A presenilin 1 mutation (L420R) in a family with early onset Alzheimer disease,seizures and cotton wool plaques,but not spastic paraparesis

Over 100 mutations in the presenilin‐1 gene (PSEN1) have been shown to result in familial early onset Alzheimer disease (EOAD), but only a relatively few give rise to plaques with an appearance like cotton wool (CWP) and/or spastic paraparesis (SP). A family with EOAD, seizures and CWP was investigated by neuropathological study and DNA sequencing of the PSEN1 gene. Aβ was identified in leptomeningeal vessels and in cerebral plaques. A single point mutation, p.L420R (g.1508T > G) that gives rise to a missense mutation in the eighth transmembrane (TM8) domain of PS1 was identified in two affected members of the family. p.L420R (g.1508T > G) is the mutation responsible for EOAD, seizures and CWP without SP in this family.     

Blutzuckerbestimmung bei Ekzem,Psoriasis, Lichen Vidal und Ulcus cruris

Zusammenfassung Bei Ekzem, Psoriasis, Lichen Vidal und Ulcus cruris konnte pathologische Erhöhung des Blutzuckerspiegels im allgemeinen nicht festgestellt werden, wenn eine Glykosurie nicht vorhanden war. Beim Lichen Vidal sind die Blutzuckerwerte zwar im Bereiche normaler Grenzen, aber in einer erheblichen Anzahl niedriger als bei den anderen Untersuchten.     

Early indices of warm ischemic damage in autotransplanted canine kidneys preserved by simple hypothermic storage

After measurement of normal renal function, dog kidneys (n = 52) were subjected to 3, 15, or 30 min of normothermic warm ischemia (WI). After 24 hr of preservation by simple hypothermic storage (SHS) in a modified Collins solution, autotransplant was done and renal function was again measured beginning at 1 hr. Compared with preharvest values, kidneys with minimal (3 min) WI had significantly decreased clearances of creatinine (Cr) and para-aminohippuric acid (PAH), PAH extraction, absolute and fractional Na reabsorption, Na excretion, and urinary Na concentration; no change in urine flow rate or K excretion; and significantly increased fractional excretion of Na, K, and H2O. Compared with minimal WI, 30-min WI produced further significant decreases in clearances of Cr, PAH, and PAH extraction; and further increases in fractional excretion of Na, K, and H2O. Urine flow was also decreased by about half and urine Na concentration rose significantly. Several parameters were very significantly correlated with the length of WI, but the most reliable index was the fractional reabsorption of Na. When several functional parameters were used together, kidneys with significant (30 min) WI prior to preservation could be identified with a high degree of statistical reliability.     

Improved anchorage in osteoporotic vertebrae with new implant designs.

The goal of our study was to evaluate two newly developed implant designs and their behavior in terms of subsidence in lumbar vertebral bodies under cyclic loading. The new implants were evaluated in two different configurations (two small prototypes vs. one large prototype with similar load-bearing area) in comparison to a conventional screw-based implant (MACS TL). A pool of 13 spines with a total of 65 vertebrae was used to establish five testing groups of similar bone mineral density (BMD) distribution with eight lumbar vertebrae each. In additional to BMD assessment via dual-energy X-ray absorptiometry, cancellous BMD and structural parameters were determined using a new generation in vivo 3D-pQCT. The specimens were loaded sinusoidally in force control at 1 Hz for 1000 cycles at three load levels (100, 200, and 400 N). A survival analysis using the number of cycles until failure (Cox regression with covariates) was applied to reveal differences between implant groups. All new prototype configurations except the large cylinder survived significantly longer than the control group. The number of cycles until failure was significantly correlated with the structural parameter Tb.Sp. and similarly with the cancellous BMD for three of five implants. In both large prototypes the cycle number until failure significantly correlated with the preoperative distance to the upper endplates. Although the direct relationship between bone structure or density and mechanical breakage behavior cannot be conclusively proven, all the prototypes adapted for poor bone structure performed better than the comparable conventional implant.     

No regression of renal AL amyloid in monoclonal gammopathy after successful autologous blood stem cell transplantation and significant clinical improvement.

