Cell-mediated immune responses to GAD and beta-casein in type 1 diabetes mellitus in Thailand

We measured the cell-mediated immune response to GAD and bovine beta-casein in 38 type 1 and 37 type 2 diabetic patients who visited diabetic clinics or who were hospitalized in Bangkok, Thailand, and in 43 normal controls, by using a lymphoproliferation assay. Positive results against GAD were found in 29/38 (76.3%) type 1, 6/37 (16.2%) type 2 diabetic patients and 1/43 (2.3%) normal controls. Positive results against bovine beta-casein were found in 18/38 (47.4%), 5/37 (13.5%) and 1/43 (2.3%) of these subjects, respectively. The frequencies of the positive results and the magnitude of the responses to both antigens in type 1 diabetic patients were significantly higher than those in the other two groups (P<0.001). In addition, the prevalence of a positive lymphoproliferative response to these antigens in type 1 diabetic patients was higher than that of anti-GAD antibody positivity in the same group of subjects (26.3%). Thus, the prevalence of positive lymphoproliferative response to GAD in type 1 diabetic patients studied was higher than the prevalence of other autoimmune markers previously reported in type 1 diabetic patients in Thailand.     

Selective management of penetrating neck injuries based on clinical presentations is safe and practical

Selective management was offered in 57 patients who had penetrating injury to the anterior neck. During the study period, decision making in patient management at our institution depended largely on clinical presentations. Indications for neck explorations were unstable hemodynamics, airway obstruction, active bleeding from the wound, and evidence of aerodigestive tract injuries. Some patients with deep wounds of zone II also underwent neck explorations. Investigations were performed in selected cases. With this selective policy, there were two unnecessary operations among 40 patients (70.2%) who underwent neck exploration. Both of them were operated because of deep wounds of zone II. The remaining 17 patients (29.8%) had uneventful conservative treatment. There was no mortality in this study. The authors concluded that selective management of penetrating neck injuries based on clinical presentations is safe and practical.     

Tissue specificity and mechanism of vitamin D receptor up-regulation during dietary phosphorus restriction in the rat

Dietary phosphorus restriction up-regulates intestinal vitamin D receptor (VDR), but the tissue specificity of the up-regulation and the mechanism of receptor accumulation remain unknown. Therefore, the effects of low phosphorus diet (LPD) on VDR content in intestine, kidney, and splenic monocytes/macrophages were examined. Male Sprague-Dawley rats weighing 50–100 g were fed a normal diet (NPD; 0.6% Ca, 0.65% P) as controls followed by an LPD (0.6% Ca, 0.1% P) for 1–10 days (D1-D10). LPD rapidly decreased serum P levels by D1 from 11.11 ± 0.19 mg/dl (mean ± SE) to 4.98 ± 0.37 mg/dl (n = 9). LPD increased total serum Ca from 10.54 ± 0.09 mg/dl to 11.63 ± 0.15, 12.17 ± 0.15, and 12.39 ± 0.18 mg/dl by D1, D2, and D3, respectively, and then remained stable. Serum 1,25-(OH)₂D₃ rapidly increased from 123 ± 5.4 pg/ml to 304 ± 35 pg/ml by D1, reached a plateau through D5, and then gradually increased to 464.9 ± 27.7 pg/ml by D10. Intestinal VDR quantitated by ligand binding assay increased 3.5-fold from 169.6 ± 13.7 fmol/mg of cytosol protein in rats fed NPD (n = 12) to a peak of 588.3 ± 141.88 fmol/mg of protein by D3 (n = 6; p < 0.001) and then decreased to a plateau level of 2.5-fold greater than NPD (p < 0.05) during D5 to D10. In contrast, LPD did not up-regulate kidney or splenic monocyte/macrophage VDR. Northern blot analysis showed that intestinal VDR mRNA increased 2-fold by D2 (n = 3) of LPD and then gradually decreased to control levels after D5. In contrast, kidney VDR mRNA levels did not change during the first 5 days of P restriction and then subsequently decreased to 50% of NPD controls. The results of these studies indicate that VDR up-regulation during dietary phosphorus restriction is tissue-specific and that the mechanism of the up-regulation is time-dependent. Acutely (D1-D5), phosphorus restriction up-regulates intestinal VDR through increased VDR gene expression, whereas chronic (D5-D10) phosphorus restriction appears to alter VDR metabolism through nongenomic mechanisms that are consistent with prolongation of the half-life of the receptor. The nature of the tissue-specific regulation of VDR during phosphorus restriction remains to be determined.     

