interpreted as giving an approximate order of magnitude and not as specifying precise rates.