The site of synthesis and functions of acute phase plasma proteins: Close relation-ship with the reticulo-endothelial system

The evidence that the acute phase glycoproteins of plasma are synthesized by the liver parenchymal cells is critically examined, and is found to be inconclusive. Some evidence is cited which favors the reticulo-endothelial system (RES) in general, and Kupffer cells in particular, as the site of synthesis of these proteins: 1. The entire RES contains non-glycogenic periodic acid Schiff-positive substances. 2. The diseases which affect glycoprotein levels are also known to affect the function of the RES. 3. When the animal is subjected to stress, the RES function is initially depressed and then stimulated. A similar biphasic behavior is shown by plasma glycoprotein levels. 4. Adrenal cortico-steriods are the major regulators of the RES function and of the synthesis of acute phase proteins. Moreover, both are stimulated at low concentrations, and depressed at high concentrations of the hormone. Some of the glycoproteins of the acute phase (prothrombin, the third component of complement, haptoglobin, transferrin and ceruloplasmin) have defense-related functions. The others seem to participate in phenomena like detoxification, promotion of phagocytosis, wound healing, prevention of tissue injury by lysosomal enzymes, prevention of trauma and recovery from inflammation. It is proposed that the acute phase proteins, together with antibodies, form major components of the defense system, and the RES attempts to deal with injury by mobilization of increased amounts of these substances.     

Increase in human platelet alpha 2-adrenergic receptor affinity for agonist in unstable angina

Spontaneous increase in platelet activity and change in coronary vasomotor tone have been implicated in the pathogenesis of acute myocardial ischemia. To define the mechanism of platelet "hypersensitivity" in acute myocardial ischemia, we examined the status of platelet alpha 2-adrenergic receptors in patients hospitalized with severe unstable angina. With the use of the specific alpha 2-receptor antagonist 3H-yohimbine, we identified a 26% decrease in the receptor binding sites on platelet membranes from patients with unstable angina compared with controls (155 +/- 32 vs. 210 +/- 29 fmol/mg protein, P less than or equal to 0.005). The dissociation constants of 3H-yohimbine binding to platelet alpha 2-receptors were similar in both groups (3.3 +/- 1.1 and 4.1 +/- 1.6 nmol/L, P not significant). To study the alterations in the affinity of platelet alpha 2-receptors for the agonists, effects of 1-epinephrine on specific binding of 3H-yohimbine were examined. We observed a marked reduction in 1-epinephrine concentration for inhibition of antagonist binding by 50% in acute myocardial ischemia (IC50: 4.2 +/- 3.9 X 10(-8) vs. 6.7 +/- 3.4 X 10(-7) mol/L, P less than or equal to 0.01), indicating increase in platelet alpha 2-receptor affinity for the agonist. Platelet aggregation and thromboxane A2 generation in response to epinephrine were also significantly increased in the acute phase of myocardial ischemia. This study suggests enhanced affinity of platelet alpha 2-receptors to the agonist 1-epinephrine as a possible mechanism of platelet hypersensitivity in acute myocardial ischemia.     

Hornification of the nose

A case report of the hornification of the nose is presented. It was present since birth, which increased with the advancing age. There were dark pigmented spots all over the body and both the conjunctiva:. Histopathology revealed the nose mass to be a horn like structure and the skin biopsy revealed it to be xeroderma. No case sofar in the literature is available of the hornification of the nose.     

Application of the medical anti-shock trouser (MAST) increases cardiac output and tissue perfusion in simulated,mild hypovolaemia

We have studied the haemodynamic effects of the application of the medical anti-shock trouser (MAST) in 10 healthy subjects in the semi-upright position in order to simulate mild hypovolaemia. Left ventricular end diastolic dimension (EDD) was measured by M-mode echocardiography and cardiac output (CO) by the Doppler ultrasound technique. Forearm blood flow (FBF) was measured by plethysmography and blood pressure (BP) by the standard cuff technique. Systematic increases in MAST pressure of up to 80 mm Hg were applied. EDD increased to a maximum of 9.3% (p0.01) which was associated with a maximum increase in CO of 31.7% (p0.05). FBF increased by a maximum of 54.2% (p0.001) whilst BP increased by a maximum of 12% (p0.001). These results demonstrate that the application of the MAST is an effective means of transferring blood to the central circulation by compression of the capacitance vessels resulting in significant increases in cardiac output and tissue perfusion. At high pressures there was evidence of compression of resistance vessels, which may be useful in reducing blood loss. The ease and rapidity with which his suit can be applied suggests that it may be useful in the short term treatment of hypovolaemia.     

