Effects of propofol and remifentanil on phrenic nerve activity and nociceptive cardiovascular responses in rabbits.

BACKGROUND: The effects of propofol, remifentanil, and their combination on phrenic nerve activity (PNA), resting heart rate (HR), mean arterial pressure (MAP), and nociceptive cardiovascular responses were studied in rabbits. METHODS: Basal anesthesia and constant blood gas tensions were maintained with alpha-chloralose and mechanical ventilation. PNA, HR, MAP, and maximum changes in HR and MAP (deltaHR, deltaMAP) evoked by electrical nerve stimulation of tibial nerves were recorded. The comparative effects were observed for propofol at infusion rates from 0.05 to 3.2 mg x kg(-1) x min(-1) (group I) and remifentanil from 0.0125 to 12.8 microg x kg(-1) x min(-1) alone (group II), and during constant infusions of propofol at rates of 0.1 and 0.8 mg x kg(-1) x min(-1) (groups III and IV, respectively). Finally, the effect of remifentanil on propofol blood levels was observed (group V). RESULTS: The infusion rates for 50% depression (ED50) of PNA, deltaHR, and deltaMAP were 0.41, 1.32, and 1.58 mg x kg-(1) x min(-1) for propofol, and 0.115, 0.125, and 1.090 microg x kg(-1) x min(-1) for remifentanil, respectively. The ratios for the ED50 values of deltaHR and deltaMAP to PNA were 3.2 and 3.9 for propofol, and 1.1 and 9.5 for remifentanil, respectively. Analysis of the expected and observed responses and isobologrms showed that although their combined effects on PNA, resting HR, and MAP, and deltaMAP were synergistic for deltaHR, they were merely additive. Remifentanil had no effect on propofol blood levels. CONCLUSION: PNA was abolished by propofol and remifentanil, alone and in combination, before significant depression of nociceptive pressor responses occurred. Their combined effects on PNA, HR, MAP, and deltaMAP are greater than additive, ie., synergistic. Unlike propofol, remifentanil obtunded pressor responses more than the resting circulation.     

Disseminated histoplasmosis 19 years after renal transplantation.

Infections with fungi like Histoplasma are rarely seen in immunocompromized patients. We report the case of a renal transplant recipient who presented with fever and was diagnosed to have disseminated histoplasmosis 19 years after transplant. The pitfalls in making a diagnosis in non-endemic areas are discussed. The literature on renal transplantation recipients with histoplasmosis has been reviewed.     

Diabetes-induced vascular dysfunction in the retina: role of endothelins

Abstract Aims/hypothesis. Vasoactive factors like endothelins, by virtue of the microvascular regulation as well as by other effects, possibly play important parts in the pathogenesis of diabetic retinal microangiopathy. We investigated retinal vascular dysfunction in streptozotocin-induced diabetes and its relation with endothelins in short- and long-term diabetes. Methods . Diabetic rats with or without an endothelin receptor antagonist (bosentan) treatment were investigated after 1 month and 6 months of follow-up. Retinal blood flow was measured and compared with age- and sex-matched non-diabetic control animals. Retinal tissues were analysed for endothelin-1, endothelin-3, endothelin A and endothelin B mRNA. Distribution of endothelin-1 and endothelin-3 was investigated by immunocytochemistry and that for endothelin receptors by ligand binding and autoradiography. Results. Diabetic animals showed hyperglycaemia, glycosuria, elevated glycated haemoglobin values and reduced body weight gain. Retinal blood flow showed an increased resistivity index, an indicator of vasoconstriction, after 1 month of diabetes which was prevented by treatment with bosentan. This functional change in diabetes was eliminated after 6 months of follow-up. The retina from the diabetic animals showed increased mRNA expression for endothelin-1, endothelin-3 and endothelin A after one month. In addition, endothelin B mRNA expression was increased after 6 months. Furthermore, endothelin-1 and endothelin-3 immunoreactivity and endothelin receptor concentrations were increased in the retina of diabetic rats. Conclusion/interpretation. The results from this study indicate that the endothelin system is of importance in mediating retinal changes in diabetes although mechanisms of the endothelin system alteration as well as their effects might vary depending on the duration of diabetes. [Diabetologia (1999) 42: 1228–1234] Received: 3 March 1999 and in final revised form: 21 May 1999     

Low plasma levels of cholecalciferol and 13-cis-retinoic acid in tuberculosis: Implications in host-based chemotherapy

ObjectiveThe aim of this study was to estimate the concentration of cholecalciferol and 13-cis-retinoic acid (RA) in the plasma and pleural fluid of patients with tuberculosis (TB) against controls.MethodsPlasma levels of cholecalciferol and 13-cis-RA were measured in 22 patients with TB and healthy controls and their pleural fluids levels were measured in 6 TB patients and diseased controls by established high-performance liquid chromatography–based procedure.ResultsCholecalciferol levels in plasma and pleural fluid of patients with TB and healthy controls were 67.45 (10.71) nmol/L and 21.40 (8.58) nmol/L compared with 117.43 (18.40) nmol/L (P < 0.001) and 94.73 (33.34) nmol/L (P = 0.0049), respectively. 13-cis-RA level in the plasma of patients with TB and healthy controls were 1.51 (0.72) nmol/L and 6.67 (0.81) nmol/L (P < 0.001), respectively. 13-cis-RA was not detectable in pleural fluid. The levels of both the agents were lower in patients with TB than in controls.ConclusionIt was observed that in patients with TB there is a combined deficiency of cholecalciferol and 13-cis-RA compared with healthy volunteers. Because cholecalciferol and 13-cis-RA are in equilibrium with active ingredients of vitamins A and D, we feel that there is a combined deficiency of these vitamins in patients with TB. There is an evidence that concomitant vitamin A and D supplementation can kill intracellular Mycobacterium tuberculosis in vitro. Therefore, the observations made in this study can pave the path for a trial of combined supplementation of available formulations of vitamin A and D (cholecalciferol and 13-cis-RA) for novel anti-tubercular drug therapy. Because such an approach is host-based it has potential to treat even multidrug-resistant and extensively drug-resistant forms of TB.     

