Fistula in ano in infants: who recurs?

Introduction  Fistula in ano is a common malady in infancy. However, relatively little literature is devoted to it. Our aim was to describe the natural history and identify predictors of which children will ultimately recur. Methods  A retrospective review of patients less than 3 years old undergoing anal fistulotomy was performed between May 2002 and November 2007 at a tertiary children’s hospital. Demographics, preoperative, operative, and postoperative characteristics were collected in each group and evaluated by biostatistical analysis. P values <0.05 were considered significant. Results  A total of 92 children undergoing anal fistulotomy were identified. The median age was 6 months. Twelve children (13%) had recurrences and two of the 12 had multiple recurrences. Children who had recurrences were older (12.9 vs. 7.5 months, P < 0.05) and were more likely to have a previous abscess (20 vs. 6%, P < 0.05). In addition, children with recurrences had pus noted at the time of surgery more than children who did not recur (23 vs. 8%, respectively, P < 0.05). There were no major complications. Conclusions  Fistula in ano in infants is a relatively benign process with most children having no serious sequelae. However, a not insignificant portion (13%) of children developed recurrences. Older children who developed fistulas were more likely to have a recurrence than younger, and children who had previous episodes of perianal abscess or pus noted at the time of surgery were more likely to recur.     

Mutations in TIMM50 cause severe mitochondrial dysfunction by targeting key aspects of mitochondrial physiology

3‐Methylglutaconic aciduria (3‐MGA‐uria) syndromes comprise a heterogeneous group of diseases associated with mitochondrial membrane defects. Whole‐exome sequencing identified compound heterozygous mutations in TIMM50 (c.[341 G>A];[805 G>A]) in a boy with West syndrome, optic atrophy, neutropenia, cardiomyopathy, Leigh syndrome, and persistent 3‐MGA‐uria. A comprehensive analysis of the mitochondrial function was performed in fibroblasts of the patient to elucidate the molecular basis of the disease. TIMM50 protein was severely reduced in the patient fibroblasts, regardless of the normal mRNA levels, suggesting that the mutated residues might be important for TIMM50 protein stability. Severe morphological defects and ultrastructural abnormalities with aberrant mitochondrial cristae organization in muscle and fibroblasts were found. The levels of fully assembled OXPHOS complexes and supercomplexes were strongly reduced in fibroblasts from this patient. High‐resolution respirometry demonstrated a significant reduction of the maximum respiratory capacity. A TIMM50‐deficient HEK293T cell line that we generated using CRISPR/Cas9 mimicked the respiratory defect observed in the patient fibroblasts; notably, this defect was rescued by transfection with a plasmid encoding the TIMM50 wild‐type protein. In summary, we demonstrated that TIMM50 deficiency causes a severe mitochondrial dysfunction by targeting key aspects of mitochondrial physiology, such as the maintenance of proper mitochondrial morphology, OXPHOS assembly, and mitochondrial respiratory capacity.     

Successful outcome with day 4 embryo transfer after preimplantation diagnosis for genetically transmitted diseases

Preimplantation genetic diagnosis was performed in 61 day 3 embryos obtained by in-vitro fertilization from seven patient carriers of haemophilia, Marfan's syndrome, Bloch-Sulzemberg syndrome (incontinentia pigmentosa) or X chromosome-linked immune deficiency, retinitis pigmentosa, and FG syndrome, which is characterized by mental retardation and hypotonia. After multiplex polymerase chain reaction, 16 embryos were diagnosed as being unaffected, and these were transferred to the uterus on the following day (day 4). Of these embryos, six (37.5%) implanted, resulting in the delivery of a singleton and a twin pregnancy, a late second trimester miscarriage (twins at week 20) and a first trimester miscarriage at week 8. All the diagnoses were confirmed by amniocentesis. We report for the first time a late day 4 transfer of biopsied human embryos undergoing preimplantation genetic diagnosis. This transfer schedule allows an extra day to perform genetic analyses on single blastomeres and to monitor any adverse effect of the biopsy procedure.      

Serum beta-lipoproteins following gynecologic surgery]

Authors have watched the changes of concentration of betalipoprotein after gynecological operations, on a large group of patients. The task of this work was to prove the existence of postcastration dyslipoproteinaemia, which had been proved in a smaller group by complex laboratory method. They have proved, using the Burstein's method, the development of dislipoproteinaemia in a larger number of vases after operation with bilateral ovarioectomy.     

Patients with reconstruction of craniofacial or intraoral defects: development of instruments to measure quality of life

Patients with reconstruction of craniofacial or intraoral defects experience a profound impact on their quality of life (QOL). This impact on QOL is influenced by the patients' medical conditions and the treatment interventions. Instruments to measure general QOL have been available for many years. A major criticism of QOL instruments is that too often the questions are not specific to the particular problems of a disease or condition. A search of the literature regarding QOL measurement for patients with maxillofacial implant-supported prostheses produced a short list of instruments, none of which were sufficiently developed or suited to the patients involved in reconstructive treatment. This study was designed to develop pretreatment and posttreatment questionnaires for measuring QOL for patients with reconstruction of a craniofacial defect and patients with reconstruction of loss of specific intraoral structures utilizing an implant-supported prosthesis (e.g., severe resorption of the maxilla or mandible or both). The goal was to develop brief, targeted instruments for this specific patient population. The produced instruments were sensitive and easy to administer and score, and no disruption of clinical care occurred with the administration of the questionnaires. The instruments were used with equal success both in face-to-face interviews and via mail.     

Increased baclofen-stimulated G protein coupling and deactivation in rat brain cortex during development

The number and affinity of GABA(B) receptors (assayed by the specific antagonist [(3)H]CGP54626A) was unchanged when compared in carefully washed cerebrocortical membranes from young (12-day-old) and adult (90-day-old) rats. In contrast, high-affinity GTPase activity, both basal and baclofen-stimulated was significantly higher (by 45% and 56%, respectively) in adult than in young rats. Similar results were obtained by concomitant determination of agonist (baclofen)-stimulated GTP gamma S binding. Under standard conditions, baclofen-stimulated GTPase activity was further considerably enhanced by exogenously added regulator of G protein function, RGS1, but not by RGS16. RGS16 was able to affect agonist-stimulated GTPase activity only in the presence of markedly increase substrate (GTP) concentrations. RGS1 alone slightly increased GTPase activity in adult rats, but neither RGS1 nor RGS16 influenced GTPase activity in membrane preparations isolated from young animals. These findings indicate increasing functional activity of trimeric G protein(s) involved in GABAergic transmission in the developing rat brain cortex and suggest a high potential of RGS1 in regulation of high-affinity GTPase activity.