Double Electroconvulsive Therapy for Resistant Depression

A case is described of psychotic depression that worsened during a course of three bilateral ECTs per week, but responded to administration of two bilateral ECTs three times per week. For some patients, ECTs may need to be given more than three times per week to obtain remission.     

Management of unruptured incidentally found intracranial saccular aneurysms

Neurosurgical Review - Unruptured intracranial saccular aneurysms occur in 3–5% of the general population. As the use of diagnostic medical imaging has steadily increased over the past few...     

Quantifying infection risks in incompatible living donor kidney transplant recipients

Desensitization has enabled incompatible living donor kidney transplantation (ILDKT) across HLA/ABO barriers, but added immunomodulation might put patients at increased risk of infections. We studied 475 recipients from our center from 2010 to 2015, categorized by desensitization intensity: none/compatible (n = 260), low (0-4 plasmaphereses, n = 47), moderate (5-9, n = 74), and high (≥10, n = 94). The 1-year cumulative incidence of infection was 50.1%, 49.8%, 66.0%, and 73.5% for recipients who received none, low, moderate, and high-intensity desensitization (P < .001). The most common infections were UTI (33.5% of ILDKT vs. 21.5% compatible), opportunistic (21.9% vs. 10.8%), and bloodstream (19.1% vs. 5.4%) (P < .001). In weighted models, a trend toward increased risk was seen in low (wIRR = _0.771.40_2.56,P = .3) and moderately (wIRR = _0.881.35_2.06,P = .2) desensitized recipients, with a statistically significant 2.22-fold (wIRR = _1.332.22_3.72,P = .002) increased risk in highly desensitized recipients. Recipients with ≥4 infections were at higher risk of prolonged hospitalization (wIRR = _2.623.57_4.88, P < .001) and death-censored graft loss (wHR = _1.154.01_13.95,P = .03). Post–KT infections are more common in desensitized ILDKT recipients. A subset of highly desensitized patients is at ultra-high risk for infections. Strategies should be designed to protect patients from the morbidity of recurrent infections, and to extend the survival benefit of ILDKT across the spectrum of recipients.     

Characterization of butyrate-dependent electroneutral Na-Cl absorption in the rat distal colon

Recent studies have established that mucosal butyrate stimulates electroneutral sodium-chloride (NaCl) absorption in the distal colon of the rat and a model in which Na-hydrogen (H) and Cl-butyrate exchanges are coupled has been proposed as the mechanism of butyrate-dependent electroneutral Na-Cl absorption. These studies were designed to examine butyrate-dependent electroneutral Na-Cl absorption in experimental conditions in which HCO₃-dependent electroneutral Na-Cl absorption is inhibited: in Na-depleted (aldosterone-treated) animals and in the presence of increased mucosal cyclic adenosine monophosphate (AMP). Butyrate-dependent electroneutral Na-Cl absorption was markedly reduced in Na-depleted rats. In contrast, the inhibition of both net Na and net Cl absorption by 5 mM serosal theophylline was significantly less in butyrate-containing, HCO₃-free Ringer solution than in butyrate-free-HCO₃-containing Ringer solution. These studies indicate that cyclic AMP does not inhibit butyrate-dependent electroneutral Na-Cl absorption and we propose that the mechanism of cyclic AMP inhibition of HCO₃-dependent electroneutral Na-Cl absorption may be a result of its inhibition of Cl-HCO₃, not Na-H exchange.