CLINICAL SIGNS, DIAGNOSIS, AND TREATMENT OF LEAD INTOXICATION IN AN ELECTRIC EEL ( ELECTROPHORUS ELECTRICUS).

An adult, wild-caught electric eel ( Electrophorus electricus), weighing 18 kg and measuring 2 m in length, presented with bilateral swellings behind the pectoral fins, lethargy, and anorexia for 2 days. Anesthesia was performed with immersion in tricaine methanesulphonate and supplemented with 0.11 mg/kg medetomidine and 2.2 mg/kg ketamine intramuscularly. Endoscopy revealed blood in the oral and gastric cavity. The stomach was grossly enlarged, flaccid, and contained a lead wire which was removed manually. Blood lead values were severely elevated. The fish was treated with 28 mg/kg calcium disodium ethylenediaminetetraacetate intramuscularly every 72 hr for 5 doses, which resulted in an improved clinical condition. Because lead values had not decreased to normal values within 4 wk of initial presentation, 35 mg/kg dimercaptosuccinic acid was given orally twice weekly for 3 wk. The electric eel made a full recovery.

Experimental evaluation of four airway devices in anaesthetized New Zealand White rabbits.

OBJECTIVE: To compare airway management during induction of anaesthesia, spontaneous ventilation (SV) and controlled mechanical ventilation (CMV), using an endotracheal tube (ETT), laryngeal mask (LM), rabbit-specific supraglottic airway device (v-gel) or facemask (FM). STUDY DESIGN: Prospective randomized crossover experiment. ANIMALS: Ten New Zealand White rabbits. METHODS: After premedication, rabbits were randomly allocated to four groups: 1) ETT; 2) LM; 3) v-gel or 4) FM. The required dose of propofol, duration and number of attempts to place an airway device and leakage during SV and CMV at different peak inspiratory pressures (6, 10, 12, 14 and 16 cmH2O) were recorded. Computed tomography (CT) of the head, neck and abdomen were performed before and after CMV. RESULTS: Significantly less propofol and time [2.0±0.5 mg kg-1, 82±34 seconds, p<0.001] were needed to place the FM compared to the three other groups [v-gel 5.1±2.1 mg kg-1, 302±124 seconds; LM 4.8±1.2 mg kg-1, 275±89 seconds; ETT 5.5±1.4 mg kg-1, 315±147 seconds]. A leak > 25% of the tidal volume occurred at the lowest pressure in FM [median (range), 6 (6-8) cmH2O], which was significantly lower than with v-gel [16 (6-no leak at 16) cmH2O], LM [>16 (6-no leak at 16)] or ETT [>16 (no leak at 16) cmH2O] (p<0.001). On CT images, the height and width of the larynx were significantly smaller with v-gel in comparison to FM and LM (p=0.004). A significant increase in the amount of gas in the stomach (p=0.007), but not gastric volume, was detected in FM and LM. CONCLUSIONS AND CLINICAL RELEVANCE: The v-gel is a practical alternative to LM and ETT for airway management and CMV, but can compress the larynx. The FM is easily placed, but significant leakage occurs during CMV.

Clinical evaluation of the v-gel supraglottic airway device in comparison with a classical laryngeal mask and endotracheal intubation in cats during spontaneous and controlled mechanical ventilation.

