Successful pregnancies and fatherhood in familial amyloidotic polyneuropathy (FAP Val30Met) patients with liver transplantation

For familial amyloidotic polyneuropathy (FAP) patients, several problems regarding reproduction are present. For males, erectile dysfunction and retrograde ejaculation are well known complications of the disease In addition, the risk of transferring a fatal disease to their offspring is a matter of concern for the patients. For transplanted fertile patients, the risk of side effects of immunosupression therapy causing congenital malformations must be addressed, and for female patients the additional risk of complications during pregnancy and delivery is a case of concern. After delivery, the problem of breast-feeding arises. In the Swedish population of transplanted patients, five successful pregnancies, of which male FAP recipients fathered three, are reported. All patients were on stable immunosuppressive therapy with cyclosporine or tacrolimus and prednisolone. From our experience, successful fatherhood and pregnancy is possible for liver transplanted FAP patients, as it has been reported for patients transplanted for other medical reasons.     

Early liver transplantation improves familial amyloidotic polyneuropathy patients' survival

Since the first liver transplantation for familial amyloidotic polyneuropathy was performed in 1990, it has become an accepted treatment for this systemic amyloid disorder. Liver transplantation halts the production of the mutated amyloidogenic transthyretin, and thereby amyloid formation, and also progression of the majority of symptoms. Improvement in survival from onset of disease in transplanted patients compared to non-transplanted subjects has of yet not been demonstrated, partly because of the natural relatively slow progression of the disease with an expected median survival of 13 years.

In this retrospective study we compared the early initial series (n = 34) of transplantations, where severely malnourished patients were accepted, with a later series (n = 27) of transplants, as well as a control group (n = 19) consisting of non-transplanted patients.

For transplanted patients with an modified body mass index (mBMI) above 600 an improved survival was noted compared with that of non-transplanted historical controls. So far no difference in survival between the early and late series has been found.

Our previous recommendation of selection of patients primarily according to their nutritional status appears to be well justified, since it is now possible to demonstrate an increased survival for the transplanted group of patients with a preserved nutritional status (mBMI > 600) compared to the control group of non-transplanted patients.     

The relation of salivary cortisol to patterns of performance on a word list learning task in healthy older adults

A pattern of performance on a word list learning task known as a reduced primacy effect has been shown to be characteristic of Alzheimer's disease (AD) and can distinguish AD from depression. Deficits in memory and hippocampal atrophy seen in AD have been associated with hypercortisolism. The present study evaluated whether the reduced primacy effect is associated with elevated salivary cortisol in a sample of 40 healthy older community-dwelling adults participating in a study of memory and stress. We found that primacy, but not recency, was associated with higher salivary cortisol levels. In addition, participants who showed a reduced primacy had higher salivary cortisol levels than those with a normal serial position curve. Results suggest that there may be value to examining both serial position curves and changes to cortisol patterns over time as potential predictors of cognitive decline in healthy older adults.     

Dynamic changes of cognitive habituation and serotonin metabolism during the migraine interval

Migraine patients show a specific cognitive processing with a loss of habituation in the interval and a normal habituation in the attack as measured by event-related potentials (ERPs). It is unknown whether the loss of habituation changes during the migraine interval or is a stable state. Serotonin (5HT) metabolism is involved in the pathophysiology of migraine and also in the generation of ERPs. We enrolled 14 patients with regular migraine attacks in order to measure visually evoked ERPs repetitively during the migraine interval and in the migraine attack. Cognitive habituation was evaluated by analysis of P3 latency. Platelet serotonin content and free serotonin plasma level were measured at the same time points. The loss of habituation increased continuously during the migraine interval and abruptly normalized in the migraine attack (p < 0.05, time series analysis). The platelet 5HT content decreased significantly in the migraine attack (p < 0.03) and was at its maximum in the middle of the interval. The P3 latency was significantly increased in the attack (p < 0.01) and was significantly inversely correlated with the platelet 5HT content (r = -0.44, p < 0.001). Free 5HT plasma levels did not show any significant change. Our findings suggest that loss of cognitive habituation continuously increases during the migraine interval until its normalization in the migraine attack. This phenomenon cannot be attributed to serotonergic transmission. In patients with regular changes of cognitive habituation before the migraine attack, it might be possible to predict the attack by analysing ERPs.     

