1型糖尿病研究新进展

40年前创立的青少年糖尿病研究基金会((JDRF)是一个致力于通过支持研究来探寻1型糖尿病(TIDM)及其并发症治疗方法的组织.20世纪70年代有学者提出,TIDM和2型糖尿病(T2DM)的发病机制有根本的不同,T1DM与主要组织相容性复合体的人白细胞抗原(HLA)有独特相关性,有胰岛细胞自身抗体.     

Strangulation in child abuse: CT diagnosis

The central nervous system is commonly affected in child abuse. Between April 1985 and July 1986 three infants were identified in whom the primary mode of injury had been strangulation. In each case computed tomography (CT) demonstrated a large cerebral infarction confined to vascular territories associated with small subdural hematomas. There was no history or visible evidence of significant head trauma. Autopsy of one infant confirmed the presence of a hemispheric infarct, thin subdural hematoma, and an area of subintimal hemorrhage in the carotid artery ipsilateral to the infarct. The remaining two patients survived with residual hemiparesis. CT findings of a large cerebral infarction with an associated subdural hematoma in an infant without a history of a significant trauma should suggest the possibility of child abuse and may be the primary manifestation of abuse in some patients.     

Intracranial abnormalities in infants treated with extracorporeal membrane oxygenation: imaging with US and CT

Findings at neuroimaging in 100 consecutive infants treated with extracorporeal membrane oxygenation (ECMO) are presented. Imaging in these infants consisted of pretreatment cranial ultrasonography (US), daily US studies while on ECMO, and follow-up cranial computed tomography (CT) after treatment. There were findings of abnormalities in 43 patients. Thirty had intracranial bleeding, often of unusual extent and distribution. Thirteen additional infants had nonhemorrhagic abnormalities alone. Bleeding considered to be major was seen in 12% of infants. Large parenchymal hemorrhages and infarcts, cerebellar hemorrhages, and diffuse edema were the most significant abnormalities, with a 50% mortality (eight of 16 patients). No lateralization was noted with respect to distribution of bleeding sites or areas of nonhemorrhagic abnormalities. US was a sensitive but imperfect screening tool for intracranial abnormalities. Abnormalities missed with US included peripheral and small parenchymal lesions, subarachnoid hemorrhage, cerebral atrophy, and sagittal sinus thrombosis.     

Incidence of red cell antibodies after multiple blood transfusion

A retrospective study was performed to estimate the frequency of alloimmunization against red cell (RBC) antigens in a multiply transfused group. Patients (n = 186) were studied who had received at least six blood transfusions during a period of at least 3 months. Some 6944 units of blood were transfused. One hundred forty patients had hematologic disorders. The patients' sera were investigated every 3 months with indirect antiglobulin tests and enzyme-treated RBCs. Twenty-two patients (11.8%) made 33 antibodies. Seven patients made more than one antibody. Eight of the 22 patients (36.4%) made their first antibody before or at the 10th transfusion. The risk of immunization increased with the number of transfusions. Influence of gender and age was not demonstrable. Nor was a relationship demonstrated between blood transfusion reactions and RBC antibody formation; no delayed hemolytic transfusion reactions occurred. Anti-E was demonstrated in 12 patients and anti-K in 15. When the gene frequencies were taken into account, it appeared that anti-E was made by 11.5 percent of E-negative patients, most of whom were immunized after an estimated three transfusions with E-positive blood. Anti-K was made by 8.7 percent of the K-negative patients, after an estimated 2.1 units of K-positive blood. It might be desirable to match red cell units for the E and K antigens in patients at relatively high risk. These are primarily patients who have already formed an antibody and are going to receive many transfusions and women of childbearing age who are to receive more than 4 units of blood.     

Pharmacokinetics of 2'-deoxycoformycin, an inhibitor of adenosine deaminase, in the rat

The distribution of the potent inhibitor of adenosine deaminase (ADA), 2'-deoxycoformycin (DCF), in the brain of the rat and its inhibition of ADA in brain and gut was determined. The accumulation of [3H]DCF in brain was maximal 2 hr after intraperitoneal injection and elimination was best described by a two compartment model having t1/2 phases of about 1-5 hr and 50 hr. The activity of ADA in gut exhibited dose-related inhibition at 1.9, 3.7 and 18.6 mumol/kg (i.p.) and returned to normal by 16 days. In brain, ADA was inhibited by about 95% at all three of these doses of DCF 2 hr after injection and activity returned to control levels by 30 days with the two smaller doses, but remained at 66% of control levels at 50 days with 18.6 mumol/kg. The t1/2 of the recovery of the activity of ADA in both brain and gut was found to be dose-dependent. The failure of the activity of ADA in brain to recover after treatment with 18.6 mumol/kg suggests either long-term down-regulation of the expression of ADA or irreversible damage to ADA-containing neurons.     