OBJECTIVE: To compare airway management during induction of anaesthesia, in spontaneous ventilation and controlled mechanical ventilation (CMV), using a cat-specific supraglottic airway device (the v-gel), a classical laryngeal mask (LM) or an endotracheal tube (ETT). STUDY DESIGN: Prospective, randomized clinical trial. ANIMALS: Forty-five healthy cats. METHODS: After premedication, cats were randomly allocated to one of three groups to secure the airway: 1) v-gel; 2) LM; or 3) ETT (cuff pressure: 20 cm H2O). Cats were anaesthetized for elective procedures. The dose of propofol necessary to insert the v-gel, LM or ETT, the number of attempts required to achieve insertion and leakage during spontaneous ventilation and CMV at different peak inspiratory pressures (8, 10, 12, 14 and 16 cm H2O) were recorded. Leakage of >20% of tidal volume was considered as a criterion for exclusion. Significance was set at a p-value of <0.05. RESULTS: Cats in the v-gel group required a median (range) of 3 mg kg(-1) (2-5 mg kg(-1)) of propofol for successful placement, which was significantly less than the 5 mg kg(-1) (3-7 mg kg(-1)) required for endotracheal intubation (p = 0.005). No significant difference in the total dose of propofol was observed between the v-gel and LM [3 mg kg(-1) (2-7 mg kg(-1))] groups or the ETT and LM groups. Significantly more cats in the ETT group were excluded for leakage of >20% during CMV at all pressure settings. CONCLUSIONS AND CLINICAL RELEVANCE: The v-gel is a practical alternative to the LM and ETT for securing the airway after induction of anaesthesia and for CMV up to 16 cm H2O in healthy cats. The v-gel can be inserted at a more superficial level of anaesthesia than the ETT and showed significantly less leakage during CMV than the ETT.

Anaesthesia with medetomidine, midazolam and ketamine in six gorillas after premedication with oral zuclopenthixol dihydrochloride.

OBJECTIVE: To evaluate the effects of medetomidine, midazolam and ketamine (MMK) in captive gorillas after premedication with oral zuclopenthixol. STUDY DESIGN: Case series. ANIMALS: Six gorillas, two males and four females, aged 9-52 years and weighing 63-155 kg. METHODS: The gorillas were given zuclopenthixol dihydrochloride 0.2 ± 0.05 mg kg(-1) per os twice daily for 3 days for premedication. On the day of anaesthesia the dose of zuclopenthixol was increased to 0.27 mg kg(-1) and given once early in the morning. Anaesthesia was induced with medetomidine 0.04 ± 0.004 mg kg(-1) , midazolam 0.048 ± 0.003 mg kg(-1) and ketamine 4.9 ± 0.4 mg kg(-1) intramuscularly (IM). Upon recumbency, the trachea was intubated and anaesthesia was maintained on 1-2% isoflurane in oxygen. Physiological parameters were monitored every 10 minutes and arterial blood gas analysis was performed once 30-50 minutes after initial darting. At the end of the procedure, 42-115 minutes after initial darting, immobilisation was antagonized with atipamezole 0.21 ± 0.03 mg kg(-1) and sarmazenil 5 ± 0.4 µg kg(-1) IM. RESULTS: Recumbency was reached within 10 minutes in five out of six animals. One animal required two additional darts before intubation was feasible. Heart rate ranged from 60 to 85 beats minute(-1) , respiratory rate from 17 to 46 breaths minute(-1) and temperature from 36.9 to 38.3 °C. No spontaneous recoveries were observed and anaesthetic level was stable. Blood gas analyses revealed mild respiratory acidosis, and mean PaO(2) was 24.87 ± 17.16 kPa (187 ± 129 mmHg) with all values being above 13.4 kPa (101 mmHg). Recovery was smooth and gorillas were sitting within 25 minutes. CONCLUSION AND CLINICAL RELEVANCE: The drug combination proved to be effective in anaesthetizing captive gorillas of various ages and both sexes, with minimal cardio-respiratory changes.

Evaluation of butorphanol, medetomidine and midazolam as a reversible narcotic combination in free-ranging African lions (Panthera leo).

