OUTCOME OF BURCH COLPOSUSPENSION IN A DISTRICT GENERAL HOSPITAL

SUMMARY Genuine stress incontinence is a problem affecting women of all ages. There are several conservative means of alleviating the condition, but surgical intervention is an alternative when these fail. The Burch colposuspension has become a popular choice of procedure. In this report of 61 patients in a district general hospital, the success rate was high (84%, which compares favourably with the literature). There was a high rate of complications (55%), some of which have not commonly been reported. Burch colposuspension is a good operation for stress incontinence, although patients should be counselled about possible postoperative difficulties.     

Interaction of cocaine with chlordiazepoxide assessed by motor activity in mice.

1. The nature of KCl-induced relaxations of the rat anococcygeus muscle was investigated. 2. The relaxations were mimicked by other K+ salts, but not by NaCl. 3. The muscle was more susceptible to the relaxant effects of KCl than the contractile effects. 4. Addition of ouabain (100 micron) had no effect on the relaxations. 5. The relaxations were abolished by tetrodotoxin (5 microgram/ml), procaine (500 micron), and by section of the inhibitory nerves. 6. The results suggest that KCl-induced relaxations are due to stimulation of the inhibitory nerves by K+.     

Radiofrequency Ablation to Improve Survival After Conversion Chemotherapy for Colorectal Liver Metastases

Introduction

Systemic chemotherapy is able to convert colorectal liver metastases (CRLM) that are initially unsuitable for local treatment into locally treatable disease. Surgical resection further improves survival in these patients. Our aim was to evaluate disease-free survival (DFS), overall survival, and morbidity for patients with CRLM treated with RFA following effective downstaging by chemotherapy, and to identify factors associated with recurrence and survival.

Materials and methods

Included patients had liver-dominant CRLM initially unsuitable for local treatment but eligible for RFA or RFA with resection after downstaging by systemic chemotherapy. Chemotherapeutic regimens consisted predominantly of CapOx, with or without bevacizumab. Follow-up was conducted with PET-CT or thoraco-pelvic CT.

Results

Fifty-one patients had a total of 325 CRLM (median = 7). Following chemotherapy, 183 lesions were still visible on CT (median = 3). Twenty-six patients were treated with RFA combined with resection. During surgery, 309 CRLM were retrieved on intraoperative ultrasound (median = 5). Median survival was 49 months and was associated with extrahepatic disease at time of presentation and recurrences after treatment. Estimated cumulative survival at 1, 3 and 4 years was 90, 63 and 45 %, respectively. Median DFS was 6 months. Twelve patients remained free of recurrence after a mean follow-up of 32.6 months.

Conclusion

RFA of CRLM after conversion chemotherapy provides potential local control and a good overall survival. To prevent undertreatment, the involvement of a multidisciplinary team in follow-up imaging and assessment of local treatment possibilities after palliative chemotherapy for liver-dominant CRLM should always be considered.

     

Cochlear otosclerosis (otospongiosis): CT analysis with audiometric correlation

Ninety patients who had suspected or confirmed fenestral or cochlear otosclerosis underwent CT examination. Foci of demineralization in the otic capsule were discovered in 20 ears (12 patients). Audiometric studies of the 12 patients revealed sensorineural hearing loss (SNHL) with distinct correlation of CT findings with progressivity and with involvement of the frequency level subtended by the specific area of the cochlea involved. Foci of abnormal increased density, presumably representing the healed phase of this disorder, were found less frequently than expected. There was a predilection for the basilar turn. All patients had static SNHL in the higher frequencies. The healed phase of this disorder is probably not consistently diagnosable with CT.     

The effects of aqueous extracts of Tetracarpidium conophorum seeds on the hormonal parameters of male guinea pigs

