Arterio-venous shunting and proliferating new vessels in acute painful neuropathy of rapid glycaemic control (insulin neuritis)

Insulin neuritis, or painful neuropathy following rapid improvement in glycaemic control, is well recognised but its aetiology is unclear. An understanding of the processes involved in the genesis of acute painful neuropathy of rapid glycaemic control may give an insight into the early pathogenetic factors leading to diabetic nerve damage in general. We have identified five subjects with insulin neuritis including one who developed severe autonomic neuropathy following treatment with insulin. Subjects underwent: 1) assessment of neuropathic symptom and deficit scores; 2) quantitative sensory and electrophysiological studies and 3) sural nerve epineurial vessel photography and fluorescein angiography in vivo. The sural nerve photographs were independently graded by an ophthalmologist. All subjects with insulin neuritis presented with severe sensory symptoms but clinical examination and electrophysiological tests were normal except in the subject with the severe autonomic neuropathy in whom all the tests were abnormal. On nerve photography, there was an abundance of epineurial nutrient vessels although these showed severe abnormalities including arteriolar attenuation, tortuosity and arterio-venous shunting in all subjects. Proliferating neural 'new vessels' which bear striking similarities to those found in the retina and that were more leaky to fluorescein than normal vessels, were observed in three subjects. Venous distension and/or tortuosity was also observed in three subjects and this was most marked in the subject with severe autonomic neuropathy. This study shows that epineurial nutrient vessel anatomy is abnormal in subjects with acute painful neuropathy of rapid glycaemic control, a condition previously thought to be purely metabolic in origin. The presence of epineurial arterio-venous shunting and a fine network of vessels resembling the new vessels of the retina, may lead to a 'steal' effect rendering the endoneurium ischaemic. This process may be important in the genesis of neuropathic pain, and further supports the importance of vascular factors in the pathogenesis of diabetic neuropathy.     

Do experienced diagnosticians agree about the diagnosis of dementia from survey data? The effects of informants' reports and interviewers' vignettes

Dementia in community settings is often diagnosed by computerized algorithms. This study examines the extent to which independent diagnosticians agreed among themselves in diagnosing dementia, severity and type when presented with data obtained during a population-based incidence study of cognitive decline and dementia. Secondly, it examines how judgements, based initially on respondents' self-reports and cognitive performance, were affected first by informants' reports and then by short case-vignettes written by trained lay interviewers. Thirdly, it compares diagnosticians' diagnosis of dementia with the algorithmic diagnosis (AGECAT). The items presented were selected from two screening interviews at wave 1 and wave 2 separated by an interval of 2 years and from wave 2 assessment and informant interviews, and included medical, psychiatric and ADL items and interviewers' own observations. The sample (N = 42) was derived from the first year of the wave 2 assessments, potential dementia cases entering consecutively while presumed normals were selected randomly. Informants were available in 30. Agreement on diagnosis and type of dementia improved with increasing information, particularly from informants, but remained poor regarding severity. The number of cases of dementia, defined operationally, increased from 10 to 12 and uncertain cases fell from eight to six, but no respondent initially diagnosed as a dementia case was rediagnosed as a non-case, or vice versa. Dementia type changed from agreement about Alzheimer's disease to agreement about vascular dementia in one case. Operational and algorithmic diagnoses showed good agreement. Causes of disagreement, the role of vignettes and the relevance of the results for population surveys are discussed.     

Aspirative lipectomy in patients with alimentary-constitutional obesity

The results of aspirative lipectomy in patients with 2nd and 3rd stage of alimentary-constitutional obesity are analysed. The effectiveness of lipectomy with surgical creation of a small ventricle and without previous surgery, has been demonstrated. The criteria of patients selection, based on their somatic and psychic features, are formulated. Aspirative lipectomy has certain advantages over other types of plastic surgery as it has the minimal rate of postoperative complications.     