OBJECTIVE: To evaluate the effects of the combination butorphanol, medetomidine and midazolam (BMM) and its reversibility in lions. STUDY DESIGN: Prospective clinical trial. ANIMALS: Thirty free-ranging lions, 10 male and 20 female, weighing 81-210 kg. METHODS: Lions were immobilised with butorphanol mean 0.31 ± SD 0.034 mg kg(-1), medetomidine 0.052 ± 0.006 mg kg(-1), midazolam 0.21 ± 0.024 mg kg(-1) and hyaluronidase 1250 IU administered intramuscularly with a dart gun. Upon recumbency, physiological parameters and anaesthetic depth were monitored 10-15 minutes after darting (T1) and repeated every 10 minutes for a further 30 minutes (T2, T3, T4). Arterial blood gas analyses were performed at T1 and T4. At the end of the procedure, 45-60 minutes after initial darting, immobilisation was reversed with naltrexone 0.68 ± 0.082 mg kg(-1), atipamezole 0.26 ± 0.031 mg kg(-1), and flumazenil 0.0032 ± 0.0007 mg kg(-1) administered intravenously and subcutaneously. RESULTS: The BMM combination rapidly induced immobilisation and lateral recumbency was reached within 7.25 ± 2.3 minutes. Median induction score [scored 1 (excellent) to 4 (poor)] was 1.4 (range 1-2). Cardio-respiratory parameters were stable. Heart rate varied from 32 to 72 beats per minute, respiratory rate from 14 to 32 breaths minute(-1) and rectal temperature from 36.6 to 40.3 °C. No sudden arousals were observed. Arterial blood gas analyses revealed a mean pH of 7.33, PaCO(2) of 33 mmHg and PaO(2) of 87 mmHg. Mild to moderate hypoxemia was seen in four lions. Recovery was smooth and lions were walking within 4.4 ± 4.25 minutes. Median recovery score [scored 1 (excellent) to 4 (poor)] was 1.3 (range 1-2). CONCLUSION AND CLINICAL RELEVANCE: The drug combination proved to be effective in immobilising free-ranging healthy lions of both sexes with minimal cardio-respiratory changes.

Fallot's tetralogy in a European beaver (Castor fiber).

A 20-mo-old, female, 9-kg European beaver (Castor fiber) presented with apathy, reduced appetite of 3-day duration and a grade 5/6 systolic heart murmur. Thoracic radiographs revealed a diffuse broncho-interstitial pattern suspicious for bronchopneumonia. The echocardiographic findings of a hypertrophied right ventricle, ventricular septal defect with overriding aorta, and infundibular pulmonic stenosis were consistent with Fallot's tetralogy. Even though the bronchopneumonia rather than the congenital cardiac defect was considered of primary importance for the presenting clinical signs, the latter was relevant for the decision not to continue any medical treatment. Both disease processes were confirmed on necropsy. Fallot's tetralogy, European beaver, Castor fiber, heart murmur, ultrasound.

Plasma lactate concentrations in free-ranging moose (Alces alces) immobilized with etorphine.

OBJECTIVE: To investigate plasma lactate concentrations of etorphine-immobilized moose in relation to environmental, temporal and physiological parameters. STUDY DESIGN: Prospective clinical study. ANIMALS: Fourteen female and five male moose (Alces alces), estimated age range 1-7 years. METHODS: The moose were darted from a helicopter with 7.5 mg etorphine per animal using projectile syringes and a dart gun. Once immobilized, the moose were approached, a venous blood sample was obtained and vital signs including pulse oximetry were recorded. Diprenorphine was administered to reverse the effects of etorphine. Timing of events, ambient temperature and snow depth were recorded. Blood samples were cooled and centrifuged before plasma was harvested and frozen. The plasma was thawed later and lactate analysed. Data were analysed using descriptive statistics and regression analysis. RESULTS: All animals recovered uneventfully and were alive 12 weeks after immobilization. Mean +/- SD plasma lactate was found to be 9.2 +/- 2.1 mmol L(-1). Plasma lactate concentrations were related positively to snow depth and negatively to time from induction of immobilization to blood sampling. The model that best described the variability in plasma lactate concentrations used induction time (time from firing the dart to the moose being immobilized). The second best model included induction time and snow depth. CONCLUSIONS AND CLINICAL RELEVANCE: Plasma lactate concentrations in these etorphine-immobilized moose were in the range reported for other immobilized wild ruminants. Decreasing induction time, which may be related to a more profound etorphine effect, and increasing snow depth possibly may increase plasma lactate concentrations in etorphine-immobilized moose.

