Effects of concomitant use of THC and irinotecan on tumour growth and biochemical markers in a syngeneic mouse model of colon cancer

Clinical treatment with the antineoplastic drug irinotecan (IRI) is often hindered by side effects that significantly reduce the quality of life of treated patients. Due to the growing public support for products with Δ⁹-tetrahydrocannabinol (THC), even though relevant scientific literature does not provide clear evidence of their high antitumour potential, some cancer patients take unregistered preparations containing up to 80 % THC. This study was conducted on a syngeneic colorectal cancer mouse model to test the efficiency and safety of concomitant treatment with IRI and THC. Male BALB/c mice subcutaneously injected with CT26 cells were receiving 60 mg/kg of IRI intraperitoneally on day 1 and 5 of treatment and/or 7 mg/kg of THC by gavage a day for 7 days. Treatment responses were evaluated based on changes in body, brain, and liver weight, tumour growth, blood cholinesterase activity, and oxidative stress parameters. Irinotecan’s systemic toxicity was evidenced by weight loss and high oxidative stress. The important finding of this study is that combining THC with IRI diminishes IRI efficiency in inhibiting tumour growth. However, further studies, focused on more subtle molecular methods in tumour tissue and analytical analysis of IRI and THC distribution in tumour-bearing mice, are needed to prove our observations.KEY WORDS: antitumour activity, cannabinoid-based preparations, oxidative stress, systemic toxicity     

Subtypes of major depression in substance dependence

Aims   This study evaluated features that differentiate subtypes of major depressive episode (MDE) in the context of substance dependence (SD).
Design   Secondary data analysis using pooled data from family-based and case–control genetic studies of SD.
Setting   Community recruitment through academic medical centers.
Participants   A total of 1929 unrelated subjects with alcohol and/or drug dependence.
Measurements   Demographics, diagnostic criteria for psychiatric and substance use disorders and related clinical features were obtained using the Semi-Structured Assessment for Drug Dependence and Alcoholism. We compared four groups: no life-time MDE (no MDE), independent MDE only (I-MDE), substance-induced MDE only (SI-MDE) and both types of MDE.
Findings   Psychiatric measures were better predictors of MDE subtype than substance-related or socio-demographic ones. Subjects with both types of MDE reported more life-time depressive symptoms and comorbid anxiety disorders and were more likely to have attempted suicide than subjects with I-MDE or SI-MDE. Subjects with both types of MDE, like those with I-MDE, were also more likely than subjects with SI-MDE to be alcohol-dependent only than either drug-dependent only or both alcohol- and drug-dependent.
Conclusions   SD individuals with both types of MDE have greater psychiatric severity than those with I-MDE only or SI-MDE only. These and other features that distinguish among the MDE subtypes have important diagnostic and potential therapeutic implications.     

Closing the Heart Failure Management Gap in the Community: Managing Hypotension and Impact on Outcomes

BackgroundPerception of risk in using recommended therapy in heart failure (HF) patients with hypotension adds to the problems of undertreatment in management. We aimed to determine the feasibility and outcomes of therapy in hypotensive HF patients.Methods and ResultsData were collected from HF clinic patients between 1999 and 2003. Exclusion criteria were: left ventricular ejection fraction (LVEF) >45%; myocardial infarction or revascularization within 3 months of referral; and consult-only visits. Criteria were met by 500 patients. Median follow-up was 6.8 years, with end points of total mortality and combined death and hospitalizations. Blood pressure measurements were done by the nursing staff after the patient was seated for at least 5 minutes. Two measures were taken per each patient encounter and the average of 2 systolic values is recorded for group categorization. Group 1 (hypotension, n = 112) subjects were younger (65 ± 14 vs. 69 ± 12; P = .003) and had lower mean LVEF (22 ± 10% vs. 25 ± 9%; P = .012) than group 2 (no hypotension, n = 338). Drug utilization was similar at 3 months, 1 year, and long-term. Systolic blood pressure (SBP) increased in group 1, but decreased in group 2. Mortality was similar at years 1 and 5 (12.8% vs. 9.9%, P = NS; 45.5% vs. 41.4%, P = .507); however, combined death and hospitalizations were negatively and independently affected by failure to receive therapy.ConclusionsWhen treated successfully with recommended therapy, SBP improved and patients with hypotension at baseline enjoyed significant benefits in outcomes. More effort is needed on mechanisms to implement guidelines to improve HF management.     

Evaluating Delivery Systems: Complex Evaluations and Plausibility Inference

Delivery system evaluation is poorly defined and therefore a barrier to achieving increased coverage of interventions. We use a pre- and post-implementation cross-sectional observational study with assessment of the intermediate processes to evaluate a new delivery system for insecticide-treated nets (ITNs) in two regions of Ghana. In Volta Region, ownership of at least one net rose from 38.3% to 45.4% (P = 0.06), and 6.5% of respondents used a voucher in the purchase. In Eastern Region, ownership of a net rose from 13.7% to 26.0% (P < 0.001) and 0.5% of households used a voucher to purchase a net. Just 40.7% and 21.1% of eligible antenatal clinic (ANC) attendees were offered a voucher in Volta and Eastern Regions, respectively, and 36.0% and 30.7% used their voucher in the purchase of an ITN. Without attributing nets to the specific delivery system, in Eastern Region the success of the new system would be overestimated.     

