Immunological parameters in girls with Turner syndrome

Disturbances in the immune system has been described in Turner syndrome, with an association to low levels of IgG and IgM and decreased levels of T- and B-lymphocytes. Also different autoimmune diseases have been connected to Turner syndrome (45, X), thyroiditis being the most common.     

A point mutation in the 5' splice site of the dystrophin gene first intron responsible for X-linked dilated cardiomyopathy

X-linked dilated cardiomyopathy (XLDC) is a familial heart disease presenting in young males as a rapidly progressive congestive heart failure, without clinical signs of skeletal myopathy. This condition has recently been linked to the dystrophin gene in some families and deletions encompassing the genomic region coding for the first muscle exon have been detected. In order to identify the defect responsible for this disease at the molecular level and to understand the reasons for the selective heart involvement, a family with a severe form of XLDC was studied. In the affected members, no deletions of the dystrophin gene were observed. Analysis of the muscle promoter, first exon and intron regions revealed the presence of a single point mutation at the first exon-intron boundary, inactivating the universally conserved 5' splice site consensus sequence of the first intron. This mutation introduced a new restriction site for MseI, which cosegregates with the disease in the analyzed family. Expression of the major dystrophin mRNA isoforms (from the muscle-, brain- and Purkinje cell-promoters) was completely abolished in the myocardium, while the brain- and Purkinje cell- (but not the muscle-) isoforms were detectable in the skeletal muscle. Immunocytochemical studies with anti- dystrophin antibodies showed that the protein was reduced in quantity but normally distributed in the skeletal muscle, while it was undetectable in the cardiac muscle. These findings indicate that expression of the muscle dystrophin isoform is critical for myocardial function and suggest that selective heart involvement in dystrophin- linked dilated cardiomyopathy is related to the absence, in the heart, of a compensatory expression of dystrophin from alternative promoters.      

Electron microscopy of the canine corneal basement membranes

The purpose of this study was to characterize the surface topographical features of the epithelial and endothelial (Descemet's) basement membranes of the canine cornea. Corneas were obtained from young, healthy dogs (<2 years old) with no history or evidence of previous ocular disease. The epithelium and endothelium was carefully removed preserving the anterior and posterior basement membranes. The specimens were examined by transmission electron microscopy and scanning electron microscopy. The epithelial and endothelial basement membrane surface topography is an intricate meshwork of pores and fibers measuring in the nanometer size range. The features of the endothelial basement membrane overall are smaller in size than the epithelial basement membrane. These surface topographical features may incite changes in epithelial and endothelial cell behavior.     

Functional analysis of human MLH1 and MSH2 missense variants and hybrid human-yeast MLH1 proteins in Saccharomyces cerevisiae

Hereditary non-polyposis colorectal cancer (HNPCC) is an autosomal dominant inherited disease caused by defects in the process of DNA mismatch repair (MMR), and mutations in the hMLH1 or hMSH2 genes are responsible for the majority of HNPCC. In addition to clear loss-of-function mutations conferred by nonsense or frameshift alterations in the coding sequence or by splice variants, genetic screening has revealed a large number of missense codons with less obvious functional consequences. The ability to discriminate between a loss-of-function mutation and a silent polymorphism is important for genetic testing for inherited diseases like HNPCC where the opportunity exists for early diagnosis and preventive intervention. In this study, quantitative in vivo DNA MMR assays in the yeast Saccharomyces cerevisiae were performed to determine the functional significance of amino acid replacements observed in the human population. Missense codons previously observed in human genes were introduced at the homologous residue in the yeast MLH1 or MSH2 genes. This study also demonstrated feasibility of constructing genes that encode functional hybrid human-yeast MLH1 proteins. Three classes of missense codons were found: (i) complete loss of function, i.e. mutations; (ii) variants indistinguishable from wild-type protein, i.e. silent polymorphisms; and (iii) functional variants which support MMR at reduced efficiency, i.e. efficiency polymorphisms. There was a good correlation between the functional results in yeast and available human clinical data regarding penetrance of the missense codon. The results reported here raise the intriguing possibility that differences in the efficiency of DNA MMR exist between individuals in the human population due to common polymorphisms.     