Orchiectomy in Testudo species: technical aspects and effect on courtship behaviour.

Courtship behaviour of tortoises includes biting, ramming, chasing, same-sex sexual behaviour, and it commonly is excessive in European tortoise species kept as pets. As a result, males are kept individually. To assess the effect of orchiectomy on excessive courtship behaviour in European tortoises, 50 tortoises (Testudo graeca , T hermanni and T marginata ) underwent endoscopically assisted orchiectomy from April through September 2013 to 2017. Statistical analyses were performed in relation to species, body mass, testicular size and season and owners were invited to fill out a follow-up questionnaire. Body mass of the tortoises ranged from 334 to 2645 g (mean 1056 g) and the age from 5 to estimated 60 years. Testicular length ranged from 1.4 to 7.0 cm (mean 2.7 cm) and testicular mass from 0.6 to 12.6 g (mean 3.9 g). A complete or partial reduction (allowing group-housing) of the excessive courtship behaviour was noted by 95 per cent of owners and 59 per cent of the owners reported a noticeable change of behaviour within a month of surgery. Given the seasonal variation in testicular size, the best period for castrations in male European tortoises is shortly after brumation (April, May), when testes are proportionally smaller.

The cardiopulmonary effects of etorphine, azaperone, detomidine, and butorphanol in field-anesthetized white rhinoceroses (Ceratotherium simum).

White rhinoceroses (Ceratotherium simum) anesthetized with etorphine combinations develop severe pathophysiologic changes, including hypoventilation, hypoxemia and metabolic acidosis. The aim of this study was to evaluate the addition of butorphanol to the immobilizing mixture on the cardiopulmonary effects in free-ranging white rhinoceroses darted from the helicopter. In the control group (n=15), the rhinoceroses were anesthetized with etorphine, azaperone, detomidine, and hyaluronidase administered intramuscularly. In the treatment group (n=16), 10-20 mg of butorphanol was added to the combination. Within 10 min of becoming immobile, vital parameters (heart rate, respiratory rate, and temperature) and blood gas analyses were taken, and measurements were repeated after 10 (treatment group) and 20 min (control group). Both groups showed respiratory and metabolic acidosis, hypoxemia, and hypercapnia. In the control group, the arterial partial pressure of oxygen was significantly higher and the alveolar-to-arterial oxygen pressure gradients were significantly lower in all body positions compared with the butorphanol group. Oxygen hemoglobin saturation in the control group was higher than in the butorphanol group only in the lateral position. Improvements in arterial oxygen levels were observed in all animals when placed in sternal recumbency. There were no significant differences in the mean induction times between groups, but the distance the butorphanol group ran was significantly less after darting than in the control group. By adding butorphanol to the immobilizing mixture, no benefits in ventilation were seen; although, size differences make comparisons difficult. Running for a shorter distance during induction could be beneficial in the prevention of severe acid-base imbalances and capture myopathy.

Computed tomography of the thorax in rabbits: a prospective study in ten clinically healthy New Zealand White rabbits.

