Initial pharmacokinetic, safety and efficacy evaluation of nasal morphine gluconate for breakthrough pain in cancer patients

Patients with controlled background pain associated with cancer frequently also experience episodes of moderate to severe intensity breakthrough pain. Opioid pharmacotherapy, particularly with oral morphine, remains the cornerstone for the management of cancer pain. Nasal administration of opioids provides a mechanism for more rapid drug absorption and more rapid onset of pain relief compared with oral dosing. This non-randomized, open-label, uncontrolled investigation evaluated the pharmacokinetics, safety and efficacy of a single 40 mg dose of nasal morphine gluconate, administered to cancer patients in response to an episode of breakthrough pain. Single dose nasal morphine gluconate administered to 11 patients was associated with effective plasma morphine concentrations (mean C(max) 64 ng/ml; range 33.8-121 ng/ml) and low plasma morphine metabolites (morphine-6-glucuronide mean C(max) 114 ng/ml; range 46-189 ng/ml; morphine-3-glucuronide mean C(max) 572 ng/ml; range 257-990 ng/ml). Side effects were minor and limited to nasal irritation. Patients reported rapid onset of pain relief (perceptible pain relief achieved in 10/11 patients, time to onset 2.4+/-2.1 min; and meaningful pain relief, achieved in five patients, 6.8+/-7.3 min to onset, mean t(max) 0.36 h). Pain intensity scores were significantly reduced at all times after dosing; pain relief scores were unchanged. Patient satisfaction ratings were high. These results show that nasal morphine has rapid absorption and apparent onset of effect. Additional multi-dose, dose-ranging and placebo-controlled studies of nasal morphine for cancer pain are warranted.     

EFFECT OF ATRIAL NATRIURETIC PEPTIDE ON COLLECTING DUCT FUNCTION EVALUATED BY STOP-FLOW IN RABBITS

1. The effect of a low dose of a synthetic atrial natriuretic peptide (ANP), rat atriopeptin II (23 amino acids), on stop-flow sodium concentrations was examined in rabbits in water diuresis. 2. Atrial natriuretic peptide (2 micrograms/kg body weight) was injected intravenously as a bolus either before or after the commencement of stop-flow. 3. Atrial natriuretic peptide induced a significant natriuresis within 2 min of injection. This natriuresis was associated with smaller increases in urine volume and potassium excretion. Atrial natriuretic peptide did not alter blood pressure. 4. Atrial natriuretic peptide did not significantly alter stop-flow sodium concentrations. 5. These findings indicate that ANP does not directly alter sodium transport across medullary collecting ducts. 6. It is proposed that ANP acts via a mediator to alter sodium movement across terminal segments of the nephron.     

Hepatocellular carcinoma with cardiac cirrhosis

Hepatocellular carcinoma is a recognized complication of hepatic cirrhosis, most commonly associated with alcohol excess, haemochromatosis and chronic hepatitis B infection. Long-standing hepatic venous congestion may cause cirrhosis. A search of the literature has not revealed a case of hepatocellular carcinoma complicating cardiac cirrhosis. A case is described and the association is discussed.     

Tiger‐snake antivenom for suspected small‐eyed snake envenomation

Despite its relative frequency and widespread distribution throughout eastern Australia, bites by the nocturnal eastern small‐eyed snake, Cryptophis nigrescens, have seldom been recorded. There is no standard laboratory test or proven antidote for its venom, which is capable of causing life‐threatening myolysis in humans. A 39‐year‐old man presenting to hospital with acute abdominal and limb muscle pains, was noted to have a pair of puncture wounds on his leg. No venom was detected in the urine with the Commonwealth Serum Laboratories’ Venom Detection Kit. The only blood abnormality was a grossly elevated creatine kinase at 48 000 IU/L. A presumptive diagnosis of Cryptophis nigrescens envenomation was made and the patient treated with tiger‐snake antivenom (3000 U). Creatine kinase levels started to fall almost immediately and the patient made a full recovery. We believe this is the first time tiger‐snake antivenom has been used specifically for suspected Cryptophis nigrescens envenomation.     

Comparing neuropsychological function before and during haemodialysis: A habituating selective deficit for prose recall

This study was based on the clinical observation that patients receiving haemodialysis(HD) showed poor retention for complex verbal information. To investigate this hypothesis, 45 patients with endstage renal disease were administered a neuropsychological (NP) test battery, including a test of prose recall on two occasions, 7 days apart (pre‐dialysis and whilst dialysing). A range of demographic, biochemical and mood variables were also assessed. Results revealed a selective deficit for prose recall whilst dialysing compared to pre‐dialysis performance, which habituated in the long‐term. Possible physiological and psychological bases of these effects in HD patients are discussed.     

Activity limitation and chronic conditions in Canada's elderly, 1986-2011.

Together with all other developed countries, Canada's population is experiencing a significant increase in the proportion that is elderly. This paper examines basic linkages between individual ageing, the prevalence of various chronic health conditions, functional limitation and the receipt of help in activities of daily living (ADL) and instrumental activities of daily living (IADL) for the Canadian population using recent data from the National Population Health Survey (NPHS) as well as the Health and Activity Limitation Surveys (HALS) and the two General Social Surveys (GSS) with health data. Presented are age- and sex-specific prevalence of chronic conditions and logistic regression is used to assess the impacts of different chronic conditions on the receipt of help for IADL and ADL. The importance of gender and living alone in influencing the receipt of help and also of use of formal agencies is presented using additional data from HALS. Findings from these analyses are also used to project changes in the distribution of health status defined by disability and receipt of help with IADL/ADL and, secondarily, by chronic condition. These analyses imply increases in demand for a range of health related services which will be 50 to 100% greater than the growth in the total elderly population.