Contents Volume 32 No. 1 (2000) Section One: International Urology and Nephrology

Table of Contents

Contents Volume 32 No. 1 (2000) Section One: International Urology and Nephrology     

Major histocompatibility complex class I peptide-pulsed host dendritic cells induce antigen-specific acquired thymic tolerance to islet cells

BACKGROUND: As T-cell receptor-major histocompatibility complex (MHC) class I/self peptide interaction regulates T-cell development in the thymus, we reasoned that presentation of peptides by self dendritic cells (DC) to developing T cells in the thymus might induce acquired thymic tolerance. This hypothesis is based on the finding that intrathymic injection of allopeptides in the adult animal induces acquired tolerance. To examine this hypothesis, we studied the effects of intrathymic (IT) injection of a single immunodominant Wistar-Furth (WF) MHC class I (RT1.Au) peptide-pulsed host DC on islet allograft survival in the WF-to-ACI rat combination. METHODS: Bone marrow-derived ACI DC expressing MHC class I and II, OX62, and ED2 present allopeptides to naive and specifically peptide-primed syngeneic T cells in mixed lymphocyte reaction. Host DC pulsed with RT1.Au peptide 5 (residues 93-109) were injected into the thymus of streptozotocin-induced diabetic ACI that were transplanted 7 days later with donor-type (WF) or third-party (Brown Norway [BN]) islets. RESULTS: Whereas IT injection of 300 microg of peptide 5 alone led to normoglycemia and permanent islet survival in three of six diabetic ACI recipients, similar treatment combined with simultaneous intraperitoneal injection of 0.5 ml of anti-lymphocyte serum (ALS) on day -7 led to 100% permanent islet allograft survival (>200 days) compared to a mean survival time of 15.0+/-2.3 days in controls treated with ALS alone. In contrast, similarly prepared animals rejected the third-party (BN) islets in an acute fashion. To address the question of indirect allorecognition in acquired thymic tolerance, we examined the effect of peptide-pulsed host DC on graft survival. Whereas IT injection of peptide-pulsed host DC alone resulted in permanent islet survival in two of five animals, IT injection of peptide-pulsed host DC combined with 0.5 ml of ALS induced 100% donor-specific permanent islet allograft survival in the WF-to-ACI rat combination. These results suggest that thymic DC take up, process, and present the administered peptide to the developing T cells by the indirect allorecognition pathway in the induction of acquired thymic tolerance. CONCLUSION: We have demonstrated a novel approach to inducing transplant tolerance to islet allografts with IT injection of allopeptide-pulsed host DC. This finding suggests that immunization strategies using DC expressing MHC allopeptides or peptide analogue might be potentially useful in the treatment of autoimmune diabetes mellitus.     

Sub-acute sensory neuronopathy as a preceding sign of recurrence in colon carcinoma

Subacute sensory neuronopathy is a paraneoplastic syndrome, which occurs mostly in lung, breast, ovarian malignancies and lymphoma. A 75-yr-old woman who was at the twentieth month of her postoperative follow-up owing to colon adenocarcinoma admitted with subacute sensory neuronopathy. Six months later from the first, neuropathic symptoms liver metastases developed. To the best of our literature review subacute sensory neuronopathy as a preceding sign of recurrence in colon adenocarcinoma has not previously been reported. We conclude that, in the case of subacute sensory neuronopathy without an obvious underlying etiological factor, an occult malignity should always be researched in clinical practice.     

Acute bronchodilatory effect of salmeterol on methacholine-induced bronchoconstriction in childhood asthma

Abstract A review of the literature highlights the need for research, particularly on the acute bronchodilatory effect of salmeterol on bronchoconstriction in the pediatric age group. The present study attempted to evaluate the acute bronchodilatory effect of salmeterol on methacholine-induced bronchoconstriction in childhood asthma and to compare it with the effect of salbutamol. Forty-four asymptomatic children with mild-to-moderate asthma (23 boys and 21 girls; aged7–17 years) were studied. At the beginning, the baseline forced expiratory volume in 1 s (FEV₁) was measured, and the methacholine challenge was performed by doubling the dose to determine PC₂₀ (provocative concentration of inhaled methacholine required to reduce FEV! by 20%). At the same time, the transcutaneous arterial oxygen saturation (S_ao₂) was also measured. Each subject inhaled a single dose of 25 μ salmeterol (n: 23, group I) or 100 μg salbutamol (n: 21, group II) following the Sp₂ measurement. The same measurements (FEV₁, S_ao₂) were repeated 5 and 20 min after the inhalation. After inhalation of salmeterol or salbutamol, the differences between the values of FEV₁ and S_aO₂ after 5 and 20 min were insignificant in both group I and group II (P > 0.05), although there was a significant improvement in both FEV₁ and S_aO₂ after 5 and 20 min (P < 0.005). From these findings it was concluded that salmeterol can be considered as effective as salbutamol on methacholine-induced bronchoconstriction.     

Placental teratoma: A case report

We present a rare case of a placental teratoma found within the fetal membranes of an otherwise normal placenta. Lack of a recognizable umbilical cord and no recognizable skeletal development are used as differential diagnostic criteria for a placental teratoma. In our case, an umbilical cord was absent; nevertheless, the tumor contained two vascular channels covered only by fetal membranes without Wharton's jelly.     

