Pronociceptive and antinociceptive neuromediators in patellar tendinopathy

BACKGROUND: The occurrence of nerve ingrowth and its relation to chronic tendon pain (tendinopathy) are still largely unknown. In healthy tendons, the innervation is confined to the paratenon, whereas the tendon proper is devoid of nerve fibers. In this study on the pathogenesis of tendinopathy, the authors examined sensory and sympathetic nerve fiber occurrence in the patellar tendon. HYPOTHESIS: Nerve ingrowth and altered expression of sensory and sympathetic neuromediators play a major role in the pathophysiology of pain in patellar tendinopathy. STUDY DESIGN: Case control study; Level of evidence, 3. METHODS: Biopsies from the patellar tendon in patients with patellar tendinopathy (n = 10) were compared with biopsies from a control group (n = 10) without any previous or current knee symptoms compatible with patellar tendinopathy. The biopsies were stained immunohistochemically for sensory and autonomic nerve markers. The biopsies from the 2 groups were compared using subjective and semiquantitative methods. RESULTS: Chronic painful patellar tendons exhibited increased occurrence of sprouting nonvascular sensory, substance P-positive nerve fibers and a decreased occurrence of vascular sympathetic nerve fibers, positive to tyroxin hydroxylase, a marker for noradrenaline. CONCLUSION: The altered sensory-sympathetic innervation suggests a role in the pathophysiology of tendinopathy. Ingrowth of sprouting substance P fibers presumably reflects a nociceptive and maybe a proliferative role, possibly as reactions to repeated microtraumata, whereas the decreased occurrence of tyroxin hydroxylase may represent a reduced antinociceptive role. These findings could be used to develop targeted pharmacotherapy for the specific treatment of tendinopathy.     

Clinical study of an amine fluoride gel and acidulated phosphate fluoride gel

Abstract This study compared caries inhibition in children by an amine fluoride and an acidulated phosphate fluoride when administered in a topically applied gel. In addition, the effects of applying amine fluoride daily and weekly were compared. Four hundred and sixty-eight children, ages 6 to 13, were randomly assigned to one of five treatment groups and received a total of five, 5-minute treatments. The treatment and interval between each of the five treatments were as follows: (A) acidulated phosphate fluoride daily, (B) amine fluoride daily, (C) amine fluoride weekly, (D) placebo daily, and (E) placebo weekly. When the children were examined for total Decayed, Missing, and Filled Surfaces (DMFS) increments 2 years later, no significant differences were observed. However, when the data were examined for effects on DMFS for a specific tooth surface, significant restriction (61 %) of occlusal increment was shown in the group which was treated with amine fluoride daily for 5 consecutive days as compared with the control group.     

Cause of death in squamous cell carcinoma of the head and neck. An autopsy study on 31 patients.

A series of 31 autopsied patients, with a history of head and neck squamous cell carcinoma is reported, with the emphasis on the cause of death. There were 26 males and 5 females; mean age being 64 years (range 44-88 years). Locoregional disease (LRD) was the cause of death in 19 patients (61%) and was present in 2 patients dying of an unrelated cause. Distant metastasis (DM) was found in 8 patients (26%) but had caused death in only 1 of them. A shorter survival time for patients with DM than for those without (8 months versus 13 months) indicates that DM is established early in the course of the disease. Therefore, a longer survival time will not result in an increase in DM and we infer that a better locoregional control will also not result in a real increase in DM but only in an apparent one, due to a shift of cause of death from LRD to DM in a group of patients that formerly would have died of LRD before the already present DM had become manifest.     

Early Signs of Atherosclerosis in Diabetic Children on Intensive Insulin Treatment: A population-based study

OBJECTIVE

To evaluate early stages of atherosclerosis and predisposing factors in type 1 diabetic children and adolescents compared with age- and sex-matched healthy control subjects.

RESEARCH DESIGN AND METHODS

All children and adolescents with type 1 diabetes, aged 8–18 years in Health Region South-East in Norway were invited to participate in the study (n = 800). A total of 40% (n = 314) agreed to participate and were compared with 118 age-matched healthy control subjects. Carotid artery intima-media thickness (cIMT) and elasticity were measured using standardized methods.

RESULTS

Mean age of the diabetic patients was 13.7 years, mean diabetes duration was 5.5 years, and mean A1C was 8.4%; 97% were using intensive insulin treatment, and 60% were using insulin pumps. Diabetic patients had more frequently elevated cIMT than healthy control subjects: 19.5% were above the 90th centile of healthy control subjects, and 13.1% were above the 95th centile (P < 0.001). Mean cIMT was higher in diabetic boys than in healthy control subjects (0.46 ± 0.06 vs. 0.44 ± 0.05 mm, P = 0.04) but not significantly so in girls. There was no significant difference between the groups regarding carotid distensibility, compliance, or wall stress. None of the subjects had atherosclerotic plaque formation. Although within the normal range, the mean values of systolic blood pressure, total cholesterol, LDL cholesterol, and apolipoprotein B were significantly higher in the diabetic patients than in the healthy control subjects.

CONCLUSIONS

Despite short disease duration, intensive insulin treatment, fair glycemic control, and no signs of microvascular complications, children and adolescents with type 1 diabetes had slightly increased cIMT compared with healthy control subjects, and the differences were more prominent in boys.Young adults with type 1 diabetes are at increased risk of early asymptomatic atherosclerosis, and cardiovascular morbidity and mortality are substantially increased in this group of patients (1–4).Carotid artery intima-media thickness (cIMT) is a reliable surrogate marker of generalized atherosclerosis because it correlates to coronary artery disease and predicts future cardiovascular events (5,6). Furthermore, it is recommended by the American Heart Association as a noninvasive imaging method for detecting atherosclerosis (6).Improved blood-glucose control obtained by intensive insulin treatment is associated with delayed atherosclerosis development and fewer cardiovascular events (2,7,8). The Oslo study, a long-term study of intensive insulin treatment in childhood-onset type 1 diabetic patients without symptomatic cardiovascular disease (CVD), demonstrated that long-term glycemic control predicted coronary atherosclerosis, as detected by coronary intravascular ultrasound (IVUS), and was correlated to cIMT (2). Likewise, the Diabetes Control and Complications Trial (DCCT)/Epidemiology of Diabetes Interventions and Complications (EDIC) study found that intensive insulin therapy reduces the progression of atherosclerosis, measured by IMT and most important the risk of cardiovascular events compared with conventional therapy (8,9).The atherosclerotic process starts in childhood and proceeds silently over a long period of time before clinical events occur (1). How early it starts and how aggressively it proceeds is, however, not quite known. Studies on cIMT in children and adolescents with type 1 diabetes have yielded conflicting results (10–13), and so far only small clinic-based studies have been performed. The present study is a population-based study in children and adolescents who use modern intensive insulin treatment, the aim of which is to evaluate early stages of atherosclerosis, its progression and predisposing factors, through follow up every 5th year. In this article, the baseline characteristics of the patients are presented, as well as the results from the first analysis.     

Croton macrostachys, a plant used in traditional medicine: purgative and inflammatory activity

Croton macrostachys seeds are widely used in Somalia as a purgative. In the present study, pharmacologic and chemical investigations confirm the laxative effect of the seeds and indicate the presence of phorbolesters. There appears to be no direct correlation between phorbolester content and laxative effect.