Successful 18-h acellular extracorporeal perfusion and replantation of porcine limbs - Histology versus nerve stimulation

The current standard for composite tissue preservation is static cold storage (SCS) and is limited to 6 h until irreversible muscle damage occurs. Extracorporeal perfusion (ECP) is a promising technique for prolonged preservation, however, functional results have been scarcely researched. This article assessed neuromuscular function and compared results to histological alterations to predict muscle damage after ECP. Forelimbs of twelve Dutch landrace pigs were amputated and preserved by 4 h SCS at 4–6 °C (n = 6) or 18 h mid-thermic ECP with University of Wisconsin solution (n = 6). Limbs were replanted and observed for 12 h. Sham surgery was performed on contralateral forelimbs (n = 12). Histology analysis scored four subgroups representing different alterations (higher score equals more damage). Muscle contraction after median nerve stimulation was comparable between ECP, SCS, and sham limbs (P = 0.193). Histology scores were higher in ECP limbs compared to SCS limbs (4.8 vs. 1.5, P = 0.013). This was mainly based on more oedema in these limbs. In-vivo muscle contraction was well preserved after 18 h ECP compared to short SCS, although histology seemed inferior in this group. Histology, therefore, did not correlate to muscle function at 12 h after replantation. This leads to the question whether histology or neuromuscular function is the best predictor for transplant success.     

Joint Nordic prospective study on human herpesvirus 8 and multiple myeloma risk

An association between human herpesvirus 8 (HHV8) and multiple myeloma (MM) has been reported, though most studies have not confirmed such association. To follow-up on a previous prospective seroepidemiological study, where HHV8 tended to associate with MM risk, we linked five large serum banks in the Nordic countries with the Nordic cancer registries and 329 prospectively occurring cases of MM were identified, together with 1631 control subjects matched by age and gender. The HHV8 seroprevalences among cases and controls were similar (12 and 15%, respectively) and HHV8 seropositivity did not associate with the risk of MM, neither when considering positivity for lytic antibodies (relative risk (RR) = 0.8, 95% confidence interval (CI) = 0.5-1.1) nor for latent antibodies (RR = 0.6, 95% CI = 0.1-2.7). Similar risks were seen when analysis was restricted to case-control sets with at least 2 years lag before diagnosis (RR = 0.8, 95% CI = 0.5-1.2 and RR = 0.9, 95% CI = 0.1-4.2). In conclusion, the data indicate that HHV8 infection is not associated with MM.     

Humoral immunity induced by a live Francisella tularensis vaccine. Complement fixing antibodies determined by an enzyme-linked immunosorbent assay (CF-ELISA)

A complement-fixing enzyme-linked immunosorbent assay (CF-ELISA) with bacterial sonicate as the antigen, human AB serum as the source of complement and alkaline-phosphatase-labelled anti-(human C3e) as the conjugate was developed for detecting antibodies to Francisella tularensis. Humoral responses after inoculation with a live attenuated tularemia vaccine were studied in 13 subjects by this method. Twelve responded with CF antibodies, which in most cases appeared 4 weeks after vaccination, the response time varying from 1 week to 2 months. The highest individual CF titres, of 140–9990, were reached 1–4 months after vaccination (average 2.4 months). The CF titres tended to decrease with time, and at 10 months two of the 12 subjects with an earlier CF positive response were negative again. CF antibodies were nevertheless still detectable in all three subjects studied 1.5 years after vaccination.     

Effects of smoking and stopping smoking on serum high-density lipoprotein cholesterol levels in a representative population sample

Serum high-density lipoprotein (HDL) cholesterol levels were assessed in a random sample of 939 men and 853 women ages 14-65 years in eastern Finland. Amount of daily smoking measured by serum thiocyanate concentration was negatively and independently associated with serum HDL cholesterol level and HDL/total cholesterol ratio in men. This negative association seemed largely to be due to low HDL cholesterol levels in heavy smokers. Both male and female current smokers had lower HDL cholesterol levels and HDL/total cholesterol ratios than those who had never smoked. This difference was found even after adjustment for age, body mass index, and beer drinking. The reduction of HDL cholesterol level seemed to be reversible, because those who had recently stopped smoking had higher HDL cholesterol levels and higher HDL/total cholesterol ratios than current smokers.     

