The role of topically administered FK506 (tacrolimus) at the time of facial nerve repair using entubulation neurorrhaphy in a rabbit model

Peripheral facial nerve palsy is a common sequela of traumatic craniofacial injury, often resulting in dramatic and sometimes permanent functional deficits. Exogenous agents and methods of repair that accelerate axonal regeneration would be of great benefit to the multitude of patients with facial nerve injuries. The objective of this study was to evaluate the effect of FK506 at the time of facial nerve repair using entubulation neurorrhaphy, and to compare entubulation neurorrhaphy versus interposition autograft in critical facial nerve gap defects. The study design was a prospective, randomized, blinded animal study with a control group. Twenty-five New Zealand White rabbits were assigned to 4 experimental groups and a control group. The buccal branch of the facial nerve was used in all procedures. Group 1 was the control group. Rabbits in group 2 underwent sham surgery. Group 3 was an interposition autograft group in which a 6-mm segment of nerve was transacted, flipped, and followed by epineural repair. Groups 4 and 5 underwent transection followed by entubulation neurorrhaphy with topical administration of either a carrier molecule (group 4) or an FK506 carrier molecule (group 5). Outcome measures included daily subjective assessment of upper lip movement; electromyographic studies at weeks 3, 5, and 8 postoperatively; and blinded quantitative histomorphometric evaluation after 8 weeks. All rabbits in all groups were noted to have spontaneous movement after 8 weeks, with 1 rabbit in group 5 obtaining the highest functional score among all study groups. Electrophysiologic studies showed polyphasic potentials, indicating reinnervation in 1 rabbit in group 5. Histomorphometric examination of group 5 rabbits revealed a similar cross-sectional area distal to transection and remyelination. Other groups showed decreased cross-sectional area and/or incomplete remyelination distal to the transection. FK506 applied topically at the time of facial nerve repair using entubulation neurorrhaphy demonstrated superior results in nerve regeneration versus entubulation neurorrhaphy carrier protein alone, and interposition autograft.     

Variation in NCB5OR: studies of relationships to type 2 diabetes, maturity-onset diabetes of the young, and gestational diabetes mellitus

Recent data show that homozygous Ncb5or(-/-) knock-out mice present with an early-onset nonautoimmune diabetes phenotype. Furthermore, genome-wide scans have reported linkage to the chromosome 6q14.2 region close to the human NCB5OR. We therefore considered NCB5OR to be a biological and positional candidate gene and examined the coding region of NCB5OR in 120 type 2 diabetic patients and 63 patients with maturity-onset diabetes of the young using denaturing high-performance liquid chromatography. We identified a total of 22 novel nucleotide variants. Three variants [IVS5+7del(CT), Gln187Arg, and His223Arg] were genotyped in a case-control design comprising 1,246 subjects (717 type 2 diabetic patients and 529 subjects with normal glucose tolerance). In addition, four rare variants were investigated for cosegregation with diabetes in multiplex type 2 diabetic families. The IVS5+7del(CT) variant was associated with common late-onset type 2 diabetes; however, we failed to relate this variant to any diabetes-related quantitative traits among the 529 control subjects. Thus, variation in the coding region of NCB5OR is not a major contributor in the pathogenesis of nonautoimmune diabetes.     

Insulin secretion in type 1 diabetes

Type 1 diabetes, a chronic autoimmune disease, causes destruction of insulin-producing beta-cells over a period of years. Although many markers of the autoimmune process have been described, none can convincingly predict the rate of disease progression. Moreover, there is relatively little information about changes in insulin secretion in individuals with type 1 diabetes over time. Previous studies document C-peptide at a limited number of time points, often after a nonphysiologic stimulus, and under non-steady-state conditions. Such methods do not provide qualitative information and may not reflect physiologic responses. We have studied qualitative and quantitative insulin secretion to a 4-h mixed meal in 41 patients with newly diagnosed type 1 diabetes and followed the course of this response for 24 months in 20 patients. Newly diagnosed diabetic patients had an average total insulin secretion in response to a mixed meal that was 52% of that in nondiabetic control subjects, considerably higher than has been described previously. In diabetic patients there was a decline of beta-cell function at an average rate of 756 +/- 132 pmol/month to a final value of 28 +/- 8.4% of initial levels after 2 years. There was a significant correlation between the total insulin secretory response and control of glucose, measured by HbA(1c) (P = 0.003). Two persistent patterns of insulin response were seen depending on the peak insulin response following the oral meal. Patients with an early insulin response (i.e., within the first 45 min after ingestion) to a mixed meal, which was also seen in 37 of 38 nondiabetic control subjects, had a significantly accelerated loss of insulin secretion, as compared with those in whom the insulin response occurred after this time (P < 0.05), and significantly greater insulin secretory responses at 18 and 24 months (P < 0.02). These results, which are the first qualitative studies of insulin secretion in type 1 diabetes, indicate that the physiologic metabolic response is greater at diagnosis than has previously been appreciated, and that the qualitative insulin secretory response is an important determinant of the rate of metabolic decompensation from autoimmune destruction.     