Iron stimulates the rate of reduction of hexavalent chromium by human microsomes

The NADPH-dependent reduction of chromium (VI), a known carcinogen, by hepatic microsomes was very similar for all five humans examined, with an apparent Km for chromate of 1.04-1.68 microM, and a Vmax of 10.4- 10.7 nmol/min/mg protein. Inhibitor studies indicate no role for cytochrome P450s, but a prominent role for flavoproteins, which could include P450 reductase, flavin-containing mono-oxygenase and cytochrome b5. Relative to anaerobic conditions, Cr(VI) reduction was inhibited only 26-37% by room air, which indicates that human microsomal Cr(VI) reduction could still proceed at significant rates, even in tissues with high O2 tensions. Studies with lung microsomes from one human exhibited Vmax and Km values that were two-thirds lower and 2.8-fold greater, respectively, than those of hepatic microsomes from the same individual; other Cr(VI)-reducing parameters were similar for lung and liver. Various forms of exogenous iron, when present at 0.76-6.3 microM, markedly enhanced both liver and lung microsomal rates and Vmax of Cr(VI) reduction, but did not significantly alter the other Cr(VI)- reducing parameters (Km, effects of O2 and inhibitors). These iron levels were 3.1- to 26-fold lower than the initial Cr(VI) concentration, which suggests that iron is serving a catalytic role. The ratio of human microsomal Cr(VI) reduction rates under aerobic versus anaerobic conditions remained fairly constant, regardless of iron concentration. Small increases in intracellular iron could therefore lead to large increases in the rate and extent of microsomal Cr(VI) reduction. Individuals that are simultaneously exposed to Cr(VI) and to agents that increase intracellular iron could therefore be at potentially greater risk for Cr(VI) toxicity and carcinogenicity.      

Changes in eating attitudes during the first year of treatment for diabetes

Eating attitudes were studied in a group of newly diagnosed insulin dependent diabetics. Thirty-two patients completed the eating attitudes test and eating disorders inventory before commencing treatment and 12 months later following routine medical management. There were significant changes in several items, some of which were predicted by virtue of the diet and weight control involved in optimum diabetic management. However, there were also changes in body image which may predispose to the development of eating disorders in this group of patients.     

Longitudinal incidence of tuberculosis in South-East Asian refugees after re-settlement.

SETTING: A State refugee screening programme in Victoria. OBJECTIVE: To determine the longitudinal incidence of tuberculosis (TB) in South-East Asian refugees in the first five years after re-settlement, and to determine predictors of risk. DESIGN: A retrospective cohort study of 1101 refugees from Laos, Cambodia and Vietnam screened for TB after arrival in Australia, in the 6-month period from July 1989 to January 1990. Incident cases of TB were identified by matching the refugee database with the TB notification database for 1989-1994, giving five years of follow-up data. Preventability was assessed for incident cases by reviewing medical records. MAIN OUTCOME: The development of active tuberculosis in the first five years after re-settlement. RESULTS: The incidence of active TB was 363/100000 during the first year after re-settlement, and 109/100000/year during the first five years. There were no incident cases of TB in refugees with initial skin test reactions <10 mm. Skin test reaction size was the only predictor of risk of TB. CONCLUSIONS: There is a high risk of tuberculosis in South-East Asian refugees, particularly in the first year after re-settlement. This risk decreases with time. Migration stress, concurrent illnesses and poor nutrition may be explanations for this observation. Refugees are at high risk for TB, even after pre- and post-migration screening, emphasising the importance of preventive therapy and follow up in this group.     

Amylin-amide: a new bone-conserving peptide from the pancreas

Amylin-amide is a new member of the family of peptides encoded by the calcitonin multigene complex. In the present study, we have compared directly, the hypocalcaemic potency and duration of action of human amylin-amide and human calcitonin in an in vivo rat bioassay and an in vitro osteoclast bone resorption assay. Amylin-amide was found to have a potency approximately 40-fold lower than human calcitonin, whilst both peptides followed the same time course. This suggests that amylin-amide is the most potent non-calcitonin hypocalcaemic peptide so far reported. An important physiological implication follows. It would seem that amylin-amide can play a central role in the maintenance of the skeleton by virtue of its inhibitory influence on osteoclastic function.