ObjectiveTo investigate the effects of the aqueous extracts of the seeds of Tetracarpidium conophorum and the effect of Proviron (12.5 mg/kg) (as standard) on the hormonal parameters of male guinea pigs, compare the effects of the seeds of Tetracarpidium conophorumand Proviron, and screen the phytochemical constituents of the seeds of Tetracarpidium conophorum.MethodsThe hormonal effects of the Tetracarpidium conophorum and Proviron were tested by hormonal assay, using enzyme immuno assay method. This was done by reaction of antibody with serum testosterone and testosterone label, magnetic solid phase separation and colour development step. Phytochemical screening was done using standard procedures.ResultsThe aqueous extract of the Tetracarpidium conophorum seeds (100–400 mg/kg) caused a statistically significant increase (P < 0.05, ANOVA) in the level of testosterone of male guinea pigs, from (2.60 ± 0.06) ng/mL to (3.40 ± 0.05) ng/mL, (3.00 ± 0.60) ng/mL and (3.30 ± 0.45) ng/mL on the 7th, 14th and 21st day of the administration of the extracts, respectively. The highest increase was obtained after the 7th day of treatment [(3.40 ± 0.05) ng/mL]. These effects were very comparable to the effects of Proviron on the testosterone of male guinea pigs, which were obtained to be (2.80 ± 0.01) ng/mL, (2.90 ± 0.16) ng/mL and (3.10 ± 0.30) ng/mL on the 7th, 14th and 21st day, respectively. These effects were dose-and time-dependent. The optimum effect on testosterone level under dose-dependent study [(4.70 ± 0.45) ng/mL] was obtained at 300 mg/kg of Tetracarpidium conophorum after 7 days treatment. Finally, the phytochemical screening of the seeds of Tetracarpidium conophorum revealed the presence of flavonoids, tannin, alkaloids, carbohydrate, volatile oils, terpenoids, saponins and cardiac glycosides.ConclusionThis study supports the claims on the use of the seeds of this plant by traditional medicine practitioners as a fertility agent. However, further studies need to be done to isolate and characterize the active principle(s) responsible for this activity in this plant.     

Short-term cultured, interleukin-15 differentiated dendritic cells have potent immunostimulatory properties

Background  

Optimization of the current dendritic cell (DC) culture protocol in order to promote the therapeutic efficacy of DC-based immunotherapy is warranted. Alternative differentiation of monocyte-derived DCs using granulocyte macrophage colony-stimulating factor (GM-CSF) and interleukin (IL)-15 has been propagated as an attractive strategy in that regard. The applicability of these so-called IL-15 DCs has not yet been firmly established. We therefore developed a novel pre-clinical approach for the generation of IL-15 DCs with potent immunostimulatory properties.     

Acquired storage pool disease in platelets during disseminated intravascular coagulation

A patient with clinical and laboratory evidence of disseminated intravascular coagulation associated with deep-vein thrombosis and pulmonary embolism developed a qualitative platelet abnormality characterized by a defective release reaction. Second-phase aggregation induced by ADP and adrenaline was impaired, and reduced collagen- induced aggregation was accompanied by defective release of ADP and ATP. The decrease in total platelet ATP and ADP, the high ATP:ADP ratio in the presence of normal amounts of metabolic adenine nucleotides, and the low content of serotonin associated with abnormal uptake and metabolism of the exogenous amine suggested that the defective platelet function was due to lack of the platelet organelles in which serotonin and nonmetabolic adenine nucleotides are normally stored. Acquired storage pool disease is likely to be related to exposure of circulating platelets to aggregating agents, with their degranulation occurring during disseminated intravascular coagulation.     

Neutral antagonist activity of naltrexone and 6β-naltrexol in na?ve and opioid-dependent C6 cells expressing a μ-opioid receptor

Background and purpose:

Adenylyl cyclase sensitization occurs on chronic agonist activation of µ-opioid receptors and is manifested by an increase in cAMP levels (overshoot) on challenge with antagonist. It has been proposed that a long lasting constitutively active receptor is formed on chronic µ-opioid exposure and that antagonists with inverse agonist activity rapidly return the receptor to a basal state causing a cAMP overshoot and a more severe withdrawal response in vivo. This hypothesis depends on an accurate characterization of neutral and inverse agonist properties of opioid antagonists.

Experimental approach:

C6 glioma and HEK293 cells expressing µ-opioid receptors were used. Opioid antagonists were examined for their ability to induce a cAMP overshoot following chronic treatment with the agonist DAMGO ([D-Ala²,N-Me-Phe⁴,Glyol⁵]-enkephalin). The compounds were also characterized as agonists, inverse agonists or neutral antagonists by using assays for competitive binding, [³⁵S]GTPγS (guanosine-5′-O-(3-[³⁵S]thio)triphosphate) binding and changes in cell surface receptor expression.

