Age dependent development of ethanol drinking in rats after inhibition of aldehyde dehydrogenase.

The purpose of this experiment was to determine the temporal characteristics associated with the age-related development of volitional consumption of ethanol induced by the pharmacological inhibition of aldehyde dehydrogenase (AlDH). To induce preference for ethanol, the AlDH inhibitor, cyanamide, was administered to male Sprague-Dawley rats which were 30 days of age. Cyanamide (n = 8) was injected subcutaneously twice daily in a dose of 10 mg/kg over a period of 3 days while the control group (n = 6) received the saline vehicle solution according to the same schedule. Then at 50, 70, 90, and 110 days of age, both groups of rats were given a standard 11-day test of preference for water versus ethanol offered in concentrations ranging from 3% through 30%. The results showed that at 70 days of age the preference for ethanol increased above the level of the 50-day test in terms of absolute g/kg intakes and proportion of ethanol to water consumed over the lower range of 3% through 15% concentrations. During the tests at 90 and 110 days of age, the cyanamide-treated rats further increased their preference for ethanol significantly over the levels at the 70-day test in terms of both g/kg and proportional intakes. The pattern of drinking of ethanol offered in the higher concentrations of 25% and 30% was unrelated to the age of the rats and the overall intakes were significantly higher than those of the lower concentrations. These findings demonstrate that the enzymatic inhibition of AlDH systematically acts in a delayed fashion to shift the pattern of preference for ethanol which is contingent on the maturation of the animal. In this instance, the volitional intake of ethanol in the cyanamide-treated rats reached its maximal level by 90-110 days of age. It is proposed that an endocrine mechanism involved in gonadal maturation may function in the intense shift in alcohol drinking.     

Fever and feeding in the rat: Actions of intrahypothalamic interleukin-6 compared to macrophage inflammatory protein-1β (MIP-1β)

The chemokines, macrophage inflammatory protein-1 (MIP-1) and its subunit MIP-1β, induce an intense fever in the rat when they are injected directly into the anterior hypothalamic, pre-optic area (AH/POA), a region containing thermosensitive neurons. The purpose of this study was to compare the central action on body temperature (T_b) of MIP-1β with that of interleukin-6 (IL-6), which also has been implicated in the cerebral mechanism underlying the pathogenesis of fever. Following the stereotaxic implantation in the AH/POA of guide cannulae for repeated micro-injections, radio transmitters which monitor T_b continuously were inserted intraperitoneally in each of 15 male Sprague-Dawley rats. Each micro-injection was made in a site in the AH/POA in a volume of 1.0 μl of pyrogen-free artificial CSF, recombinant murine MIP-1β, or recombinant human IL-6. MIP-1β in a dose of 25 pg evoked an intense fever characterized by a short latency, a mean maximum rise in T_b of 2.4 ± 0.21°C reached by 3.7 ± 0.42 hr, and a duration exceeding 6.5 hr. Injected into homologous sites in the AH/POA, IL-6 induced a dose dependent fever of similar latency and a mean maximal increase in T_b of 1.2 ± 0.25°C, 1.8 ± 0.15°C, and 2.1 ± 0.22°C and duration of 6.2 ± 1.28 hr, 6.7 ± 0.49 hr, and 6.8 ± 0.65 hr when given in doses of 25, 50, and 100 ng, respectively. These results show that MIP-1β and the highest dose of IL-6 induce a fever of comparable intensity, but MIP-1β exerts its action in a much lower concentration. Thus, the de novo synthesis and subsequent action of the MIP-1 family of cytokines on neurons of the AH/POA in response to a pyrogen challenge apparently play a functional role in the pathogenesis of fever. Further, the endogenous activity of IL-6 in the hypothalamus which is enhanced in response to a lipopolysaccharide also may reflect its essential part in the acute phase response to a bacterial challenge. Copyright © 1994 Wiley-Liss, Inc.     

