Prevention and reversal of LV remodeling with neurohormonal inhibitors

Opinion statement Left ventricular (LV) remodeling refers to alterations in ventricular mass, chamber size, and shape that result from myocardial injury, pressure, or volume overload. Numerous studies have demonstrated that LV remodeling correlates with the incidence of heart failure and death, supporting a causative role for remodeling in heart failure progression. Heart failure trials have shown that neurohormonal antagonists, including angiotensin-converting enzyme (ACE) inhibitors and β-adrenergic receptor blockers (β blockers), reduce remodeling in parallel with improved clinical outcomes. Existing data favor using angiotensin II type 1 (AT1) receptor antagonists (or “ARBs”), although their anti-remodeling effects are less well established. Recently, mineralocorticoid receptor antagonists have gained substantial interest based on favorable clinical trial results, although data regarding their effects on remodeling are limited. Thus, an optimal medical regimen to prevent or limit LV remodeling in patients with LV dysfunction should include both an ACE inhibitor and β-adrenergic receptor antagonist, irrespective of the degree of LV dysfunction and symptom status. For patients intolerant to ACE inhibitors, an AT1 receptor antagonist should be substituted. An aldosterone antagonist should be administered to patients with severe, New York Heart Association class III to IV heart failure who have normal or only mildly impaired renal function, or to those patients with depressed LV function following an acute myocardial infarction. Through the aggressive pharmacologic inhibition of both the renin-angiotensin-aldosterone and sympathetic nervous systems, progressive LV remodeling can be prevented or hindered, thereby favorably altering the natural history of the heart failure syndrome.     

Perioperative management of benign hepatic tumors in patients with glycogen storage disease type Ia

Glycogen storage disease type Ia (GSD-Ia; von Gierke disease) is an inherited disorder caused by glucose-6-phosphatase deficiency, and there have been some reports of hepatic tumors in patients with this disease. We report two patients with benign hepatic tumors with GSD-Ia. One is a 19-year-old man who underwent segmentectomy 4 for a focal nodular hyperplasia, and the other is a 31-year-old woman who underwent segmentectomies 3, 5, and 6 for hepatic adenomas. Two significant perioperative complications, resulting from the carbohydrate metabolic disorders, hypoglycemia and metabolic acidosis, occurred in both patients. We managed the metabolic complications successfully by administering a sufficient volume of glucose intravenously. Close perioperative monitoring of blood glucose and lactate concentrations is essential in the perioperative management of patients with GSD-Ia. The intravenous administration of glucose, starting with a smaller dose and then increasing the dose, is adequate management for lactic acidosis with or without hypoglycemia during the perioperative period.     

Large periampullary villous tumor of the duodenum

A 67-year-old woman, who had symptoms of epigastric pain and abdominal distension, was found, on endoscopy, to have a large sessile villous adenoma of the periampullary duodenum. Despite the lack of evidence of malignancy, a pancreaticoduodenectomy procedure was performed, mainly because of the tumor size and site, involving the ampulla of Vater. The presence of the carcinoma was diagnosed only in the resected specimen by definitive histology. Because there is no general consensus on the optimal surgical procedure for the treatment of villous tumors of the duodenum, especially for the early stages, the indications for the operative procedure are discussed, based on a review of the literature.     

A case of factor X (FX) deficiency due to novel mutation V196M,FX Hofu

The patient, a 20-year-old male, was found to have a slightly prolonged prothrombin time (PT). No episodes of bleeding were noted. The measurement of coagulation factors revealed that the level of factor X (FX) activity was solely deficient, 51% (normal range: 70–130% ), and that of FX antigen was 100%. Analysis of the entire FX gene revealed the novel missense mutation of GTG to ATG, resulting in the substitution of the 196th amino acid valine → methionine. The mother and younger brother had a normal PT time and expressed no episode of bleeding. The mother exhibited a normal level of FX activity and antigen; however the younger brother showed a slight decrease in both the parameters. This mutation was not observed in the mother and younger brother. Polymorphism is not observed at this point in healthy persons. The present novel FX mutation was named FX Hofu.     

Two cases of Kallmann syndrome associated with empty sella

Kallmann syndrome (KS) is a developmental disease characterized by the association of isolated hypogonadotropic hypogonadism and anosmia/hyposmia. We report an unusual presentation of two females with KS and empty sella. These females, aged at 20 and 29-year-old, presented primary amenorrhea with prepubertal estradiol and low gonadotropin levels. No other significant clinical signs were observed. Empty sella was observed on MRI in both cases. Sequencing of FGFR1 gene, recently implicated in autosomal form of KS, was performed and one splicing mutation (IVS14 + 1G > A) was identified in one patient.     

Does Physicians’ Case Volume Impact Inpatient Care Costs for Pneumonia Cases?

