Neonatal islet cell transplantation in the diabetic rat: effect on hepatic enzyme activity and glucose homeostasis.

Intraperitoneal transplantation of collagenase-digested, isogeneic, neonatal rat pancreatic tissue successfully reversed streptozotocin-induced diabetes in 77% of recipients. The low serum immunoreactive insulin, hyperglycaemia, glycosuria and weight loss, characteristic of the diabetic animal, were corrected and the reduced activities of hepatic glucokinase and pyruvate kinase, and the low glycogen concentration of the liver of diabetic rats were restored to normal. Forty-three per cent of the successfully transplanted rats became normoglycaemic within 1 month of transplantation whereas 57% took from 1 to 6 months to achieve normoglycaemia and displayed a mild glucose intolerance when subjected to a glucose load. The rats which had not become normoglycaemic 6 months after transplantation showed some amelioration of the diabetic state, as shown by increased serum immunoreactive insulin and hepatic glycogen concentration and a slow weight gain compared with diabetic controls.     

Overdentures on primary mandibular implants in patients with oral cancer: a follow-up study over 14 years

We aimed to assess oral functioning, patients’ satisfaction, condition of peri-implant tissues, and survival of implants up to 14 years after their insertion in patients with oral cancer who had had mandibular overdentures placed over primary implants. Endosseous dental implants were inserted prospectively in the interforaminal region of the mandible during resection of the tumour in 164/180 patients with oral cancer. All 58 patients were evaluated by questionnaires and clinical assessments during a final assessment in 2012. Implant-retained mandibular overdentures were inserted, and prosthetic rehabilitation and oral functioning were not associated with primary site or stage of the tumour, number or type of implants inserted, or the type of reconstruction. Over time the peri-implant mucosa was usually free of inflammation. More implants were lost in patients treated by radiotherapy (27/318, 8.5%) than in those not so treated (1/206, 0.5%). Patients who had been treated by irradiation reported more problems in oral functioning and less satisfaction than those who had not. Patients with an implant-retained mandibular overdenture reported fewer problems in oral functioning than patients without an overdenture.     

Post-translational polymodification of b1-tubulin regulates motor protein localization in platelet production and function

In specialized cells, the expression of specific tubulin isoforms and their subsequent post-translational modifications drive and coordinate unique morphologies and behaviors. The mechanisms by which b1-tubulin, the platelet and megakaryocyte (MK) lineage restricted tubulin isoform, drives platelet production and function remains poorly understood. We investigated the roles of two key post-translational tubulin polymodifications (polyglutamylation and polyglycylation) on these processes using a cohort of thrombocytopenic patients, human induced pluripotent stem cell derived MK, and healthy human donor platelets. We find distinct patterns of polymodification in MK and platelets, mediated by the antagonistic activities of the cell specific expression of tubulin tyrosine ligase like enzymes and cytosolic carboxypeptidase enzymes. The resulting microtubule patterning spatially regulates motor proteins to drive proplatelet formation in megakaryocytes, and the cytoskeletal reorganization required for thrombus formation. This work is the first to show a reversible system of polymodification by which different cell specific functions are achieved.     

Past,Present and Future of Home video-electroencephalographic telemetry: A review of the development of in-home video-electroencephalographic recordings

Video-electroencephalographic (EEG) monitoring is an essential tool in epileptology, conventionally carried out in a hospital epilepsy monitoring unit. Due to high costs and long waiting times for hospital admission, coupled with technological advances, several centers have developed and implemented video-EEG monitoring in the patient's home (home video-EEG telemetry [HVET]). Here, we review the history and current status of three general approaches to HVET: (1) supervised HVET, which entails setting up video-EEG in the patient's home with daily visiting technologist support; (2) mobile HVET (also termed ambulatory video-EEG), which entails attaching electrodes in a health care facility, supplying the patient and carers with the hardware and instructions, and then asking the patient and carer to set up recording at home without technologist support; and (3) cloud-based HVET, which adds to either of the previous models continuous streaming of video-EEG from the home to the health care provider, with the option to review data in near real time, troubleshoot hardware remotely, and interact remotely with the patient. Our experience shows that HVET can be highly cost-effective and is well received by patients. We note limitations related to long-term electrode attachment and correct camera placing while the patient is unsupervised at home, and concerns related to regulations regarding data privacy for cloud services. We believe that HVET opens significant new opportunities for research, especially in the field of understanding the many influences in seizure occurrence. We speculate that in the future HVET may merge into innovative new multisensor approaches to continuously monitoring people with epilepsy.     

