Financial effect of clinical decisions: case study of a dialysis center

This paper explores, in the isolated guinea-pig ileum, the effects of temperature on the acute development of opioid dependence and on the precipitation of the abstinence response, using as reference the effect of temperature on the response to a standard nicotine concentration. Additionally, the influence of temperature on acute morphine neurodepression was examined. Three experimental groups were included. In the first, the bath temperature was adjusted and maintained along the experimental session (2.5 h) at one of the following values: 28, 32, 36 or 40 degrees C. In the second, the different values of bath temperature were applied only during the period of morphine exposure before testing the abstinence response at 36 degrees C. In the third, all segments were initially incubated at 36 degrees C for 1 h, and afterwards, abstinence and the nicotine response were elicited at the different temperatures mentioned. In all the series, a single challenge naloxone dose (3.1, 10, 31, 100, 316, 1000 or 3160 nM) was administered after 1h of morphine and complete naloxone concentration-response curves were obtained. The abstinence response was expressed as a percentage of the nicotine reference response. All segments showed robust nicotine responses at all the experimental protocols tested indicating that, at the temperature range studied, the contractile mechanisms were impaired. This study showed that changes in bath temperature modify the magnitude of acute morphine neurodepression, and of the abstinence response but did no affect the development of acute opioid dependence. These data, along with several lines of evidence, strongly suggest that acute neurodepression, the development of opiate dependence and antagonist-precipitated abstinence are separable. Results are discussed on the basis of drug-receptor interactions.     

Effect of contact lens wear on the conjunctival mucous system

Biopsy specimens from the upper tarsal conjunctiva of 20 contact lens wearers with a clinically evident increase in mucus and ten non-lens wearing subjects were examined by light microscopy and scanning and transmission electron microscopy to determine the effect of contact lens wear on the mucous cell system(s). Three types of crypts associated with mucous secretion were found in all specimens: those with intracellular openings (type I, 0.1 to 0.2 mum) associated with non-goblet mucous secretory cells; those with small intercellular openings (type II, 1 to 2 mum) usually associated with goblet cells, and those with intraepithelial and intrastromal crypts with large intercellular openings (type III, 10 to 60 mum) lined with goblet and non-goblet mucous secretory cells. Contact lens wearers had increased numbers of non-goblet cells with mucous secretory vesicles lining the surface of the conjunctiva and the epithelial infoldings of type III crypts than did the normal subjects. We conclude that increased mucous secretion in contact lens wearers is associated with an increased number of cells and number of secretory vesicles involved in the non-goblet cell mucous system.     

The role of angiotensin AT1 receptors in the diuretic, natriuretic, kaliuretic and blood pressure responses induced by angiotensin II activation of the median preoptic nucleus in conscious rats

We determined the effects of two classical angiotensin II (ANG II) antagonists, [Sar1, Ala8]-ANG II and [Sar1, Thr8]-ANG II, and losartan (a nonpeptide and selective antagonist for the AT1 angiotensin receptors) on diuresis, natriuresis, kaliuresis and arterial blood pressure induced by ANG II administration into the median preoptic nucleus (MnPO) of male Holtzman rats weighing 250-300 g. Urine was collected in rats submitted to a water load (5% body weight) 1 h later. The volume of the drug solutions injected was 0.5 microliters over 10-15 s. Pre-treatment with [Sar1, Ala8]-ANG II (12 rats) and [Sar1, Thr8]-ANG II (9 rats), at the dose of 60 ng reduced (13.7 +/- 1.0 vs 11.0 +/0 1.0 and 10.7 +/0 1.2, respectively), whereas losartan (14 rats) at the dose of 160 ng totally blocked (13.7 +/- 1.0 vs 7.6 +/- 1.5) the urine excretion induced by injection o 12 ng of ANG II (14 rats). [Sar1, Ala8]-ANG II impaired Na+ excretion (193 +/- 16 vs 120 +/- 19), whereas [Sar1, Thr8]-ANG II and losartan block Na+ excretion (193 +/- 16 vs 77 +/- 15 and 100 +/- 12, respectively) induced by ANG II. Similar effects induced by ANG II on K+ excretion were observed with [Sar1, Ala8]-ANG II, [Sar1, Thr8]- ANG II, and losartan pretreatment (133 +/- 18 vs 108 +/- 11, 80 +/- 12, and 82 +/- 15, respectively). The same doses as above of [Sar1, Ala8]-ANG II (8 rats), [Sar1, Thr8]-ANG II (8 rats), and losartan (9 rats) blocked the increase in the arterial blood pressure induced by 12 ng of ANG II (12 rats) (32 +/- 4 vs 4 +/- 2, 3.5 +/- 1, and 2 +/- 1, respectively. The results indicate that the AT1 receptor subtype participates in the increases of diuresis, natriuresis, kaliuresis and arterial blood pressure induced by the administration of ANG II into the MnPO.     