The role of positron emission tomography in selecting patients with metastatic cancer for adrenalectomy

Metastases to the adrenal glands usually signal disseminated disease. However, isolated metastases do occur that may be curable with adrenalectomy. Functional imaging with positron emission tomography (PET) can differentiate benign from malignant pathology and isolated from disseminated metastases. The purpose of this study was to determine whether PET scanning can influence the outcome of adrenalectomy for metastatic disease. We conducted a retrospective review of eight patients undergoing adrenalectomy for presumed isolated metastatic disease from 1985 through 1997. The patients included six women and two men with an average age of 58 (range, 36-74). Their primary tumors were six lung carcinomas, one renal cell carcinoma, and one colon carcinoma. The adrenal masses were located on the right in six patients, on the left in one, and bilaterally in one. Before operation, all patients were evaluated by chest and abdominal CT. Four patients were also evaluated by PET scan. Six right, one left, and one bilateral adrenalectomies were performed. Associated organ resections included two right partial nephrectomies and one right total nephrectomy, one left partial nephrectomy, two distal pancreatectomies, one splenectomy, and two partial hepatic resections. All eight patients survived operation. There were no major perioperative complications, but one patient required readmission for congestive heart failure. Three of the four patients who did not have PET scanning died from 4 to 48 months after operation with disseminated disease from lung, colon, and renal carcinoma respectively. The remaining patient who did not have PET scanning is alive and well 11 years later. Two of the four patients who had PET scans showing isolated disease are alive at 28 and 43 months after operation, whereas the other two died of disseminated disease at 29 and 36 months after operation. We conclude that 1) adrenalectomy can provide survival benefit in patients with isolated metastases, and 2) PET scanning is useful in confirming isolated metastatic disease and selecting patients for adrenalectomy.     

Men and reproductive health in rural Pakistan: the case for increased male participation.

OBJECTIVES: In Pakistan, the role of men has always been considered to dominate in the decision-making process pertaining to women's fertility and birth spacing. This study was done to explore men's knowledge, perceptions and behavior on various reproductive health issues. METHODS: A cross-sectional survey was carried out among 180 married adult males in 12 rural districts of Pakistan in 2000. The study was qualitative, utilizing tools such as in-depth and key-informant interviews. RESULTS: The findings pointed out gaps in knowledge and misconceptions among men on a range of reproductive health issues and stress the need for health education. The findings suggest that strategies such as couple counseling, door-to-door campaigns by village-based male family planning workers and small group meetings could be effective. This study indicates a pressing need for incorporating effective intervention strategies, both at the community and the clinic level, backed with efficient counseling, motivation, and provision of services with appropriate education of males in rural areas. CONCLUSION: The findings suggest that investment into promotion of healthy fertility control practices among men will be effective in the near future, as they are interested in acquiring new knowledge and are willing to become partners.     

WONCA Online电子病例介绍——胰腺转移癌

患者,女,62岁,因颈部肿块就诊。既往32年前因胆囊疾病行胆囊切除术。15年前因多发性甲状腺结节行甲状腺次全切除术,病理结果为小灶性甲状腺癌。10年前因血尿诊断为肾癌,行右肾切除术。.体格检查:锁骨上可触及一5.0cm×3.0cm大小肿块(穿刺细胞学检查结果不能定性)。.辅助检验:腹     

Osteonecrosis of the jaws by long term therapy with bisphosphonates]

For several decades bisphosphonates have been used to reduce skeletal related events in patients with both osteoporosis or bone metastases. Under long term application, besides the known therapy side effects, a new clinical picture has been described within the last few years. This is osteonecrosis of the jaws, which is characterized by its difficulty in treatment. Besides exposed jaw bone, the start of the disease usually lacks any symptoms. The typical clinical symptoms then are foetor ex ore, swelling, exsudation, loosening of teeth, pain or paresthesia. Later oro-antral/nasal or oro-cutaneous fistula can develop. The X-ray shows persisting tooth sockets after extractions and later cloudy radio-lucency, sequestra or fractures. The patient exposed to bisphosphonate can be grouped according to the risk for osteonecrosis: high risk patients with intravenous bisphosphonate therapy and additional chemo-, radiation or corticoid therapy--predominantly patients with a malignant underlying disease and bone metastases low risk patients with an oral bisphosphonate therapy without additional chemo-, radiation or corticoid therapy--preferably patients with non-corticoid-induced osteoporosis. Before starting a bisphosphonate therapy possible causes of infection should be treated and risk of injuries to the mucosa should be reduced according to the individual risk profile. This is supplemented by information of the patient about the risk of necrosis and the possibilities for prevention. Regular dental recall under bisphophonate therapy is emphasised for early recognition of possible problems. Prophylaxis is recommended for the prevention of periodontal infection combined with a follow up of removable denture for possible ulcera. Generally, conservative treatment measures are preferred to surgical ones. Inevitable operations are carried out non-traumatically using broad spectrum antibiotic prophylaxis until the day of suture removal (not before day 10). Long term follow up examinations are recommended.Patients with dental implants inserted before a bisphophonate therapy should be subject to intensive recall examinations. For patients undergoing or following a bisphosphonate therapy the indication for dental implants should be as strict as for patients following head and neck radiation therapy. In the present for patients with osteonecrosis, even after healing, dental implants are regarded as contra-indication. Therapy of the necrosis often requires general anaesthesia, hospitalisation, naso-gastral feeding tube and intravenous, systemic antiinfective treatment. The necrosis is removed completely and a tension free wound closure with vascularised tissue is intended. A literature review shows the metabolic effect of biphosphonates, the known pathogenesis of the bisphosphonate-induced jaw necrosis. It is essential to develop interdisciplinary communication, aiming at a joint care for this group of concerned patients and involving not only those medical disciplines, which order and use bisphosphonates, but especially dentists and maxillofacial surgeons.