Opiate withdrawal and electro-stimulation. Double blind experiments

A rapid detoxification technique for heroin addicts is described. The technique uses an impulsional electric current developed by Limoge. The treatment is nonaggressive, very well tolerated by the addicts and leads to a good psychotherapeutic relationship with the medical staff. A successful physical detoxification is achieved in more than 80% of the cases (this figure is based on 400 patients treated by the method). The technique was subjected to two double-blind experiments. The first experiment tested the real efficacity of the electrical stimulation. The difference between the group of subjects stimulated and the unstimulated control group had a "p-value" which was significant at the 0,5% level. This leads us to believe that the electrical stimulation has a real positive effect. The second experiment reconfirmed the efficacity of the stimulation and showed that 24 hour continuous stimulation was not sufficient to produce a lasting effect. After about 50 hours stimulation a Naloxone test produced little or no reaction in the patients.     

Preoperative transhepatic biliary decompression in pancreatic and periampullary cancer

Pancreatic resection for pancreatic and periampullary cancer between 1969 and 1975 at The Ohio State University Hospitals had an associated operative mortality rate of 30% and a morbidity rate of 80%. Transhepatic biliary decompression (THD) has been accepted as a method of preoperative risk reduction in the deeply jaundiced patient and an alternative to surgical biliary decompression. The use of preoperative THD in pancreatic and periampullary cancer was examined. Of 44 patients with bilirubin greater than 10 mg/100 ml, 17 had radical resection (THD=7, no THD=10), and 27 had palliative operation (THD=17, no THD=10). Preoperative serum bilirubin in the THD group was 7.3±1.0 compared to 16.3 ±1.5 in the no THD group (p < 0.05). Operative morbidity rate was: radical surgery: THD (40%), no THD (70%); palliative surgery: THD (18%), no THD (20%). Operative mortality rate was: radical surgery: THD (28%), no THD (60%); palliative surgery: THD (6%), no THD (0%). Catheter-related complications were minimal. Preoperative THD tends to reduce the risk of curative resection for pancreatic and periampullary cancer, but does not alter the outcome of palliative surgery. Long-term THD may be an alternative if palliative surgical biliary decompression either fails or is not technically possible in the patient with unresectable cancer.

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Resumen Se ha agudizado el debate relativo al papel de la resección curativa en el tratamiento del carcinoma pancreático y periampular. Mucha de la discusión se deriva de la excesiva morbilidad y mortalidad de la pancreatoduodenectomía y de la pancreatectomía total. Las cifras sobrepasan el porcentaje de supervivencia a 5 anos en todas las series mayores, y en algunos reportes la mortalidad operatoria es igual o mayor que el porcentaje de pacientes que sobreviven un año.La resección pancreática para cáncer pancreático y periampular entre los años 1969 y 1975 en los Hospitales de la Universidad del Estado de Ohio estuvo asociada con una mortalidad de 30% y una morbilidad de 80%. La descompresión biliar transhepática (DBT) ha sido aceptada como un método de reducción preoperatoria del riesgo quirúrgico en los pacientes intensamente ictéricos y como una alternativa a la descompresión biliar quirúrgica. El uso de la DBT preoperatoria en el cancer pancreático y periampular fué analizado. De 44 pacientes con bilirrubina mayor de 10 mg/100 ml, 17 fueron sometidos a resección radical (DBT = 7, no DBT = 10), y 27 tuvieron una operación paliativa (DBT = 17, no DBT = 10). La bilirrubina sérica en el grupo con DBT fué de 7.3±1.0, comparada con 16.3±1.5 en el grupo sin DBT (p < 0.05). La siguiente fué la morbilidad operatoria: cirugía radical: DBT 40%, no DBT 70%; cirugía paliativa: DBT 18%, no DBT 20%. La siguiente fué la mortalidad operatoria: cirugía radical: DPT 28%, no DPT 60%; cirugía paliativa: DBT 6%, no DBT 0. La DBT preoperatoria tiende a reducir el riesgo de la resección curativa para cáncer pancreático y periampular, pero no modiflca el resultado de la cirugía paliativa. La DBT prolongada puede ser una alternativa si la descompresión biliar quirúrgica falla o no es técnicamente posible en el paciente con cáncer no resecable.

