Vaccination of boars with a GnRH vaccine (Improvac) eliminates boar taint and increases growth performance.

Peri- and postpubertal boars accumulate substances (e.g., androstenone and skatole) in their fatty tissue that are responsible for boar taint in pork. The objective of this study was to assess the efficacy of a GnRH vaccine, Improvac, in eliminating boar taint. Three hundred male (200 intact boars, 100 barrows) crossbred (Large White x Landrace) pigs were used in a 2 x 3 factorially arranged experiment. The respective factors were sex group (barrows, boars treated with placebo, or boars treated with Improvac) and slaughter age (23 or 26 wk). Vaccines were administered 8 and 4 wk before slaughter. All Improvac-treated pigs exhibited anti-GnRH titers. Testes and bulbo-urethral gland weights in treated pigs were reduced by approximately 50% (P < 0.001) and serum testosterone levels were below 2 ng/mL in the majority of treated boars (94 and 92% across both age groups at 2 and 4 wk, respectively). Boar taint, as assessed by the concentration of androstenone and skatole in s.c. fat, was suppressed to low or undetectable levels in 100% of Improvac-treated boars. No Improvac-treated pigs had significant concentrations of either androstenone (> 1.0 microg/g) or skatole (> 0.20 microg/g). In contrast, 49.5% of placebo-treated controls had significant androstenone and 10.8% had significant skatole levels, resulting in 10% of the control boars with high concentrations of both compounds. The mean concentrations of taint compounds in the Improvac-treated pigs were not significantly different from those in barrows. Improvac-treated boars grew more rapidly (P = 0.051 and < 0.001 for pigs slaughtered at 23 and 26 wk of age, respectively) than control boars over the 4 wk after the secondary vaccination, possibly because of reduced sexual and aggressive activities. Compared with barrows, Improvac-treated boars were leaner and had superior feed conversion efficiency. The vaccine was well tolerated by the pigs, and no observable site reactions could be detected at the time of slaughter. Vaccination of boars with Improvac allows production of heavy boars with improved meat quality through prevention and control of boar taint.

Treatment of prolactin-secreting macroadenomas with the once-weekly dopamine agonist cabergoline.

Dopamine agonist administration is the primary therapy for macroprolactinomas, but bromocriptine is the only agent approved in the United States. Its use is limited by a high incidence of side effects, a short duration of action, and a lack of effectiveness in some patients. Cabergoline is a long-acting dopamine agonist specific for the D2 receptor that is more effective and better tolerated than bromocriptine in women with microadenomas or idiopathic hyperprolactinemia. However, experience with cabergoline in the treatment of patients with macroadenomas is limited. We report the first study of chronic administration of cabergoline conducted exclusively in patients with macroprolactinomas. Fifteen patients (8 women, 7 men) ages 18-76 yr were studied in an open-label 48-week dose escalation trial of cabergoline administered once per week. Eleven patients had received prior therapy with other dopamine agonists. Mean prolactin (PRL) levels decreased by 93.6%, and normal levels were attained in 73% of patients at doses of 0.5-3.0 mg per week. Three of five patients who had failed to normalize PRL on prior dopamine agonists achieved normal levels. Gonadal function was restored in all hypogonadal men and in 75% of premenopausal women with amenorrhea. Tumor size decreased in 11 of the 15 patients. Side effects were minimal. Of the 5 patients who had experienced side effects in prior dopamine agonists, 4 had none on cabergoline, and the fifth had milder symptoms. During two further years of follow up, the improvement in PRL levels, gonadal function, and tumor size has persisted during cabergoline administration, and three patients have experienced a further decline in PRL and/or tumor size. This study demonstrates the effectiveness and minimal side effects of once-weekly cabergoline for treatment of macroprolactinomas.

A biochemical profile for predicting the chronic exposure of sheep to Microcystis aeruginosa, an hepatotoxic species of blue-green alga.

Sheep which grazed on the shoreline of a fresh-water lake which had a toxic bloom of Microcystis aeruginosa were studied for evidence of chronic poisoning, and a serum biochemical profile was developed to indicate sub-lethal, chronic poisoning in the sheep which had been exposed to microcystins. The profile included measurements of glutamate dehydrogenase (GLDH), gamma-glutamyl transferase (gamma GT), bile acids, bilirubin and albumin. Of 18 sheep which were exposed to M aeruginosa for more than three months, 100 per cent had high serum concentrations of bile acids, 94 per cent had high activities of GLDH and gamma GT, 83 per cent had high bilirubin and 72 per cent had low albumin concentrations compared with the median values of unexposed animals. Other sheep which were exposed for shorter periods, showed evidence of hepatic injury after one week of exposure. The majority of the sheep showed no preference for an alternative, uncontaminated source of water.

Clinical biochemical reference ranges for female alpacas (Lama pacos).

