Adverse placental effect of formic acid on hCG secretion is mitigated by folic acid.

AIMS: Formic acid has recently been detected in maternal blood and umbilical cord blood of infants born to alcohol abusing mothers. This toxic metabolite of methanol requires folate for detoxification. We hypothesized that formic acid produced in the maternal circulation will transfer across the placenta and will be toxic to the placenta. Our objectives were, first, to determine whether formic acid transfers across the human placenta and whether it is toxic to the placenta and second, to determine whether folate can decrease transplacental transfer of formic acid and mitigate toxicity. METHODS: Dual perfusion of a single placental lobule ex vivo was used to characterize the transfer of formic acid across the placenta. After a 1-h control period, formic acid (2 mM) was introduced into the maternal circulation with (n = 4) or without folate (1 µM) (n = 4) and was allowed to equilibrate for 3 h. RESULTS: Formic acid transferred rapidly from the maternal to the fetal circulation, and transfer was not altered with the addition of folate. Compared with the control period, there was a significant decrease in hCG secretion (P = 0.03) after addition of formic acid. The addition of folic acid to the perfusate mitigated the decrease in hCG. CONCLUSIONS: Formic acid rapidly transfers across the placenta and thus has the potential to be toxic to the developing fetus. Formic acid decreases hCG secretion in the placenta, which may alter steroidogenesis and differentiation of the cytotrophoblasts, and this adverse effect can be mitigated by folate.

Alcohol and breast feeding: calculation of time to zero level in milk.

OBJECTIVE: To create a nomogram that will guide lactating women who drink socially on how to avoid neonatal exposure to ethanol through breast milk. DESIGN: Pharmacokinetic modeling of ethanol elimination from milk based on reference values. Calculation of the time to zero alcohol in breast milk for a range of doses and body weights. RESULTS: The elimination of alcohol and time-to-zero levels in breast milk are described in a nomogram as a function of the amount of alcohol consumed and the body weight of the woman. CONCLUSIONS: Careful planning of a breast feeding schedule, by storing milk before drinking and/or waiting for complete alcohol elimination from the breast milk, can ensure women that their babies are not exposed to any alcohol.

Is chronic poisoning with acetaminophen in children a frequent occurrence in Toronto?

BACKGROUND: Acetaminophen is a common cause of poisoning in children. Recent American studies suggest that acetaminophen poisonings pose serious risks in children, particularly in the case of chronic poisoning caused by therapeutic error. OBJECTIVE: To evaluate whether chronic acetaminophen poisoning in children is a frequent occurrence in a large, Canadian, urban population. PATIENTS AND METHODS: Retrospective study. Charts of all patients admitted to The Hospital for Sick Children, Toronto, Ontario from January 1, 1990 to June 31, 1996 with an acetaminophen overdose were reviewed. RESULTS: A total of 110 patients were admitted within the study period; only four of whom were preschool children (younger than five years of age). Among the preschool children, three had an acute overdose and one had possible chronic poisoning by therapeutic error. All preschool children were treated with N-acetylcysteine; one developed hepatotoxicity (aspartate aminotransferase or alanine aminotransferase greater than 1000 U/L) after presenting 24 h after acute ingestion. Of the remaining patients, all were adolescents; 102 had acute intentional overdose and four had staggered intentional overdoses. Fifty-three adolescents were treated with N-acetyl cysteine. Hepatotoxicity was present in 13 of 63 adolescents (21%). No patients required liver transplantation or died. CONCLUSIONS: Contrary to American experience, chronic acetaminophen poisoning, including therapeutic error in children in Toronto, is a rare occurrence--most cases of acetaminophen poisonings are acute intentional ingestion in adolescents.

Contamination of antibiotics resulting in severe pediatric methadone poisoning.

