Death by caffeine: presumptive malicious poisoning of a dog by incorporation in ground meat.

BACKGROUND: A 4-year-old, 37 kg, male German shepherd developed hyperthermia, tachycardia, and agitation following consumption of ground meat found in the backyard of its owner. When presented to a veterinary clinic, plasma ethylene glycol (EG) testing was positive, and the dog was given ethanol and lactated Ringer's solution intravenously. Approximately 11 h postexposure the dog died. DISCUSSION: Among tissues submitted for toxicological analysis, urine was negative for EG, ground meat was negative for certain drugs of abuse, and gastric contents were negative for zinc/aluminum phosphide and metaldehyde. Analysis of gastric contents by gas chromatography-mass spectrometry confirmed the presence of caffeine. Caffeine concentration in the ground meat was estimated at 1 %. Caffeine is a methylxanthine alkaloid with a reported canine oral median lethal dose (MLD(50)) of 140 mg/kg (range 120-200 mg/kg). A commercially available 200-mg tablet formulation of caffeine was considered to be a possible source but this was not confirmed. By conservative estimates, the dog would need to ingest approximately 500-550 g of the meat to reach the MLD(50). Acute intoxication affects the cardiovascular, pulmonary, neurologic, gastrointestinal, and metabolic systems. Although no tablet remnants were observed in the bait, tablets could have been crushed and/or dissolved. Other potential caffeine sources include guarana, brewed and concentrated coffee, and caffeine-containing beverages. Based on the history, clinical signs, and the detection of caffeine in the gastric contents and meat, a presumptive diagnosis of malicious caffeine poisoning was made. A suggested treatment regimen for caffeine intoxication in dogs is described. While few cases of accidental ingestion of caffeine by dogs have been described, the intentional use of a concentrated caffeine source to cause mortality in a dog has not been previously reported.

Antacids in the initial management of metallic zinc ingestion in dogs.

Zinc poisoning in dogs, following ingestion of post-1982 U.S. one cent coins is an increasingly common toxicological syndrome causing gastrointestinal abnormalities, hemolytic anemia, pancreatitis and renal failure. Thermodynamic laws predict that the rate of the chemical reaction between HCl and metallic zinc, which releases absorbable zinc anions, is dependent on pH. The significance of the relation between pH and dissolution is, however, apparently contradicted by the fact that recent veterinary toxicology texts are silent on the use of antacids in the early management of zinc ingestion in dogs. A series of experiments were conducted to test the hypotheses that the degree to which zinc dissolution is pH dependent is likely to be of clinical importance and that the use of antacids will be of benefit in preventing zinc poisoning in dogs that had ingested metallic zinc. Zinc dissolution was strongly dependent on pH in an exponential manner, indicating that clinically achievable upward adjustment of gastric pH using antacids is likely to have significant effects on the rate of zinc absorption in dogs. These data clearly support the use of antacids during the initial treatment of metallic zinc ingestion in dogs.

Outcome of acute myeloid leukaemia in adults: a retrospective analysis.

BACKGROUND: There are little data from India on the management of acute myeloid leukaemia. With better understanding of the biology of the disease, and routine use of high-dose cytarabine as post-remission therapy with or without haematopoietic blood stem cell transplantation (HSCT), the results have improved in the past two decades. We analysed our results in a cohort of recently treated patients. METHODS: A total of 166 newly diagnosed patients with AML (excluding acute promyelocytic leukaemia), 15-60 years of age were treated with daunorubicin (60 mg/m2/day x3 days) or idarubicin (12 mg/m2/day x3 days) with cytarabine (100 mg/m2/day continuous i.v. infusion x7 days) induction chemotherapy. Post-remission therapy included 2 cycles of high-dose cytarabine (15-18 g/m2) followed by monthly cycles of outpatient maintenance chemotherapy x4 cycles, consisting of daunorubicin (45 mg/m2 i.v. x1 day and cytarabine 100 mg/ m2 s.c. twice daily x5 days). Six patients in remission received sibling donor allogeneic HSCT. RESULTS: Morphological complete remission was achieved in 69.9% of the patients. Resistant disease after induction chemotherapy was seen in 14.6% and early mortality occurred in 16%. Relapse-free survival and event-free survival at a median of 36 months was 34% and 22%, respectively. Relapse occurred in 43.9%. The median duration of remission was 12 months. CONCLUSIONS: Our results conform to the published literature from larger cooperative studies from the West. Currently available cytotoxic drugs are unlikely to improve the results any further.

