Emergency Pylorus-Preserving Pancreatoduodenectomy Followed by Second-Stage Pancreatojejunostomy for a Gastrointestinal Stromal Tumor of the Duodenum with an Intratumoral Gas Figure: Report of a Case

We report a case of a duodenal gastrointestinal stromal tumor (GIST) necessitating urgent surgery because of a gas figure on computed tomography (CT). A 46-year-old woman, complaining chiefly of upper abdominal pain and tarry stools, consulted a local doctor. A gastrointestinal fiberscopy revealed an ulcer in the second part of the duodenum, and the patient was admitted to our hospital where a dynamic CT scan showed a hypervascular solid tumor in the pancreatic head. A repeat CT scan done 4 days later showed a gas figure in the tumor, necessitating an emergency pylorus-preserving pancreatoduodenectomy (PpPD). First, we performed a tube pancreatostomy for complete external drainage of the pancreatic juice, and planned a second-stage pancreatojejunostomy for the near future. Histopathologically, the tumor was diagnosed as a GIST originating in the duodenum. The patient was discharged on postoperative day 23 after an uneventful postoperative recovery. Her local doctor completed the second-stage pancreatojejunostomy.     

Attenuation of Postmenopausal Bone Loss in Patients with Transient Hypoparathyroidism After Total Thyroidectomy

Background

Increased bone mineral density (BMD) has been reported in patients with postsurgical permanent hypoparathyroidism. Hypoparathyroidism may attenuate the high-turnover bone loss in postmenopausal women. We reported previously that patients who had transient hypoparathyroidism postoperatively were at subclinical hypoparathyroid (hP) status even 5 years after surgery. We hypothesized that patients with transient hypoparathyroidism (ThP) may have altered BMD.

Methods

A total of 140 women who underwent total thyroidectomy had BMD measurements of the lumbar spine, femoral neck, and radius 3 years after surgery. At surgery, 99 patients were ≥50 years and 41 were <50 years. They were divided into three groups according to their postoperative parathyroid function: There were 80 patients in the no hP (NhP) group, 54 in the ThP group, and 6 in the permanent hP (PhP) group.

Results

Among the 99 patients aged ≥50 years, 36 ThP patients had median Z scores of the BMD in all three areas (lumbar spine, femoral neck, radius) that were significantly higher (by 1.083, 0.533, and 1.047, respectively) than those in the 60 NhP patients aged ≥50 years. The BMDs in the three PhP patients ≥50 years were higher than those in the NhP and ThP patients, but the difference did not reach significance except for in the femoral neck. Multivariate logistic regression analyses showed that Z scores > 0 were significantly associated only with the presence of ThP postoperatively. In the patients <50 years, the BMD values were not significantly different among the three groups except at the radius in PhP patients, which was significantly lower than those of the other patients.

Conclusions

We found that ThP was associated with increased BMD in postmenopausal women. This may be due to attenuation of the high-turnover bone loss in postmenopausal women.     

Amlodipine, but not MDR1 polymorphisms, alters the pharmacokinetics of cyclosporine A in Japanese kidney transplant recipients

BACKGROUND: Cyclosporine A (CsA) is a critical immunosuppressive drug with a narrow therapeutic range and wide interindividual variation in its pharmacokinetics. Many factors, including P-glycoprotein (PGP), influence the oral bioavailability and interpatient variability of CsA. A number of polymorphisms have been identified in the human MDR1 gene, and some of them have been found to be associated with an altered expression of PGP. We have investigated the role of these polymorphisms in CsA absorption from kidney transplant recipients. In addition, we also investigated the effect of amlodipine on CsA absorption. METHODS: The area under the time-concentration curve from 0 to 2 hr (AUC(0-2)) estimated by the trapezoidal rule was used for the evaluation of extent of CsA absorption. The genotypes were identified by a polymerase chain reaction, restriction fragment length polymorphism analysis. RESULTS: No association was found between polymorphisms in the MDR1 and CsA AUC(0-2)/dose/kg. In contrast, the combination of amlodipine significantly increased CsA AUC(0-2)/dose/kg (706.2 microg x hr/L to 819.2 microg x hr/L, P<0.05). Furthermore, we attempted to compare MDR1 polymorphisms and the absorption of CsA again without patients receiving amlodipine, but there was still no significant difference. CONCLUSIONS: There is no relationship between polymorphisms for MDR1 and CsA absorption, suggesting polymorphisms for MDR1 cannot account for the interpatient variability of CsA. Amlodipine, which is the substrate of PGP, significantly increased CsA absorption. These results indicate that PGP plays a significant role in CsA absorption, but its polymorphisms could not influence the CsA absorption.     