OBJECTIVE: To report an accidental contamination of antibiotic suspension by methadone that occurred in a retail Canadian pharmacy, leading to severe poisoning in a young child. CASE SUMMARY: A 4 1/2-year-old healthy Asian boy was prescribed amoxicillin suspension for cough and fever. Shortly after receiving the second dose of 5 mL he became drowsy and less responsive. On admission, he was arousable by deep pain, and pinpoint pupils were noted. A urine sample sent for a toxicology screen revealed the presence of methadone and its metabolite. Blood methadone concentrations were 0.23 and 0.14 mg/L, five and nine hours after the second dose of amoxicillin was given, respectively. The amoxicillin suspension was tested for methadone and was found to have a concentration of 2.4 g/L. The child gradually improved and was discharged on day 4 in good condition. The pharmacy in which the antibiotic was dispensed has been a dispensing center for a local methadone maintenance program, and methadone was accidentally mixed with the antibiotics. DISCUSSION: In this case, a near fatal outcome occurred when methadone was inadvertently mixed with antibiotics in a community pharmacy. A literature search revealed two previous reports of opiate toxicity in children following ingestion of oral antibiotic preparations. CONCLUSIONS: Prompt action is needed in Canadian pharmacies that dispense methadone in order to minimize such errors in the future. General practitioners, pediatricians, and emergency department physicians should recognize and suspect this rare cause of opiate toxicity in a child. In a patient presenting with a decreased level of consciousness and miosis, with or without respiratory depression, naloxone administration should be considered, whether or not a history of opioid ingestion is obtained.

Pancreaticogastrostomy for reconstruction of pancreatic stump after pancreaticoduodenectomy for ampullary carcinoma.

BACKGROUND: Management of the pancreatic stump after pancreaticoduodenectomy (PD) is still a matter of debate. Pancreaticojejunostomy (PJ) is used commonly but is associated with a significant incidence of pancreatic leaks. Pancreaticogastrostomy (PG) is an alternative that has been reported to be safer. METHODS: The study is a retrospective analysis of all patients having PD for ampullary carcinoma in one surgical unit at All India Institute of Medical Sciences over 18 years, with PG being the only drainage procedure for the pancreatic stump. RESULTS: Among 125 patients having PD for ampullary carcinoma, overall morbidity rate was 28%, mortality rate was 4.8%, with no cases of leakage from the pancreaticogastrostomy. CONCLUSIONS: In world literature (including the current series), the leakage rate of PG is 2.5% (14 of 553) with only 2 deaths (2 of 14) due to leakage from PG. Our large experience and these data conclusively prove the safety of pancreaticogastrostomy, which should be the drainage procedure of choice for the pancreatic stump following pancreaticoduodenectomy.

Gender and alcohol dosing: a procedure for producing comparable breath alcohol curves for men and women.

Gender differences in peak breath alcohol concentrations (BrACs) reached in alcohol administration studies can make the interpretation of study findings difficult. This study evaluated the CBAC computer program as a way of minimizing gender differences in the BrAC curve. After consuming a predrink meal that was adjusted by body mass, 31 female and 27 male subjects consumed an alcoholic beverage targeted for either 0.04% or 0.08%. Mean peak BrACs for women and men were not significantly different. Similarly, the four BrAC readings obtained over the first 2 hr postdrink showed no gender differences. A dose x gender interaction was observed on time to peak BrAC, with women reaching peak BrAC faster than men only in the high dose groups. By decreasing gender differences in BrAC curves, this dosing procedure can aid in reducing the potential confound of dose and gender.

Risk factors for wound infection following elective cholecystectomy.

A study of risk factors for wound infection among patients undergoing elective cholecystectomy was undertaken. Over a 2-Year period 177 patients who underwent elective cholecystectomy for symptomatic gall stone disease were randomized into groups, one receiving antibiotics (96 patients) and the other not receiving antibiotics (81 patients). Gall bladder bile and wound swab were cultured to detect bacterial growth. Duration of preoperative hospital stay, type of skin incision and operating time were noted for each patient. Postoperatively wound infection developed in 22/177 (12%) patients. The infection rate was lower in the antibiotic group 3/96 (3%) as compared to the non-antibiotic group 19/81 (23.5%). Wound sepsis occurred in 11/37 (23%) of patients with bactibilia as compared to 11/140 (7.8%) patients with sterile bile. Stepwise logistic regression analysis showed that bactibilia and use of prophylactic antibiotics were the most significant predictors of wound infection in low risk patients undergoing elective cholecystectomy.

