Select types of supporting cell in the inner ear express aquaporin-4 water channel protein

Aquaporins (AQPs) confer a high water permeability on cell membranes and play important parts in secretory and absorptive epithelia in kidney and other organs. Here we investigate whether AQPs are expressed in the sensory epithelia of the inner ear, where a precise volume regulation is crucial. By use of specific antibodies it was found that the inner ear contains AQP1 and 4 while being devoid of detectable levels of AQP2, 3 or 5. Immunofluorescence and postembedding immunogold labelling revealed a strictly non-epithelial distribution of AQP1, confirming previous data. In contrast, AQP4 protein and mRNA (visualized by in situ hybridization) were concentrated in select types of supporting cell, including Hensen's cells and inner sulcus cells. Immunogold particles signalling AQP4 were confined to the basolateral plasma membrane of Hensen's cells and to the basal plasma membrane of Claudius cells and inner sulcus cells. AQP4 was also found in supporting cells of the vestibular end organs, but was absent from transitional epithelial cells and dark cells. Strong labelling for AQP4 and AQP4-mRNA was associated with the central part of the cochlear and vestibular nerves. Hair cells were consistently unlabelled. Our findings indicate that AQP4 may facilitate osmotically driven water fluxes in the sensory epithelia of the inner ear and thus contribute to the volume and ion homeostasis at these sites.     

Need for bilateral arthroplasty for coxarthrosis 1, 477 replacements in 1, 199 patients followed for 0-14 years

During the 10-year period 1981-1990, 1, 199 patients in the county of South Jutland, Denmark, had 1, 477 primary total hip arthroplasties (THA) performed because of primary arthrosis (OA).

The patients were followed until the end of 1994, with a mean follow-up of 5.6 (0-14) years. Bilateral operations were performed on 356 patients, whereas 248 patients had died with only 1 THA.

The cumulated risk of replacement of the contralateral hip was approximately 0.15 1 year after replacement of the first hip, 0.20 after 2 years, 0.29 after 5 years and 0.47 after 10 years, respectively.

During the follow-up period, the demand for a THA of the contralateral hip continued to be approximately 15 times higher than in the general population.     

Functional mri of human brain activation combining high spatial and temporal resolution by a cine flash technique

Functional mapping of human brain activation has been accomplished at high spatial and temporal resolution (voxel size 4.9 μl, temporal increment 100 ms). The approach was based on oxygenation-sensitive long-echo time FLASH MRI sequences synchronized to multiply repeated cycles of visual stimulation in a CINE acquisition mode. This high temporal resolution revealed that stimulus-related signal intensity changes in human visual cortex display an initial latency followed by increases extending over several seconds. Furthermore, the temporal characteristics of the complete CINE MRI signal time course depended on the absolute and relative durations of activation and control periods and, for example, caused an apparent absence of a poststimulation “undershoot” phenomenon. Complementing hyperoxygenation due to rapid hemodynamic adjustments, these results suggest signal intensity modulation by enhanced oxygen consumption and concomitant deoxygenation during prolonged and/or repetitive stimulation.     

Treatment of systemic sclerosis with recombinant interferon-gamma. A phase I/II clinical trial.

OBJECTIVE. A phase I/II trial to examine the safety and efficacy of interferon-gamma (IFN gamma) therapy for patients with systemic sclerosis (SSc). METHODS. An 18-week open-label study was performed. Eighteen patients with rapidly progressive SSc were enrolled, 14 of whom completed at least 16 weeks of the study. These 14 patients had a mean age of 40 years and had been diagnosed as having SSc an average of 10.1 months prior to study entry. Recombinant IFN gamma was injected intramuscularly 3 times weekly for 18 weeks. Six patients received a 0.1 mg/m2 dose, while 8 patients received a 0.5 mg/m2 dose. Patients who completed the 18-week trial were offered maintenance therapy at a dose of up to 0.5 mg/m2. The effects of IFN gamma on skin involvement were assessed by 2 methods: 1) evaluation of skin thickness, by scoring 15 zones according to a 0 (normal skin) to 3 (hidebound skin) scale; and 2) determination of the total body surface area involved, by using 2-dimensional body diagrams to indicate areas affected, and then having a second, "blinded," assessor calculate the area score with a planimeter. RESULTS. The mean skin thickness score decreased from a baseline of 25.9 to 19.1 (P < 0.03), and the mean area scores declined from 33.1 to 19.6 (P < 0.02) after 18 weeks of IFN gamma treatment. Ten patients had a > 25% decrease in area score. Five patients had a > or = 70% decrease in area score, and 3 of them have not experienced disease recurrence for 6 to 17 months after discontinuation of IFN gamma. Five patients withdrew before the study ended. Three of these patients developed renal crisis, which may reflect the severity of the SSc in the study group, although an adverse effect of IFN gamma in SSc cannot be excluded. CONCLUSION. IFN gamma was associated with a beneficial effect on the skin involvement in most of this series of patients with rapidly progressive SSc. A placebo-controlled study will be necessary to confirm these results.     

