Acute myocardial infarction following hormone replacement in hypothyroidism

Patients with hypothyroidism have an increased risk of coronary artery disease because of significant changes in lipid metabolism and arterial hypertension. We report a 67-year-old man who developed acute myocardial infarction following hormone replacement in hypothyroidism in spite of no previous cardiac symptoms and no ischemia in intravenous dipyridamole myocardial perfusion imaging. Careful examination for ischemic heart disease should be performed before hormone replacement in hypothyroidism.     

Intestinal ischemia induces late preconditioning against myocardial infarction: a role for inducible nitric oxide synthase

OBJECTIVE: We tested the hypothesis that occlusion of the superior mesenteric artery induces late preconditioning against myocardial infarction and examined the effects of pharmacological modifiers of inducible nitric oxide synthase activity on the late preconditioning in anesthetized rats. METHODS: Rats underwent an intestinal ischemia preconditioning protocol (30 min occlusion of the superior mesenteric artery) or were sham-operated. They were subjected to a sustained 30 min of coronary occlusion and 180 min of reperfusion 24 h later. RESULTS: In rats receiving no pharmacological intervention, the percentage of myocardial infarct within the area at risk and left ventricle was 72+/-4% and 31+/-2%, respectively, in sham-operated rats, and these were significantly reduced to 44+/-4% and 23+/-2% (P<0.01) 24 h after intestinal ischemia preconditioning. Myeloperoxidase activity was significantly reduced by intestinal ischemia preconditioning. Administration of aminoguanidine (300 mg/kg, s.c.) or S-methylisothiourea sulfate (3 mg/kg, i.v.), both relative inducible NO synthase inhibitors, 60 or 30 min before sustained myocardial ischemia not only abolished the late preconditioning afforded by intestinal ischemia, but also inhibited the ability of intestinal ischemia preconditioning to significantly reduce neutrophil infiltration. A change in inducible NO synthase activity was not observed in normal myocardium 24 h after intestinal ischemia, but 30 min of coronary occlusion significantly increased the inducible NO synthase activity in the preconditioned group, which was abolished by aminoguanidine or S-methylisothiourea sulfate. CONCLUSIONS: These data provide pharmacological evidence that induction of inducible nitric oxide synthase, following intestinal ischemia, is associated with increased myocardial tolerance to infarction 24 h later.     

Prevention of corticosteroid-induced osteonecrosis in rabbits by intra-bone marrow injection of autologous bone marrow cells

Objectives. Femoral head osteonecrosis (ON) is a serious complicationof steroid administration. We evaluated bone marrow transplantation(BMT) for preventing corticosteroid-induced ON. Methods. Rabbits, injected with methylprednisolone (MPSL; 20mg/kg), were divided into four groups: (i) MPSL alone; MPSLinjection only, (ii) MPSL+needling; 2 days after MPSL injection,a hole (1.2 mm diameter) was drilled from the outer cortex 2.5cm distal to the proximal end of the greater trochanter, (iii)MPSL+saline; 2 days after MPSL injection, 2 ml saline was injecteddirectly into the bone marrow cavity, and (iv) MPSL+BMT; 2 daysafter MPSL injection, 1 x 10⁷/2 ml bone marrow cells (BMCs)were injected directly into the bone marrow cavity. Platelets,fibrinogen, prothrombin time and total cholesterol in peripheralblood were measured before and after treatment. Tissues werestained with haematoxylin and eosion and terminal deoxynucleotidyl-mediateddeoxyuridine triphosphate nick-end labelling stain and immunostainedfor VEGF, while cell proliferation and viability of whole BMCsin the femur were analysed by cell cycle analysis and [³H]-thymidineuptake. Results. The ON incidence in rabbits treated with MPSL alone,MPSL+needling and MPSL+saline was 72.7, 70.0 and 66.7%, respectively,while in the MPSL+BMT group, the incidence was 0%. Serologicalfindings in the MPSL+BMT group were almost normalized. VEGFand TUNEL staining were reduced in the MPSL+BMT group comparedwith all other groups. There were significantly fewer BMCs inG1 phase from the MPSL+BMT group than the other groups, whileuptake of [³H]-thymidine was significantly increased. Conclusion. Direct injection of autologous BMCs into femursprevents corticosteroid-induced ON following treatment withhigh-dose, short-term steroids. KEY WORDS: Corticosteroid, Osteonecrosis, Animal model, Bone marrow transplantation, Bone marrow cells Submitted 10 June 2007; revised version accepted 15 January 2008.     