BACKGROUND: Literature investigating the normal cross-sectional anatomy of rabbits with computed tomography (CT) is sparse and incomplete. The purpose of the present study was to investigate the normal thoracic structures, in particular the cranial thorax, with CT angiography in 10 clinically healthy New Zealand White (NZW) rabbits. RESULTS: Absolute and relative measurements of the trachea, heart, thoracic caudal vena cava and aorta, right and left principal bronchi, right and left caudal lobar bronchi and the accompanying branches of the right and left pulmonary artery and vein, right and left lung volume and lung density were taken. The three lobes of the thymus (right ventral, right dorsal and left thoracic lobes) were identified in all rabbits. Both the right dorsal and left thoracic lobes of the thymus extended between the heart and thoracic wall in all individuals with the left lobe reaching more caudally in seven animals. Consequently, the craniocaudal extension of the left lung was smaller than the right lung in these rabbits. Volume of the left lung was significantly smaller than the right (P = 0.005). The cranial mediastinal, right and left tracheobronchial and the aortic thoracic lymph nodes were very small and identified in four, four, seven and ten rabbits, respectively. The heart took up a median of 4.0 intercostal spaces, and in seven rabbits, it was located in the 2nd-5th intercostal space. Median relative cardiac height and width measured 74 and 88%, respectively. The median angle of the trachea to the spine was 5°. Median density between the right and left lung did not significantly differ (- 549 and - 583 Hounsfield units, respectively). In all but one rabbit, atelectasis was present and classified as mild, moderate or severe in six, two and one individuals, respectively. Mild subclinical bronchopneumonia was diagnosed in seven rabbits. CONCLUSIONS: The present study provides species-specific anatomical CT information and reference values for structures in the thorax of the NZW rabbit. Subclinical bronchopneumonia appears to be a common CT finding.

Pulmonary gas exchange and acid-base status during immobilisation of black rhinoceroses (Diceros bicornis) in Zimbabwe.

When immobilising wildlife, adverse side effects can include hypoxaemia, acidosis and hypertension. Pulmonary gas exchange and acid-base status were evaluated during immobilisation of 25 free-ranging and one boma-held black rhinoceros (Diceros bicornis) in Zimbabwe. The effect of different body positions on arterial oxygenation was evaluated. A combination of the following drugs was used: an opioid (etorphine or thiafentanil), azaperone and an a2 -adrenoceptor agonist (detomidine or xylazine). Respiratory and heart rates, rectal temperature and pulse oximetry-derived haemoglobin oxygen saturation were recorded. Serial arterial blood samples were analysed immediately in the field. Marked hypoxaemia and hypercapnia were recorded in immobilised free-ranging black rhinoceroses. Arterial oxygenation was higher during sternal compared to lateral recumbency. Most rhinoceroses developed acidaemia of respiratory and metabolic origin. Initially high lactate concentrations in free-ranging rhinoceroses decreased during immobilisation. Pulse oximetry was unreliable in the detection of hypoxaemia. Positioning in sternal recumbency and routine use of oxygen supplementation are recommended in the management of immobilised rhinoceroses as measures to improve arterial oxygenation.

Bombesin receptor subtypes in human cancers: detection with the universal radioligand (125)I-[D-TYR(6), beta-ALA(11), PHE(13), NLE(14)] bombesin(6-14).

PURPOSE: Bombesin and bombesin receptors have been shown to play a role in cancer. Whereas the gastrin-releasing peptide (GRP) receptor is a bombesin receptor subtype frequently expressed by tumors, the other three subtypes, the neuromedin B (NMB), BB3, and BB4 receptors, have been poorly investigated in human tissues. EXPERIMENTAL DESIGN: We investigated 161 human tumors for their bombesin receptor subtype expression using in vitro receptor autoradiography with the universal bombesin radioligand (125)I-[D-Tyr(6), beta-Ala(11), Phe(13), Nle(14)]bombesin(6-14) in displacement experiments with unlabeled GRP, bombesin, NMB, and [D-Tyr(6), beta-Ala(11), Phe(13), Nle(14)]bombesin(6-14). The distinct rank order of potencies of these analogues for each receptor subtype allows us to identify the predominant subtype expressed by each tumor. RESULTS: Twelve of 12 prostate cancers, 41 of 57 breast cancers, and 5 of 5 gastrinomas expressed predominantly GRP receptors; 11 of 24 intestinal, 1 of 26 bronchial, and 1 of 1 thymic carcinoids had preferentially NMB receptors; 9 of 26 bronchial carcinoids, 1 large cell neuroendocrine lung carcinoma, and 4 of 9 small cell lung carcinomas had preferentially BB3 receptors, whereas 3 of 9 small cell lung carcinomas had GRP receptors. Renal cell carcinomas had GRP receptors in 6 of 16 cases and BB3 receptors in 4 of 16 cases. Finally, 2 of 10 Ewing sarcomas had BB3 receptors. In situ hybridization detected BB3 receptor mRNA in neuroendocrine tumors expressing the BB3 protein. CONCLUSIONS: This is the first study detecting the proteins of BB3, NMB, and GRP receptors in a group of human tumors using differential binding techniques. Particularly relevant is the BB3 expression in lung carcinoids and other neuroendocrine lung tumors, whereas gastrointestinal carcinoids preferably express NMB receptors. These tumors may be targets for diagnostic and radiotherapeutic applications of subtype-selective bombesin analogues.