Biochemical mediators of meningeal inflammatory response to group B streptococcus in the newborn piglet model

The meningeal inflammatory response to a heat-killed mutant unencapsulated strain of type III group B Streptococcus (GBS) was studied in a newborn piglet model. GBS (10(9) colony-forming unit equivalents) or saline (control) was inoculated intraventricularly. Serial cerebrospinal fluid measurements were done at baseline and over the course of the next 24 h for cytochemical changes and production of tumor necrosis factor (TNF) and prostaglandins. In separate experiments, we defined the time course of early changes during the first 6 h and dose response relationship over a range of inocula 10(6) to 10(9) colony-forming unit equivalents. The intraventricular inoculation of the heat-killed unencapsulated GBS induced marked leukocytosis and increased protein by 6 h. These changes were preceded by a several hundredfold increase in TNF (maximum at 2 h) and prostaglandins (maximum at 2-4 h). The early and sharp rise in TNF suggests its pivotal role in initiating the inflammatory cascade. The magnitude of the inflammatory response increased with increasing bacterial dose over the range studied. To study the effect of encapsulation of GBS in the induction of meningeal inflammation, we compared the response to the unencapsulated mutant strain with that to the encapsulated parent strain. The encapsulated strain produced much smaller inflammatory changes, and only with high doses of bacteria. The GBS cell wall appeared to be the primary bacterial product triggering inflammation. Intraventricular injection of the heat-killed unencapsulated GBS with exposed cell wall can serve as a valid model for studying neonatal meningitis.     

Glomerular and tubular function in glycogen storage disease

Urinary protein and calcium excretion were assessed in 77 patients with the hepatic glycogen storage diseases (GSD): 30 with GSD-I (median age 12.4 years, range 3.2-32.9 years), 25 with GSD-III (median age 10.5 years, range 4.2-31.3 years) and 22 with GSD-IX (median age 11.8 years, range 1.2-35.4 years). Inulin (Cinulin) and para-aminohippuric acid (CPAH) clearances were also measured in 33 of these patients. Those with GSD-I had significantly greater albumin (F = 15.07, P < 0.001), retinol-binding protein (RBP) (F = 14.66, P < 0.001), N-acetyl-beta-D-glucosaminidase (NAG) (F = 9.41, P < 0.001) and calcium (F = 7.41, P = 0.001) excretion than those with GSD-III and GSD-IX. GSD-I patients (n = 18) also had significantly higher Cinulin (F = 5.57, P = 0.009), but CPAH did not differ (F = 0.77, NS). Renal function was normal in GSD-III and GSD-IX patients. In GSD-I, Cinulin (r = -0.51, P = 0.03) and NAG excretion (r = -0.40, P = 0.03) were inversely correlated with age, whereas albumin excretion was positively correlated with age (r = +0.41, P = 0.03). RBP and calcium excretion were generally high throughout all age groups. Hyperfiltration in GSD-I is associated with renal tubular proteinuria that occurs before the onset of significant albuminuria. Deficiency of glucose-6-phosphatase within the proximal renal tubule may primarily cause tubular dysfunction, glomerular hyperfiltration being a secondary phenomenon.