Local brain surface temperature compared to temperatures measured at standard extracranial monitoring sites during posterior fossa surgery

Mild hypothermia is assumed to protect against secondary brain injury. However, the accuracy of brain temperature estimation remains debatable if direct measurement in the target area is to be avoided or is impossible. Furthermore, intracerebral temperature gradients exist, especially under intraoperative conditions. We aimed to establish how brain surface temperatures (TBrain) relate to temperatures taken at standard sites in posterior fossa surgery. Ten patients undergoing cerebellopontine angle tumor removal were monitored for TBrain, esophageal temperature (TEso), bladder temperature (TBlad), ipsi- and contralateral tympanic membrane (TTymp-I, TTymp-C), and scalp temperatures (TScalp). During monitoring, TEso increased from 35.3+/-0.2 degrees C to 36.0+/-0.3 degrees C. After dura opening, TBrain was -0.14+/-0.1 degrees C below TEso. At the end of tumor removal, this difference increased to -0.43+/-0.31 degrees C (P < 0.05). TTymp-C was -0.29+/-0.18 degrees C below TBrain at dura opening. TTymp-C reflected the behavior of TEso adequately (r = 0.938), however, with a mean difference of -0.39+/-0.04 degrees C. In contrast, TTymp-I readings closely followed temperature changes in the area of surgery. TBlad reflected TEso except in periods of rapid temperature changes. In posterior fossa (PF) surgery, local TBrain is most accurately reflected by TEso. For clinical use TBlad and TTymp-C are also sufficient to assess brain surface temperature in the PF. Intraoperative surface cooling of the brainstem is less than the previously described cooling rate of exposed cerebral cortex.     

Long-term follow-up of living kidney donors: quality of life after donation

The University of Minnesota has been a strong advocate of living donor kidney transplants. The benefits for living donor recipients have been well documented. The relative low risk of physical complications during donation has also been well documented. Less well understood is the psychosocial risk to donors. Most published reports have indicated an improved sense of well-being and a boost in self-esteem for living kidney donors. However, there have been some reports of depression and disrupted family relationships after donation, even suicide after a recipient's death. To determine the quality of life of our donors, we sent a questionnaire to 979 who had donated a kidney between August 1, 1984, and December 31, 1996. Of the 60% who responded, the vast majority had an excellent quality of life. As a group, they scored higher than the national norm on the SF-36, a standardized quality of life health questionnaire. However, 4% were dissatisfied and regretted the decision to donate. Further, 4% found the experience extremely stressful and 8% very stressful. We used multivariate analysis to identify risk factors for this poor psychosocial outcome and found that relatives other than first degree (odds ratio=3.5, P=0.06) and donors whose recipient died within 1 year of transplant (odds ratio=3.3, P=0.014) were more likely to say they would not donate again if it were possible. Further, donors who had perioperative complications (odds ratio=3.5, P=0.007) and female donors (odds ratio=1.8, P=0.1) were more likely to find the overall experience more stressful. Overall, the results of this study are overwhelmingly positive and have encouraged us to continue living donor kidney transplants.     

Outcome of liver transplantation for transthyretin amyloidosis: follow-up of Japanese familial amyloidotic polyneuropathy patients

The majority of peripheral seventh cranial nerve palsy cases remain without an identified etiology and will eventually be diagnosed as idiopathic or Bell's palsy. Some features of this condition may be characteristic of a viral infection. Indeed, several herpes viruses have been implicated as potential causative pathogens. Besides varicella-zoster virus, shown to cause Bell's palsy under the Ramsay-Hunt syndrome, recent years have seen an increased interest and focus on the possible herpes simplex virus type 1 (HSV-1) etiology in idiopathic facial paralysis. We review the clinical, biological and virological basis for the potential herpetic cause of Bell's palsy and the rational for antiviral therapy in this condition.     

Variant transthyretin (TTR) amyloidosis in Argentina. Detection of the trait by electrospray ionization mass spectrometry of lyophilized TTR immunoprecipitate

We have developed a quick and reliable diagnostic method for detecting variant forms of transthyretin (TTR); namely, centrifugal concentration followed by electrospray ionization mass spectrometry (ESI-MS). Argentinian patients from three families with neuropathic amyloidosis and their relatives were screened for mutated TTR by ESI-MS. In order to facilitate transportation, we investigated the impact storage had on lyophilized anti-TTR-antibody precipitates' mass spectra. For this investigation, plasma samples from three Swedish patients with known TTR amyloidosis were analysed. We detected identical, additional peaks corresponding to a variant form of TTR in 10 members of the families, and also in a lyophilized sample sent unfrozen by mail from Argentina. All except one symptomatic subject had additional peaks, the exception having undergone a liver transplantation for the disease. All patients were early onset cases, i.e. below 35 years of age, and family history suggests an aggressive, rapidly progressing disease. Lyophilized anti-TTR-antibody precipitates stored at room temperature for 1 week exhibited only minor differences compared with plasma samples stored at -70 degrees C. In a new Argentinian study on familial amyloidotic polyneuropathy, the variant TTR was quickly identified and typed by ESI-MS. To facilitate transportation, dry-frozen samples can be used and the quality of the spectra is similar to that of samples stored at -70 degrees C.