Trials have reported clinical improvement and reduced need for amputation in critical limb ischemia (CLI) patients receiving therapeutic angiogenesis with stem cells. Our objective was to test peripheral stem cell therapy efficacy and safety to gain experiences for further work.
We included nine CLI patients (mean age 76.7 ±9.7). Stem cells were mobilized to the peripheral blood by administration of G-CSF (Filgrastim) for 4 days, and were collected on day five, when 30 mL of a stem cell suspension was injected into 40 points of the limb. The clinical efficacy was evaluated by assessing pain relief, wound healing and changes in ankle-brachial pressure index (ABI). Local metabolic and inflammatory changes were measured with microdialysis, growth factors and cytokine level determination. Patients were followed for 24 weeks.
Four patients experienced some degree of improvement with pain relief and/or improved wound healing and ABI increase. One patient was lost to follow up due to chronic psychiatric illness; one was amputated after two weeks. Two patients had a myocardial infarction (MI), one died. One patient died from a massive mesenteric thrombosis after two weeks and one died from heart failure at week 11. Improved patients showed variable effects in cytokine-, growth factor- and local metabolic response.
Even with some improvement in four patients, severe complications in four out of nine patients, and two in relation to the bone marrow stimulation, made us terminate the study prematurely. We conclude that with the increased risk and the reduced potential of the treatment, peripheral blood stem cell treatment in the older age group is less appropriate. Metabolic and inflammatory response may be of value to gain insight into mechanisms and possibly to evaluate effects of therapeutic angiogenesis.
The aim of this study was to assess the influence of social environmental factors on school performance and behavioural problems among 14-year-old children who had been exposed to amphetamine during foetal life. The study group comprised a cohort of 65 children who had suffered intrauterine exposure to amphetamine due to maternal drug abuse. This group has been followed since birth and examined at regular intervals. Information regarding the academic performance of the children was gathered from the school authorities. The psychosocial environment of the children was determined through interviews and through information obtained from the social authorities. Of the 64 children who attended a school within the state school system, 10 (15%) were a year behind for their age. The mean grades were significantly lower than those of their classmates. Behavioural problems were mentioned in the social authority documentation of one-third of the children, regardless of whether the child was placed in a foster home or was residing with the biological mother. A positive significant correlation was found between maternal age and the outcome of the children, as well as between therapy during pregnancy and outcome, whilst several environmental factors, particularly during the child's first four years, correlate negatively to outcome. Psychosocial factors early in life influence the outcome at 14 years. The positive effect of intervention during pregnancy illustrates the importance of early identification preferable during pregnancy.
Sixty-five children born to women who all abused amphetamine during pregnancy have been followed prospectively since their birth in 1976-77. At the age of 14-15 years, information about growth and school achievement was collected from school records. For comparison of school achievements the means of schoolmates were used, and for growth a group of Stockholm children born in the same year. By the age of 14 years only 14 children (22%) had stayed with their biological mothers for the whole period since birth. In the eighth grade, 10 (15%) were one grade lower than indicated by their biological age. The norm for Sweden is less than 5%. The means of the points in mathematics, Swedish language and sports were statistically below those of their classmates. At the age of 10 years the girls were significantly shorter and lighter than their peers born in 1976. At the age of 14 years the boys were statistically taller and heavier than their peers. It can be concluded that maternal amphetamine abuse during pregnancy will influence children at lest up to the age of 14-15 years even though many of them have been living in foster homes since a young age.
In two counties of Sweden, Gotland and Umeå, lower leg or thigh amputations were performed during 1971-1980 in 111 and 71 diabetic patients, respectively. These figures correspond to 20.5 and 6.5 per 100 000 inhabitants and year, respectively. The corresponding incidence for Umeå city and the rural area surrounding Umeå was 3.1 and 13.8/100 000 inhabitants and year, respectively. The lower frequency of amputations in Umeå was probably the consequence of a restricted period of systematic search for early signs of gangrene, as a part of a research program, but other factors could also be of importance and these are discussed. The death rate of the patients was high in both series, after 2 years only about one third of the patients were still alive.
Two clinical series (n = 96 + 90) and one record-linkage study (n = 492) were used for estimation of the health care utilization for the treatment of BPH patients, mainly by TURP, in Sweden during one year before and 5-7 years after surgery. The total cost for a single patient amounted to ca. 33000 SEK in 1900 prices (5850 USD). Costs for surgery dominated and for a TURP amounted to about 70% of the Total. The costs during one year preoperatively and 5 years postoperatively each amounted to 15% of the total costs. In the present study the outcome of surgery was similar to other reports from the same period. The surgical mortality was 0.4% and the readmission rate because of complications of surgery or manifestations of BPH was 25% after 7 years of observation. Of the patients 11% were reoperated on within 7 years. When transurethral resection of the prostate (TURP) replaced open surgery in Sweden during the 1970's it had several of the attributes of the new methods introduced for treatment of benign prostate hyperplasia (BPH) currently in use. However, the spread of TURP resulted in wider indications for surgery and an increase in the total number of surgical procedures. An important argument for the adoption of the new, less invasive methods for treatment of BPH is the lower cost. To make a fair comparison of the costs of different methods for treatment of BPH the long-term costs have to be included in the calculation.