Summary Background Increasing physician case volumes are documented to reduce costs and improve outcomes for many surgical procedures but not for medical conditions such as pneumonia that consume significant health care resources. Objective This study explored the association between physicians’ inpatient pneumonia case volume and cost per discharge. Design The design was a retrospective, population-based, cross-sectional study, using National Health Insurance administrative claims data. Setting The setting was Taiwan. Participants The participants were a universal sample of 270,002 adult, acute pneumonia hospitalizations, during 2002–2004, excluding transferred cases and readmissions. Measurements Hierarchical linear regression modeling was used to examine the association of physician’s volume (three volume groups, designed to classify patients into approximately equal sized groups) with cost, adjusting for hospital random effects, case severity, physician demographics and specialty, hospital characteristics, and geographic location. Results Mean cost was NT$2,255 (US$1 = NT$33 in 2004) for low-volume physicians (≤100 cases) and NT$1,707 for high-volume physicians (≥316 cases). The adjusted patient costs for low-volume physicians were higher (US$264 and US$235 than high- and medium-volume physicians, respectively; both P < .001), with no difference between high- and medium-volume physicians. High-volume physicians had lower in-hospital mortality and 14-day readmission rates than low-volume physicians. Conclusions Data support an inverse volume–cost relationship for pneumonia care. Decision processes and clinical care of high-volume physicians versus low-volume physicians should be studied to develop effective care algorithms to improve pneumonia outcomes and reduce costs.     

Unusual case of camptocormia triggered by lumbar-disc herniation

A 21-year-old male patient with low back pain and marked forward bending was presented. The exaggerated lumbar flexion was preventing him to stand in erect posture but disappeared while lying. The symptoms had begun after he had lifted a heavy object. Straight-leg-raising test could not be performed properly because of the exaggerated pain. The light-touch sense was decreased on L5 and S1 dermatomes. There was no loss of muscle strength. The deep-tendon reflexes were normal. Plain graph showed mild narrowing in the L4–5 and L5–S1 intervertebral spaces. Lumbar magnetic resonance imaging revealed disc protrusions in L4–5 and L5–S1 levels. During his stay in the department, the patient was given tizanidine and tramadol, and physical therapy was performed. A paravertebral intramuscular injection with lidocaine was applied. Moreover, the patient was referred to psychiatrist for evaluation regarding his medical history of conversive seizures and possible efforts for secondary gain. No response was obtained from all the treatments. The final diagnosis was camptocormia triggered by lumbar-disc herniation. He was applied supportive psychotherapy, psychoeducation regarding secondary gain, strong suggestions to improve posture, positive reinforcement, and behavioral therapy. His postural abnormality resolved and disappeared completely with mild pain. Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users.     

Phagocytosis of co-developing neutrophil progenitors by dendritic cells in a culture of human CD34<Superscript>+</Superscript> cells with granulocyte colony-stimulating factor and tumor necrosis factor-α

Tumor necrosis factor-alpha (TNF-alpha) has been shown to induce the differentiation of CD34(+) cells toward dendritic cells (DCs). We have previously shown that DCs are co-generated from human CD34(+) cells during erythroid or megakaryocytic differentiation in the presence of TNF-alpha, and those DCs are able to stimulate autologous T cell proliferation. The aim of this study was to learn whether the co-stimulation of granulocyte colony-stimulating factor (G-CSF) and TNF-alpha would generate neutrophil progenitors and DCs together from human CD34(+) cells, and if this was the case, to clarify the phenotypic and functional characteristics of these DCs. When highly purified human CD34(+) cells were cultured for 7 days with G-CSF alone, the generated cells predominantly expressed a granulocyte marker, CD15, and then differentiated into neutrophils after 14 days of culture. The addition of TNF-alpha with G-CSF markedly decreased the number of CD15(+) cells without affecting the total number of cells during 7 days of culture. Almost one third of the generated cells were positive for CD11c and CD123. Furthermore, CD11c(+) cells were found to phagocytose CD15(+) cells and were able to induce allogeneic, but not autologous, T cell proliferation in the mixed lymphocyte reaction (MLR). On the other hand, the CD11c(+) cells generated by TNF-alpha and cytokines capable of inducing erythroid differentiation were able to stimulate autologous T cells. There was a difference in the expression of CD80, CD83 and CD86 among CD11c(+) cells induced by G-CSF plus TNF-alpha and those generated by interleukin-3, stem cell factor, and erythropoietin plus TNF-alpha. These results indicate that the co-stimulation of human CD34(+) cells with G-CSF and TNF-alpha induces the phagocytosis of co-developing neutrophil progenitors by DCs, and the stimulatory effects of these DCs on autologous T cells is different from that of DCs generated from CD34(+) cells during erythroid differentiation.