Schedule-induced polydipsic choice between cocaine and lidocaine solutions: critical importance of associative history

Two groups of rats given daily, 3-h, intermittent food-pellet sessions, which induced polydipsia, drank either cocaine (COC) or lidocaine (LIDO) solutions. Then water was made available concurrently, but neither group preferred drug solution. When drug was presented in a glucose-saccharin vehicle, which was subsequently faded out, both the COC and LIDO groups acquired a strong preference for drug solution rather than water. Half of each group was continued, and half was directly faded to a preference for the other drug solution rather than water. Then COC and LIDO solutions were available concurrently and animals overwhelmingly preferred the drug solution that historically had been associated with the glucose-saccharin vehicle. Finally, the COC-preferring and LIDO-preferring groups had the concentrations of their preferred drug increased step-wise several times and preferences were maintained. Thus, acquired drug preferences remained stable as preferred drug concentration was increased, making it more bitter than the nonpreferred drug. The abuse potential of COC affords it little advantage over LIDO in the institution and maintenance of oral drug preference, suggesting that the post-ingestive pharmacological action of a drug is less important for acquiring drug-taking than is a history of associating the drug with another reinforcing event.     

Bupivacaine 0.1% does not improve postoperative epidural fentanyl analgesia after abdominal or thoracic surgery

Epidural infusions of fentanyl, in a 10 micrograms.ml-1 concentration, combined with bupivacaine 0.1% were compared with epidural infusions of fentanyl alone for postoperative analgesia following abdominal or thoracic surgery. There were no detectable differences between the two groups in analgesia (mean visual analogue scale pain scores ranging between 15-35 mm), average infusion rates of 7-9 ml.hr-1, and serum fentanyl concentrations which reached 1-2 ng.ml-1. There was no difference in postoperative pulmonary function (pH, PaCO2, SaO2), or bowel function (time to flatus or po fluids). The incidence of side-effects including somnolence, nausea and vomiting, pruritus and postural hypotension was also similar. Of the patients receiving fentanyl and bupivacaine 0.1%, three developed a transient unilateral sensory loss to pinprick and ice, and two of these patients had unilateral leg weakness equal to a Bromage 1 score. The addition of bupivacaine 0.1% does not improve epidural infusions of fentanyl using a 10 micrograms.ml-1 concentration following abdominal or thoracic surgery.     

The importance of employing stringent methods to recruit fertile male controls

Two methods of recruiting fertile male controls were evaluated and compared. The first group was recruited from the partners of women attending an antenatal clinic without obtaining details of their reproductive history. The second group was recruited after obtaining a detailed reproductive history from the couple and employing stringent entry criteria. Entry criteria for the second group included a length of exposure to the risk of pregnancy of not more than 12 months and no previous episode of involuntary infertility for either partner. There were significant differences between the distributions of semen parameters obtained from the two groups, indicating that the selection criteria for "fertile" men significantly influence results obtained and therefore that it is important to employ stringent criteria for the recruitment of fertile male controls. The group which was recruited by stringent criteria (mean length of exposure to the risk of pregnancy of 3 months) was characterised by a significantly higher median concentration of spermatozoa which exhibited slow linear or nonlinear motility. This confirms the findings of a previous study which suggested that slow linear or nonlinear motility are superior forms of spermatozoal motion.     

Dissociation of autonomic and cognitive effects of THC in man

Intravenous THC, 30–44.8 g/kg, was administered to four subjects. Each received THC on four occasions preceded by either i.v. saline, 0.04 mg/kg atropine sulfate, 0.2 mg/kg propranolol, or both drugs together. Heart rates, subjective intoxication and symptom ratings, time productions, and EEG activity were measured. In the absence of autonomic blocking drugs, THC produced characteristic tachycardia, subjective intoxication, and EEG effects. After combined autonomic blockade, THC had no effect on heart rate, while subjective and EEG changes remained as intense. These findings argue against the hypothesis that the subjective and EEG effects of THC are mediated by autonomic receptors or by interoception of peripheral autonomic actions of THC.To whom offprint requests should be sent     

Toxicity of 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin in larval and adult forms ofRana catesbeiana

Summary Varying doses of TCDD ranging from 25 to 1000 g/kg were administered to the larval and adult forms of the American bullfrog,Rana catesbeiana. Doses of TCDD as high as 1 mg/kg failed to have any significant effect upon survival or completion of metamorphosis in tadpole and doses of up to 500 g/kg had no effect on survival of adult frogs. Histopathological examination of various tissues from the metamorphosed tadpoles and adult frogs failed to show any abnormalities.This work was supported by USPHS Grant ES00267. The Training support of ES 07028 is also gratefully acknowledged.     

