Partial sternotomy ("C" incision) as standard access for full range of adult cardiac operations.

OBJECTIVE: In our institute, partial sternotomy has been adopted for standard access in the full range of adult cardiac operations, including coronary artery bypass grafting. In this study, our clinical experience is reviewed. METHODS: Since April 1998, of 100 cardiac surgical patients, 64 underwent partial sternotomy, while 36 patients had the traditional full sternotomy because of high surgical risk factors or anatomical reasons. Most of the patients having minimal access had a "C" incision, that is, a left lower partial sternotomy. RESULTS: The procedures performed with the "C" incision were coronary artery bypass grafting, valve surgery, aortic root replacement, closure of atrial septal defect, and so on. There were two hospital deaths after partial sternotomy. Compared with full sternotomy patients, partial sternotomy patients had a shorter hospital stay, while their bypass times were longer. Their skin incisions were 11.7 cm on average. CONCLUSION: The "C" incision can provide satisfying results and can serve as the standard approach in the full range of cardiac operations.     

Granulocyte colony-stimulating factor (G-CSF) does not improve recovery from antithyroid drug-induced agranulocytosis: a prospective study.

Agranulocytosis is the most serious side effect of antithyroid drug (ATD) therapy. We conducted prospective and randomized studies to examine whether granulocyte colony-stimulating factor (G-CSF) is actually effective for ATD-induced agranulocytosis. Twenty-four patients with Graves' disease who developed agranulocytosis during ATD therapy were randomly divided into a G-CSF group (n = 14) and an untreated group (n = 10). Subcutaneous injection of G-CSF (100 to 250 microg) was given daily until neutrophil counts rose to greater than 1000/microL. The untreated group received antibiotic therapy only. Recovery time, which is defined as the number of days required for neutrophil counts to exceed 500/microL, was monitored by daily complete blood count (CBC). Recovery time in the G-CSF-treated group did not differ from that of the untreated group in those patients with moderate and severe agranulocytosis; thus, prolonged use of G-CSF treatment is generally ineffective for ATD-induced agranulocytosis.     

Transient hyperthyroidism after withdrawal of antithyroid drugs in patients with Graves' disease

The development of silent thyroiditis in patients with a history of Graves' disease is common, especially in the postpartum period. We describe herein patients with Graves' disease who developed transient hyperthyroidism but not silent thyroiditis after withdrawal of antithyroid drug (ATD). If such patients are diagnosed as recurrence of Graves' disease, they may receive ATD or radioiodine therapy unnecessarily. We investigated the characteristics of these patients to prevent unnecessary therapy. We retrospectively studied 22 patients with Graves' disease who showed transient thyrotoxicosis after withdrawal of ATD. Two of 22 patients were male and the mean ages (+/- SD) were 33.7 +/- 12.6 yr. We observed these patients for 28.5 +/- 12.8 (mean +/- SD; range 12-53) months after transient thyrotoxicosis, and measured TSH, FT4, and TSH binding inhibitor immunoglobulin in sera. Radioiodine uptake was measured in 6 of them. The radioiodine uptake in the 4 patients was not suppressed (27.5%, 28.0%, 32.7%, 38.1%). These uptake levels indicate that their thyrotoxicosis was not caused by silent thyroiditis. Most of the 22 patients became euthyroid within 6 months. This study suggests a new therapeutic option as follows: in the case of young patients with mild thyrotoxicosis after withdrawal of ATD, physicians should follow them up for one month without medication unless they have unbearable symptoms or complications.     

Role of elevated platelet-associated immunoglobulin G and hypersplenism in thrombocytopenia of chronic liver diseases