Pain and continued opioid use in individuals receiving buprenorphine–naloxone for opioid detoxification: Secondary analyses from the Clinical Trials Network

Pain complaints are common among individuals with opioid dependence. However, few studies investigate pain during opioid detoxification or the impact this pain has on continued opioid use. This secondary analysis utilized data from two Clinical Trials Network randomized controlled trials of buprenorphine–naloxone for short-term opioid detoxification to examine the extent to which pain was associated with continued opioid use during and immediately following a 13-day detoxification protocol. At follow-up, more severe pain was associated with a greater number of self-reported days of opioid use during the prior 30 days (p < .05) but was not associated with urine toxicology results collected at follow-up. These results, although mixed, have potentially important clinical implications for assessing and addressing pain during opioid detoxification. Pain that is experienced during and immediately following medically monitored detoxification may be associated with continued opioid use. These findings lend further support for continued research on pain among patients with opioid dependence.     

Clinical significance of the RT-PCR positive sentinel node in melanoma

BACKGROUND: The clinical relevance of RT-PCR positivity for melanoma markers in the sentinel node remains controversial. Our purpose was to determine whether patients with a histologically negative but RT-PCR positive node were at an increased risk for recurrence than their RT-PCR negative counterparts. METHODS: Thirty-nine adult patients underwent sentinel node biopsies for melanoma between 1998 and 2000. Each sentinel node was bivalved. Half was serially sectioned and examined by routine hematoxylin and eosin (H&E) and immunohistochemistry (IHC; S100, HMB-45, melanA, and tyrosinase). The other half was analyzed by a nested RT-PCR assay for tyrosinase. RESULTS: Patients were followed for recurrence with a mean follow-up of 71.1 months. The odds ratio of recurrence for RT-PCR positive versus RT-PCR negative patients was 1.39 (0.34, 5.62; p = 0.73). Within the histology negative subgroups, the risk of recurrence in the RT-PCR positive group (26.7%) was not significantly different from the risk of recurrence in the RT-PCR negative group (22.2%) (p = 0.33 chi-squared). RT-PCR of the sentinel node was not a predictor for recurrence on multivariate analysis (p = 0.65). CONCLUSION: Sentinel node RT-PCR positivity did not risk stratify histologically negative melanoma patients beyond routine pathologic examination in this series.     

Regulation of matrix metalloproteinase-9 (MMP-9) in TNF-stimulated neutrophils: novel pathways for tertiary granule release

Matrix metalloproteinase-9 (MMP-9) is present in the tertiary granules of neutrophils and is rapidly released following stimulation. We examined the pathways that regulate tumor necrosis factor (TNF)-mediated MMP-9 release and found this to be dependent on the TNF receptor I. TNF rapidly activated extracellular signal-regulated kinase and p38 mitogen-activated protein kinases, but neither of these pathways was critical for MMP-9 release. Many neutrophil responses to TNF require beta2-integrin-dependent signaling and subsequent Src family kinase activation. In contrast, we found that MMP-9 release from tertiary granules was only partially affected by blocking beta2-integrin-mediated adhesion. Similarly, blocking Src family kinases with the inhibitor PP2 only attenuated TNF-induced MMP-9 release. Blocking beta2-integrin-mediated adhesion and Src family kinases did not result in additive inhibition of MMP-9 release. In contrast, inhibiting protein kinase C (PKC) with a pan-specific inhibitor blocked greater than 85% of MMP-9 release. Inhibitors against specific PKC isoforms suggested a role for PKC alpha and PKC delta in maximal MMP-9 release. These data suggest that MMP-9 release from tertiary granules uses beta2-integrin-independent signaling pathways. Furthermore, PKC isoforms play a critical role in regulating tertiary granule release.     

Gestational trophoblastic tumor at a tertiary level cancer center: a retrospective study

OBJECTIVE: To retrospectively analyze gestational trophoblastic disease at a tertiary level cancer center. STUDY DESIGN: Thirty-six cases of gestational trophoblastic tumor at a tertiary level cancer hospital during the period 1996-2004 were studied. Various epidemiologic features were studied, diagnosed an and patients were classified according to the International Federation of Gynecology and Obstetrics scoring system. Chemotherapy was the main mode of treatment. RESULTS: There was 100% success in low-risk cases and 90% success in high-risk cases. CONCLUSION: Gestational trophoblastic tumors have an excellent prognosis if diagnosed and treated in time, and the potential for childbearing can be maintained.