Perioperative hypertension due to undiagnosed aortic coarctation: are current standards of care adequate?

A 12-year-old male presented for a superficial parotidectomy for chronic parotitis. The patient had an unremarkable past medical history and was admitted on the day of surgery for his procedure without further anaesthetic or surgical review. During the patient's intraoperative course, higher than expected blood pressures were noted and treated with clonidine. After further high blood pressure readings in the postoperative care unit, close surveillance of blood pressures for the following 24 h was arranged. The hypertension was ongoing, and further examination and investigation confirmed the diagnosis of coarctation of the aorta. We examine the possible reasons for failure to diagnose this patient's hypertension preoperatively and suggest that there is a need for greater surveillance of blood pressures in the paediatric population presenting for surgery. A discussion of the significance of hypertension in paediatrics and recommendations for minimum standards of care to address shortcomings in the diagnosis and treatment of paediatric hypertension are proposed.     

The relationship between oral health and nutrition in older people

The oral health of older people is changing with reducing numbers of people relying on complete dentures for function, and retaining some natural teeth. Despite this there are substantial numbers of older people whose ability to chew foods is compromised by their oral health status, either because they have few or no natural teeth. This alteration results in individuals selecting a diet that they can chew in comfort. Such diets are low in fruits and vegetables intake with associated reduction in both non-starch polysaccharide and micronutrient intakes. There is also a trend for reduced dietary intake overall. Salivary flow and function may have an impact in relation to the ability to chew and swallow. Whilst there are few differences in salivary function in fit healthy unmedicated subjects, disease resulting in reduced salivary flow and particularly polypharmacy, with xerostomia as a side effect, are likely to have a role in older people. This paper explores the relationships between oral health status and food's choice and discusses the potential consequences for the individual of such dietary change.     

The rationale for sitting elderly patients in hospital out of bed for long periods is medically unsubstantiated and detrimental to their recovery

The notorious statement by Asher about the dangers of bed rest [Brit Med J 1947; ii: 967-8] which continues to be quoted out of context in leading medical journals today is inapplicable to modern short stay elderly hospital patients and has little medical foundation. 'Blood clotting in the veins' is more likely to result from venous stasis during sitting than from lying down. 'Lime draining from the bones' refers to subjects' spending weeks, not hours, in the horizontal position and similar losses have been shown to occur in healthy people immobilised in chairs for long periods during the day. Constipation is common in sick old people and there is no evidence that 'scybala stacking up the colon' is more likely to occur in bed than in a chair. The 'flesh rotting from the seat', or pressure sores, occur as frequently or more frequently, in sick patients nursed in chairs as in bed. 'Urine leaking from the distended bladder' may be reduced in very debilitated old people sitting in chairs, but at the expense of impaired renal function associated with reduced perfusion in the upright posture and exacerbated incontinence due to a compensatory diuresis at night. The 'spirit evaporating from the soul' today is more likely to afflict old patients who are exhausted by prolonged chair nursing and orthostatic hypotension due to age or illness. Recent studies in intensive care patients have highlighted the hypotension due to vasodilatation which can occur in infection and trauma. There is no evidence that nosocomial pneumonia is reduced by sitting patients out of bed, and lack of sleep is likely to exacerbate infection and delay recovery. Preventing patients from lying down when they feel the need is a violation of their rights and has been shown to be probably as injurious as the Victorian practice of preventing healthy patients from getting up. Physiotherapy is obviously important but patients should be allowed to decide for themselves how long they spend in or out of bed.