BACKGROUND AND AIM: Thrombocytopenia typically worsens with the progression of liver disease and can become a major clinical complication. Several mechanisms that contribute to thrombocytopenia have been proposed, including hypersplenism accompanied by increased platelet sequestration, platelet destruction mediated by platelet-associated immunoglobulins (PAIgG), and diminished platelet production stimulated by thrombopoietin (TPO). The purpose of the present study was to evaluate the role of each of these mechanisms in patients with liver disease-associated thrombocytopenia. METHODS: Twenty-nine patients with liver cirrhosis (LC), 20 of whom were hepatitis C virus (HCV)-seropositive, 29 chronic hepatitis (CH) patients, 24 of whom were HCV-seropositive, and 16 control patients without liver or hematopoetic disease were enrolled in this study. Serum TPO levels, PAIgG, and liver-spleen volumes were determined and correlation analyses were performed. RESULTS: No differences in serum TPO levels were observed among the three groups. The PAIgG levels were significantly elevated in CH and LC patients (mean +/- SD: 56.5 +/- 42.3 and 144.6 +/- 113.6 ng/107 cells, respectively) compared with the controls (18.9 +/- 2.5 ng/107 cells, P < 0.001 for both). Spleen volume was significantly higher only in LC (428 +/- 239) compared with CH (141 +/- 55) and control (104 +/- 50 cm3) (P < 0.001), while liver volume was not significantly different between the three groups. Correlation analyses demonstrated a significant negative correlation between platelet count with PAIgG (r = - 0.517, P < 0.001) and spleen volume (r = - 0.531, P < 0.001), and no relationship between platelet count and serum TPO level (r = 0.076). CONCLUSIONS: Serum TPO level may not be directly associated with thrombocytopenia in patients with chronic hepatitis and liver cirrhosis. In contrast, spleen volume and PAIgG are associated with thrombocytopenia in such patients, suggesting that hypersplenism and immune-mediated processes are predominant thrombocytopenic mechanisms.     

Roles of interleukin-1 alpha and -1 beta in endotoxin-induced suppression of plasma gonadotropin levels in rats.

Using specific antagonists to rat interleukin (IL)-1 alpha and IL-1 beta, the roles of these IL-1s in endotoxin-induced suppression of plasma gonadotropin levels in freely-moving rats were studied. In orchiectomized rats, recombinant rat IL-1 alpha and IL-1 beta administered into the lateral ventricles almost equipotently suppressed plasma LH levels. Twenty five micrograms of bacterial endotoxin or lipopolysaccharide (LPS) administered similarly showed a comparable effect as that of 1 microgram IL-1 alpha or IL-1 beta, and completely lowered plasma LH levels by 60 min after the injection. To examine the roles of endogenous IL-1 alpha and IL-1 beta, anti-rat IL-1 alpha antiserum (anti-IL-1 alpha) and a recombinant human IL-1 receptor antagonist (IL-1ra) were used as specific blockers for IL-1 alpha and IL-1 beta, respectively. Anti-IL-1 alpha (10 microliters) or IL-1ra (10 micrograms) administered intracerebroventricularly (icv) with 25 micrograms LPS, significantly attenuated the LPS-induced effect on plasma LH levels during the first 60 min after LPS infusion, but not during the second 60 min. LPS at a dose of 5 micrograms induced smaller but still significant changes in plasma LH levels compared with 25 micrograms LPS or 1 microgram IL-1 beta. IL-1ra (10 micrograms) completely blocked LH suppression induced by 1 microgram IL-1 beta, but did not completely reverse the changes of LH induced by 5 micrograms LPS. IL-1ra injected iv also significantly attenuated the early suppressive effect of iv administered LPS, but not its late effect on plasma LH levels. However, iv administered IL-1ra had no influence on the effects of icv administered LPS. These data indicate that at least a part of plasma LH suppression caused by icv administered LPS is mediated via IL-1 alpha and IL-1 beta synthesized within the brain, while factor(s) other than IL-1 also participate in the LPS-induced change, particularly during the later period. A similar mechanism may also work peripherally in the case of iv administered LPS-induced plasma LH suppression.     

Serial changes in liver function tests in patients with thyrotoxicosis induced by Graves' disease and painless thyroiditis.