A military health care facility has high in vitro fertilization success rates

The purpose of this study is to describe in vitro fertilization (IVF) success rates at our military health care facility. A retrospective analysis was performed for all IVF cycles initiated at Wilford Hall Medical Center from January 1, 1996, to December 31, 1998. During this period, there were 214 IVF cycles initiated with gonadotropin therapy. The overall pregnancy rate, with an intrauterine pregnancy identified by transvaginal ultrasonography, was 45.3%. IVF services can be provided at a military health care facility with a high rate of success.     

Evaluation of osteopontin as biomarker for pancreatic adenocarcinoma.

OBJECTIVES: Pancreatic adenocarcinoma is a deadly disease with an overall 5-year patient survival of less than 5%. This dismal prognosis of pancreatic cancer is largely due to the advanced stage of the disease at presentation. If pancreatic cancer could be diagnosed more readily and accurately using serum markers, patient survival could theoretically be improved by enabling more patients to avail of surgical resection. One candidate tumor marker recently identified by global gene expression analysis of pancreatic cancer is the secreted glycophosphoprotein osteopontin (OPN). In this study, we evaluate OPN as a serum marker of pancreatic adenocarcinoma. METHODS: In situ hybridization for OPN was performed on a pancreatic adenocarcinoma tissue microarray. Serum OPN levels were determined in preoperative sera from 50 patients with pancreatic cancer and 22 healthy control individuals by competitive ELISA. RESULTS: In situ hybridization for OPN performed on a tissue microarray revealed strong OPN mRNA signal in tumor-infiltrating macrophages in 8 of 14 pancreatic adenocarcinomas. In contrast, OPN expression was not seen in the pancreatic cancer cells themselves, nor was it seen in normal pancreatic tissue or in the macrophages distant from the infiltrating cancer. Serum OPN levels, as measured by ELISA, were elevated in the sera of 50 patients with resectable pancreatic adenocarcinoma compared to 22 healthy control individuals (mean +/- SD for OPN was 482 +/- 170 ng/ml and 204 +/- 65 ng/ml, respectively; P < 0.001). Using a cutoff level of 2 SD above the mean for healthy individuals, elevated OPN had sensitivity of 80% and specificity of 97% for pancreatic cancer. In contrast, only 62% of these patients with resectable pancreatic cancer had elevated CA19-9. CONCLUSIONS: Serum OPN may have utility as a diagnostic marker in patients with pancreatic cancer.     

Alteration in urinary matrix metalloproteinase-9 to tissue inhibitor of metalloproteinase-1 ratio predicts recurrence in nonmuscle-invasive bladder cancer.

PURPOSE: The purpose is to assess the prognostic significance of matrix metalloproteinase (MMP)-9 in patients with bladder cancer using a combination of ELISA (to measure MMP-9 in voided urine) and immunohistochemistry (to study MMP-9 in bladder tumors). The relationship between MMP-9 and its principal inhibitor, tissue inhibitor of metalloproteinase (TIMP)-1 (in voided urine samples) was also studied. EXPERIMENTAL DESIGN: A total of 134 patients with bladder tumors (7 cis, 76 T(a), 27 T(1), 24 T(2)-T(4); 40 G1, 43 G2, and 44 G3), 33 patients with benign urological conditions, and 36 healthy volunteers was studied. Samples from 106 patients with bladder cancer and 12 controls were stained for MMP-9. Clinical follow-up data were available on 116 patients (median: 25 months; range: 4-36 months). RESULTS: MMP-9 was present in all urine samples analyzed. There were no differences between patients with cancer and patients with benign disorders. However, patients had significantly higher urinary MMP-9 than normal volunteers (P = 0.0167). Urinary MMP-9 was associated with bladder tumors of advanced stage (P = 0.0065) and large size (P < 0.0001) but not with grade (P = 0.14), multiplicity (P = 0.31), recurrence (P = 0.55), progression (P = 0.83), or survival (P = 0.55). Low MMP-9:TIMP-1 ratios in patients with nonmuscle-invasive tumors were associated with higher recurrence rates (P = 0.0035). Sixty percent (64 of 106) of bladder tumor specimens expressed MMP-9 compared with none of 12 normal urothelial biopsies (P < 0.0001). MMP-9 staining was associated with tumor size (P = 0.014), disease progression (P = 0.005), and poor disease-specific survival (P = 0.022) but was unrelated to tumor stage (P = 0.46), grade (P = 0.26), multiplicity (P = 0.85), or recurrence rate (P = 0.62). CONCLUSIONS: High urinary MMP-9 levels are associated with large bladder tumors. A low urinary MMP-9:TIMP-1 ratio may indicate a higher risk of intraluminal nonmuscle-invasive tumor recurrence and may assist in planning follow-up surveillance protocols.     

