Isolated Rheumatic Tricuspid Stenosis with Reverse Lutembacher's Physiology

Tricuspid valve dysfunction occurs frequently in patients with rheumatic heart disease and is usually manifested as functional or organic tricuspid regurgitation. Rheumatic tricuspid stenosis is less common and occurs characteristically in the presence of concomitant mitral valve disease. In this report, we describe the clinical and echocardiographic findings in a patient with isolated rheumatic tricuspid stenosis and a right-to-left shunt across the interatrial septum, likely as a result of a patent foramen ovale, resulting in central cyanosis. This case illustrates an interesting association of tricuspid stenosis and an interatrial right-to-left shunt suggestive of a reverse Lutembacher's physiology.     

Association between dynamic cerebral autoregulation and mortality in severe head injury

The objective of the study was to test the hypothesis that dynamic cerebral pressure-autoregulation is associated with the outcome of patients with severe head injury and to derive optimal criteria for future studies on the predictive value of autoregulation indices. Repeated measurements were performed on 32 patients with severe head injury. Arterial blood pressure (ABP) was measured continuously with an intravascular catheter, intracranial pressure (ICP) was recorded with a subdural semiconductor transducer and cerebral blood flow velocity (CBFV) was measured with Doppler ultrasound in the middle cerebral artery. Transfer function analysis was performed on mean beat-to-beat values, using ABP or CBFV as input variables and CBFV or ICP as the output variables. A dynamic index of autoregulation (ARI) ranging between 0 and 9 was extracted from the CBFV step response for a change in ABP. No significant differences between survivors and non-survivors were found due to mean values of ICP, ABP, CPP, CBFV, pCO2, GCS, age or heart rate. The transfer functions between ABP-ICP and CBFV-ICP did not show any significant differences either. The median [lower, upper quartiles] ARI was significantly lower for non-survivors compared with survivors [4.8 (0.0, 5.9) v. 6.9 (5.9, 7.4), p= 0.004]. The correlation between ARI and GOS was also significant (r=0.464, p=0.011). Cohen's coefficient was optimal for a threshold of ARI= 5.86 (kappa 0.51, p=0.0036), leading to a sensitivity for death of 75%, specificity=76.5%, odds ratio =9.75 and overall precision = 75.8%. The difference in ARI values between survivors and non-survivors persisted when results were adjusted for GCS (p = 0.028). A similar analysis for the Marshall CT scale did not reach significance (p = 0.072). A logistic regression analysis confirmed that apart from the ARI, no other variables had a significant contribution to predict outcome. In this group of patients, death following severe head injury could not be explained by traditional indices of risk, but was strongly correlated to indices of dynamic cerebral pressure-autoregulation extracted by means of transfer function analysis. Future studies using a prospective design are needed to validate the predictive value of the ARI index, as estimated by transfer function analysis, in relation to death and other unfavourable outcomes.     

Meal pattern changes associated with temporomandibular joint inflammation/pain in rats; analgesic effects

Establishing a valid animal model to study temporomandibular joint (TMJ) pain has proven extremely difficult. Using complete Freund's adjuvant (CFA) to induce TMJ inflammation, we recently showed that meal pattern analysis could be used as a noninvasive biological marker to study TMJ pain in an animal model. The purpose of this study was to further validate our animal model by determining whether aspects of CFA-induced TMJ inflammation/pain are reversed with ibuprofen (IBU) treatment. In the first trial, 48 male rats were used and in the second trial, 32 female ovariectomized rats, given 17beta-estradiol replacement, were used. The rats were assigned to one of four groups: control (CON-CON); control+IBU (CON+IBU); CFA-CON; and CFA+IBU. In the male trial, CFA injection (P<.01) caused TMJ swelling and chromodacryorrhea (CFA-CON); IBU eliminated these changes in the CFA+IBU group. Meal pattern analysis showed the pertinent CFA-induced change and the IBU effect was that meal duration was increased in the CFA-CON group (P<.01), but normal in the CFA+IBU-treated group on the first, but not second, day postinjection. In the female trial, CFA increased TMJ swelling, but did not cause significant chromodacryorrhea (CFA-CON); IBU eliminated swelling in the CFA+IBU group. Meal duration was increased (P<.01) in the CFA-CON group, but was normal in the CFA+IBU-treated group on both the first and second days postinjection. In both trials, interleukin-1beta (IL-1beta) levels were increased similarly in CFA-CON and CFA+IBU groups (P<.01). This study shows that CFA-induced TMJ inflammation/pain can cause changes in meal patterns (i.e., meal duration), which may be used as a behavioral marker for TMJ inflammation/pain.     

