A randomized, parallel group, double-blind, multicentre study comparing the efficacy and safety of Avandamet (rosiglitazone/metformin) and metformin on long-term glycaemic control and bone mineral density after 80 weeks of treatment in drug-naïve type 2 diabetes mellitus patients.

AIM: The purpose of this study was to evaluate if superior glycaemic control could be achieved with Avandamet® (rosiglitazone/metformin/AVM) compared with metformin (MET) monotherapy, and if glycaemic effects attained with AVM are durable over 18 months of treatment. Bone mineral density (BMD) and bone biomarkers were evaluated in a subgroup of patients. METHODS: This was a phase IV, randomized, double-blind, multi-centre study in 688, drug naÏve, male and female patients who had an established clinical diagnosis of type 2 diabetes mellitus (T2DM). Patients were randomized in a 1 : 1 ratio either to AVM or MET. RESULTS: As initial therapy in patients with T2DM, AVM was superior to MET in achieving statistically significant reductions in glycated haemoglobin (HbA1c) (p < 0.0001) and fasting plasma glucose (FPG) (p < 0.001), with more patients reaching recommended HbA1c and FPG targets for intensive glycaemic control. The glycaemic effects attained with AVM compared to MET monotherapy were durable over 18 months of treatment. In the bone substudy, AVM was associated with a significantly lower BMD in comparison with MET at week 80 in the lumbar spine and total hip (p < 0.0012 and p = 0.0005, respectively). Between-treatment differences were not statistically significant for distal one-third of radius BMD, femoral neck BMD or total BMD. CONCLUSION: Superior glycaemic control was achieved with AVM compared with MET monotherapy. The superior glycaemic effects were shown to be durable over 18 months of treatment. AVM was associated with a significantly reduced BMD in comparison with MET at week 80 in the lumbar spine and total hip.

Expression of the genes encoding CCAAT-enhancer binding protein isoforms in the mouse mammary gland during lactation and involution.

Transcription factors belonging to the CCAAT-enhancer binding protein (C/EBP) family have been implicated in the activation of gene expression in the mammary gland during lactation. We have therefore investigated the detailed expression profile of the C/EBP family during lactation and involution of the mouse mammary gland. The expression of C/EBPbeta and C/EBPdelta mRNA was low during lactation, increased dramatically at the beginning of involution and remained constant thereafter. In contrast, C/EBPalpha mRNA expression was relatively high during the early stages of lactation, declined to low levels during the late stages of lactation and at the start of involution, and increased again during involution. Electrophoretic mobility-shift assays showed a close correlation between the expression of the C/EBP genes and the functional C/EBP DNA-binding activity and, additionally, demonstrated the participation of heterodimers, formed from among the three proteins, in DNA-protein interactions. The DNA-binding activity of the activator protein 1 (AP1) family of transcription factors was also induced during involution. These results therefore point to potentially important regulatory roles for both the C/EBP and the AP1 family during lactation and involution of the mammary gland.

Disseminated toxoplasmosis with sepsis in AIDS.

A 24-year-old woman with acquired immunodeficiency syndrome was admitted with septic fever of unknown origin and a 2-week history of diarrhea. Clinical diagnostic procedures did not reveal the cause of sepsis. Broad-spectrum antibiotics and intensive symptomatic therapy could not prevent progressive deterioration. The patient developed septic shock and consumptive coagulopathy and died 6 days after admission. Autopsy revealed disseminated infection with toxoplasma gondii and multiple organ manifestations. We conclude that disseminated toxoplasmosis should be considered in AIDS patients with septic disease of unknown origin. Extremely elevated lactate dehydrogenase may suggest disseminated toxoplasma gondii infection. New procedures such as polymerase chain reaction for detection of toxoplasmosis may be helpful diagnostic tools.

[Lymph follicle formation and development of intestinal metaplasia in antrum mucosa as a reaction to Helicobacter pylori infection]. / Zur Frage der Lymphfollikelbildung und der Entstehung der intestinalen Metaplasie in der Antrumschleimhaut als Reaktion auf eine Helicobacter pylori-Infektion.