Involvement of the endosomal autoantigen EEA1 in homotypic fusion of early endosomes

In mammalian cells, fusion between early endocytic vesicles has been shown to require the ubiquitous intracellular fusion factors N-ethylmaleimide-sensitive factor (NSF) and alpha-SNAP, as well as a factor specific for early endosomes, the small GTPase Rab5 [1-3]. We have previously demonstrated an additional requirement for phosphatidylinositol 3-kinase (PI 3-kinase) activity [4]. The membrane association of early endosomal antigen 1 (EEA1), a specific marker of early endosomes [5,6], has recently been shown to be similarly dependent on PI 3-kinase activity [7], and we therefore postulated that it might be involved in endosome fusion. Here, we present evidence that EEA1 has an important role in determining the efficiency of endosome fusion in vitro. Both the carboxy-terminal domain of EEA1 (residues 1098-1411) and specific antibodies against EEA1 inhibited endosome fusion when included in an in vitro assay. Furthermore, depletion of EEA1, both from the membrane fraction used in the assay by washing with salt and from the cytosol using an EEA1-specific antibody, resulted in inhibition of endosome fusion. The involvement of EEA1 in endosome fusion accounts for the sensitivity of the endosome fusion assay to inhibitors of PI 3-kinase.     

Respective roles of human cytochrome P-4502E1, 1A2, and 3A4 in the hepatic microsomal ethanol oxidizing system

The microsomal ethanol oxidizing system comprises an ethanol-inducible cytochrome P-4502E1, but the involvement of other P-450s has also been suggested. In our study, human CYP2E1, CYP1A2, and CYP3A4 were heterologously expressed in HepG2 cells, and their ethanol oxidation was assessed using a corresponding selective inhibitor: all three P-450 isoenzymes metabolized ethanol. Selective inhibitors-4-methylpyrazole (CYP2E1), furafylline (CYP1A2), and troleandomycin (CYP3A4)-also decreased microsomal ethanol oxidation in the livers of 18 organ donors. The P-450-dependent ethanol oxidizing activities correlated significantly with those of the specific monooxygenases and the immunochemically determined microsomal content of the respective P-450. The mean CYP2E1-dependent ethanol oxidation in human liver microsomes [1.41+/-0.11 nmol min(-1) (mg protein)(-1)] was twice that of CYP1A2 (0.61+/-0.07) or CYP3A4 (0.73+/-0.11) (p < 0.05). Furthermore, CYP2E1 had the highest (p < 0.05) specific activity [28+/-2 nmol min(-1) (nmol CYP2E1)(-1) versus 17+/-3 nmol min(-1) (nmol CYP1A2)(-1), and 12+/-2 nmol min(-1) (CYP3A4)(-1), respectively]. Thus, in human liver microsomes, CYP2E1 plays the major role. However, CYP1A2 and CYP3A4 contribute significantly to microsomal ethanol oxidation and may, therefore, also be involved in the pathogenesis of alcoholic liver disease.     

Heat shock proteins and proliferative activity of cultured hepatocytes after hyperthermia

Hepatocytes in cell culture have been studied for their sensitivity to mitogenic effect of the epidermal growth factor, epidermal growth factor and insulin, 10% of cattle blood serum after hyperthermia. It is established that heat shock (43 degrees C, 90 min) induces hypersensitivity of hepatocytes to the mentioned mitogens, its maximum being observed 20-24 h after hyperthermia and coinciding in time with the development of thermotolerance and intensification of protein biosynthesis after the heat shock 68, 70, 94 kD.     

Nuclear morphometry of the myocardial cells as a diagnostic tool in cases of sudden death due to coronary thrombosis

One general signalling mechanism used to transfer the information delivered by agonists into appropriate intracellular compartments involves the rapid redistribution of ionised calcium throughout the cell, which results in transient elevations of the cytosolic free Ca2+ concentration. Various physiological stimuli increase [Ca2+]i transiently and, thereby, induce cellular responses. However, under pathological conditions, changes of [Ca2+]i are generally more pronounced and sustained. Marked elevations of [Ca2+]i activate hydrolytic enzymes, lead to exaggerated energy expenditure, impair energy production, initiate cytoskeletal degradation, and ultimately result in cell death. Such Ca(2+)-induced cytotoxicity may play a major role in several diseases, including neuropathological conditions such as chronic neurodegenerative diseases and acute neuronal losses (e.g. in stroke).