1. Serum samples were collected from 352 healthy female alpacas and tested for 17 clinical biochemical analytes. 2. From the total population of alpacas tested, 205 were pregnant, 68 were not pregnant and 79 had an unknown pregnancy status. 3. Reference ranges for the female alpacas were determined for all the biochemical analytes, and compared to ranges reported for llamas, cattle, sheep and goats. 4. The mean values for pregnant and non-pregnant females were compared and any statistically significant differences identified. 5. The biochemical values reported here are suitable as reference ranges for pregnant and non-pregnant female alpacas.

Gluconate metabolism of Klebsiella pneumoniae NCTC 418 grown in chemostat culture.

The metabolism of gluconate by Klebsiella pneumoniae NCTC 418 was studied in continuous culture. Under all gluconate-excess conditions at low culture pH values (pH 4.5-5.5) the majority (70-90%) of the gluconate metabolized was converted to 2-oxogluconate via gluconate dehydrogenase (GADH), although specific 2-oxogluconate production rates under potassium-limited conditions were significantly lower than under other gluconate-excess conditions. At high culture pH values, metabolism shifted towards production of acetate. Levels of GADH were highest at low culture pH values and synthesis was stimulated by the presence of (high concentrations of) gluconate. An increase in activity of the tricarboxylic acid cycle was accompanied by a decrease in GADH activity in vivo and in vitro, suggesting that the GADH serves a role as an alternative energy-generating system. Anaerobic 2-oxogluconate production was found to be possible in the presence of nitrate as electron acceptor. Levels of gluconate kinase were highest when K. pneumoniae was grown under gluconate-limited conditions. Under carbon-excess conditions, levels of this enzyme correlated with the intracellular catabolic flux.

Anaerobic 2-ketogluconate metabolism of Klebsiella pneumoniae NCTC 418 grown in chemostat culture: involvement of the pentose phosphate pathway.

Under anaerobic 2-ketogluconate-limited growth conditions (D = 0.1 h-1), Klebsiella pneumoniae NCTC 418 was found to convert this carbon source to biomass, acetate, formate, CO2, ethanol and succinate. The observed fermentation pattern is in agreement with the simultaneous functioning of the pentose phosphate pathway and the Entner-Doudoroff pathway in 2-ketogluconate catabolism. When cultured at pH 8.0 apparent YATP values were lower than those found at culture pH 6.5. This difference can be explained by assuming that at high culture pH values approximately 0.5 mol ATP was invested in the uptake of 1 mol 2-ketogluconate. Sudden relief of 2-ketogluconate-limited conditions led to lowering of the intracellular NADPH/NADP ratio and (possibly as a result of this) to inhibition of biosynthesis. Whereas production of ethanol stopped, lactate was produced at high rate. This product was formed, at least partly, via the methylglyoxal bypass.

Quantitative aspects of glucose metabolism by Escherichia coli B/r, grown in the presence of pyrroloquinoline quinone.

Escherichia coli B/r was grown in chemostat cultures under various limitations with glucose as carbon source. Since E. coli only synthesized the glucose dehydrogenase (GDH) apo-enzyme and not the appropriate cofactor, pyrroloquinoline quinone (PQQ), no gluconate production could be observed. However, when cell-saturating amounts of PQQ (nmol to mumol range) were pulsed into steady state glucose-excess cultures of E. coli, the organisms responded with an instantaneous formation of gluconate and an increased oxygen consumption rate. This showed that reconstitution of GDH in situ was possible. Hence, in order to examine the influence on glucose metabolism of an active GDH, E. coli was grown aerobically in chemostat cultures under various limitations in the presence of PQQ. It was found that the presence of PQQ indeed had a sizable effect: at pH 5.5 under phosphate- or sulphate-limited conditions more than 60% of the glucose consumed was converted to gluconate, which resulted in steady state gluconate concentrations up to 80 mmol/l. The specific rate of gluconate production (0.3-7.6 mmol.h-1.(g dry wt cells)-1) was dependent on the growth rate and the nature of the limitation. The production rate of other overflow metabolites such as acetate, pyruvate, and 2-oxoglutarate, was only slightly altered in the presence of PQQ. The fact that the cells were now able to use an active GDH apparently did not affect apo-enzyme synthesis.

Aerobic 2-ketogluconate metabolism of Klebsiella pneumoniae NCTC 418 grown in chemostat culture.

Klebsiella pneumoniae NCTC 418 is able to convert 2-ketogluconate intracellularly to 6-phosphogluconate by the combined action of an NADPH-dependent 2-ketogluconate reductase and gluconate kinase. Synthesis of the former enzyme was maximal under 2-ketogluconate-limited growth conditions. An instantaneous transition to a 2-ketogluconate-excess condition resulted in an acceleration of catabolism of this carbon source, accompanied by complete inhibition of biosynthesis. It is suggested that the cause of this inhibition resides in depletion of the NADPH pool due to the high rate at which NADPH is oxidized by 2-ketogluconate reductase.

