Canadian recommendations for the management of breakthrough cancer pain.

Breakthrough cancer pain (btcp) represents an important element in the spectrum of cancer pain management. Because most btcp episodes peak in intensity within a few minutes, speed of medication onset is crucial for proper control. In Canada, several current provincial guidelines for the management of cancer pain include a brief discussion about the treatment of btcp; however, there are no uniform national recommendations for the management of btcp. That lack, accompanied by unequal access to pain medication across the country, contributes to both regional and provincial variability in the management of btcp. Currently, immediate-release oral opioids are the treatment of choice for btcp. This approach might not always offer optimal speed for onset of action and duration to match the rapid nature of an episode of btcp. Novel transmucosal fentanyl formulations might be more appropriate for some types of btcp, but limited access to such drugs hinders their use. In addition, the recognition of btcp and its proper assessment, which are crucial steps toward appropriate treatment selection, remain challenging for many health care professionals. To facilitate appropriate management of btcp, a group of prominent Canadian specialists in palliative care, oncology, and anesthesiology convened to develop a set of recommendations and suggestions to assist Canadian health care providers in the treatment of btcp and the alleviation of the suffering and discomfort experienced by adult cancer patients.

Septic systems drive nutrient enrichment of groundwaters and eutrophication in the urbanized Indian River Lagoon, Florida.

Effluent from septic systems can pollute groundwater and surface waters in coastal watersheds. These effects are unknown for the highly urbanized central Indian River Lagoon (CIRL), Florida, where septic systems represent > 50% of wastewater disposal. To better understand these impacts, water quality was assessed along both canals and a tributary that drain into the CIRL. Dissolved nutrient concentrations were higher near septic systems than in natural areas. δ15N values of groundwater (+7.2‰), surface water (+5.5‰), and macrophytes (+9.7‰) were within the range for wastewater (>+3‰), as were surface water concentrations of the artificial sweetener sucralose (100 to 1700 ng/L) and fecal indicator bacteria density. These results indicate that septic systems are promoting eutrophication in the CIRL by contributing nutrient pollution to surface water via groundwater. This study demonstrates the need to reduce reliance on septic systems in urbanized coastal communities to improve water quality and subsequently mitigate harmful algal blooms.

Nutrient content and stoichiometry of pelagic Sargassum reflects increasing nitrogen availability in the Atlantic Basin.

The pelagic brown macroalgae Sargassum spp. have grown for centuries in oligotrophic waters of the North Atlantic Ocean supported by natural nutrient sources, such as excretions from associated fishes and invertebrates, upwelling, and N2 fixation. Using a unique historical baseline, we show that since the 1980s the tissue %N of Sargassum spp. has increased by 35%, while %P has decreased by 44%, resulting in a 111% increase in the N:P ratio (13:1 to 28:1) and increased P limitation. The highest %N and δ15N values occurred in coastal waters influenced by N-rich terrestrial runoff, while lower C:N and C:P ratios occurred in winter and spring during peak river discharges. These findings suggest that increased N availability is supporting blooms of Sargassum and turning a critical nursery habitat into harmful algal blooms with catastrophic impacts on coastal ecosystems, economies, and human health.

Atmospheric nitrogen deposition from a remote source enriches macroalgae in coral reef ecosystems near Green Turtle Cay, Abacos, Bahamas.

Over the past several decades, the fixation of "new" nitrogen to the biosphere has doubled. For the early 21st century, the most significant rate increases in atmospheric nitrogen deposition are predicted for developing nations. Wet nitrogen deposition was assessed on the remote island of Green Turtle Cay, Bahamas in a dry and wet season from January to July 2000. Episodic deposition of nitrate (approximately 1-137 microM) and ammonia (approximately 2-122 microM) represented a mean deposition rate of approximately 0.2 mgDIN m(-2) yr(-1). Wet deposition of nitrogen to the climatologically-linked east coast of Florida is approximately 4 times greater than the estimated annual wet nitrogen deposition value at Green Turtle Cay, suggesting the continental US as a principal airshed for this loading source. Short-term bioassays of macroalgal productivity with a 5% rainfall solution caused depressed net productivity and increased dark respiration, well known "transient metabolic" responses by nutrient-limited tropical macroalgae. Wet deposition of inorganic nitrogen from episodic rainfall events may provide up to 20% of the "new" nitrogen necessary to meet growth demands of macroalgae on coral reefs near Green Turtle Cay.

Quality of life in HIV disease as measured by the McGill quality of life questionnaire.

OBJECTIVE: To test the acceptability, validity, and internal consistency reliability of the McGill quality of life questionnaire (MQOL) for persons living with HIV/AIDS. DESIGN: The validity of MQOL was tested by having HIV-seropositive outpatients complete the 16-item MQOL, a single-item scale (SIS) measuring overall quality of life (QOL), and a physical symptom questionnaire. METHODS: Factor analysis was used as a guide for construction of MQOL subscales. Validity was studied by determining the correlation between MQOL and SIS, and between MQOL physical measures, CD4 counts and the physical symptoms questionnaire. Multiple regression was employed to determine how best to combine MQOL subscales to predict SIS. RESULTS: MQOL was acceptable to this patient population. Factor analysis suggests that MQOL can be represented by live measures: a single item measuring physical well-being and four subscales representing physical symptoms, psychological symptoms, existential well-being, and support. Multiple regression analyses suggest that the existential domain contributes greatly to QOL for people with advanced HIV disease (CD4 counts < 100 x 10(6)/l). CONCLUSION: MQOL is an acceptable and valid measure of QOL for people living with HIV/AIDS, with meaningful and reliable subscales as well as a summary score. The inclusion of a measure of existential well-being in MQOL may make it a more valid measure of QOL, especially for people with advanced disease, than QOL instruments which do not include this domain.