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Résumé La résection pancréatique pour cancer périampullaire ou pour cancer du pancréas entre 1969 et 1975 à Ohio State University Hospital accuse une mortalité opératoire de 30% et une morbidité de 80%. Le drainage biliaire transhépatique (transhepatic biliary decompression: T.H.D.), en présence de ces résultats, a été employé à titre pré-opératoire pour diminuer les risques de l'intervention chez les malades très ictériques et comme alternative au drainage biliaire chirurgical.Chez 44 malades qui présentaient un taux de bilirubine supérieur à 10 mg/dl, 17 ont subi une exérèse (7 après drainage transhépatique, 10 sans drainage transhépatique), 27 ont été traités par une intervention palliative (17 après drainage, 10 sans drainage). Le taux de bilirubine pré-opératoire fut ramené à 7.3±10 chez les malades drainés alors qu'il atteignait 16.3± 1.5 chez les malades qui n'avaient pas subi de drainage préalable.La morbidité opératoire fut en cas de chirurgie radicale de 40% après drainage et de 70% en l'absence de drainage; en cas de chirurgie palliative elle fut de 18% après drainage et de 20% en l'absence de drainage. La mortalité opératoire fut en cas de chirurgie radicale de 28% après drainage et de 60% en l'absence de drainage; en cas de chirurgie palliative elle fut de 6% après drainage et de 0% en l'absence de drainage. Les complications du drainage sont très rares. En un mot le drainage biliaire pré-opératoire réduit les risques de l'exérèse des cancers pancréatiques et des cancers périampullaire mais elle est sans influence en cas d'intervention palliative. Le drainage biliaire transhépatique prolongé offre une alternative au drainage chirurgical lorsque celui-ci échoue ou quand le cancer ne peut être réséqué.

     

UK food and nutrition security during and after the COVID‐19 pandemic

The COVID‐19 pandemic is a major shock to society in terms of health and economy that is affecting both UK and global food and nutrition security. It is adding to the ‘perfect storm’ of threats to society from climate change, biodiversity loss and ecosystem degradation, at a time of considerable change, rising nationalism and breakdown in international collaboration. In the UK, the situation is further complicated due to Brexit. The UK COVID‐19 Food and Nutrition Security project, lasting one year, is funded by the Economic and Social Research Council and is assessing the ongoing impact of COVID‐19 on the four pillars of food and nutrition security: access, availability, utilisation and stability. It examines the food system, how it is responding, and potential knock on effects on the UK’s food and nutrition security, both in terms of the cascading risks from the pandemic and other threats. The study provides an opportunity to place the initial lessons being learnt from the on‐going responses to the pandemic in respect of food and nutrition security in the context of other long‐term challenges such as climate change and biodiversity loss.     

The effect of lengthening the gastrocnemius muscle in chronic therapy resistant plantar fasciitis

BackgroundThe aetiology of chronic therapy resistant plantar fasciitis (CTRPF) is multifactorial with more focus in recent times on the gastroc-soleus complex. This study evaluates the effect of lengthening the gastrocnemius muscle in CTRPF.MethodsAll patients with CRTPF complaints for at least one year underwent the same standard conservative treatment prior to surgery. 32 patients failed this treatment and underwent gastrocnemius recession. Silfverskiöld test, questionnaires and plantar pressure measurements were obtained at 5 visits.ResultsOne year follow up showed a significantly increase in dorsiflexion of the ankle (16 degrees), a decrease in VAS; 78 (SD: 19) to 20 (SD: 24) and significant improved functional scores. Plantar pressure measurements showed an increase of pressure under the medial proximal part of the midfoot and the 1 st metatarsal and a decrease under the hallux.ConclusionsA gastrocnemius recession results in a significant gain in dorsiflexion, altered loading of the foot and good clinical outcome in patients with CTRPF.Level of EvidenceLevel 2