Prognosis of Patients with Benign Thyroid Diseases Accompanied by Incidental Papillary Carcinoma Undetectable on Preoperative Imaging Tests

Background Despite the recent wide availability of ultrasonography and fine-needle aspiration biopsy, endocrine surgeons often encounter incidental papillary carcinoma (IPC), that is a papillary carcinoma that had gone undetected by preoperative imaging studies but was identified by pathological examination of surgical specimens resected for benign thyroid diseases. Methods The present study was developed to investigate the prognoses of 317 patients who underwent surgery for benign diseases involving IPC in comparison with the prognoses of 1,674 patients with clinically apparent papillary carcinoma detected preoperatively and diagnosed. Results None of the patients underwent further surgery such as completion total thyroidectomy and node dissection immediately after the diagnosis of IPC. To date, 7 patients (2.2%) have had recurrences; 6 of those were locoregional recurrences and one was a bone metastasis. None of the patients have died of thyroid carcinoma. The disease-free survival of IPC patients was significantly better than that of clinically apparent papillary carcinoma patients and was similar to that of the subset of patients with papillary microcarcinoma without clinically apparent metastasis. Conclusions Because IPC is associated with good prognosis, further surgery, such as completion total thyroidectomy or lymph node dissection immediately after the diagnosis of IPC is not necessary.     

A highly potent 26,27-Hexafluoro-1a,25-dihydroxyvitamin D3 on calcification in SV40-transformed human fetal osteoblastic cells

26,27-hexafluoro-1a,25-dihydroxyvitamin D3 (F6-D3) has been reported to be 5-10 times more potent than 1a,25-dihydroxyvitamin D3[1,25(OH)2D3] in biological systems in vivo and in vitro. However, the effect of F6-D3 on bone formation has yet to be clarified. In the present study, we investigated the effect of F6-D3 on SV40-transfected human fetal osteoblastic cells (SV-HFO) and found it to be about 100 times greater than that of 1,25(OH)2D3 in stimulating calcification. F6-D3 was also about 100 times more effective than 1,25(OH)2D3 in enhancing the expression of mRNA for alkaline phosphatase (ALP), osteocalcin (OCN), and osteopontin (OPN). In the presence of 10?8 M F6-D3 and 10?6 M 1,25(OH)2D3, the calcification began on day 9 and increased up to day 19. Expression of mRNA for ALP and OCN reached a maximum on day 4 and thereafter declined. On the other hand, when osteoblastic cells were incubated with a low level of [1b-3H]-F6-D3- or [1b-3H]-1,25(OH)2D3, each radioactive peak could not be detected. However, on the incubation of osteoblastic cells and radioactive substrate in the presence of ketoconazole, a selective inhibitor of CYP24, a clear peak for each substrate was detected. This suggested that F6-D3 as well as 1,25(OH)2D3 is metabolized by CYP24. Osteoblastic cells were incubated with 10?8 M[1b-3H]-F6-D3 or 10?8 M[1b-3H]-1,25(OH)2D3 for 4, 9, and 14 days. A small peak of 1,25(OH)2D3 was observed and thereafter its level decreased. In addition, two unknown peaks increased when the culture period was extended. In the case of F6-D3, peaks of F6-D3 and 26,27-hexafluoro-23-oxo-1a,25(OH)2D3(23-oxo-F6) were clearly detected, the latter being about 4 times higher than the former. Both peaks was retained up to day 14. The amount of unlabeled F6-D3 and 23-oxo-F6 calculated from the specific radioactivity in the cells may be similar to the amount of 1,25(OH)2D3 and its metabolites. The strong activity of F6-D3 in stimulating calcification may be due to the fact that F6-D3 is much more potent than 1,25(OH)2D3 in enhancing the expression of mRNA for ALP, OCN, and OPN and that the amount of F6-D3 and 23-oxo-F6 accumulated in the cells is much greater than that of 1,25(OH)2D3 and its metabolite.     