Allogeneic blood stem cell transplantation in chronic myeloid leukaemia-chronic phase following conditioning with busulphan and cyclophosphamide: a follow up report.

BACKGROUND: Allogeneic bone marrow transplantation (BMT) or peripheral blood stem cell transplantation remains the only modality of treatment that can eradicate a leukaemia clone in the majority of patients with chronic myeloid leukaemia (CML). However, the advent of the targeted molecule imatinib mesylate (formerly STI-571) against the bcr-abl chimeric protein in the disease has brought the issue of managing newly diagnosed CML patients, especially those with available donors, to the crossroads. Although the curative potential of this agent remains unknown, it can produce complete cytogenetic response in > 60% of newly diagnosed patients. METHODS: From May 1991 to October 2002, a total of 55 Ph+ CML-chronic phase patients received oral busulphan 16 mg/kg and cyclophosphamide 120 mg/kg i.v. as a conditioning regimen. All patients received human leucocyte antigen (HLA)-identical sibling donor haematopoletic stem cells--bone marrow in 41 patients (74.5%) and peripheral blood stem cells in 14 (25.4%). Post-transplant prophylaxis for graft-versus-host disease included a short course of methotrexate (on days +1, +3, +6 and +11) and cyclosporin till day +180 in 38 patients (69.1%), while a combination of cyclosporin and methylprednisolone was used in the remaining 17 (29%). RESULTS: At a median follow up of 48 months (10-144 months), 26 patients (47.3%) are alive. Early mortality (100-day) occurred in 17 patients (30.9%). Acute graft-versus-host disease developed in 37 patients (67.3%), and was grade IV in 6 of them. Chronic graft-versus-host disease developed in 17 patients (30.9%). Relapse occurred in only 2 patients (3.6%) till date. The leukaemia-free survival is 64.3% in the peripheral stem cell group, whereas it is 41.5% in the bone marrow recipient group. CONCLUSION: Allogeneic BMT appears to result in eradication of CML and ensure disease-free survival in about half the patients. However, efforts should be made to prevent graft-versus-host disease and minimize early mortality.

Use of a reduced-intensity conditioning regimen for allogeneic transplantation in patients with chronic myeloid leukemia.

Reduced-intensity conditioning that harnesses the potential of a graft-versus-tumor (GVT) effect has been proposed as an alternative to conventional myeloablative allogeneic stem cell transplantation. The primary aim is engraftment and this can be achieved with minimal immunosuppression. In this report, we describe the use of such regimens for CML in 17 patients who received human leukocyte antigen (HLA)-matched sibling allografts. Conditioning was with fludarabine, antithymocyte globulin (ATG) and busulfan for the first 11 patients, whereas fludarabine, busulfan and TBI were used for the remaining six patients. Engraftment was prompt in most of the cases. Complications and need for supportive therapy in the immediate post-transplant period were reduced drastically. Only two patients (both in the TBI group) died within the first 100 days. Acute graft-versus-host disease (GVHD) grade II-IV was seen in seven patients. Complications occurred later on. Chronic GVHD was observed in 11/17 patients. Lung infection and GVHD were the major killers. In surviving patients, after a median follow-up of 30 months (range 37-21 months), 6/17 (35.3%) are alive. Five are disease free and one patient is still in relapse even after a second donor lymphocyte infusion. Total treatment time and cost were more than with conventional transplants. We conclude that reduced-intensity transplantation still requires further refinement.