Capsaicin sensitive neurons role in the inflamed TMJ acute nociceptive response of female and male rats

Computerized meal pattern analysis, and more specifically meal duration, has recently been used as a non-invasive biological marker of nociception in the temporomandibular joint (TMJ). Cells responsible for the nociceptive response in the inflamed TMJ may include capsaicin (CAP) sensitive neurons. To test the role of CAP sensitive neurons in acute nociceptive responses first, male and female rats were treated neonatally with vehicle or CAP, an agent known to destroy a majority of C fibers. Second, after 56 days the rats were divided into four groups: neonatal vehicle-injected and treated with and without complete Freund's adjuvant (CFA). Treatment groups included neonatal non-CAP vehicle treated and TMJ not-injected (CON); vehicle treated and TMJ CFA injected (CFA); CAP-treated and not-injected (CAP); and CAP-treated and CFA injected (CAP + CFA). Meal patterns were analyzed for two days after injection. CFA-injection in non-CAP-treated rats lengthened meal duration on the first and second day after treatment in the males, but only on the first day in the females. CAP treatment in male and female rats prevented significant lengthening of meal duration induced by CFA. CAP treatment attenuated the CFA-induced increase in calcitonin gene-related peptide expression in the trigeminal ganglia similarly in males and females. The data suggests CAP-sensitive neurons are responsible, in part, for transmission of acute nociceptive responses associated with CFA administration and suggest gender can affect nociception in the inflamed TMJ region.     

Angiotensin induction of PAI-1 expression in endothelial cells is mediated by the hexapeptide angiotensin IV.

Recent studies from this laboratory have demonstrated that angiotensin II (Ang II) stimulates the expression of plasminogen activator inhibitor 1 (PAI-1) in cultured endothelial cells. This response does not appear to be mediated via an interaction with either the AT1 or the AT2 receptor subtype. Since a novel angiotensin receptor has been identified in a variety of tissues that specifically binds the hexapeptide Ang IV (Ang II, [3-8]), we therefore examined the effects of Ang IV on the expression of PAI-1 mRNA in bovine aortic endothelial cells. Ang IV stimulated dose- and time-dependent increases in the expression of PAI-1 mRNA. The effect of Ang IV (10 nM) was not inhibited by Dup 753 (1.0 microM), a highly specific antagonist of the AT1 receptor, or by PD123177 (1.0 microM), a highly specific antagonist of the AT2 receptor. In contrast, the AT4 receptor antagonist, WSU1291 (1.0 microM), effectively prevented PAI-1 expression. Although larger forms of angiotensin (i.e., Ang I, Ang II, and Ang III) are capable of inducing PAI-1 expression, this property is lost in the presence of converting enzyme or aminopeptidase inhibitors. These results indicate that the hexapeptide Ang IV is the form of angiotensin that stimulates endothelial expression of PAI-1. This effect appears to be mediated via the stimulation of an endothelial receptor that is specific for Ang IV.     

Inhibition of thyroid-stimulating hormone stimulation of protein kinase, glucose oxidation, and phospholipid synthesis in thyroid slices previously exposed to the hormone.

Prior exposure of thyroid slices to thyrotropin (TSH) induced refractoriness to subsequent stimulation of the cyclic AMP system by the hormone. Although the inhibition is incomplete, we examined whether the reduction in cyclic AMP was sufficient to alter other metabolic effects of TSH. Bovine or dog thyroid slices were incubated with or without 5-100 mU/ml TSH for 1-2h, washed, and then incubated without hormone for 1-2h. Half of the slices not exposed to TSH initially were then incubated with buffer and half were exposed to 5-100 mU/ml TSH. Slices initially incubated with TSH were also incubated with or without TSH in the third incubation. During the refractory period, TSH activation of protein kinase was inhibited even though the hormone still caused some increase in cyclic AMP concentrations. However, protein kinase activity was fully responsive to dibutyryl cyclic AMP when slices were incubated with it during the third incubation. Stimulation of glucose oxidation by TSH was significantly decreased in thyroid slices previously incubated with the hormone. During refractoriness, stimulation of glucose oxidation caused by prostaglandin E1 and dibutyryl cyclic AMP was also significantly diminished but that due to acetylcholine was not. Thus even though dibutyryl cyclic AMP could fully activate protein kinase activity during refractoriness, its effect on glucose oxidation was still inhibited, suggesting that the metabolic block responsible for this refractoriness was distal to activation of protein kinase. Stimulation of 32Pi incorporation into phospholipid by TSH and acetylcholine was also inhibited during refractoriness. Despite reduction of the stimulatory effect of TSH, binding of 125ITSH was not modified by prior incubation of thyroid slices with TSH. These results indicate that changes in the TSH receptor are not responsible for the development of refractoriness and other metabolic sites besides activation of adenylate cyclase appear to be involved.