Major amputation for intractable extremity melanoma after failure of isolated limb perfusion.

AIM: The aim of this study was to analyse indications and results of amputation for intractable extremity melanoma after failure of isolated limb perfusion (ILP). METHODS: Between 1978 and 2001, 451 patients with loco-regional advanced extremity melanoma underwent 505 ILPs. Amputation of the affected extremity had to be carried out for intractable recurrent disease in 11 of these patients. RESULTS: The indications for amputation were uncontrollable pain (n=2), extensive loco-regional tumour progression (n=4), loss of ankle function due to local tumour growth (n=1), and ulcerating and fungating lesions, not responding to other treatments (n=4). Four patients developed stump recurrence after amputation. Ten patients died of melanoma metastases after a median of 11 months (range 2-110 months). Two patients survived more than 5 years after amputation. CONCLUSIONS: Major amputation is rarely indicated for intractable extremity melanoma but long-term survival can be achieved in selected patients.     

Surfer's ear: external auditory exostoses are more prevalent in cold water surfers.

OBJECTIVE: The study goal was to demonstrate the prevalence and severity of external auditory exostoses (EAEs) in a population of surfers and to examine the relationship between these lesions and the length of time surfed as well as water temperature in which the swimmers surfed. It was hypothesized that subjects who predominantly surfed in colder waters had more frequent and more severe exostoses. METHODS: Two hundred two avid surfers (91% male and 9% female, median age 17 years) were included in the study. EAEs were graded based on the extent of external auditory canal patency; grades of normal (100% patency), mild (66% to 99% patency), and moderate-severe (<66% patency) were assigned. Otoscopic findings were correlated with data collected via questionnaires that detailed surfing habits. RESULTS: There was a 38% overall prevalence of EAEs, with 69% of lesions graded as mild and 31% graded as moderate-severe. Professional surfers (odds ratio 3.8) and those subjects who surfed predominantly in colder waters (odds ratio 5.8) were found to be at a significantly increased risk for the development of EAEs. The number of years surfed was also found to be significant, increasing one's risk for developing an exostosis by 12% per year and for developing more severe lesions by 10% per year. Individuals who had moderate-severe EAEs were significantly more likely to be willing to surf in colder waters than were those who had mild EAEs (odds ratio 4.3). CONCLUSIONS: EAEs are more prevalent in cold water surfers, and additional years surfing increase one's risk not only for developing an EAE but also for developing more severe lesions.     

Cholesterol and atherosc lerosis

Cholesterol is an essential component of cellular membranes, but when present in excess in the circulation, can be deposited in the arterial wall, leading to the formation of atherosclerotic lesions. The principal plasma carrier of cholesterol, low density lipoprotein (LDL), is removed from the circulation by LDL receptors in the liver. This process plays a critical role in regulating plasma LDL levels. The unique structure and composition of the LDL particle makes it particularly susceptible to modification by oxidative reactions. Current evidence suggests that the production of oxidised LDL in the intima, and the removal of oxidised LDL particles by scavenger receptors on macrophages, play a central role in the development and progression of atherosclerotic lesions.     

Angle-dependent backscatter from the arterial wall

The anisotropic nature of intra-arterial echographic images is reported, and the source of this anisotropy is investigated using postmortem human iliac arteries. A 27 MHz transducer, mounted on an ultrasonic microscope, is used to quantify the angular dependence of the backscatter power versus the angle of incidence, and these results are correlated with histological findings. Besides the observed differences in the acoustic response of morphologically different tissues, significant variations in backscatter power are found in both media and internal elastic lamina due to variations in the angle of incidence. This angle dependence is caused by the dominant orientation of fibers in tissue layers and by the shape and size various scattering particles. The results indicate that long microscopic structures with one main orientation are responsible for the backscattered signal and that the angular-dependent response is related to the histologically determined orientation of these fibers. These results may have an impact on the assessment of intra-arterial echographic images.     

Paget's disease of bone in The Netherlands: a population-based radiological and biochemical survey--the Rotterdam Study.