NOCTURNAL 8mg DEXAMETHASONE SUPPRESSION TEST: A PRACTICAL AND ACCURATE TEST FOR IDENTIFICATION OF THE CAUSE OF ENDOGENOUS CUSHING'S SYNDROME

SUMMARY The efficacy of a nocturnal 8mg dexamethasone suppression test (nocturnal DST) was compared with that of the standard high-dose dexamethasone suppression test (standard DST) in identifying the cause of endogenous Cushing's syndrome in 10 proven cases with Cushing's disease, 20 with adrenal tumours, and one with ectopic ACTH syndrome. The nocturnal test compared serum cortisol concentration at 8am before and after administration of a single dose of 8mg dexamethasone at 11pm. Suppression of serum cortisol level to <50% of the baseline value indicated a diagnosis of Cushing's disease, while a lack of suppression below that limit indicated one of the other two causes of Cushing's syndrome: glucocorticoid-secreting adrenal tumour or ectopic ACTH syndrome. The nocturnal DST had a sensitivity of 90%, a specificity of 100%, an accuracy of 96.8%, a positive predictive value of 100%, and a negative predictive value of 95.5%. These values are comparable to the efficacy of the standard DST in distinguishing Cushing's disease from glucocorticoid-secreting adrenocortical tumour or ectopic ACTH syndrome. Furthermore, this rapid test does not require hospitalisation or urine collection like the standard DST. The nocturnal 8mg dexamethasone suppression test is practical, fairly reliable, and an effective alternative with which to identify the cause of endogenous Cushing's syndrome.     

Operative management of small bowel fistulae associated with open abdomen

BACKGROUND: Gastrointestinal fistulae associated with open abdomen are serious complications following trauma or other major abdominal surgery. Management is extremely difficult and the mortality is still high in spite of modern medical advances. Patients who survive initial physiological and metabolic derangements require operative closure of the fistula, which is technically demanding and poorly described in the literature. METHODS: A retrospective study of patients with small bowel fistulae associated with open abdomen was performed. Only patients who were stabilized sufficiently to undergo surgical closure of the fistula were enrolled in the study. The operative techniques comprised three important steps: exploratory laparotomy and resection of small bowel fistulae with end-to-end anastomosis; bridging the abdominal wall defect with a sheet of polyglycolic acid mesh; and covering the mesh with bilateral bipedicle anterior abdominal skin flaps. RESULTS: Eight patients were included in the study. The number of operations before surgical closure of the fistula ranged from one to six (mean, 3.6). The time from first operation to surgery for fistula closure ranged from 2.5 to 7.5 months (mean, 4.4 months). Three patients had recurrent fistula, and one died (mortality, 12.5%). Hospital stay ranged from 101 to 311 days (mean, 187 days). CONCLUSION: We present a method of closure of small bowel fistulae associated with open abdomen and hope that this will provide surgeons encountering such complications with a good alternative for surgical management.     

Efficacy of single daily dosage of methimazole vs. propylthiouracil in the induction of euthyroidism

OBJECTIVE: Previous studies of the treatment of hyperthyroidism with a single daily dose of antithyroid drugs have demonstrated a favourable result with methimazole (MMI). However, the efficacy of a single daily dose of propylthiouracil (PTU) was inconsistent. The present prospective randomized study was conducted to compare the efficacy of a single daily dose of MMI and PTU in the induction of euthyroidism in patients with Graves' disease. SUBJECTS: Seventy-one patients with newly diagnosed Graves' disease were studied. METHODS AND MEASUREMENTS: Patients were randomized to two groups to receive once daily dose of either 15 mg MMI or 150 mg PTU for 12 weeks. The therapeutic efficacy was determined biochemically by serum total T3, total T4 and TSH levels at baseline and at 4, 8 and 12 weeks during the study period. RESULTS: There was no significant difference in baseline characteristics. Serum total T3 levels of the MMI group were significantly lower than those of the PTU group after four weeks of the treatment (3.54 +/- 0.72 vs. 5.49 +/- 2.74 nmol/l, P < 0.05) through the end of the study (2.22 +/- 1.42 vs. 4.30 +/- 1.78 nmol/l, P < 0.05). The changes in serum total T4 levels occurred in the same direction as serum total T3 levels but a significant difference was observed only after eight weeks of the treatment (MMI vs. PTU; 101.67 +/- 54.05 vs. 176.32 +/- 66.92 nmol/l, P < 0.05). At the end of the study, more patients in the MMI group had both serum total T3 and T4 levels less than the upper limit of the normal range compared to the PTU group (77.1% vs. 19.4%). Hypothyroidism was observed in 31.4% of the patients in the MMI group but not in the PTU group. CONCLUSIONS: During 12-weeks' treatment of Graves' hyperthyroidism, a single daily dose of 15 mg of MMI was much more effective in the induction of euthyroidism than a single daily dose of 150 mg of PTU. Once daily regimen of MMI not only decreased serum T3 and T4 levels more rapidly but also induced euthyroidism four times more effectively than did the once daily regimen of PTU. In the doses used in this study, MMI is preferable to PTU when a once-daily regimen of antithyroid drug is considered for the treatment of hyperthyroidism.     

