Effects of ligand priming and multiple-dose injection on tissue uptake of 111In-pentetreotide in rats

In patients undergoing somatostatin receptor scintigraphy, treatment with octreotide (Sandostatin) is usually discontinued 24-48 h before and after injection with the radioligand 111In-pentetreotide ([111In-DTPA(O)]octreotide) (Octreoscan) because octreotide competes with radioligand for the same receptors. However, D?rr et al. and Soresi et al. reported improved visualization of carcinoid and small cell lung cancer lesions, respectively, during continued octreotide treatment. We found that intravenous administration of unlabeled octreotide to rats inhibited the binding of an optimal dose (0.5 microg) of 111In-pentetreotide to somatostatin receptors in pancreas and adrenals in a mass- and time-dependent way. Pretreatment with unlabeled octreotide never increased receptor binding of 111In-pentetreotide. Administration of 100 microg of octreotide decreased receptor-bound radioactivity if given simultaneously with or 10 or 20 min after injection of the radioligand, but had no effect if given 30 min after the radioligand. These findings indicate rapid processing of receptor-bound octreotide and suggest that octreotide treatment of patients undergoing 111In-pentetreotide scintigraphy may be reinitiated as soon as 1 h after radioligand administration.     

Effects of docosahexaenoic acid on serum lipoproteins in patients with combined hyperlipidemia: a randomized, double-blind, placebo-controlled trial

OBJECTIVE: The objective of this study was to evaluate the effects of daily dietary supplementation with 1.25 g or 2.5 g of docosahexaenoic (DHA), in the absence of eicosapentaenoic acid (EPA), on serum lipids and lipoproteins in persons with combined hyperlipidemia (CHL) [serum low-density lipoprotein cholesterol (LDL-C) 130 to 220 mg/dL and triglycerides 150 to 400 mg/dL]. METHODS: After a 6-week dietary stabilization period, subjects entered a 4-week single-blind placebo (vegetable oil) run-in phase. Those with adequate compliance during the the run-in were randomized into one of three parallel groups (placebo, 1.25, or 2.5 g/day DHA) for 6 weeks of treatment. Supplements were administered in a triglyceride form contained in gelatin capsules. Primary outcome measurements were plasma phospholipid DHA content, serum triglycerides, high-density lipoprotein cholesterol (HDL-C). LDL-C and non-HDL-C. RESULTS: The DHA content of plasma phospholipids increased dramatically (2 to 3 fold) in a dose-dependent manner. Significant (p < 0.05) changes were observed in serum triglycerides (17 to 21% reduction) and HDL-C (6% increase) which were of similar magnitude in both DHA groups. Non-HDL-C [+1.6 (NS) and +5.7% (p < 0.04)] and LDL-C [+9.3% (NS) and +13.6% (p < 0.001)] increased in the DHA treatment groups. All lipid effects reached an apparent steady state within the first 3 weeks of treatment. CONCLUSION: Dietary DHA, in the absence of EPA, can affect lipoprotein cholesterol and triglyceride levels in patients with combined hyperlipidemia. The desirable triglyceride and HDL-C changes were present at a dose which did not significantly increased non-HDL-C or LDL-C. These preliminary findings suggest that dietary supplementation with 1.25 g DHA/day, provided in a triglyceride form, may be an effective tool to aid in the management of hypertriglyceridemia.     

Automated lumen definition from 30 MHz intravascular ultrasound images

One prerequisite for standard clinical use of intravascular ultrasound imaging is rapid evaluation of the data. The main quantities to be extracted from the data are the size and the shape of the lumen. Until now, no accurate, robust and reproducible method to obtain the lumen boundaries from intravascular ultrasound images has been described. In this study, 21 different (semi-)automated binary-segmentation methods for determining the lumen are compared with manual segmentation to find an alternative for the laborious and subjective procedure of manual editing. After a preprocessing step in which the catheter area is filled with lumen-like grey values, all approaches consist of two steps: (i) smoothing the images with different filtering methods and (ii) extracting the lumen by an object definition method. The combination of different filtering methods and object definition methods results in a total of 21 methods and 80 experiments. The results are compared with a reference image, obtained from manual editing, by use of four different quality parameters--two based on squared distances and two based on Mahalanobis distances. The evaluation has been carried out on 15 images, of which seven are obtained before balloon dilation and eight after balloon dilation. While for the post-dilation images no definite conclusions can be drawn, an automated contour model applied to images smoothed with a large kernel appears to be a good alternative to manual contouring. For pre-dilation images a fully automated active contour model, initialized by thresholding, preceded by filtering with a small-scale median filter is the best alternative for manual delineation. The results of this method are even better than manual segmentation, i.e. they are consistently closer to the reference image than the average distance of all individual manual segmentations.     