Effect of dietary copper on colonic tumor production and aortic integrity in the rat

Gastrointestinal malignancy has been associated with aortic aneurysmal disease in humans, while metabolic derangement of copper has been incriminated as a possible promotor of aneurysmal development of the aorta. An animal model utilizing the carcinogen 1,2-dimethylhydrazine (DMH) was selected to evaluate levels of dietary copper on both colonic tumor production and morphologic changes in the rat aorta. Six groups, each including 10 Sprague-Dawley rats, received 16 weekly doses (20 mg/kg) of DMH beginning at 4 weeks of age. Groups were maintained on either normal (25 ppm), low (0.6 ppm), or high (100 ppm) copper chow during the entire experimental period. After 25 weeks, all animals were sacrificed to assess colonic tumor production and to perform scanning (SEM) and transmission electron microscopic (TEM) studies of the rat aorta. Results showed a significant increase in colonic tumor production (3.14 +/- 0.39 tumors per centimeter colon) in rats treated with low-copper chow and DMH when compared with rats on normal chow and DMH (0.74 +/- 0.07 tumors per centimeter colon) and animals maintained on high-copper diets and DMH (0.76 +/- 0.08 tumors per centimeter colon). In addition, morphologic study showed disruption of the intima and media in rats maintained on low-copper diet alone, and also on low-copper diet plus DMH. The results of this study showed that DMH and low dietary copper significantly increase (P less than 0.001) the yield of colonic tumors and produce loss of aortic integrity when studied morphologically. Copper levels may be important in the association of neoplasia and aneurysm formation in the clinical setting.     

The changing face of reoperative parathyroidectomy: a single-centre comparison of 147 parathyroid reoperations

IntroductionReoperative parathyroidectomy for persistent and recurrent primary hyperparathyroidism is dependent on radiology. This study aimed to compare outcomes in reoperative parathyroidectomy at a single centre using a combination of traditional and newer imaging studies.Materials and methodsRetrospective case note review of all reoperative parathyroidectomies for persistent and recurrent primary hyperparathyroidism over five years (June 2014 to June 2019; group A). Imaging modalities used and their positive predictive value, complications and cure rates were compared with a published dataset spanning the preceding nine years (group B).ResultsFrom over 2000 parathyroidectomies, 147 were reoperations (101 in group A and 46 in group B). Age and sex ratios were similar (56 vs 62 years; 77% vs 72% female). Ultrasound use remains high and shows better positive predictive value (76% vs 57 %). 99mTc-sestamibi use has declined (79% vs 91%) but the positive predictive value has improved (74% vs 53%). 4DCT use has almost doubled (61% vs 37%) with better positive predictive value (88% vs 75%). 18F-fluorocholine positron emission tomography-computed tomography and ultrasound-guided fine-needle aspiration for parathyroid hormone are novel modalities only available for group A. Both carried a positive predictive value of 100%. Venous sampling with or without angiography use has decreased (35% vs 39%) but maintains a high positive predictive value (86% vs 91%). Cure rates were similar (96% vs 100%). Group A had 5% permanent hypoparathyroidism, 1% permanent vocal cord palsy and 1% haematoma requiring reoperation. No complications for group B.ConclusionOptimal imaging is key to good cure rates in reoperative parathyroidectomy. High-quality, non-interventional imaging techniques have produced a shift in the preoperative algorithm without compromising outcomes.     

An immunohistochemical study of adenomatoid tumors utilizing keratin and factor VIII antibodies. Evidence for a mesothelial origin

Fifteen adenomatoid tumors were examined immunohistochemically using antibody probes to keratin and factor VIII-related antigen. Cells lining adenoid structures labeled using keratin antibody in all 15 tumors but failed to label with factor VIII-related antigen antibodies in any case. In one case tissue was retrieved from a paraffin block and studied by immunoelectron microscopy using the two antibody probes. Immunoprecipitate was demonstrated in adenoid cells adjacent to desmosomes using keratin antibody but was absent using factor VIII-related antigen antibodies. Of the two prevailing theories of origin for adenomatoid tumors, based on ultrastructural and histochemical data to date, these results are additional evidence for a mesothelial origin and fail to support an endothelial origin.     

The challenges of implementing quality improvement in small rural hospitals

In the five years since launching its QI initiative, Mason General Hospital has dealt with many of the challenges that commonly arise in healthcare organizations during TQM implementation, including involving physicians and training staff. It also had to address a host of issues common to small rural organizations. At first glance, one might suspect that the move toward QI would be easier in a small organization because there are fewer leaders to orient, fewer people involved in work processes, and fewer levels of management. In fact, the small organization presents special challenges, including limited staff and financial resources, high turnover rates in key medical staff leadership positions, and small sample sizes. The strategies used by Mason General Hospital to respond to these and other challenges provide a model for small rural healthcare organizations.