Dietary habits of gallstone patients in Northern India.

Dietary intake and plasma lipids were estimated in 200 patients with gallstones and 98 control subjects from a hospital in Northern India and were matched for age, sex, and social class. The intake of total calories and carbohydrates and the plasma triglyceride values were higher in all gallstone patients as compared with controls (p < 0.05 and p < 0.01, respectively). The dietary intake of refined carbohydrates was higher than in controls, but only in the female patients with gallstones (35.6 +/- 32.9 g/day compared with 24.5 +/- 11.8 g/day; p < 0.001). By contrast, the male patients with gallstones had an increased intake of fat (patients 79.0 +/- 38.1 g/day vs. controls 60.2 +/- 24.3 g/day; p < 0.05) and had increased plasma cholesterol values (patients 166.4 +/- 54.2 mg/dl vs. controls 140.3 +/- 32.8 mg/dl; p < 0.01). Such sex differences in the dietary intake and plasma lipid values may form a special feature of gallstone disease in Northern India and should be studied further.

Analysis of symptomatic patients after cholecystectomy: is the term post-cholecystectomy syndrome an anachronism?

Of 171 patients who were followed-up prospectively for 2.8 years after cholecystectomy, 31 developed postcholecystectomy symptoms, 24 of them being mild to moderate and 7 severe. Symptomatic patients mostly had functioning gall bladders preoperatively and longer duration of symptoms prior to cholecystectomy. The causes of postcholecystectomy symptoms could be identified in all of them except 9 patients who were labelled as having "essential dyspepsia". The symptoms in the latter syndrome as well as in other conditions diagnosed in the symptomatic postcholecystectomy patients appeared unrelated to the absence of gallbladder. Hence, we feel the term postcholecystectomy syndrome is an anachronism and should be redefined.

Multicentric liposarcoma: report of two cases.

We present herein two unusual cases of multicentric liposarcoma which highlight the problems associated with the management of this disease entity. When the surgeon is confronted with multicentric liposarcomas, it is necessary to define whether they are secondary tumors or independently arising multicentric liposarcomas, since the latter situation merits a more aggressive approach. Guidelines for this differentiation are suggested in the discussion following the case reports. Surgery, which is often multiple, remains the mainstay of treatment, although adjuvant chemotherapy and radiotherapy are also usually required.

Enzymes and circulating proteins as markers of alcohol abuse.

The identification of alcohol abuse is an important social and clinical objective for which various biochemical procedures have been utilized, serum enzymes and circulating proteins being predominant. Tests are required to detect alcohol abuse as screening procedures in the general population as well as for the specific diagnosis of those presenting as hospital inpatients or outpatients, especially when liver disease is present or suspected. The amino-transferases are of limited value, although the mitochondrial isoenzyme of aspartate amino-transferase has been strongly advocated and is quite useful in detecting alcoholics among patients with liver disease. Gammaglutamyl transferase, by contrast, is raised in all forms of liver disease but can identify 30-50% of those consuming excessive amounts of alcohol before organic damage becomes manifest. Serum carbohydrate-deficient transferrin (CDT) is raised in many alcohol abusers without and most with liver damage, but is rarely elevated in other forms of liver disease. Haemoglobin-associated acetaldehyde, the newest biochemical index to be evaluated in alcoholics, is one of several adducts formed by the reaction of acetaldehyde with various proteins, and antibodies to these adducts may contribute, at least in part, to immunological tissue damage provoked by chronic excessive consumption of alcohol. Its assay is technically complex and it appears to be present in higher concentrations in heavy drinkers than in those who fulfill the criteria of addictive alcohol abuse. Many other markers have been introduced in the last decade but the search for a reliable index continues. CDT comes closest at the present time to matching the desired specificity, although it is of limited value in screening unselected non-hospitalized subjects.