The noninfectious respiratory complications of infection with HIV

Infection with HIV was first recognized through a clustering of unusual respiratory infections. The lung has been a major target manifesting many of the infectious complications of the immunodeficiency. Noninfectious pulmonary complications in HIV-infected individuals are also common and have been recognized since the advent of the AIDS epidemic. Malignancies involving the respiratory system, specifically Kaposi's sarcoma and non-Hodgkin's lymphoma, are epidemiologically linked to infection with HIV. Although other cancers have been identified in patients with HIV, these malignancies have a relationship to HIV infection that is unknown. Nonetheless, all cancers in the HIV-infected individual appear to follow a very deadly course. Interstitial pneumonitis and an alveolitis are also seen in individuals infected with HIV. Their relationship to the virus is unknown but may involve the lung's immune response to HIV. Pneumothorax and bullous lung disease are the sequela of pulmonary infections in the HIV-infected host. Pulmonary hypertension has been reported in HIV-infected patients, and like the other noninfectious respiratory complications, the link between the disease process and HIV is unknown. Bronchiectasis is now commonly recognized in AIDS patients who have survived prolonged immunosuppression and infection. Bronchoscopists have accumulated a collection of endobronchial lesions uncommonly seen in non-HIV-related pulmonary consultation. In the following review, we discuss the epidemiology, pathology, pathogenesis, clinical features, diagnostic findings, prognosis, and therapeutic options available for each noninfectious pulmonary complication. As the life expectancy for HIV-infected patients increases, the incidence of noninfectious pulmonary complications will rise.     

First year serologic response to treatment for syphilis: a model for prediction of seroreversion

There is no straightforward test available, within weeks of treatment for syphilis, to assess adequacy of serologic response. We propose a method to predict non-treponemal seroreversion based on short term response. To develop and illustrate this method, we used data from 370 individuals with infectious syphilis. Individual serologic response appears to be a linear function of (log) time, suggesting the possibility of using rapid plasma reagin titres recorded in the first few months after treatment to determine the slope of the linear treatment response line. The slope of the response line, during the first year after treatment, is an important predictor of seroreversion but must be considered in conjunction with pre-treatment titre. We recommend development of an action line be developed based on these variables. Such a line would indicate the necessity for retreatment if the line plotted from the patient's first year response failed to fall below the action line.     

Effects of halothane on the phrenic nerve responses to carbon dioxide mediated by carotid body chemoreceptors in vagotomized dogs

BACKGROUND: Previous studies in dogs showed that the phrenic nerve response to an acute hypoxic stimulus was dose dependently depressed by 0.5-2.0 minimum alveolar concentration (MAC) of halothane but not abolished. Because a carbon dioxide stimulus is transduced by a different mechanism in the carotid body chemoreceptors (CBCRs) than is a hypoxic stimulus, inhalational anesthetics may preferentially depress one of these transduction processes, the central neuronal processing, or both, of the integrated responses to these two types of inputs. METHODS: Carotid body chemoreceptor stimulation was produced by short (1-1.5 s), bilateral, 100% carbon dioxide in saline infusions into the carotid arteries during neural inspiration in unpremedicated, halothane-anesthetized, paralyzed, vagotomized dogs during constant mechanical ventilation. The phrenic neurogram quantified the neural inspiratory response. Four protocols were performed in the study: (1) the dose-dependent effects of halothane anesthesia (0.5-2.0 MAC) during hyperoxic hypercapnia on phrenic nerve activity, (2) the effects of three background levels of the partial pressure of carbon dioxide (PaCO2) on the magnitude of the carbon dioxide infusion responses at 1 MAC halothane, (3) the effects of anesthetic type on the magnitude of the carbon dioxide infusion response, and (4) the effects of CBCR denervation. RESULTS: Peak phrenic nerve activity (PPA) increased significantly during the carbon dioxide-stimulated phrenic burst in protocols 1-3; after denervation there was no response (protocol 4). Halothane produced a dose-dependent reduction in the PPA of control and carbon dioxide infusion-stimulated phrenic bursts and in the net carbon dioxide response. The net PPA responses for the different PaCO2 background levels were not different but were somewhat larger for sodium thiopental anesthesia than for 1.0 MAC halothane. CONCLUSIONS: The phrenic nerve response to an acute, severe carbon dioxide stimulus was dose dependently depressed by surgical doses of halothane. The observed responses to carbon dioxide infusion were mediated by the CBCRs because they were eliminated by CBCR denervation. These results suggest that the CBCR transduction and central transmission of the carbon dioxide signal in terms of inspiratory excitatory drive are not abolished at surgical levels of halothane anesthesia.     