Transurethral Cystoscopy and Endoscopic Urolith Removal in Female Guinea Pigs (Cavia porcellus).

Urinary diseases are commonly found in guinea pigs. Diagnostic workup includes clinical examination, blood testing, imaging studies, urine culture, and urinalysis. This article describes the use of transurethral cystoscopy in female guinea pigs as an ancillary tool to diagnose abnormalities within the bladder and urethra. In addition, the transurethral cystoscopic removal of uroliths measuring up to 5 mm and situated within the urinary bladder is described.

Novel sst(4)-selective somatostatin (SRIF) agonists. 1. Lead identification using a betide scan.

Hypothesizing that structural constraints in somatostatin (SRIF) analogues may result in receptor selectivity, and aiming to characterize the bioactive conformation of somatostatin at each of its five receptors, we carried out an N(beta)-methylated aminoglycine (Agl) scan of the octapeptide H-c[Cys(3)-Phe(6)-Phe(7)-dTrp(8)-Lys(9)-Thr(10)-Phe(11)-Cys(14)]-OH (SRIF numbering) (ODT-8) that is potent at all SRIF receptor subtypes (sst's) but sst(1). We found that H-c[Cys-LAgl(N(beta)Me,benzoyl)-Phe-DTrp-Lys-Thr-Phe-Cys]-OH (4), H-c[Cys-Phe-LAgl(N(beta)Me,benzoyl)-Trp-Lys-Thr-Phe-Cys]-OH (6), H-c[Cys-Phe-LAgl(N(beta)Me,benzoyl)-dTrp-Lys-Thr-Phe-Cys]-OH (8), and H-c[DCys-Phe-LAgl(N(beta)Me,benzoyl)-DTrp-Lys-Thr-Phe-Cys]-OH (10) had high affinity (IC(50) = 14.3, 5.4, 5.2, and 3.4 nM, respectively) and selectivity for sst(4) (>50-fold over the other receptors). The l-configuration at positions 7 and 8 (l(7), l(8)) yields greater sst(4) selectivity than the l(7), d(8) configuration (6 versus 8). Peptides with the d(7), l(8) (7) and d(7), d(8) (9) configurations are significantly less potent at all receptors. H-c[Cys-Phe-Phe-DTrp-LAgl(betaAla)-Thr-Phe-Cys]-OH (16), H-c[Cys-Phe-Phe-DTrp-DAgl(betaAla)-Thr-Phe-Cys]-OH (17), and their N(beta)Me derivatives at position 9 (18, 19) were essentially inactive. Potent but less sst(4)-selective were members of the Agl-scan at positions 10, H-c[Cys-Phe-Phe-dTrp-Lys-lAgl(N(beta)Me,HO-Ac)-Phe-Cys]-OH (20, IC(50) = 6.5 nM), and 11, H-c[Cys-Phe-Phe-DTrp-Lys-Thr-LAgl(N(beta)Me,benzoyl)-Cys]-OH (22, IC(50) = 6.9 nM), while the d-configuration at positions 10 (21) and 11 (23) led to reduced affinity. One of our best analogues, 8, is an agonist when tested for its ability to inhibit forskolin-stimulated cAMP accumulation in sst(4)-transfected CCL39 cells (EC(50) = 1.01 nM). All Agl-containing analogues were first synthesized using unresolved Fmoc-Agl(N(beta)Me,Boc)-OH, and the diastereomers were separated using HPLC. Chiral assignment at the Agl-containing residue was subsequently done using enzymatic degradation and by de novo synthesis in the cases of H-c[Cys-Phe-DAgl(N(beta)Me,benzoyl)-DTrp-Lys-Thr-Phe-Cys]-OH (9) and H-c[DCys-Phe-DAgl(N(beta)Me,benzoyl)-DTrp-Lys-Thr-Phe-Cys]-OH (11), starting with the papain-resolved Fmoc-DAgl(Boc). These results suggested that the orientation of side chains at position 6, 7, or 11 with respect to the side chains of residues 8 and 9 may be independently responsible for sst(4) selectivity.

