Glucose tolerance behaviour before the onset of type I (insulin-dependent) diabetes in young people as a predictor of the further course of the disease: a retrospective analysis of 33 cases

A study was made of glucose tolerance and insulin secretion in 33 persons who later developed insulin-dependent diabetes (aged 4-24 years) and observation continued further in the first years after manifestation. Patients who developed the typical labile type of diabetes were of normal weight and had either normal glucose tolerance tests before diagnosis or had impaired glucose tolerance (IGT) for a short interval of 2-16 months. Subjects with IGT over a significantly (p less than 0.01) longer period of 32.30 +/- 6.25 (normal body weight) or 94.71 +/- 20.62 (obese) months developed a milder form of diabetes with retarded insulin dependency in obese subjects. The severe and mild form of IDDM are distinct with respect to insulin requirement (0.75 +/- 0.03 or 0.28 +/- 0.04 U/kg b.w., P less than 0.01) and glucagon stimulated C-peptide (0.18 +/- 0.05 or 1.41 +/- 0.27, P less than 0.01) in the first 2.5-3.5 years after onset. The two forms were not different regarding HLA-DR antigens. Islet cell surface antibodies investigated in 15 probands at 27 occasions before diabetes onset had no prognostic value. The development of a mild form of IDDM may be expected in cases with pre-existing IGT for more than one year. The insulin secretion is of low predictive value under these conditions. The observation is of practical use and theoretical interest.     

Decrease of glucose in the human visual cortex during photic stimulation.

Localized proton NMR spectroscopy was used to study cerebral metabolism in the visual cortex of healthy adults during rest and photic stimulation. Basal lactate levels showed considerable interindividual differences ranging from below detectability (less than 0.3 mM) to about 1 mM without consistent alteration during photic stimulation. Local brain glucose levels were significantly reduced (approximately 50%) during the entire period of photic stimulation and recovered to resting levels (approximately 0.8 mM) within 10 min after the end of stimulation. This decrease reflects the establishment of a new equilibrium due to enhanced delivery (blood flow) and enhanced consumption. The absence of lactate accumulation supports the hypothesis of a rapid efflux of lactate from brain tissue under activated conditions.     

Genetic instability in human chromosome region 3p12-p21 in renal cell carcinoma and lung cancer

contributed equally to this work     

Regulation of calcium levels in brain tissue from adult and aged rats.

The possibility that regulation of Ca2+ levels in brain nerve terminals is altered as the brain ages was examined in synaptosomes from adult and aged Fischer 344 rats. Free intrasynaptosomal [Ca2+]i was monitored with fura-2 as synaptosomes were depolarized with KCl, veratridine and ibotenic acid. With all three depolarizing agents, synaptosomes from aged animals reached higher free Ca2+ levels, and the maximal Ca2+ increases (delta Ca2+) estimated from computer assisted-fitting of the curves, ranged from 35% to 80% greater in synaptosomes from aged animals. The total Ca2+ content of the brain and of synaptosomes was also found to be considerably higher in aged than in adult animals. These results suggest that the aging process in brain is accompanied by alterations in both dynamic aspects of Ca2+ handling in nerve endings and the overall content of Ca2+ in the brain and synaptic terminals.     

Multicontrast MRI of remyelination in the central nervous system

Although magnetic resonance imaging (MRI) represents the most sensitive tool for the detection of white matter abnormalities in patients with multiple sclerosis (MS), the heterogeneity of MS placques severely hampers the elucidation of specific pathophysiological processes. In order to identify putative MRI markers for de- and remyelination, we employed the cuprizone mouse model which leads to a selective and reversible demyelination of the corpus callosum with little or no axonal damage. Apart from histopathology, animals were studied with high-resolution three-dimensional MRI in vivo using multiple contrasts. While individual MRI findings significantly correlated with electron microscopy, the differentiation of regions with normal, demyelinated or remyelinated white matter by one contrast alone was less specific than by histology or electron microscopy. However, an accurate MRI prediction of the in vivo myelin status was achieved by a discriminant function analysis using a combination of T1, T2 and magnetization transfer contrast. With a correct assignment of 95% of all animals examined, the procedure will allow for the survey of new therapeutic approaches aiming at improved remyelination.     

Properties of afferent nerve fibres supplying the saphenous vein in the cat.

1. We examined the responses of primary afferent neurones supplying a vascularly isolated segment of the saphenous vein to mechanical and chemical stimuli in anaesthetized cats. Activity was recorded from centrally cut axons of afferent nerve fibres which were isolated from the saphenous nerve near its junction with the femoral nerve. 2. A total of thirty units responded to one of these stimuli and twenty-three of them were activated by local mechanical stimulation of the venous wall. Most receptive fields were circular spots. The response of the isolated venous segment to distension was tested in fifteen out of thirty units and eight out of fifteen were activated. Intravasal threshold pressures inducing discharges were in the range of 35-250 mmHg with a mean of 120 mmHg. 3. Twenty-seven out of the thirty units were tested for both mechano- and chemosensitivity. Thirteen were classified as A fibres and fourteen as C fibres with conduction velocities of 5-30 m s-1 and less than 2.5 m s-1 respectively. Twenty fibres (12/13 A, 8/14 C) were mechanosensitive. Two-thirds of the mechanosensitive A (8/12) and all of the mechanosensitive C fibres (8/8) responded to at least one of the chemical stimuli used: hypertonic saline, bradykinin (BK) or capsaicin. 4. The remaining seven units (6 C, 1 A) were activated by injection of BK into the isolated venous segment but failed to respond to mechanical stimuli. Six were found during five experiments in which BK was used as a search stimulus. Injection of bradykinin into the isolated venous segment repeatedly induced an increase in systemic blood pressure. 5. The proportion of unmyelinated fibres responding to mechanical stimulation of the venous segment was systematically examined in three experiments and amounted to about 1% of the unmyelinated afferents in the saphenous nerve. 6. In conclusion, a small proportion of afferent nerve fibres in the saphenous nerve responds to presumably noxious mechanical and/or chemical stimuli applied to the saphenous vein. These fibres, together with some chemospecific venous afferents, may be capable of encoding nociceptive information from the vein especially under pathological conditions.     

Townes-Brocks syndrome

Townes-Brocks syndrome (TBS) is an autosomal dominant disorder with multiple malformations and variable expression. Major findings include external ear anomalies, hearing loss, preaxial polydactyly and triphalangeal thumbs, imperforate anus, and renal malformations. Most patients with Townes-Brocks syndrome have normal intelligence, although mental retardation has been noted in a few.