Contribution of bone marrow cells to liver regeneration after partial hepatectomy in mice

BACKGROUND/AIMS: We examined whether bone marrow (BM) cells can commit to liver-consisting cells during liver regeneration after partial hepatectomy, using mice transplanted with green fluorescent protein (GFP) positive BM from GFP transgenic mice. METHODS: Partial hepatectomy or sham operation was performed. Lineage marker analysis of GFP positive liver cells was by immunostaining and flow cytometry. DiI-labeled acetylated low-density lipoprotein uptake or microsphere phagocytosis was examined in vitro. Lineage marker expression in BM and peripheral blood (PB) cells, and the vascular endothelial growth factor (VEGF) concentration in the liver were also examined. RESULTS: In hepatectomized mice, significantly more GFP positive cells participated in liver sinusoid than in sham-operated mice, expressing CD31 but not albumin. The percentage of cells that incorporated acetylated low-density lipoprotein but not microspheres was 69.5+/-3.4%, while 28.3+/-2.6% incorporated both, revealing sinusoidal endothelial and Kupffer cells, respectively. Increased expression of the CD31 and CD16/CD32 on GFP positive liver cells was also detected. The elevation of the VEGF concentration during liver regeneration and the increase in the CD34 and Flk-1 expression in the liver, BM, and PB cells suggested endothelial progenitor cell mobilization. CONCLUSIONS: GFP cell-marking provided direct evidence of the BM cells participation in liver regeneration after hepatectomy, where the majority was committed to sinusoidal endothelial cells probably through endothelial progenitor cell mobilization.     

Association of estimated plasma volume and weight loss after long-term administration and subsequent discontinuation of the sodium-glucose cotransporter-2 inhibitor tofogliflozin

Sodium-glucose cotransporter-2 inhibitors (SGLT2) are drugs that have been reported to have several effects through the regulation of plasma volume, for example, antihypertensive effects. This study aimed to clarify the impact of long-term administration and subsequent discontinuation of the SGLT2 inhibitor tofogliflozin on estimated plasma volume (ePV), brain natriuretic peptide (BNP) and the relationship between changes in ePV, BNP and body weight (BW). Data from 157 participants with type 2 diabetes receiving tofogliflozin monotherapy in a phase 3 study were analysed. Changes in variables or correlations among them during a 52-week administration and a 2-week post-treatment period were investigated. Percent change in ePV was calculated using the Strauss formula. Significant decreases in BW, ePV and ln-transformed BNP (ln-BNP) were noted by week 52. %ΔBW was not significantly correlated with %ΔePV and Δln-BNP, while %ΔePV was significantly correlated with Δln-BNP. Two weeks after discontinuation of tofogliflozin, BW, ePV and ln-BNP were significantly increased. %ΔBW was significantly correlated with %ΔePV and Δln-BNP. Furthermore, ePV and BNP were significantly higher than baseline levels.     

The recovery of the fluid balance after hemodialysis and hemofiltration.

Dialysis dysequilibrium syndrome is a frequent complication of renal replacement therapy and seems to be related to changes in fluid balance. From previous studies it is known that these changes are less pronounced during hemofiltration (HF), leading to a lower incidence of complaints compared to hemodialysis (HD). To assess the severity and duration of the dysequilibrium syndrome, intracellular (ICV) and extracellular fluid volumes (ECV) were measured during and after HD and HF by means of a non-invasive conductivity method. Blood volume changes were calculated from pre- and post-treatment erythrocyte counts. Seven HD and eight HF patients were studied. Ultrafiltration volume did not differ between both groups. Blood volume decrease was less during HF due to a significant decrease in ICV, the latter being in contrast to an ICV increment during HD. The significant decrease in ICV led to a less severe decrease in ECV (90 versus 85%). Overall, this resulted in a better vascular refill during HF. At the end of treatment ICV and ECV were not in equilibrium yet. During the recovery period ICV increased roughly 3% in the HF group. In the HD group some patients showed an increase while others showed a decrease in ICV. Overall, no change in ICV was noticed. During recovery ECV decreased further in both groups. The measured recovery period was significantly shorter after HF (245 +/- 68 min) than after HD (299 +/- 37), supporting the hypothesis that HF is a more physiological way of treatment compared to HD.     

κ I light chain AL amyloidosis presenting with rapidly progressive renal and hepatic failure with unusual renal amyloid distribution

A 65-year-old man suffering from generalized edema and jaundice was admitted to our hospital. Laboratory findings revealed marked renal dysfunction with heavy proteinuria as well as liver dysfunction with severe obstructive jaundice. On renal biopsy, the diagnosis of AL amyloidosis associated with κ I light chain was made. Interestingly, amyloid deposits were restricted to the glomeruli. Although hemodialysis was initiated, the patient died due to further deterioration of hepatic function. On autopsy, severe intrahepatic cholestasis was observed, and there was marked deposition of AL amyloid in the liver. Literature reviews showed that rapidly progressive renal failure is common in AL amyloidosis patients who presented with acute hepatic failure due to severe intrahepatic cholestasis. However, the detailed renal pathology in this condition has not been documented. The present case is very interesting because rapidly progressive renal and hepatic failure was simultaneously observed, and renal amyloid deposition was restricted to the glomeruli.     

Incidental67Ga uptake into an appendiceal mucocele in a patient with sigmoid colon cancer

We report a case of sigmoid colon cancer in which visualization of an appendiceal mucocele was unexpectedly found during⁶⁷Ga scintigraphy, and discuss a proposed mechanism of uptake.