Queensland Paediatric Cardiac Service: Lessons from evolution to a unified service in a tertiary children's hospital

We describe a complex change process for the paediatric cardiac service in Queensland that involved transitioning the service out of an essentially adult hospital into one of two children's hospitals in Brisbane. This initial step was complex as the governance was changed from Queensland Health to Mater Health, an independent faith‐based organisation who became the new employer. Six years later, the service was again transitioned; this time to the newly constructed Queensland Children's Hospital, with a Hospital and Health Services Board as the employer under the aegis of Queensland Health. This was a complex journey. As with all change processes there was resistance to change on the part of some individuals. Five years on from the second major change, the service is settled, has an excellent workplace culture, has excellent clinical outcomes and has become research intensive.     

Proton beam therapy: a promising method of locoregional cancer control

Proton beams offer superior characteristics for clinical radiation therapy, including the capability to localize precisely the dose to the desired target volume. Such precision enables the radiation therapist to give higher doses to the tumor while avoiding intolerable doses to adjacent normal tissues. Locoregional control is thus increased, and treatment morbidity and side effects are decreased. When it opens in late spring 1990, Loma Linda University Medical Center's proton treatment facility will feature the world's first accelerator and proton therapy system designed for patient care. During the next decade, other similarly-designed proton therapy systems will be built in Canada, England, France, Belgium, Germany, Japan, and South Africa, as well as at Massachusetts General Hospital in the United States.     

Age-related changes in binding to excitatory amino acid uptake site in temporal cortex of human brain.

The binding of D-[3H]aspartate to the specific uptake site for the excitatory amino acids glutamate and aspartate was measured in homogenates of temporal lobe cortex taken at postmortem from 76 human infant and adult brains. Binding levels were very low in brains of preterm and term infants but increased rapidly during the first 20 postnatal weeks to reach levels which exceeded those in adult brains. Linear regression analysis which compared the amount of D-[3H]aspartate binding with the age of the infant, showed a positive correlation up to 25 postnatal weeks. Saturation analysis showed that the maximum number of D-[3H]aspartate binding sites (Bmax) in temporal cortex from infants aged 20 postnatal weeks was 3 times greater than the number of sites in adult brain. The findings show that the number of excitatory amino acid uptake sites, which may be associated in part with presynaptic terminals, increase in number rapidly after birth. Furthermore, the data may indicate that a slow regression of excitatory amino acid terminals occurs during the later stages of brain development.     

Mortality from heart disease in a cohort of 23,000 patients with insulin-treated diabetes

AIMS/HYPOTHESIS: Although ischaemic heart disease is the predominant cause of mortality in older people with diabetes, age-specific mortality rates have not been published for patients with Type 1 diabetes. The Diabetes UK cohort, essentially one of patients with Type 1 diabetes, now has sufficient follow-up to report all heart disease, and specifically ischaemic heart disease, mortality rates by age. METHODS: A cohort of 23,751 patients with insulin-treated diabetes, diagnosed under the age of 30 years and from throughout the United Kingdom, was identified during the period 1972 to 1993 and followed for mortality until December 2000. Age- and sex-specific heart disease mortality rates and standardised mortality ratios were calculated. RESULTS: There were 1437 deaths during the follow-up, 536 from cardiovascular disease, and of those, 369 from ischaemic heart disease. At all ages the ischaemic heart disease mortality rates in the cohort were higher than in the general population. Mortality rates within the cohort were similar for men and women under the age of 40. The standardised mortality ratios were higher in women than men at all ages, and in women were 44.8 (95%CI 20.5-85.0) at ages 20-29 and 41.6 (26.7-61.9) at ages 30-39. CONCLUSIONS/INTERPRETATION: The risk of mortality from ischaemic heart disease is exceptionally high in young adult women with Type 1 diabetes, with rates similar to those in men with Type 1 diabetes under the age of 40. These observations emphasise the need to identify and treat coronary risk factors in these young patients.