Synchronous double malignant tumors of the gall bladder. A case-report of squamous cell carcinoma with an angiosarcoma.

The first case of synchronous double malignant tumors of the gall bladder having squamous cell carcinoma and an angiosarcoma at different sites is being reported in the world literature. The etiologic, diagnostic and therapeutic aspects of these malignancies and the significance of their concurrence are discussed.

Role of enteral hyperalimentation in patients of carcinoma oesophagus.

The nutritional status of 24 patients of carcinoma oesophagus was assessed before and after central hyperalimentation with a liquid blenderized diet containing 3000-3500 cal and 100-120 g protein. The overall prevalence of malnutrition was found to be 70.8 per cent before the initiation of therapy. Of the various parameters used for assessment of nutritional status weight loss was the most common finding (91.6%) followed by alteration in midarm circumference, haemoglobin, triceps skin fold thickness, midarm muscle circumference and serum albumin. Enteral hyperalimentation for 10 days improved nutritional status by inducing significant gain in body weight (74.1%), triceps skin fold thickness (50%), midarm circumference (58%), midarm muscle circumference (62.5%) and serum albumin levels (91.6%). There was no significant change in haemoglobin levels.

Alcohol and drug use among motor vehicle collision victims admitted to a regional trauma unit: demographic, injury, and crash characteristics.

This study examined the incidence of alcohol and drugs in a sample of seriously injured motor vehicle collision victims, and differences related to pre-crash use of alcohol and/or other drugs on demographic variables, injury severity measures, and crash variables. The sample selected were all motor vehicle collision admissions to the Regional Trauma Unit at the Sunnybrook Health Science Centre in Toronto, Ontario, over a 37-month period (N = 854). Prospective demographic and injury-related information were collected from hospital charts, and crash data were collected from motor vehicle collision police reports. Blood samples were routinely collected on admission and tested for blood alcohol concentration (BAC). We found 32.0% of the BAC-tested motor vehicle collision admissions and 35.5% of drivers tested positive for blood alcohol. The drivers' mean BAC on admission was found to be 145.2 mg/100 ml, and the mean estimated BAC at crash time was 181 mg/100 ml. Drug screens were performed on a two-year subsample (n = 474), of whom 339 were drivers. Drug screens revealed that 41.3% of drivers tested positive for other drugs in body fluids, and 16.5% were positive for alcohol in combination with other drugs. Other than alcohol, the drugs most frequently detected in the drivers were cannabinoids (13.9%), benzodiazepines (12.4%), and cocaine (5.3%). Investigation of differences on demographic, injury, and crash characteristics related to precrash use of alcohol and/or drugs yielded significant findings. In the drug screened sample we found sex, admission type, and occupant status were related to precrash alcohol use. Also, use of drugs was found to interact with admission type and mean BAC on admission. Elapsed time was found to be significantly different for BAC by other drug use, with a greater length of elapsed time found for the subjects testing other drug positive but BAC negative. We found that BAC-positive drug-screened drivers were significantly more likely to be male, involved in a single-vehicle collision, not wearing a seat belt, ejected from the vehicle, and travelling at higher speeds than BAC negative drivers. No significant differences were found between BAC and/or other drug use on injury severity measures.

Hydatidemesis: a bizarre presentation of abdominal hydatidosis.

A 31 year old male presented with high grade fever and abdominal pain of 20 days duration. At the age of 9 he had been operated on for a solitary retroperitoneal hydatid cyst and had been asymptomatic until the age of 21 when he sustained a blunt injury to the abdomen. An exploratory laparotomy for splenic rupture revealed multiple intra-abdominal hydatid cysts, which were removed. The patient remained well until the present episode. An ultrasound examination revealed multiple intra-abdominal hydatid cysts. Seven days after admission, the patient developed hydatidemesis (hydatid cysts and membranes in the vomitus) and hydatidenteria (passage of hydatid membranes in the stools), and his pain and fever subsided. A Gastrografin study and a computerized tomography (CT) scan revealed hydatid cysts communicating with the stomach and duodenum. In view of his disseminated recurrent abdominal hydatidosis, he was treated with high dose, long-term albendazole along with regular follow up. This is the first documented case of disseminated abdominal hydatidosis presenting with a cystogastric fistula and hydatidemesis.