Novel sst(4)-selective somatostatin (SRIF) agonists. 2. Analogues with beta-methyl-3-(2-naphthyl)alanine substitutions at position 8.

We present a family of human sst(4)-selective, high-affinity (IC(50) = 2-4 nM) cyclic somatostatin (SRIF) octapeptides. These peptides result from the substitution of dTrp(8) in H-c[Cys(3)-Phe(6)-Phe(7)-DTrp(8)-Lys(9)-Thr(10)-Phe(11)-Cys(14)]-OH (SRIF numbering) (ODT-8) by one of the four conformationally biased stereoisomers of beta-methyl-3-(2-naphthyl)alanine (beta-Me2Nal). Whereas H-c[Cys-Phe-Phe-DNal-Lys-Thr-Phe-Cys]-OH (ODN-8, 2) has high affinity and marginal selectivity for human sst(3) (Reubi et al., Proc. Natl. Acad. Sci. U.S.A. 2000, 97, 13973-13978), H-c[Cys-Phe-Tyr-D-threo-beta-Me2Nal-Lys-Thr-Phe-Cys]-OH (5) has high affinity for all sst's except for sst(1); H-c[Cys-Phe-Tyr-L-threo-beta-Me2Nal-Lys-Thr-Phe-Cys]-OH (6) has high affinity for sst(4) (IC(50) = 2.1 nM), with more than 50-fold selectivity toward the other receptors. Analogues 7 and 8, containing d- and l-erythro-beta-Me2Nal instead of the corresponding threo derivatives at position 8, are essentially inactive at all receptors. Substitution of Tyr(7) in 5 and 6 by Aph(7) resulted in 9 and 10 with similar affinity patterns overall yet lowered affinity. The substitution of DCys(3) for Cys(3) in 5 and 6 yielded H-c[DCys-Phe-Tyr-D-threo-beta-Me2Nal-Lys-Thr-Phe-Cys]-OH (11) and H-c[DCys-Phe-Tyr-L-threo-beta-Me2Nal-Lys-Thr-Phe-Cys]-OH (12), with biological profiles almost identical to those of their parents 5 and 6 (i.e., high affinity for sst(2-5) for 11 and high affinity and selectivity for sst(4) for 12). Analogue 12, with high sst(4) affinity combined with the highest sst(4) selectivity among all tested compounds, is an agonist in the cAMP accumulation assay (EC(50) = 1.29 nM). Cold monoiodination of 12 yielded 14, with loss of sst(4) selectivity and loss of high affinity (IC(50) = 21 nM). Introduction of Tyr(2) in 9 and 10 and substitution of Cys(3) by dCys(3), to yield 15 and 16 (IC(50) = 9.8 and 61 nM, respectively, for sst(4) and limited selectivity), failed to generate a high-affinity (125)iodinatable sst(4)-selective ligand. Substitution of Phe by Tyr at position 11 in H-c[DCys-Phe-Phe-L-threo-beta-Me2Nal-Lys-Thr-Phe-Cys]-OH yielded 18 (IC(50) = 11.8 nM at sst(4)), with limited sst(4) selectivity (30-fold or greater at the other receptors) yet only slightly improved affinity over that of 14. Cold monoiodination of 18 yielded 20 (IC(50) = 30 nM at sst(4) and high selectivity). Whereas we were able, in this study, to identify a new family of sst(4)-selective, high-affinity compounds, our additional goal, to identify highly potent and sst(4)-selective ligands amenable to (125)iodination, could not be achieved satisfactorily. On the other hand, some of the diastereomers identified in this study, such as 5, 11, 17, and 19, are very potent ligands at all receptors but sst(1).