Abdominal ultrasound versus intravenous urography in the evaluation of infravesically obstructed males

In a prospective study intravenous urography (IVP) and abdominal ultrasonography (US) were compared in 100 consecutively admitted male patients with symptoms of infravesical obstruction. No pathology was found in 67 patients on IVP and in 61 patients on US. Both modalities disclosed 5 bilateral, 4 unilateral hydronephroses and one patient with contracted kidneys. IVP found 7 renal masses: one solid tumour, 2 "possibly solid" tumours and 4 "possibly cysts", whereas US found one solid tumour and 16 cysts. Both modalities detected 3 kidney stones, 5 bladder stones and 3 bladder tumours. It is concluded that "imaging" of the urinary tract is only indicated in cases of haematuria, elevated creatinine, history of renal calculous disease and other clinical suspicion of upper urinary tract disease. It is further concluded that US is preferable to IVP in this patient category due to (1) better characterization of renal masses, (2) the possibility of investigating the liver and the retroperitoneum in the same setting, (3) better evaluation of the prostate with respect to size, (4) better evaluation of the bladder, and (5) last but not least for economical reasons. However, bone metastases will be missed.     

Inflammatory regulation of extracellular matrix remodeling in calcific aortic valve stenosis.

BACKGROUND: Calcific aortic stenosis (AS), the most frequent heart valve disorder in developed countries, leads to the calcification and fibrous thickening of the valve. While several studies have addressed the process of valvular calcification, the molecular pathomechanisms of the extensive matrix remodeling remain unclear. Because inflammation is present in stenotic valves, we hypothesized that the proinflammatory cytokine tumor necrosis factor alpha (TNFalpha) might influence cell proliferation and regulate the expression and activation of matrix metalloproteinases (MMPs)--enzymes that are thought to be involved in calcific AS. METHODS: Immunohistochemistry for leukocytes, TNFalpha, MMP-1, and the endogenous MMP inhibitor tissue inhibitor of metalloproteinase (TIMP)-1 was performed on human stenotic (n = 19) and control (n = 8) valves. Primary cultures of human aortic valve myofibroblasts were incubated with and without TNFalpha, and cell proliferation was assessed. The expression and activation of MMP-1 were detected by Western blotting and a specific MMP-1 activity assay. RESULTS: Control valves showed scattered macrophages and low expression of TNFalpha, MMP-1, and TIMP-1. In stenotic valves, leukocyte infiltration and a strong, colocalized expression of TNFalpha and MMP-1 were present, while TIMP-1 remained unchanged. Double-label immunofluorescence localized TNFalpha mainly to macrophages. In cultured human aortic valve myofibroblasts, TNFalpha stimulated proliferation and induced a time-dependent increase in MMP-1 expression and activation, while TIMP-1 remained unchanged. CONCLUSION: The results indicate that matrix remodeling in calcific AS involves the expression and activation of MMPs. Activated leukocytes, by the secretion of TNFalpha, may stimulate valvular myofibroblasts to proliferate and express MMPs, thus regulating actively the matrix remodeling in calcific AS.     