Apolipoprotein E ε4 allele frequency is increased in Parkinson’s disease only with co-existing Alzheimer pathology

We determined the apolipoprotein E (apoE) genotype in clinically diagnosed and neuropathologically verified cases of Parkinson’s disease (PD) (n = 45), with or without Alzheimer (AD)-type changes, and compared the apoE genotype with that in healthy age-matched controls (n = 59). The PD cases were divided into two groups according to the CERAD criteria: “O + A”, with no or only uncertain histological findings of AD, and “B + C” with histological findings suggestive or indicative of AD. DNA was isolated from frozen brain samples, and the apoE genotypes were determined using polymerase chain reaction amplification and subsequent restriction analysis by HhaI enzyme. The frequency of the apoɛ4 allele (29.4%) was significantly increased in the B + C group. The odds ratio for an apoɛ4 allele in the B + C group was 2.5 as compared to controls (95% confidence interval, 1.2–5.2). In the 0 + A group, the frequency of apoɛ4 allele (13.6%) was similar to that in controls (14.4%) and the risk of an apoɛ4 allele was not increased (odds ratio 0.94). The PD cases with an apoɛ4 allele had a greater number of cortical (P = 0.02) but not nigral Lewy bodies than those without an apoɛ4 allele (P = 0.57). The results show that neuropathologically verified PD as such is not associated with increased apoɛ4 allele frequency. Received: 15 January 1998 / Revised, accepted: 24 March 1998     

Past incidence and future demand for knee arthroplasty in Sweden: A report from the Swedish Knee Arthroplasty Register regarding the effect of past and future population changes on the number of arthroplasties performed

By combining data from the Swedish Knee Arthroplasty Register and Swedish census registers we have calculated the past age-specific incidence of primary knee arthroplasties and predicted the demand. During the last 20 years, osteoarthrosis has accounted for the largest increase in number of knee arthroplasties while operations for rheumatoid arthritis remained constant. The mean yearly number of operations between the periods 1976-1980 and 1996-1997 increased more than five-fold, while only 6% of that increase could be explained by changes in the age-profile of the population. Most operations were performed on persons of 65 years and older who also had the largest increase in incidence. By using the incidences for 1996 and 1997 and taking into account the expected future changes in the age profile of the Swedish population, we estimate that, in the absence of an effective preventive treatment, the number of knee arthroplasties will increase by at least one third until 2030.     

Human leucocyte antigen and TNFalpha polymorphism association in microscopic colitis

OBJECTIVES: Coeliac disease (CD) is common in patients with microscopic colitis (MC). The human leucocyte antigen (HLA)-DR3-DQ2 haplotype is strongly associated with CD, and there is evidence for an association with MC. We analysed the genetic background of MC by assessing the haplotypes of HLA-DR3-DQ2 and HLA-DR4-DQ8. In addition, TNFalpha gene polymorphism (-308) associated with susceptibility to several autoimmune diseases was studied. METHODS: Eighty patients with MC including 29 with collagenous colitis (CC) and 51 with lymphocytic colitis (LC) were typed for HLA-DR3-DQ2, and HLA-DR4-DQ8 molecule encoding genes using either an allele-specific PCR, or hybridization with sequence-specific oligonucleotides. Duodenal biopsies (N=78) confirmed the diagnosis of CD in 15 (18.8%) patients. TNFalpha(308) alleles were analyzed in 78 patients with MC (27 with CC and 51 with LC). A control group of 3627 patients was used in the HLA study and 178 patients in the TNFalpha study. RESULTS: HLA-DR3-DQ2 haplotype was more frequent in patients with MC (43.8%) including both subgroups (LC, 44.8%; CC, 43.1%; P<0.001), and MC with CD (86.7%; P<0.001) and without CD (33.3%; P=0.003), compared with the controls (18.1%). Similarly, the TNF2 carrier rate was higher in MC (46.2%; P<0.001) including both CC (44.4%; P=0.031) and LC (47.1%; P=0.001), and both MC patients with CD (66.7%; P=0.001) and without CD (39.3%; P=0.019), compared with the controls (23%). CONCLUSION: Both CC and LC are associated with the HLA-DR3-DQ2 haplotype and with TNF2 allele carriage. These associations are present also in MC patients without CD. The shared predisposing HLA-DR3-DQ2 haplotype and the high prevalence of CD in patients with MC suggest an epidemiological overlap, and probably some similarities in the pathogenesis of CD and MC.