Predictors for subsequent need for immunosuppressive therapy in early Crohn's disease.

BACKGROUND AND AIMS: The clinical course of Crohn's disease (CD) is highly variable with a subgroup of patients developing a progressive disease course necessitating immunosuppressive therapy (IT). However, reliable, stable and non-invasive individual clinical parameters in order to identify patients at risk for undergoing subsequent IT have not been sufficiently established. We therefore aimed to identify such clinical parameters. METHODS: A retrospective, multicenter analysis of CD patients from 6 German tertiary IBD centers was performed. Patients were classified into two groups depending on requiring IT or not. Personal data, clinical and laboratory parameters during the first 3 months after CD diagnosis and effects of initial medical therapy were compared between these two groups. RESULTS: In 218 (61.8%) of the 353 patients the CD course necessitated IT. Those patients were significantly younger at symptom onset and diagnosis, and required significantly more often a systemic corticosteroid therapy. Furthermore, significant differences in serological markers of inflammation were observed. Age, gender and the effect of initial steroid therapy were used to develop a prognostic model predicting the individual probability of necessitating IT. CONCLUSIONS: The simple clinical items age at diagnosis, gender, and need for systemic steroid therapy can predict a progressive disease course in early CD. Our model based on these parameters allows an individualized estimation of each patient's risk to develop a progressive disease course. Thereby, our model can help in deciding if patients will need immunosuppressive drugs early in the disease course or if a careful watch and wait strategy is justified.

Total intravenous anesthesia with midazolam, ketamine, and xylazine or detomidine following induction with tiletamine, zolazepam, and xylazine in red deer (Cervus elaphus hippelaphus) undergoing surgery.

Sixteen captive female red deer were successfully anesthetized to surgically implant a telemetry system. The deer were immobilized with (mean±SD) 1.79±0.29 mg/kg xylazine and 1.79±0.29 mg/kg tiletamine/zolazepam given intramuscularly with a dart gun. Anesthesia was maintained for 69±2 min using a total intravenous protocol with a catheter placed in the jugular vein. Group X received xylazine (0.5±0.055 mg/kg/hr) and group D, detomidine (2±0.22 µg/kg/hr), both in combination with ketamine (2±0.02 mg/kg/hr) and midazolam (0.03±0.0033 mg/kg/hr), as a constant rate infusion. Anesthesia was reversed with 0.09±0.01 mg/kg atipamezole and 8.7±1.21 µg/kg sarmazenil given intravenously in both groups. These drug combinations provided smooth induction, stable anesthesia for surgery, and rapid recovery. Respiratory depression and mild hypoxemia were seen, and we, therefore, recommend using supplemental intranasal oxygen.

Brachial plexus block using electrolocation for pancarpal arthrodesis in a dog.

Conduction blockade was achieved at the brachial plexus of a dog undergoing surgery for pancarpal arthrodesis. The lidocaine/bupivacaine mixture used was the sole analgesic treatment applied during surgery and for 3 hours post-operatively. Location of the plexus brachialis was facilitated using a nerve stimulator. A low volume of lidocaine and bupivacaine (0.26 mL kg(-1)) resulted in successful blockade, which was evident from stable cardiorespiratory variables at low end-tidal (1.3-1.4%) isoflurane concentrations. Pain scoring and examination of motor and sensory function indicated adequate pain relief for 7 hours. While localization of the plexus brachialis can be performed 'blindly', electrolocation improves the success rate for less experienced anaesthetists.