Management of Upper Extremity Vascular Injury: Outcome Related to the Mangled Extremity Severity Score

Background  The Mangled Extremity Severity Score (MESS) is an objective criterion for amputation prediction after lower extremity injury as well as for amputation prediction after upper extremity injury. A MESS of ≥7 has been utilized as a cutoff point for amputation prediction. In this study, we examined the result of upper extremity vascular injurty (UEVI) management in terms of the amputation rate as related to the MESS. Methods  During January 2002 to July 2007, we reviewed patients with UEVIs at our institution. Data collections included demographic data, mechanism of injuries, injury severity score (ISS), ischemic time, MESS, pathology of UEVI, operative management, and amputation rate. Decisions to amputate the injured limbs at our institution were made individually by clinically assessing limb viability (i.e., color and capillary refill of skin; color, consistency, and contractility of muscles) regardless of the MESS. The outcome was analyzed in terms of the amputation rate related to the MESS. Results  There were 52 patients with UEVIs in this study: 25 (48%) suffered blunt injuries and 27 (52%) suffered penetrating injuries. The age ranged from 15 to 59 years (mean 28.7 years). The mean ischemia time was 10.07 h. The mean ISS was 17.52. There were 12 patients (23%) with subclavian artery injuries, 3 patients (5.76%) with axillary artery injuries, 18 patients (34.61%) with brachial artery injuries, and 19 patients (36.54%) with radial artery and/or ulnar artery injuries. Primary repairs were performed in 45 patients (86.54%), with ligations in 3 patients (5.77%). An endovascular stent-graft was used in one patient (1.92%). Primary amputations were performed in three patients (5.77%). Secondary amputations (amputation after primary operation) were done in 4 of 49 patients (secondary amputation rate 8.16%). All amputation patients suffered blunt injuries and had a MESS of ≥7 (range 7–11). The overall amputation rate in this study was 13.46% (7/52 patients). Multivariate analysis revealed that the only factor significantly associated with amputation was the MESS. There were no amputations in 33 patients who had a MESS of <7. We could avoid amputation in 12 of 19 patients who had a MESS ≥7. There were no mortalities among 52 UEVI patients. Conclusions  MESS, an outcome score used to grade the severity of extremity injuries, correlates well with the risk of amputation. Nevertheless, a MESS of ≥7 does not always mandate amputation. On the other hand, the MESS is a better predictor for patients who do not require amputation when the score is <7. The decisions to amputate in patients should be made individually based on clinical signs and an intraoperative finding of irreversible limb ischemia.     

Adrenal hemorrhage as the first presentation of hepatocellular carcinoma

We report a 67-year-old man who presented with sudden onset of pain in the left flank in association with anemia and hypotension. Imaging studies revealed hepatocellular carcinoma (HCC) at the right lobe of the liver with bilateral adrenal metastases and recent hemorrhage in the left adrenal gland. His serology for hepatitis C was positive. Abdominal exploration with left adrenalectomy was performed. The postoperative course of the patient was uneventful and three cycles of transarterial chemoembolization (TACE) were administered. His general condition gradually deteriorated, and he died 6 months after surgery. Spontaneous massive AH due to metastatic HCC is unusual. Considering the high incidence of HCC in Asia, clinicians should be aware of this atypical and fatal presentation.     

Immediate closure of the open abdomen with bilateral bipedicle anterior abdominal skin flaps and subsequent retrorectus prosthetic mesh repair of the late giant ventral hernias

BACKGROUND: Management of the open abdomen in trauma and nontrauma patients is difficult, and some areas of controversy remain. Gastrointestinal fistulas are serious complications that are associated with significant mortality. We present our method for management of patients with open abdomen and also present a logical technique of subsequent repair of the late giant ventral hernias that uniformly occur in these patients. METHODS: From January 1992 to December 2001, nine patients with open abdomen underwent successful immediate closure with bilateral bipedicle anterior abdominal skin flaps. The major points of this technique of abdominal closure are coverage of abdominal viscera with absorbable mesh and mobilization of the skin and subcutaneous tissue on both sides of the abdominal wound to cover the absorbable mesh. All patients had uneventful recovery and also had subsequent late giant ventral hernias. Repair of the late giant ventral hernias was performed several months later by inserting a large sheet of nonabsorbable mesh under the rectus abdominis muscles that form the neck of the ventral hernia bilaterally. This technique of ventral hernia repair is also called retrorectus prosthetic mesh repair. RESULTS: Five men and four women were entered into the study. The age ranged from 22 to 53 years (median, 35 years). Seven patients suffered from blunt and penetrating trauma and two patients suffered from nontrauma causes. All patients with immediate closure of the open abdomen had uneventful recovery. Late giant ventral hernias (diameter, > 10 cm) occurred in all patients. The time from closure of the open abdomen to subsequent repair of the giant ventral hernias ranged from 7 to 48 months (median, 14 months). Follow-up after hernia repair ranged from 1 to 72 months (median, 9 months), and we have seen no evidence of recurrence. CONCLUSION: Immediate closure of the open abdomen with bilateral bipedicle anterior abdominal skin flaps is an effective technique for dealing with such potentially complicated problems. Management of late giant ventral hernias with retrorectus prosthetic mesh repair is theoretically reasonable and, so far, no recurrence has been observed in our patients.