Modulation of heteronymous reflexes from ankle dorsiflexors to hamstring muscles during human walking

In 16 human subjects, stimulation of the common peroneal nerve (CPN) was applied during walking and standing. The effect of the stimulation was evaluated from the rectified and averaged biceps femoris (BF) electromyographic (EMG) activity. In the swing phase of walking, the CPN stimulation evoked a suppression in the BF EMG in 12 of the subjects. In the early stance phase, the suppression was replaced by facilitation at a similar latency in 9 of the subjects. Of the other 3 subjects, in whom a suppression was observed during swing, a decrease in the suppression was observed in the stance phase in two of them. During a voluntary co-contraction of BF and tibialis anterior while standing, a suppression similar to that observed in the swing phase was observed. The thresholds of the suppression and facilitation were identical, suggesting that afferents of similar diameter were responsible. Cutaneous stimuli, which mimicked the sensation evoked by the CPN stimulation, but without activation of muscle afferents, did not produce similar effects in the BF EMG activity. It is suggested that the observed response and reflex reversal may reflect opening of an excitatory group I pathway in the early stance phase of walking with a concomitant shut-down of heteronymous group I inhibition.     

Investigation of TSH dependency, circulating thyroid autoantibody, and morphological features of recurrent nontoxic goitre

Pathogenetical factors possibly responsible for recurrence of nontoxic goitre in a nonendemic area are evaluated. A group of 22 female patients admitted for surgical treatment of recurrent nontoxic goitre was compared with a control group of 86 female nontoxic goitrous patients not operated upon before. Preoperative serum baseline thyrotrophin levels in the recurrent goitre group were low normal and did not differ significantly from those in the control group. Circulating thyroid microsomal autoantibodies, thyroglobulin antibody titers, and the densities of lymphocytic aggregation in goitrous tissue did not differ significantly in the two groups. Thus, none of the parameters studied were likely explanations of regrowth of goitre.     

Local muscle blood flow and sustained contractions of human arm and back muscles

The endurance during sustained contraction of elbow, flexors, elbow extensors, and back extensors was tested in 3 human subjects. The force level used was varied between ca. 15 and ca. 75% of maximal isometric strength (IS). The clearance of¹³³Xe from contracting muscles was registered during and after the endurance test. In this way it was possible to determine whether muscle blood flow (MBF) was increased or had stopped during the contraction. Experiments with artificial ischaemia of the upper arm together with MBF measurements showed that MBF was of no importance for continuing sustained contractions above a certain force level, which was 50, 25, and 40% of IS for elbow flexors, elbow extensors and back extensors, respectively. However, the level where longer lasting (>15 min) sustained contraction is possible is directly related to MBF. These levels were 22, 15, and 20% IS for elbow flexors, elbow extensors, and back extensors, respectively.     

Dimensional changes of proximal tubules and cortical capillaries in chronic obstructive renal disease

Summary The study was carried out to determine the proximal tubular length, surface area and length of peritubular capillaries and the nephron numbers in kidneys with chronic nephropathy and varying increase in the cortical interstitial volume. Kidneys of pigs with varying chronic obstructive nephropathy were used for the experiments. Two subgroups of ureterobstructed kidneys were defined arbitrarily according to the volume of cortical interstitium. One subgroup (I) comprised kidneys with a volume fraction of cortical interstitium less than 30% (mean 17.2%; mean of controls 9.7%). The other subgroup (II) consisted of kidneys with severe chronic nephropathy and with a volume fraction of interstitium more than 30% (mean 44.5%). Proximal tubular length and length and surface area of peritubular capillaries were assessed by conventional morphometric techniques on 1 m thick sections of plastic embedded material. Nephron numbers were determined by a stereological method for counting glomeruli.The results demonstrated that proximal tubular length and capillary dimensions were significantly reduced in subgroup II, whereas no significant changes were observed in subgroup I. The mean number of glomeruli was not significantly different from control values in any of the subgroups.The results are in line with observations from previous quantitative analyses of proximal tubular cross-sections indicating that proximal tubular dimensions become reduced mainly at advanced stages of chronic nephropathy. The results also indicate that shortening of individual tubules rather than loss of entire nephrons is responsible for the observed reduction in total length of proximal tubules. Finally, the present observations suggest that reduced dimensions of the cortical capillary network may have pathogenetic significance for ongoing proximal tubular atrophy in chronic renal desease.