To study the association between the ankle-brachial pressure index (ABPI), premature death and the need for surgical treatment for lower limb ischaemia.
Population based cohort study.
Three hundred and fifty-three men and women, 50-89 years old, underwent a leg pain questionnaire and measurement of ABPI and was then followed for 10 years.
All cause mortality, vascular procedures and major amputations.
A low ABPI was independently associated with premature all cause mortality in the multiple regression analysis, carrying a relative risk of 3.4 (95% confidence interval 2.0-5.9) and 2.1 (1.3-3.3) for ABPIs or=1.0. Individuals with an ABPI in the interval 0.81-0.99 suffered only a slight, not statistically significant risk increase compared to normals. A low ABPI at baseline implied a continuous constant increased risk of death throughout the study period. The same risk was observed among elderly (70-89, median 77 years), and in the middle aged (50-69, median 63 years) individuals. The vast majority of those subjected to vascular intervention or major amputation during follow-up had an ABPI
The two North Atlantic eel species, the European eel (Anguilla anguilla) and the American eel (Anguilla rostrata), spawn in partial sympatry in the Sargasso Sea, providing ample opportunity to interbreed. In this study, we used a RAD (Restriction site Associated DNA) sequencing approach to identify species-specific diagnostic single-nucleotide polymorphisms (SNPs) and design a low-density array that combined with screening of a diagnostic mitochondrial DNA marker. Eels from Iceland (N=159) and from the neighboring Faroe Islands (N=29) were genotyped, along with 94 larvae (49 European and 45 American eel) collected in the Sargasso Sea. Our SNP survey showed that the majority of Icelandic eels are pure European eels but there is also an important contribution of individuals of admixed ancestry (10.7%). Although most of the hybrids were identified as F1 hybrids from European eel female × American eel male crosses, backcrosses were also detected, including a first-generation backcross (F1 hybrid × pure European eel) and three individuals identified as second-generation backcrosses originating from American eel × F1 hybrid backcrosses interbreeding with pure European eels. In comparison, no hybrids were observed in the Faroe Islands, the closest bodies of land to Iceland. It is possible that hybrids show an intermediate migratory behaviour between the two parental species that ultimately brings hybrid larvae to the shores of Iceland, situated roughly halfway between the Sargasso Sea and Europe. Only two hybrids were observed among Sargasso Sea larvae, both backcrosses, but no F1 hybrids, that points to temporal variation in the occurrence of hybridization.
Elucidating barriers to gene flow is important for understanding the dynamics of speciation. Here we investigate pre- and post-zygotic mechanisms acting between the two hybridizing species of Atlantic eels: Anguilla anguilla and A. rostrata. Temporally varying hybridization was examined by analyzing 85 species-diagnostic single-nucleotide polymorphisms (SNPs; FST ?0.95) in eel larvae sampled in the spawning region in the Sargasso Sea in 2007 (N=92) and 2014 (N=460). We further investigated whether genotypes at these SNPs were nonrandomly distributed in post-F1 hybrids, indicating selection. Finally, we sequenced the mitochondrial ATP6 and nuclear ATP5c1 genes in 19 hybrids, identified using SNP and restriction site associated DNA (RAD) sequencing data, to test a previously proposed hypothesis of cytonuclear incompatibility leading to adenosine triphosphate (ATP) synthase dysfunction and selection against hybrids. No F1 hybrids but only later backcrosses were observed in the Sargasso Sea in 2007 and 2014. This suggests that interbreeding between the two species only occurs in some years, possibly controlled by environmental conditions at the spawning grounds, or that interbreeding has diminished through time as a result of a declining number of spawners. Moreover, potential selection was found at the nuclear and the cytonuclear levels. Nonetheless, one glass eel individual showed a mismatch, involving an American ATP6 haplotype and European ATP5c1 alleles. This contradicted the presence of cytonuclear incompatibility but may be explained by that (1) cytonuclear incompatibility is incomplete, (2) selection acts at a later life stage or (3) other genes are important for protein function. In total, the study demonstrates the utility of genomic data when examining pre- and post-zyotic barriers in natural hybrids.
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