Renal functions in obstructive jaundice: a pre and post operative assessment.

Surgery in patients with surgical obstructive jaundice is known to be associated with increased risk of post-operative acute renal failure. A prospective study was carried out to evaluate the renal function in patients with obstructive jaundice. Renal functions of thirty two patients with jaundice secondary to mechanical obstruction of the biliary tract were evaluated pre-operatively and 7 days after surgical biliary decompression. Although no significant difference was seen in the mean values of pre and post operative renal function variables, two patients had overt renal failure, one with pre-operative cholangitis and acute tubular necrosis and another with carcinoma of the pancreas and postoperative acute renal failure. The overall satisfactory outcome in our obstructive jaundice patients may be related to pre-operative and intraoperative preparation with intravenous fluids and mannitol. It is concluded that patients with obstructive jaundice can be satisfactorily treated with special preoperative care including good hydration and mannitol therapy during anaesthesia and surgery.

Drug-testing methods and clinical interpretations of test results.

In the present paper, major issues related to drug testing are discussed. For example, drug-testing techniques measure the presence of a drug or drugs but are not sophisticated enough to measure impairment from drug use. Moreover, it is difficult to determine the route of drug administration, quantity or frequency, as well as when the drug was taken, on the basis of the laboratory results. Selection of the drug to be tested should depend on the local availability of the drug, its abuse potential and clinical effects, as well as on the availability of analytical technology and expertise in testing and in interpreting laboratory results. The most sophisticated drug-testing approach is gas chromatography coupled with mass spectrometry (GC/MS), which is regarded as a "gold standard"; it is used in confirmatory testing. Typically, GC/MS is preceded by a rapid immunoassay method to eliminate the majority of the "negative" samples. Despite the existence of sophisticated drug-testing methods, it is still possible to obtain incorrect test results. Such results may be caused by the presence of interfering substances or adulteration of the urine sample. A number of techniques can be employed to reduce the likelihood of obtaining erroneous results and to detect adulterated urine samples. A "positive" drug finding can have a serious impact on the livelihood of an individual, therefore, persons conducting such tests should adhere to the strictest standards of laboratory performance. Only qualified and experienced individuals with proper laboratory equipment should perform these analyses. The standards of laboratory performance must meet local legal and forensic requirements. Access to patient samples and laboratory records must be restricted in order to prevent the tampering of samples and results. In order to maintain confidentiality, the results must be communicated only to the medical review officer. Chain-of-custody documents and all file so that they can be examined in case of a legal challenge. The laboratory must have a complete record on quality control. Finally, specific initial and confirmatory testing requirements should be met.

Influence of intraperitoneal drainage after cholecystectomy; a prospective ultrasonographic study.

One hundred and fifty patients were prospectively randomised into 3 groups (50 in each group); to receive a passive drain, closed suction drain or no drain after elective cholecystectomy. The drain was removed within 24 hours in 84% of patients and was continued longer only if the amount of drainage was excessive or bilious. On the 3rd post-operative day, an ultrasound examination was performed in all patients for detection of subhepatic/subphrenic collection. Collections were more frequently encountered in the patients without any drain (42%) followed by passive drain (26%) and suction drain group (20%). Chest complications were frequently noted (passive drain; 6% suction drain, 12%, and no drain, 8%), however, occurrence of this complication in various groups was similar (p > 0.1). Two patients (4%) without drain required ultrasound guided aspiration of subhepatic collection. Mean post-operative hospital stay was nearly equal for all the groups (passive drain: 4.22 +/- 1 days, suction drain: 4.26 +/- 1.4 days and no drain: 4.62 +/- 2.3 days). Drainage reduced the incidence of post-cholecystectomy collections and need for invasive intervention for collection related complications. However, the type of drainage (active or passive) did not influence the incidence of collection, frequency of complications and duration of post-operative hospital stay.