Serum ALP may be a good indicator of Paget's disease in epidemiologic studies. Subjects with raised and normal ALP from a population cohort were matched (1 in 6, total 548), and radiographs were taken. ALP was an excellent marker of the disease (RR, 10.9), but the majority of those affected had normal ALP. INTRODUCTION: Evidence from radiographic surveys of limited skeletal sites has shown that Paget's disease of bone (PDB) is common in the elderly and has a distinct geographic variation. There is no information, however, about the relation of serum alkaline phosphatase (ALP) activity, a marker of the disease, and its prevalence in the population. MATERIALS AND METHODS: We analyzed data from a well-defined Dutch population cohort (the Rotterdam study) with the following specific aims: (1) to assess the relationship between serum ALP activity and prevalence of radiographically diagnosed PDB, (2) to estimate the overall prevalence of the disease in the Netherlands, and (3) to assess the appearance of the disease with time. Using a nested case-control design, subjects with an increased serum ALP and normal serum liver enzymes were matched for gender and age (1 to 6) with subjects with normal serum ALP activity. Radiographs of the thoracic and lumbar spine, pelvis, proximal femurs, knees, wrists, and hands were taken. RESULTS AND CONCLUSIONS: PDB was diagnosed in 20.5% of subjects with elevated serum ALP activity and in 2.3% in those with normal serum ALP activity, increasing with age in both groups. The relative risk (RR) for PDB in the presence of raised serum ALP activity was 10.9 (95% CI, 4.8, 24.9). The estimated prevalence of PDB in the population was 3.6%, and the large majority (about 86%) had normal serum ALP activity, contrasting findings in bone clinics where the opposite is the case. Finally, in subjects with normal and raised serum ALP activity but no PDB at baseline, radiographs taken 6-9 years later showed no evidence of the disease. This study demonstrated that serum ALP activity is a sensitive marker of PDB in men and women >55 years of age, but the majority of those affected have normal serum ALP activity.     

Induced luteolysis in the primate: rapid loss of luteinizing hormone receptors

The molecular mechanisms involved in luteolysis are still unclear in the primate. This study aimed to investigate the effect of induced luteolysis on the ovarian luteinizing hormone (LH) receptor and the steroidogenic enzyme, 3beta-hydroxysteroid dehydrogenase (3beta-HSD) in the marmoset monkey. Luteolysis was induced in the mid-luteal phase either directly by systemic prostaglandin F2alpha (PGF2alpha), or indirectly by LH withdrawal using systemic gonadotrophin releasing hormone antagonist (GnRHant) treatment. The LH receptor was studied by isotopic mRNA in-situ hybridization and in-situ ligand binding and 3beta-HSD expression was studied using isotopic mRNA in-situ hybridization and immunohistochemistry. Induced luteolysis was associated with a reduction in the expression of LH receptor (P < 0.0001) and 3beta-HSD mRNA, closely followed by a reduction in the LH receptor (P < 0.05) and 3beta-HSD protein concentrations within 24 h. There were no differences in the findings whether luteolysis was induced with PGF2alpha or GnRHant. This study shows that disparate mechanisms to induce luteolysis in the primate result in an identical rapid loss of the LH receptor and 3beta-HSD. In conclusion, induced luteolysis leads to rapid loss of the steroidogenic pathway in luteal cells.      

Lethal encephalitis in myeloid differentiation factor 88-deficient mice infected with herpes simplex virus 1

Herpes simplex virus 1 (HSV-1), a large DNA virus from the Herpesviridae family, is the major cause of sporadic lethal encephalitis and blindness in humans. Recent studies have shown the importance of Toll-like receptors (TLRs) in the immune response to HSV-1 infection. Myeloid differentiation factor 88 (MyD88) is a critical adaptor protein that is downstream to mediated TLR activation and is essential for the production of inflammatory cytokines. Here, we studied the relationship between MyD88 and HSV-1 using a purified HSV-1 isolated from a natural oral recurrent human infection. We observed the activation of TLR-2 by HSV-1 in vitro using Chinese hamster ovary cells stably transfected with a reporter gene. Interestingly, we found that only peritoneal macrophages from MyD88-/- mice, but not macrophages from TRL2-/- or from wild-type mice, were unable to produce tumor necrosis factor-alpha in response to HSV-1 exposure. Additionally, although TLR2-/- mice showed no enhanced susceptibility to intranasal infection with HSV-1, MyD88-/- mice were highly susceptible to infection and displayed viral migration to the brain, severe neuropathological signs of encephalitis, and 100% mortality by day 10 after infection. Together, our results suggest that innate resistance to HSV-1 is mediated by MyD88 and may rely on activation of multiple TLRs.