We examined 171 patients (76 females and 95 males) with definite type B-Gastritis. Antrum specimens were taken from all participants for histological examination. We studied the correlations between the formation of lymphoid follicles, the severity of gastritis, the degree of activity of gastritis and the density of Helicobacter pylori colonization. In addition we noted the distribution and extent of the intestinal metaplasia. In patients with high degree HP-colonization we found formation of lymphoid follicles in 59.8%, in patients with low degree HP-colonization in 35% and in patients without colonization only in 10.2% (high degree vs. low degree colonization p less than 0.05, low degree vs. absent colonization p less than 0.025, high degree vs. absent colonization p less than 0.0005). In patients with high grade type B-Gastritis we detected formation of lymphoid folliclesin 58%. There was no case of formation of lymphoid follicles in patients with low grade type B-Gastritis. Patients with a high grade activity of the type B-Gastritis displayed a formation of lymphoid follicles in a higher percentage as patients with a low grade activity of the gastritis (66% vs. 33%, p less than 0.0005). In the antrum intestinal metaplasia of the types I and II could be found significantly more frequent in patients with high grade Type B-Gastritis than in patients with low grade Type B-Gastritis (34.1% vs. 8.8%, p less than 0.005). Intestinal metaplasia was found more frequently in connection with high and low activity of type B-Gastritis than without activity (p less than 0.005 and p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

The American Board of Surgery in-training examination.

Since 1975, the American Board of Surgery has annually offered a multiple-choice in-training examination to directors of accredited general surgery programs in the United States for administration to residents in their programs. Residents' scores for the total examination and the five body-system categories are provided to program directors, along with normative data for comparison of their residents' performance against that of all examinees. Each year, residents' scores have correlated well with their level of training. Reliability coefficients have verified that the examinations have functioned effectively as test instruments. The increasingly wide use of the examination and its favorable acceptance by program directors have indicated that the examination is making a significant contribution to surgical education in the United States.

A national self-assessment program in internal medicine.

The Medical Knowledge Self-Assessment Program of the American College of Physicians is one of the largest continuing medical education programs in the United States. The scope and educational rationale for each of the components of the program are described. More than 32,000 physicians used one or more components during 1977 and 1978. Performance on the self-assessment examinations showed that, on the average, participants who submitted answer sheets scored in the range of 65% to 75% correct responses. Participants performed better in areas reflecting their special interests and, in general, performance appeared to improve for groups that were closer to the completion of formal training in internal medicine. Specific suggestions have been made as to how the program might be improved in future years.

[Bone maturation in the fetus and newborn infant]. / Maturation osseuse du foetus et du nouveau-né.

On the basis of a study of X-ray films of the lower limbs of 994 babies (included 245 hypotrophics) a "bone age" scale of the fetus between 28 and 42 weeks of gestation has been established. The Acheson's method has been used and the bone age determined by addition of notes given to different evolutive phases of the first five ossification centers of the ankle and the knee. To more practical purpose, the results of boys and girls have been joined, although the bone age is in advance among the girls and a theorical scale established with the 10th, 50th and 90th percentiles curves. The comparison with the curves established among 245 hypotrophic newborns, seems to prove that the bone age is a more resistant criteria to malnutrition than the weight and even the length. This new criteria to determine the fetal age does not escape to the criticisms given to the other existing criteria, but radiograph is an objective and fixed document. Its repetition allows to follow the growth of the child and probably to study the role of various factors, mainly nutritional, on this growth. The measure of the length of the tibia and of its increament on the same X-ray films is an other possible method of great interest for the same purpose.

Vasoconstrictor and pilomotor fibres in skin nerves to the cat's tail.

Postganglionic neurones to the tail's skin of the cat were investigated with regard to their spontaneous activity, response characteristics to somatic stimuli and asphyxia, the conduction velocity of their axons, and the conduction velocity of the preganglionic axons converging on them. The cats were anaesthetized with chloralose, immobilized, and arteficially ventilated. With this regimen the postganglionic neurones were divided into two types: 1. Type 1 neurones are spontaneously active and exhibit reflexes upon somatic stimulation. During asphyxia they are mostly first depressed and then excited for about 2-3 min. Their axons conduct with 0.57 +/- 0.13 m/s (mean +/- SD). The pregaglionic axons converging on them conduct with 5.4 +/- 1.6 m/s. 2. Type 2 neurones are not spontaneously active and exhibit with few exceptions no reflexes on somatic stimuli. During asphyxia they are activated after 3-4 min, concomitantly with piloerection, when the activity in type 1 neurones is already decreasing. Their axons conduct with 0.84 +/- 0.14 m/s, the preganglionic axons converging on them conduct with 9.9 +/- 2.9 m/s. 3. From these characteristics it is concluded that type 1 neurones have vasomotor function and most type 2 neurones pilomotor function.