Hormonal regulation of type II glucocorticoid receptor messenger ribonucleic acid in rat brain.

Differences in the regulation of type II glucocorticoid receptor (GR) mRNA levels in female rat brain regions involved in the control of the hypothalamic-pituitary-adrenal axis were studied by Northern blot analysis after chronic administration of corticosterone or dexamethasone to adrenalectomized (ADX), ovariectomized (OVX), and ADX/OVX animals. The effect of chronic estradiol or progesterone treatment of intact animals was also studied. Our results show that type II GR mRNA levels of ADX animals were significantly increased above control values in amygdala (140%) and hippocampus (196%), but not in hypothalamus. These increased transcript levels were down-regulated by corticosterone or dexamethasone, with the exception of those in the amygdala, where corticosterone had no effect. Ovariectomy significantly increased hypothalamic GR mRNA content (174%) over control values, and this increase was sensitive to dexamethasone. The combined effect of adrenalectomy/ovariectomy on GR mRNA levels was greater than that of adrenalectomy only in amygdala. Corticosterone increased amygdala transcript levels in OVX and ADX/OVX animals. Estradiol administration to intact animals raised the GR mRNA content of amygdala, while progesterone treatment had no effect on any of the brain regions studied. We conclude that there exists heterogeneity with respect to type II GR mRNA regulation by corticosterone and dexamethasone in brain regions of ADX female rats, and that certain limbic structures show greater sensitivity to these hormonal manipulations, suggesting a more prominent role in the regulation of the hypothalamic-pituitary-adrenal axis. Our results also suggest that circulating estrogens can influence the sensitivity of brain structures (i.e. hypothalamus and amygdala) to glucocorticoids by altering GR mRNA levels. These regions may represent integration sites at which gonadal steroids are able to alter stress hormone secretion.

A multicentre open-label safety and efficacy study of tetrodotoxin for cancer pain.

BACKGROUND: Cancer pain is highly prevalent, and existing treatments are often insufficient to provide adequate relief. OBJECTIVES: We assessed the long-term safety and efficacy of subcutaneous tetrodotoxin treatment in reducing the intensity of chronic cancer-related pain. METHODS: In this multicentre open-label longitudinal trial, 30 µg tetrodotoxin was administered subcutaneously twice daily for 4 days in a heterogeneous cohort of patients with persistent pain despite opioids and other analgesics. "Responder" was defined as a mean reduction of 30% or more in pain intensity from baseline; and "clinical responder" as some pain reduction, but less than 30%, plus agreement on the part of both the patient and the physician that a meaningful analgesic response to treatment had occurred. RESULTS: Of 45 patients who entered the longitudinal trial, 41 had sufficient data for analysis. Of all 45 patients, 21 (47%) met the criteria for "responder" [16 patients (36%)] or "clinical responder" [5 patients (11%)]. Onset of pain relief was typically cumulative over days, and after administration ended, the analgesic effect subsided over the course of a few weeks. No evidence of loss of analgesic effect was observed during subsequent treatments (2526 patient-days in total and a maximum of 400 days in 1 patient). One patient withdrew from the study because of adverse events. Toxicity was usually mild (82%) or moderate (13%), and remained so through subsequent treatment cycles, with no evidence of cumulative toxicity or tolerance. CONCLUSIONS: Long-term treatment with tetrodotoxin is associated with acceptable toxicity and, in a substantial minority of patients, resulted in a sustained analgesic effect. Further study of tetrodotoxin for moderate-to-severe cancer pain is warranted.

Anesthetics can alter subsequent in vitro assessment of contractility in slow and fast skeletal muscles of rat.

Anesthetic agents can interfere with measurement of skeletal muscle contractility in vivo or in situ. Data obtained in vitro are however believed to be unaffected by such drugs. Our objective was to compare in vitro contractile measurements of fast- and slow-twitch muscles dissected from rats anesthetized with pentobarbital sodium (PS, 50 mg/kg ip) or with a mixture of ketamine and xylazine (KX, 87. 5:12.5 mg/kg ip). The soleus (Sol) and extensor digitorum longus (EDL) muscles were precisely dissected 10 and 20 min after induction of anesthesia and equilibrated for 20 min in vitro before measuring contractile properties. All data obtained from PS rats were comparable with published values obtained under similar conditions. In EDL, maximum tetanic tension (Po) in KX rats was significantly decreased at both times compared with that in PS muscles. In the Sol, only the muscles exposed for 20 min to KX showed a decreased Po. These results clearly emphasize the need for investigators assessing skeletal muscle contractility in vitro to take into account the type of anesthetics used and the time of in vivo exposition to the drug.