Key results:

Naltrexone, 6β-naltrexol and naloxone were indistinguishable to the µ-opioid receptor in the opioid-naïve or dependent state and acted as neutral antagonists. The δ-opioid receptor inverse agonist RTI-5989-25 [(+)-N-[trans-4′-(2-methylphenyl)-2′-butenyl]-(3R,4R)-dimethyl-4-(3-hydroxyphenyl)piperidine], a 3,4-dimethyl-4-(3-hydroxyphenyl)-piperidine, was an inverse agonist at the µ-opioid receptor, and the peptide antagonist CTAP (H-D-Phe-Cys-Tyr-D-Trp-Arg-Thr-Pen-Thr-NH₂) showed variable, assay-dependent properties. All the antagonists precipitated the same degree of cAMP overshoot in opioid-dependent cells.

Conclusions and implications:

Antagonists at the µ-opioid receptor may be neutral or show inverse agonist activity. Formation of a constitutively active µ-opioid receptor is not a requirement for the development or expression of adenylyl cyclase sensitization.     

Fructose-1,6-bisphosphate reduces inflammatory pain-like behaviour in mice: role of adenosine acting on A1 receptors

Background and purpose:

D-Fructose-1,6-bisphosphate (FBP) is an intermediate in the glycolytic pathway, exerting pharmacological actions on inflammation by inhibiting cytokine production or interfering with adenosine production. Here, the possible antinociceptive effect of FBP and its mechanism of action in the carrageenin paw inflammation model in mice were addressed, focusing on the two mechanisms described above.

Experimental approach:

Mechanical hyperalgesia (decrease in the nociceptive threshold) was evaluated by the electronic pressure-metre test; cytokine levels were measured by elisa and adenosine was determined by high performance liquid chromatography.

Key results:

Pretreatment of mice with FBP reduced hyperalgesia induced by intraplantar injection of carrageenin (up to 54%), tumour necrosis factor α (40%), interleukin-1 β (46%), CXCL1 (33%), prostaglandin E₂ (41%) or dopamine (55%). However, FBP treatment did not alter carrageenin-induced cytokine (tumour necrosis factor α and interleukin-1 β) or chemokine (CXCL1) production. On the other hand, the antinociceptive effect of FBP was prevented by systemic and intraplantar treatment with an adenosine A₁ receptor antagonist (8-cyclopentyl-1,3-dipropylxanthine), suggesting that the FBP effect is mediated by peripheral adenosine acting on A₁ receptors. Giving FBP to mice increased adenosine levels in plasma, and adenosine treatment of paw inflammation presented a similar antinociceptive mechanism to that of FBP.

Conclusions and implications:

In addition to anti-inflammatory action, FBP also presents an antinociceptive effect upon inflammatory hyperalgesia. Its mechanism of action seems dependent on adenosine production but not on modulation of hyperalgesic cytokine/chemokine production. In turn, adenosine acts peripherally on its A₁ receptor inhibiting hyperalgesia. FBP may have possible therapeutic applications in reducing inflammatory pain.     

Pharmacological modulation by celecoxib of cachexia associated with experimental arthritis and atherosclerosis in rabbits

BACKGROUND AND PURPOSE

Non-steroidal anti-inflammatory drugs improve inflammatory cachexia in several conditions. Thus, we have explored inhibition of cyclooxygenase-2 (COX-2) in an experimental model of rheumatoid cachexia in rabbits.

EXPERIMENTAL APPROACH

Chronic arthritis was induced in immunized rabbits by repeated intra-articular injections of ovalbumin. To increase the degree of systemic inflammation and also to induce atherosclerotic lesions, the animals were fed a hyperlipidaemic diet (2% cholesterol and 6% peanut oil) and were given an endothelial injury of the femoral artery. Rabbits were randomized to receive the COX-2 inhibitor celecoxib (10 mg·kg⁻¹·day⁻¹) or no treatment. After 4 weeks, sera, peripheral mononuclear cells and vessel specimens were collected.

KEY RESULTS

Inhibition of COX-2 by celecoxib modulated the systemic inflammatory response and increased total cholesterol and triglyceride levels. Celecoxib also minimized weight loss and prevented serum albumin fall. At a vascular level, celecoxib reduced COX-2 protein in the femoral arterial wall, but did not modify size or the macrophage infiltration of femoral lesions nor the percentage of rabbits with spontaneous aortic plaques.

CONCLUSIONS AND IMPLICATIONS

Our animal model induced a severe inflammatory cachexia, comparable to that of persistently active rheumatoid arthritis. The inhibition of COX-2 by celecoxib improves this state, suggesting that COX products play an important role in its development, without affecting the development or the progression of vascular lesions. Overall, these results suggest that celecoxib might be considered as a new therapeutic tool for the treatment of rheumatoid cachexia.