BACKGROUND: High-dose chemotherapy followed by autologous blood stem cell transplantation induces remission of plasma cell dyscrasia in patients with AL amyloidosis. The impact of this treatment on the glomerular amyloid mass is still unknown. METHODS: In the present study, the quantity of the renal amyloid mass before and more than 3 years after high-dose melphalan treatment and autologous blood stem cell transplantation was assessed in two patients. At the time of the second renal biopsy, both patients were in complete remission without detectable serum and urinary monoclonal IgA-lambda and a normal percentage of plasma cells in the bone marrow. RESULTS: In both patients with biopsy-proven AL amyloidosis, urinary protein excretion decreased from 7 g/24 h to <2 g/24 h more than 3 years after autologous blood stem cell transplantation. In contrast, glomerular amyloid deposits persisted, as shown in the second biopsy. CONCLUSION: Despite complete remission of the plasma cell dyscrasia and improvement of glomerular permeability, the amount of glomerular amyloid mass did not regress.     

Neue Gesichtspunkte zur Behandlung der kompletten und isolierten diaphysären Unterarmfrakturen im Kindesalter

From 1984 to 1992 153 children were treated at the pediatric surgical department of the University of Mainz, of whom 19 had fractures of the radius, 9 of the ulna and 125 had a combination of both in the diaphysis of the forearm. Factors like patient's age, type of fracture and therapeutic methods were analyzed. One hundred and forty-one children were treated conservatively, 12 by operation. One hundred and one of these patients were healthy, when discharged (about 8 weeks after accident). Follow-up was possible in 69 cases. We found that occasional a remaining dislocation angle does not impair function: in 65 cases the result was “good” and “very good”, but only “moderate” in 4 cases. These 4 children had been treated conservatively by reposition and plaster cast; 2 of these 4 children showed bone reconstruction without dislocation. Twenty-two of the 56 X-ray follow-up's showed persisting dislocation. To prevent functional problems (2 of our cases) it is essential to obtain a very exact reposition of diaphyseal forearm fractures. Therefore we would recommand a more generous indication for operation, preferably using elastic-stable Nancy pins.     

环孢菌素A阻断人HL－60抗药性细胞于G_1期而诱导敏感细胞凋亡

进一步研究了抗三尖杉酯碱的ＨＬ－６０细胞（ＨＲ２０）抗细胞凋亡的机制及该抗性和抗药性的关系。结果表明，环孢菌素Ａ（ＣｓＡ）２０，１０μｇ·ｍｌ￣（－１）诱导ＨＬ－６０细胞发生凋亡，而阻断ＨＲ２０细胞于Ｇ＿１期，就不能诱导细胞发生凋亡。低浓度的ＣｓＡ明显增加柔红霉素在ＨＲ２０细胞内的积聚，其逆转抗药性作用与阻断细胞周期运行无关。ＣｓＡ１０μｇ·ｍｌ￣（－１）处理ＨＲ２０细胞，可引起５０ｋＤａ的蛋白质高度磷酸化。结果提示：环孢菌素Ａ阻断抗三尖杉酯碱的ＨＬ－６０细胞于Ｇ＿１期，而诱导敏感的ＨＬ－６０细胞发生凋亡，其阻断作用与抗药性无关     

Morphology of retinal ganglion cells in lungless salamanders (fam. Plethodontidae): an HRP and Golgi study

The family Plethodontidae consists of nearly two-thirds of all living urodeles; most of them possess highly developed visual abilities. We investigated the morphology of retinal ganglion cells (RGCs) in four representative species by means of the horseradish peroxidase method in flatmounts and in transverse sections and with the Golgi method in transverse sections. In flatmount preparations, four classes of RGCs were found, differing in dendritic arborization, dendritic field size, and stratification pattern of dendrites in the inner plexiform layer (IPL). Class-1 cells had small dendritic fields (29-44 microns 2) and arborized throughout the entire depth of the IPL. Class-2 cells had medium to large dendritic fields (75-206 microns 2) and mostly arborized in two or three laminae or in a diffuse fashion in the IPL. Class-3 cells had medium to large dendritic fields (72-200 microns 2) but sparse dendritic arborization. They only arborized in the proximal lamina of the IPL. Class-4 cells had large dendritic fields (273-626 microns 2) and branched in the most sclerad stratum of the IPL. No large differences in intraspecific soma size of the different RGC classes were detected (although interspecific soma size varied to a considerable degree) and no "giant" cells typically found in other vertebrate retinas were present. The results suggest that, with respect to the pattern of arborization and stratification of dendrites, lungless salamanders possess morphological classes of RGC similar to those found in frogs, but the morphology of RGCs in lungless salamanders seems to be simplified in comparison to frog RGCs. This simplification might be a consequence of paedomorphosis.