CONTEXT: When the liver function tests are aggravated after starting antithyroid drugs (ATDs) in Graves' hyperthyroidism, discontinuation of ATDs is generally considered. However, a question arises whether such aggravation constitutes an adverse effect of the drugs or not. OBJECTIVE: The aim of this study was to clarify the influence of thyrotoxicosis on liver function tests, comparing the results with those in thyrotoxicosis induced by painless thyroiditis. DESIGN: We prospectively studied liver biochemical tests in 30 patients with Graves' disease and in 27 patients with painless thyroiditis. MAIN OUTCOMES: Twenty-three (76.7%) untreated Graves' disease patients and 14 (51.9%) untreated painless thyroiditis patients were found to have at least one liver function test abnormality. One month after starting ATD therapy in patients with Graves' disease, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) elevations from initial values were observed in 16 (53.3%). Similar elevations of AST and ALT from initial values at 1 month were observed in 10 (37.0%) and 7 (25.9%) patients with painless thyroiditis, respectively. Alkaline phosphatase (ALP) increased gradually after starting ATD therapy and maintained an elevated value for 3-5 months in Graves' disease. In painless thyroiditis, ALP also increased gradually, similarly to that in Graves' disease, but changes were mild. Elevation of ALT after 1 month of ATD therapy in Graves' disease was significantly higher in patients whose estimated disease duration was 6 months or more compared to those with duration of less than 6 months. Elevated AST and ALT at 1 month after ATD therapy decreased to normal ranges, even though patients were receiving the same ATDs in Graves' disease. CONCLUSION: Similar serial changes in liver function tests in both Graves' disease and painless thyroiditis strongly suggest that increases of AST and ALT after starting ATD therapy may not be due to ATD side effects but may be induced by changes in thyroid function.     

Effects of rat growth hormone (rGH)-releasing factor and somatostatin on the release and synthesis of rGH in dispersed pituitary cells

The effects of rat hypothalamic GH-releasing factor (GRF) and somatostatin (SRIF) on the release and biosynthesis of rat GH were studied by RIA and quantitative immunoprecipitation using monolayer cultures of rat anterior pituitary cells. In kinetic studies, GRF stimulation of GH release appeared at the first sampling time (20-min incubation) and the effect began to diminish after 2-h incubation with GRF. On the other hand, total (cell plus medium) content of GH significantly increased only after 24-h incubation. To examine the GH-synthesizing effect of GRF more directly, newly synthesized GH labeled by [35S]methionine during incubation with GRF was quantified by immunoprecipitation. The amount of immunoprecipitable GH increased significantly and specifically (compared with the total amount of labeled proteins) also only after 24-h incubation. When GH pools were labeled with [35S]methionine under different schedules, the basal release of newly synthesized GH, which was labeled for 1 h immediately before chase incubation was lower during the first 15 min than stored GH which had been labeled earlier. Basal newly synthesized GH secretion exceeded stored GH secretion after 30 min. GRF stimulated the release of GH from both pools but the stimulation of stored GH was greater. In this system, SRIF suppressed both the basal and stimulated release of GH but did not modify GH biosynthesis under either condition. Newly synthesized GH showed significant degradation during 24-h incubation; neither GRF nor SRIF affected the rate of GH degradation during the same incubation period. These results indicate that 1) GRF stimulates both release and synthesis of GH; 2) these two effects have different kinetics and different sensitivities to SRIF; and 3) GRF stimulates the release of GH from heterogeneous pools disproportionally.     

Expression of prostaglandin E receptor EP4 subtype in rat adrenal zona glomerulosa: involvement in aldosterone release

We examined the role of prostaglandin (PG) E receptors in the secretion of aldosterone. PGE2 is known to exert its various biological functions by binding to PGE receptors. There are four subtypes of PGE receptors, EP1, EP2, EP3, and EP4. Among the PGE receptors EP2 and EP4 subtypes are coupled to Gs protein and stimulate adenylyl cyclase. In this study, PGE2 caused a dose-dependent increase in aldosterone production from the rat adrenal zona glomerulosa cells in vitro accompanied with an increase in intracellular cAMP concentration. A specific agonist for EP2, butaprost, did not increase the cAMP production or the aldosterone release, suggesting the possibility that EP4 mediates the secretion of aldosterone by PGE2. Northern blot hybridization analysis disclosed that EP4 gene was expressed in the rat adrenal gland but that EP2 gene was not. In situ hybridization revealed that EP4 mRNA is present abundantly in the zona glomerulosa of rat adrenal gland. These findings suggest that the PGE2-EP4 system is involved in the regulation of aldosterone secretion from the rat adrenal gland.