Reconstruction of large abdominal wall defects

Reconstruction of a large abdominal defect is a technically demanding procedure. A single flap is sometimes insufficient for cover. Compound procedures play an important role in solving this problem. The case of a 35-year-old man with a large abdominal hernia as a result of a traumatic defect on the right abdomen, previously covered by a skin graft, is presented. The reconstructive method was initially expansion of posterior and upper parts of the defect and also of the tensor fascia lata in situ and then deepithelization of the previous skin graft over the intestinal serosa. The defect was covered by Prolene mesh, the upper and dorsal expanded skin was approximated, and an expanded tensor fascia lata flap was transposed to complete the cover. During follow-up examinations, there were no complications such as infection or recurrence of the hernia. Received: 29 January 1999 / Accepted: 14 June 1999     

Epigenetic Regulation of Milk Production in Dairy Cows

It is well established that milk production of the dairy cow is a function of mammary epithelial cell (MEC) number and activity and that these factors can be influenced by diverse environmental influences and management practises (nutrition, milk frequency, photoperiod, udder health, hormonal and local effectors). Thus, understanding how the mammary gland is able to respond to these environmental cues provides a huge potential to enhance milk production of the dairy cow. In recent years our understanding of molecular events within the MEC underlying bovine lactation has been advanced through mammary microarray studies and will be further advanced through the recent availability of the bovine genome sequence. In addition, the potential of epigenetic regulation (non-sequence inheritable chemical changes in chromatin, such as DNA methylation and histone modifications, which affect gene expression) to manipulate mammary function is emerging. We propose that a substantial proportion of unexplained phenotypic variation in the dairy cow is due to epigenetic regulation. Heritability of epigenetic marks also highlights the potential to modify lactation performance of offspring. Understanding the response of the MEC (cell signaling pathways and epigenetic mechanisms) to external stimuli will be an important prerequisite to devising new technologies for maximising their activity and, hence, milk production in the dairy cow.     

Granulomatous Mastitis: Clinical,Pathological Features,and Management

Abstract: This clinical study was conducted to present clinical, radiologic, and histopathologic features of Granulomatous Mastitis (GM) and evaluate the result of surgical and steroid treatment. Sixteen cases diagnosed histologically as GM were reviewed. Patient characteristics, clinical presentation, radiologic imaging, microbiologic, histopathologic assessment, treatment modalities, recurrence, morbidity, and follow‐up data were analyzed. Majority of the patients were child bearing age and all of the patients had a history of breast feeding. Radiologic findings were nonspecific. Histopathology showed the characteristic distribution of granulomatous inflammation in all cases. In 12 cases, surgical excision of the lesion with negative margins was performed. Four cases required quadranectomy because of wideness of the disease. Three patients who had local reoccurrence and three resistant patients were treated by oral prednisone after surgical attempt. Complete remission was obtained and no further recurrence was observed in this patients. GM predominantly occurs in premenopausal women and the clinical symptoms might be misjudged as breast cancer. Histopathologic examination remains the gold standard for the diagnosis. Wide excision of the lesions is the recommended therapy and we suggest steroid therapy in resistant or recurrent disease following the idea that the disease has an autoimmune component.     

Evaluation of dysthymic disorder with technetium-99 m hexamethylpropylene amine oxime brain single-photon emission tomography

Dysthymic disorder is a chronic disorder characterised by the presence of a depressed mood and is classified as a distinct category in DSM-IV, separately from major depression. Although brain imaging studies have been performed in major depressive disease, there have to date been no reports of such studies in dysthymic disorder. In this study 36 patients with dysthymic disorder were compared with 16 normal subjects using technetium-99m hexamethylpropylene amine oxime brain single-photon emission tomography. A relative blood flow ratio was calculated for each region of interest using the average tissue activity in the region divided by activity in the cerebellum. There were significant differences in the bilateral inferior frontal, bilateral parietal, right superior frontal and left posterior temporal regions in the patients with dysthymic disorder compared with the healthy controls. These findings support the hypothesis that the biological bases for dysthymic disorder and major depression are similar. Recognition of these regional abnormalities may have clinical utility in both the diagnosis and the treatment of dysthymic disorder. Further studies are needed to confirm our results and to assess the influence of treatment in patients with dysthymic disorder. Received 14 August and in revised form 24 October 1998     

Investigation of the peripheral inflammation (neutrophil–lymphocyte ratio) in two neurodegenerative diseases of the central nervous system

Neurological Sciences - Alzheimer’s disease (AD), and idiopathic Parkinson’s disease (IPD) are the neurodegenerative diseases of the central nervous system (CNS). Cognitive impairment...