Liver transplantation in familial amyloid polyneuropathy. Case report and review of the literature

A 59-year old male of German origin noticed exercise-independent cardiac arrhythmia two years before admission. An alanine 47 transthyretin variant of Familial Amyloid Polyneuropathy with hypertrophic cardiomyopathy, peripheral sensory-motor polyneuropathy, I, degree AV heart block was diagnosed. To diminish production and deposition of mutant transthyretin and to prevent disease progression orthotopic liver transplantation was performed. Prior to transplant the patient complained of inappetence. Postoperatively, he received a chemically defined enteral nutrition regime that was discontinued after 30 months until return of appetite and weight gain indicated marked improvement. However, a duodenal biopsy still demonstrated amyloid deposits 24 months after transplantation. Echocardiographic findings remained unchanged. Neurologic examination showed an improvement of sensory-motor polyneuropathy with regression of electromyographic changes. Only traces of variant transthyretin were detectable in plasma samples taken 12 months after the operation. During the 3 year follow-up, no additional symptoms have occurred and progression of amyloidosis was prevented. Currently, orthotopic liver transplantation is the only specific treatment to prevent progression of familial amyloid polyneuropathy.     

Age- and sex-related differences in nuclear lipid content and nucleoside triphosphatase activity in the JCR:LA-cp corpulent rat

The putative role of the nuclear nucleoside triphosphatase (NTPase) is to provide energy to the nuclear pore complex for poly A(+) mRNA export. Previous work has demonstrated that liver nuclear NTPase activity is greater in 6 month old corpulent (cp/cp) female JCR:LA rats, a hyperlipidemic rat model, compared to lean (+/?) animals. This increase appeared to be related to increases in nuclear membrane cholesterol content. The current study extended these initial data to compare NTPase activity as a function of age and sex in isolated JCR:LA-cp rat liver nuclei, to further test the hypothesis that nuclear membrane cholesterol may modulate NTPase activity. NTPase activity was increased in cp/cp female animals compared to +/? females at all ages studied, with Vmax values increased by 60-176%. Membrane integrity of cp/cp female nuclei was reduced compared to +/? female nuclei. Nuclear membrane cholesterol levels increased linearly with age by 50, 150 and 250% in 3, 6 and 9 month old cp/cp females over leans. In contrast, nuclei from cp/cp males exhibited only minor, isolated changes in NTPase activity. Furthermore, there were no significant changes in nuclear cholesterol content or membrane integrity in the less hyperlipidemic male animals at any age. These data suggest that altered lipid metabolism may lead to changes in nuclear membrane structure, which in turn may alter NTPase activity and functioning of the nuclear pore complex.     

When is a lifting movement too asymmetric to identify low-back loading by 2-D analysis?

In ergonomics research, two-dimensional (2-D) biomechanical models are often used to study the mechanical loading of the low back in lifting movements. When lifting movements are asymmetric, errors of unknown size may be introduced in a 2-D analysis. In the current study, an estimation of these errors was made by comparing the outcome of a 2-D analysis to the results of a recently developed and validated 3-D model. Four subjects made two repetitions of five lifting movements, differing in the amount of asymmetry. The results showed a significant underestimation of the peak torque by 20, 36 and 61% when the initial position of a box was rotated 30, 60 and 90 degrees with respect to the sagittal plane of the subject. The main cause of this underestimation was a pelvic twist, resulting in an erroneous projection of a pelvic marker on to the sagittal plane due to pelvic twist. It is suggested that from 30 degrees box rotation a 2-D analysis may easily lead to wrong conclusions when it is used to study asymmetric lifting.     

Altering conception of dairy cattle by gonadotropin-releasing hormone preceding luteolysis induced by prostaglandin F2 alpha

The objective of these experiments was to determine the effect on fertility of GnRH when used in conjunction with one or two injections of PGF2alpha. In Experiment 1, GnRH was administered 7 d before the second of two injections of PGF2alpha (14 d apart). The control group received two injections of PGF2alpha without GnRH. Conception was reduced from 63.5% for 74 controls to 48.7% for the 79 heifers and cows that had been treated with GnRH, but estrus detection and pregnancy rates were similar. In Experiment 2, 85 heifers and cows received GnRH at a random stage of the estrous cycle, followed in 7 d by PGF2alpha. Thirty to 32 h after PGF2alpha, a second dose of GnRH was given to induce ovulation of the preovulatory follicle, followed by one fixed-time insemination 18 to 19 h later (treatment designated as GnRH, PGF2alpha, and GnRH). Controls (n = 85) were given PGF2alpha and inseminated at estrus. Although conception rate was not different, one fixed-time insemination after the GnRH, PGF2alpha, and GnRH treatment tended (35.3%) to reduce fertility compared with effects of the control (47.1%). It is unclear how an injection of GnRH during the intervening week between two injections of PGF2alpha reduced fertility in Experiment 1. However, in Experiment 2, when GnRH was given 7 d before one injection of PGF2alpha and when ovulation was induced with a second GnRH injection, one fixed-time insemination seemed to produce acceptable fertility in dairy cows but probably less than that when inseminations were based on detected estrus.     

Increased formation of distinct F2 isoprostanes in hypercholesterolemia

BACKGROUND: F2 isoprostanes are stable, free radical-catalyzed products of arachidonic acid that reflect lipid peroxidation in vivo. METHODS AND RESULTS: Specific assays were developed by use of mass spectrometry for the F2 isoprostanes iPF2alpha-III and iPF2alpha-VI and arachidonic acid (AA). Urinary excretion of the 2 F2 isoprostanes was significantly increased in hypercholesterolemic patients, whereas substrate AA in urine did not differ between the groups. iPF2alpha-III (pmol/mmol creatinine) was elevated (P<0.0005) in homozygous familial hypercholesterolemic (HFH) patients (85+/-5. 5; n=38) compared with age- and sex-matched normocholesterolemic control subjects (58+/-4.2; n=38), as were levels of iPF2alpha-VI (281+/-22 versus 175+/-13; P<0.0005). Serum cholesterol correlated with urinary iPF2alpha-III (r=0.41; P<0.02) and iPF2alpha-VI (r=0. 39; P<0.03) in HFH patients. Urinary excretion of iPF2alpha-III (81+/-10 versus 59+/-4; P<0.05) and iPF2alpha-VI (195+/-18 versus 149+/-20; P<0.05) was also increased in moderately hypercholesterolemic subjects (n=24) compared with their controls. Urinary excretion of iPF2alpha-III and iPF2alpha-VI was correlated (r=0.57; P<0.0001; n=106). LDL iPF2alpha-III levels (ng/mg arachidonate) were elevated (P<0.01) in HFH patients (0.32+/-0.08) compared with controls (0.09+/-0.02). The concentrations of iPF2-III in LDL and urine were significantly correlated (r=0.42; P<0.05) in HFH patients. CONCLUSIONS: Asymptomatic patients with moderate and severe hypercholesterolemia have evidence of oxidant stress in vivo.