Neural network analysis of combined conventional and experimental prognostic markers in prostate cancer: a pilot study.

Prostate cancer is the second most common malignancy in men in the UK. The disease is unpredictable in its behaviour and, at present, no single investigative method allows clinicians to differentiate between tumours that will progress and those that will remain quiescent. There is an increasing need for novel means to predict prognosis and outcome of the disease. The aim of this study was to assess the value of artificial neural networks in predicting outcome in prostate cancer in comparison with statistical methods, using a combination of conventional and experimental biological markers. Forty-one patients with different stages and grades of prostate cancer undergoing a variety of treatments were analysed. Artificial neural networks were used as follows: eight input neurons consisting of six conventional factors (age, stage, bone scan findings, grade, serum PSA, treatment) and two experimental markers (immunostaining for bcl-2 and p53, which are both apoptosis-regulating genes). Twenty-one patients were used for training and 20 for testing. A total of 80% of the patients were correctly classified regarding outcome using the combination of factors. When both bcl-2 and p53 immunoreactivity were excluded from the analysis, correct prediction of the outcome was achieved in only 60% of the patients (P = 0.0032). This study was able to demonstrate the value of artificial neural networks in the analysis of prognostic markers in prostate cancer. In addition, the potential for using this technology to evaluate novel markers is highlighted. Further large-scale analyses are required to incorporate this methodology into routine clinical practice.     

A prospective randomized trial comparing transurethral resection of the prostate and laser therapy in men with chronic urinary retention: The CLasP study

PURPOSE: We assessed the effectiveness of laser therapy versus transurethral prostatic resection in men with symptomatic chronic urinary retention secondary to benign prostatic enlargement. MATERIALS AND METHODS: This trial was multicenter, pragmatic and randomized. Analysis was done by intent to treat. Laser therapy involved neodymium:YAG noncontact visual prostate ablation, while transurethral prostatic resection was performed by standard electroresection. Patients were included in our study if they reported moderate to severe lower urinary tract symptoms with an International Prostate Symptom Score (I-PSS) of 8 or more, benign prostatic enlargement and a persistent post-void residual urine volume of more than 300 ml. Followup was 7.5 months. Primary outcome measures included the I-PSS, I-PSS quality of life score, maximum urinary flow and post-void residual urine volume. Secondary outcome measures included treatment failure, complications, hospital stay and catheterization time. RESULTS: A total of 82 patients agreed to be randomized to receive laser therapy (38) or transurethral prostatic resection (44). There were significant improvements in all primary outcomes in each group from randomization to followup. Transurethral prostatic resection was significantly better than laser therapy for I-PSS and maximum urinary flow values (p = 0.035 and 0.029, respectively) but there were no differences in post-void residual urine volume and I-PSS quality of life score between the groups. We noted significantly more treatment failures with laser therapy than resection (8 versus 0, p = 0.0014), although only 3 patients required resection after laser therapy because of persistent symptoms. In addition, hospital stay after resection was 2-fold that after laser therapy (ratio of geometric means 2.01, 95% confidence interval 1.54 to 2.61, p <0.0001). However, time to catheter removal was 9 times longer in the laser therapy group (p <0. 0001). Complication rates were significantly higher for transurethral prostatic resection (chi-square 5.05, 1 df, p = 0.025). CONCLUSIONS: Transurethral prostatic resection is more effective than laser ablation in men with chronic urinary retention in terms of symptom score, maximum urinary flow and failure. However, men who underwent resection had significantly more treatment complications and were hospitalized longer than those who received laser therapy. This finding implies that laser ablation therapy may have a role in patients at higher risk who are willing to accept a lower level of effectiveness in exchange for decreased complication rates and hospital stay.