Risk of hypoglycaemia with oral antidiabetic agents in patients with Type 2 diabetes.

In patients with Type 2 diabetes, the appropriate intensity of glucose control is determined by age, life expectancy, and the presence of concomitant disease. Geriatric patients are especially susceptible to hypoglycaemia and therefore particular care should be taken in this group characterized by polypharmacy, renal or hepatic dysfunction, cardiovascular multimorbidity and malnutrition. As hypoglycaemia is a significant cause of morbidity and mortality, treatment regimens for diabetes should minimize the occurrence of hypoglycaemic episodes and be tailored to the patient's individual needs. The pharmacological options for treating Type 2 diabetes have increased considerably and the risk of hypoglycaemia of the currently available drugs varies considerably. Metformin, thiazolidinediones, and acarbose, oral antidiabetic drugs that decrease insulin resistance or postprandial glucose absorption, are associated with a low risk of hypoglycaemia. These drugs can also be used effectively in various combination regimens; however, by improving insulin sensitivity, combinations of metformin and thiolidinediones with sulphonylureas or meglitinides may considerably increase the risk of hypoglycaemia. On account of its complex pharmacoprofile glibenclamide is a problematic substance carrying a high risk of hypoglycaemia. There are limited preliminary data indicating that, under routine conditions, glimepiride may be associated with a lower risk of hypoglycaemia than glibenclamide and is no more likely to cause hypoglycaemia than other shorter-acting agents such as gliclazide and glipizide. Nateglinide and repaglinide as short-acting insulin secretagogues may be associated with a reduced risk of hypoglycaemia compared with glibenclamide, in particular when dosed flexibly. Repaglinide might be beneficial in individuals with renal impairment.     

Notfallversorgung eines seltenen malignen Nervenscheidentumors

BACKGROUND: Malignant peripheral epineurial tumours are a group of tumours that derive histomorphologically from peripheral nerve sheaths. They occur sporadically, with an incidence of approximately 0.001%, and very rarely require emergency operation. PATIENT AND PROCEDURE: An athletic 19-year-old man presented to an orthopaedic outpatient clinic with lumboischialgia and weakness of the third and fourth left toes. A 12 x 10 x 8-cm paravertebral/retroperitoneal tumour was diagnosed by CT, and the patient was referred to our clinic. For classification, CT-assisted puncture of the tumour was carried out. A haemorrhage into the tumour resulted from the puncture, with consequently lower Hb level and progressive peripheral sensomotoric deficits demanding emergency surgery on a weekend. On this occasion, the tumour was resected together with the L5 and S1 nerve roots through cooperation between the general surgical and neurosurgical departments and was classified as a malignant peripheral epineurial tumour in the rapid stage. Due to the spinal R2 resection, after-loading probes were inserted and the tumour bed was clip-marked. Percutaneous radiotherapy and brachytherapy followed postoperatively. Shortly afterwards, relaparotomy had to be performed due to an adhesive ileus, from which the patient recovered quickly. Chemotherapy was carried out due to a G2 tumour classification. The patient is currently undergoing rehabilitation, during which the peripheral neurological deficits are improving gradually. CONCLUSION: This rare case of a malignant peripheral epineurial tumour with acute symptoms demonstrates the ability of hospitals with maximum care facilities to maintain services even in times of financial cuts in health care services.     

Localization of a gene for otosclerosis to chromosome 15q25-q26

Among white adults otosclerosis is the single most common cause of hearing impairment. Although the genetics of this disease are controversial, the majority of studies indicate autosomal dominant inheritance with reduced penetrance. We studied a large multi- generational family in which otosclerosis has been inherited in an autosomal dominant pattern. Five of16 affected persons have surgically confirmed otosclerosis; the remaining nine have a conductive hearing loss but have not undergone corrective surgery. To locate the disease- causing gene we completed genetic linkage analysis using short tandem repeat polymorphisms (STRPs) distributed over the entire genome. Multipoint linkage analysis showed that only one genomic region, on chromosome 15q, generated a lod score >2.0. Additional STRPs were typed in this area, resulting in a lod score of 3.4. STRPs FES (centromeric) and D15S657 (telomeric) flank the 14. 5 cM region that contains an otosclerosis gene.      

EVIDENCE FOR MULTIPLE DISTINCT MAJOR HISTOCOMPATIBILITY COMPLEX CLASS I LINEAGES IN TELEOSTEAN FISH*

In the context of studies on the expression of MhcCyca-Z sequences of the common carp, PCR amplifications of exon 4 were performed on cDNA obtained from pooled thymi of 20 carp F1 individuals. Five recombinant clones (Cyca-TC3, -TC13, -TC15, -TC17 and -TC18) were found to be 96% similar to the exon 4 region of Cyca-ZA1. Each of the five sequences was unique, and differed in a few positions in both the nucleotide and the derived amino acid sequences from any of the Cyca-Z sequences known to date. These data suggest that multiple Z genes per locus are present in the carp, which are transcribed in the thymus. In the course of analysing the amplified Cyca-Z sequences, serendipity yielded a clone, Cyca-TC16, containing a class I-like sequence substantially different from any other carp class I sequence. The predicted amino acid sequence of Cyca-TC16 was most similar to the class I genes (Lach-U) from the coelacanth (42–46% amino acid identity). Cyca-TC16 contains three conserved β2-microglobulin contact residues, and the secondary structure was predicted by computer algorithms to be similar to that of the α3 domain of HLA-A2. Phylogenetic analysis shows that carp class I sequences reside in four distinct clusters: (i) Cyca-Z, Cyca-TC3, -TC13, -TC15, -TC17 and -TC18 together with Caau-Z from ginbuna crucian carp, (ii) Cyca-U with Bree-U (zebrafish) and Sasa-p30 (Atlantic salmon), (iii) Cyca-TC16 with Lach-U (coelacanth), and (iv) Cyca-C4.     

L—门冬酰胺酶前体脂质体对小鼠毒性及对实验性肿瘤作用

目的：研究L－门冬酰胺酶（L－Asparaginase,L-A)前体脂质体（Proliposome,PL)[L-APL]iv对小鼠的毒性及对荷瘤小鼠的抗肿瘤活性。方法：以小鼠的急性毒性和外周血中白细胞数及血小板数为指标观察药物对小鼠的毒性及以荷瘤小鼠的瘤重和生命延和工率观察药物的抗肿瘤活性;结果：L－APL iV对小鼠的急性毒性与L－A相比明显降低,L－APL对正常小鼠外周血中白细胞数,血小板数无明显影响,而相同剂量L－A对小鼠外周血中白细胞数,血小板数明显降低。与对照组相比,L－APL和L－Aip可明显延长腹水型小鼠移瘤L1210,P388的存活天数,与同剂量L－A相比,L－APL高剂量有明显延长腹水型小鼠移植瘤的存活天数作用。L－APL及L－A ip对小鼠移植瘤Heps,EC实体型的肿瘤生长具有明显的抑制作用,两者抑瘤作用相近。结论：L－APL对小鼠的毒性明显小于相同剂量的L－A,L－APL不仅保持了L－A的抗肿瘤活性,而且有明显的增效作用。