AT1 receptor blockade reduces cardiac calcineurin activity in hypertensive rats

The possible role of calcineurin in the attenuation of cardiac hypertrophy and fibrosis by blockade of the angiotensin II type 1 (AT1) receptor was investigated in Dahl salt-sensitive (DS) rats. The effect of the calcineurin inhibitor FK506 was also studied. DS rats progressively developed severe hypertension when fed a diet containing 8% NaCl from 7 weeks of age. In addition, marked cardiac hypertrophy and fibrosis were apparent and the activity of calcineurin and its mRNA expression in the myocardium was increased in these animals at 12 weeks in comparison with age-matched Dahl salt-resistant rats. The abundance of angiotensin-converting enzyme (ACE) and transforming growth factor (TGF)-beta1 mRNAs was also increased in the hearts of DS rats at 12 weeks. Treatment of DS rats with a non-antihypertensive dose of the selective AT1 receptor blocker candesartan (1 mg/kg per day) or FK506 (0.1 mg/kg per day) from 7 to 12 weeks attenuated both calcineurin activity and its mRNA expression in the heart, as well as the development of cardiac hypertrophy and fibrosis, without affecting cardiac function. Treatment with candesartan, but not FK506, prevented the upregulation of ACE and TGF-beta1 gene expression. Both candesartan and FK506 prevented the load-induced induction of fetal-type cardiac genes. These results demonstrate that AT1 receptor blockade attenuates the development of cardiac hypertrophy and fibrosis as well as the activation of calcineurin, without an antihypertensive effect, in rats with salt-sensitive hypertension. Calcineurin may be downstream from TGF-beta1 in AT1 receptor-mediated angiotensin II signaling in vivo.     

Urinary sorbitol measurement and the effect of an aldose reductase inhibitor on its concentration in the diabetic state

The amounts of sorbitol (SOR) excreted in 24-h urine were determined on two groups, i.e., diabetic and nondiabetic patients, using an improved method in which ion exchange resin column processing was applied, and these levels were compared with SOR levels in whole blood. Urinary SOR concentration was also determined in diabetic and normal rats in the same manner and its relationship to aldose reductase (AR) activity in whole blood was investigated. Changes in SOR levels in urine and whole blood were compared in diabetic rats after administration of an AR inhibitor (ARI). Whole blood SOR levels and urinary SOR excretion were significantly higher in diabetic patients than in nondiabetic patients. The same results were obtained in the animal models. In diabetic rats, the urinary SOR excretion was about five times higher than that in control rats, and the AR activity in whole blood was also significantly higher. The increase in urinary SOR excretion and whole blood SOR levels, as well as AR activity, in blood in the diabetic state was inhibited by ARI administration. The influence of the diabetic state and the efficacy of the ARI were more marked in urinary SOR excretion than in whole blood SOR levels. These data indicate that determinations of urinary SOR excretion and AR activity are easily measurable and of benefit to assessing the diabetic condition.     

Changes in cyclic nucleotide phosphodiesterase activity and calmodulin concentration in heart muscle of cardiomyopathic hamsters

Cyclic nucleotides (cAMP and cGMP) phosphodiesterase (PDE) activities and expression are altered in the cardiac muscle of cardiomyopathic heart failure, and PDE inhibitors improve the abnormal muscle condition through changing the cyclic nucleotide concentration. These observations prompted us to investigate the role of calmodulin (CaM) in the regulation of cyclic nucleotide PDE activities, and moreover to study the modulation of the PDE isozymes in heart failure, using cardiac muscles of cardiomyopathic hamster. The CaM concentrations in the heart muscle of the normal control and cardiomyopathic hamsters (each of three to four hamsters) varied with cell fraction and with the age of the animal. The CaM concentrations in the soluble fraction obtained from cardiomyopathic hamster tissue were significantly increased at 25 and 32 weeks of age (2.02 +/- 0.62 microg/mg protein (mean +/- S.E.), and 3.21 +/- 0.95) compared with that obtained from the control (0.60 +/- 0.04) or cardiomyopathic (0.95 +/- 0.12) hamsters at 8 weeks of age. The solubilized PDE isolated from the hamster heart muscle (three or four hamsters in each age) by column chromatography on diethylaminoethyl (DEAE)-cellulose revealed three peaks of activity, which may correspond to the isozymes of PDE classified recently, namely PDE I, II, and III. These three peaks of activity, particularly peak III, seen in the soluble fraction of cardiomyopathic hamster heart declined in proportion to the age of the animal compared with that of the control hamster heart. In the cGMP-PDE assay system, the concentration of CaM inhibitor W-7 required for 50% inhibition (IC(50)) of PDE I, II, and III peak activities was 140, 29, and 46 microM, respectively, suggesting that PDE II is more sensitive to W-7. These results suggest that alteration in these isozyme activities accompanied with changes of CaM concentration may influence the cardiac muscle contractility in cardiomyopathic hamster via changes of cyclic nucleotide concentration.     

A case of adalimumab-associated interstitial pneumonia with rheumatoid arthritis

A 64-year-old woman with rheumatoid arthritis (RA) began to complain of recurrent non-productive cough 5 months after starting adalimumab. The chest radiograph and high-resolution computed tomographic findings revealed diffuse ground-glass attenuation. Her clinical course suggested that interstitial pneumonia (IP) may have been induced by adalimumab, and she was successfully treated with a medium dose of corticosteroid. This case indicates that adalimumab-associated IP should be considered if a RA patient develops non-productive cough following adalimumab therapy.