Effects on nutrient digestion of wheat processing and methods of tallow addition to the diets of lactating dairy cows

Five multiparous Holstein cows in midlactation that were fitted with ruminal and duodenal cannulas were used in a 3 x 5 incomplete Latin square. The objective of this study was to examine the effects on nutrient digestion of wheat processing and method of tallow addition to the diets of lactating dairy cows. Diets consisted of 45% forage and 55% concentrate, and each diet contained 20% wheat and 2% tallow (as-fed basis). Treatments were dry-rolled wheat with tallow added to the concentrate, steam-rolled wheat with tallow added to the concentrate, and steam-rolled wheat with tallow added first to the wheat. The dry matter intake; digestion of starch, fiber, and fatty acids; ammonia N concentration; and molar proportions of volatile fatty acids in ruminal fluid were not affected by treatments. The apparent digestibility in the total tract of organic matter and nitrogenous compounds was significantly higher for the steam-rolled treatment with tallow added first to the wheat. Mean ruminal fluid pH was similar across treatments; however, cows fed the diet containing steam-rolled wheat with tallow added first to the wheat had the smallest pH change from 0 to 2 h postfeeding. Milk yield did not differ, regardless of cow diet. Method of tallow addition had marked effects on the apparent digestibility of organic matter and N in the total tract of lactating dairy cows.     

Blockade by ifenprodil of high voltage-activated Ca2+ channels in rat and mouse cultured hippocampal pyramidal neurones: comparison with N-methyl-D-aspartate receptor antagonist actions

1. The block by ifenprodil of voltage-activated Ca2+ channels was investigated in intracellular free calcium concentration ([Ca2+]i) evoked by 50 mM K+ (high-[K+]o) in Fura-2-loaded rat hippocampal pyramidal neurones in culture and on currents carried by Ba2+ ions (IBa) through Ca2+ channels in mouse cultured hippocampal neurones under whole-cell voltage-clamp. The effects of ifenprodil on voltage-activated Ca2+ channels were compared with its antagonist actions on N-methyl-D-aspartate- (NMDA) evoked responses in the same neuronal preparations. 2. Rises in [Ca2+]i evoked by transient exposure to high-[K+]o in our preparation of rat cultured hippocampal pyramidal neurones are mediated predominantly by Ca2+ flux through nifedipine-sensitive Ca2+ channels, with smaller contributions from nifedipine-resistant, omega-conotoxin GVIA-sensitive Ca2+ channels and Ca2+ channels sensitive to crude funnel-web spider venom (Church et al., 1994). Ifenprodil (0.1-200 microM) reversibly attenuated high-[K+]o-evoked rises in [Ca2+]i with an IC50 value of 17 +/- 3 microM, compared with an IC50 value of 0.7 +/- 0.1 microM for the reduction of rises in [Ca2+]i evoked by 20 microM NMDA. Tested in the presence of nifedipine 10 microM, ifenprodil (1-50 microM) produced a concentration-dependent reduction of the dihydropyridine-resistant high-[K+]o-evoked rise in [Ca2+]i with an IC50 value of 13 +/- 4 microM. The results suggest that ifenprodil blocks Ca2+ flux through multiple subtypes of high voltage-activated Ca2+ channels. 3. Application of the polyamine, spermine (0.25-5 mM), produced a concentration-dependent reduction of rises in [Ca2+]i evoked by high-[K+]o. The antagonist effects of ifenprodil 20 micro M on high-[K+]0-evoked rises in [Ca2+]. were attenuated by spermine 0.25 mM but not by putrescine 1 or 5 mM. In contrast,spermine 0.1 mM increased rises in [Ca2+]i evoked by NMDA and enhanced the ifenprodil (5 micro M) block of NMDA-evoked rises in [Ca2+]i.4. Similar results were obtained in mouse cultured hippocampal pyramidal neurones under whole-cell voltage-clamp. Ifenprodil attenuated both the peak and delayed whole-cell IB. with an IC% value of 18 +/- 2 micro M, whilst it attenuated steady-state NMDA-evoked currents with an IC50 of 0.8 +/- 0.2 micro M. Block of IBa by ifenprodil 10 JaM was rapid in onset, fully reversible and occurred without change in thecurrent-voltage characteristics of Ba. The ifenprodil block of IBa was enhanced on membrane depolarization and was weakly dependent on the frequency of current activation. Spermine 0.1 mM potentiated control NMDA-evoked currents but attenuated IB,. In agreement with the microspectrofluorimetric studies, co-application of spermine produced a small enhancement of the inhibitory effect of ifenprodil 10 micro M on NMDA-evoked responses whereas the reduction of I4 by ifenprodil 10 micro M in the presence of spermine was less than expected if the inhibitory effects of ifenprodil and spermine on IBa were simply additive.5. The results indicate that ifenprodil blocks high voltage-activated Ca2+ channels in rat and mouse cultured hippocampal pyramidal neurones. Although the Ca2+ channel blocking actions of ifenprodil are observed at higher concentrations than those associated with NMDA antagonist activity, Ca2+ channel blockade may contribute, at least in part, to the established neuroprotective and anticonvulsant properties of the compound.