Evaluating a staff development physical assessment program.

This program evaluation assessed whether nursing staff who took a mandatory physical assessment course were using the information in their daily practice. A questionnaire designed to assess clinical usage of 17 physical assessment skills was sent to the nurses who completed the first four classes of the assessment course. The results showed that the majority of the nurses used only nine of the 17 skills on a daily basis. Skills used most frequently were mental status and skin system assessments. The skills reported as least used were assessments for extraocular movements, cranial nerves, and jugular vein distention. These results imply that nurses may be applying only those skills required by the patient population on their particular unit. Staff development educators need to reassess physical assessment course content and tailor the courses to teach the skills required for specialty patient populations.

Atypical hepatic vein leiomyoma extending into the right atrium: an unusual cause of the Budd-Chiari syndrome.

A 14-year-old male presented with a one week history of weakness, lightheadedness and vomiting. Bilateral pleural effusions were evident on chest radiography; electrocardiogram revealed decreased voltages. Echocardiogram, abdominal ultrasound and magnetic resonance imaging revealed a mass in an hepatic vein and the inferior vena cava extending up to and filling the right atrium. Under deep hypothermia and extracorporeal circulation the mass was removed en bloc. It originated from the hepatic vein. Pathology revealed a smooth muscle tumour intermediate between benign and malignant (atypical leiomyoma). This is the first reported pediatric primary leiomyoma of the hepatic vein. It caused the Budd-Chiari syndrome, a rare pediatric entity.

The influence of hydrochlorothiazide and tripamide on serum and urinary amylase.

Pancreatitis and asymptomatic elevations of serum amylase have been reported after therapy with thiazide diuretics. In the current study, the effects of hydrochlorothiazide and tripamide treatment on serum and urinary amylase excretion were investigated in 12 hypertensive volunteers. Two patients developed modest elevations of the serum amylase above the normal range after 12 weeks of treatment with hydrochlorothiazide 50 mg daily, but the mean serum amylase did not change. Hydrochlorothiazide did not produce a statistically significant increase in urinary amylase excretion but did reduce the ratio of salivary amylase/creatinine clearance in a two-hour urine collection. Tripamide 10 mg daily had no effect on serum or urinary amylase.

Efficacy of mesna in preventing further cyclophosphamide-induced hemorrhagic cystitis.

Mesna is a sulfhydryl compound that reacts with the metabolites of cyclophosphamide that are excreted in the urine and may produce bladder wall irritation. Mesna is converted in the blood to a biochemically inactive compound that is reduced back to mesna in the kidneys. In this way it has the potential to protect the bladder mucosa without interfering with the antineoplastic effect of cyclophosphamide. Twenty-two patients who had developed hemorrhagic cystitis from cyclophosphamide were treated again with cyclophosphamide and mesna prophylaxis. A total of 68 cycles of cyclophosphamide were given with mesna, with a median of three cycles per patient. A recurrence of cystitis was prevented in all but one patient. Thus, mesna is effective in preventing recurrent cystitis in patients receiving further cyclophosphamide.

Effect of tripamide on glucose tolerance in patients with hypertension.

The effects of tripamide and hydrochlorothiazide on blood pressure and glucose tolerance were studied in 20 hypertensive patients, half of whom had type II diabetes mellitus. Each patient underwent intravenous glucose tolerance testing before and after 4 weeks of treatment with tripamide, 10 mg, and, at a separate time, hydrochlorothiazide, 50 mg. Both tripamide and hydrochlorothiazide lowered blood pressure; for both drugs, the magnitude of the reduction in mean arterial pressure was positively correlated with the pretreatment mean arterial pressure. Hydrochlorothiazide produced a greater fall in serum potassium than did tripamide. In the nondiabetics, neither drug produced a significant change in the glucose disappearance curve or the plasma insulin response. In the diabetics, hydrochlorothiazide produced an increase in serum glucose levels, but the plasma insulin response, which was blunted in comparison to the nondiabetics, did not change. Tripamide did not affect serum glucose or plasma insulin levels in either group of patients. Tripamide at a dose of 10 mg daily does not affect glucose tolerance in either nondiabetic hypertensive patients or patients with type II diabetes mellitus.

Therapeutic trial of tilorone in ALS: lack of benefit in a double-blind, placebo-controlled study.

Sixteen patients with amyotrophic lateral sclerosis (ALS) participated in a double-blind, placebo-controlled study using tilorone hydrochloride, a drug active against a variety of DNA and RNA viruses in animals. On the basis of neurologic examination, pulmonary function studies, quantitative muscle examination, speech recording, and periodic filming of functional muscle strength, it was concluded that at a dose of 1 gm per week, tilorone did not alter the course of ALS.