Background: Somatic cutaneous small sensory fiber neuropathy (SSFN) can be an early manifestation of impaired glucose tolerance and diabetes mellitus and/or insulin resistance among obese subjects and is often associated with pain, wound occurrence and impaired wound healing. It is yet unclear as to whether SSFN is prevalent among obese individuals without glucose and/or insulin dysregulation despite abundant evidence of delayed wound healing. Objective: To observe whether there is hypofunctioning of stimulated capsaicin-sensitive cutaneous nerves (small sensory fibers) in obese subjects with/without hyperglycemia and hyperinsulinemia. Design, setting and participants: Fifty-eight morbidly obese and 15 lean subjects were recruited for small fiber testing of the forearm in a cross-sectional study. Hyperglycemia was observed in 35 obese subjects. Of 25 obese subjects, hyperinsulinemia was noted in 15, 14 of which were hyperglycemic. No subjects demonstrated symptoms/signs of neuropathy over the hairy skin of the forearm. In fact, a neurological examination revealed that 37 subjects were asymptomatic in the legs and only four complained of a neuropathic pain in the foot. Virtually all subjects were exposed to a set of capsaicin-sensitive tests and measures which were identified by capsaicin desensitization procedures. These tests, conducted while in a supine position in bed at the Banner Good Samaritan Medical Center, Phoenix, examined the two principle roles of cutaneous SSFs, namely conveying pain signals to the CNS and controlling local neurogenic vasodilatation (flare; axon-reflex). Main outcome measures: Heat-induced pain was assessed by verbal reports of sensation after accommodation and heat-, capsaicin-, and transcutneous stimulation-induced blood flow was measured by laser Doppler flowmetry with probes placed at the site of stimulation and 1 cm remote from the site, the latter to evaluate flare latency and intensity of flare. Results: Significant depression of pain and flare responses were observed in the obese subjects in all but one test. Decreased pain and flare responses were noted in all subjects without hyperglycemia and hyperinsulinemia. Age negatively correlated with capsaicin-induced flare in both the obese and normal groups. Conclusion: SSFN was prevalent in the cohort of morbidly obese subjects in a skin area without neurological symptoms or signs and in subjects with/without hyperglycemia and hyperinsulinemia. SSFN may be a serious factor in observations of impaired wound healing among obese subjects, a particularly worrisome problem in an obese aging population given the propensity for small fiber impairment in aging subjects. Small fiber impairment in the younger obese population may signal an early aging phenomenon.

This study reveals wide prevalence but limited transcriptional activity of HPV in IP. No correlation between HPV transcriptional activity and progression, recurrence, or malignant transformation was identified. These data suggest that transcription of HPV may contribute to the pathogenesis of IP, but prospective data are needed to definitively demonstrate this connection. These results also suggest that RNAscope may be more sensitive than PCR in detecting HPV activity in IP.

These observations suggest a statistically significant reduction in serum PSA level that is associated with the onset of statin therapy.

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