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Biomedical subjects

M D Davis

Publications and source records attributed to M D Davis.

At least 55 records · Page 3Linked to original sources
PubMed1998

Exaggerated arthropod-bite lesions in patients with chronic lymphocytic leukemia: a clinical, histopathologic, and immunopathologic study of eight patients.

BACKGROUND: Unusual papulovesicular lesions resembling arthropod bites have been described in patients with chronic lymphocytic leukemia (CLL). OBJECTIVE: Our purpose was to describe and characterize further the clinical, histopathologic, and immunopathologic features of these lesions. METHODS: Eight patients were identified retrospectively who had CLL and characteristic skin lesions. Clinical and histologic features were recorded. Skin biopsy specimens were analyzed immunohistochemically for eosinophil granule major basic protein, eosinophil-derived neurotoxin, neutrophil elastase, and mast cell tryptase. RESULTS: The clinical features, including the lesional distribution, suggested arthropod bites, although most patients could not recall having been bitten. Mixed T- and B-cell lymphoid cell infiltrates were present within lesions, along with prominent eosinophil infiltration and eosinophil granule protein deposition. CONCLUSION: Exuberant papulovesicular lesions develop in patients with CLL apparently as an exaggerated response to arthropod bites. Prominent eosinophil infiltration and degranulation within these lesions likely contribute to the severity of symptoms.

Aged↗
PubMed1998

Familial eosinophilic cellulitis, dysmorphic habitus, and mental retardation.

BACKGROUND: Eosinophilic cellulitis is a polymorphous, chronic disease characterized by eosinophil infiltration and granulomatous inflammation. OBJECTIVE: Our purpose was to describe the clinical, histologic, and immunohistologic findings in three family members who have had eosinophilic cellulitis since childhood associated with mental retardation and abnormal body habitus. METHODS: Family members were evaluated. Multiple skin biopsy specimens were obtained and examined after hematoxylin-and-eosin staining, by immunofluorescence and by electron microscopy. Blood specimens were analyzed by immunoassays for eosinophil granule proteins and eosinophil active cytokines. RESULTS: Three short-statured, mentally retarded family members with abnormal body habitus in at least two generations had recurrent eosinophilic cellulitis. Peripheral blood and bone marrow eosinophilia was present. Plasma eosinophil granule major basic protein and eosinophil-derived neurotoxin levels were elevated with normal plasma eosinophil cationic protein levels. Eosinophil survival in culture was increased by patients' plasma and was blocked with monoclonal interleukin-5 antibody. The level of plasma interleukin-5 was elevated. Lesional skin biopsy specimens showed massive staining for three eosinophil granule proteins. Electron microscopy showed eosinophil disruption. CONCLUSION: Eosinophilic cellulitis, mental retardation, and abnormal body habitus were likely inherited as a dominant syndrome in this family in which eosinophil involvement was striking.

Abnormalities, Multiple↗
PubMed1998

Brain extracellular levels of the putative antipsychotic CI-1007 and its effects on striatal and nucleus accumbens dopamine overflow in the awake rat.

The compound CI-1007 (R-(+)-1,2,3,6-tetrahydro-4-phenyl-1 [(3-phenyl-3-cyclohexen-1-yl)methyl]pyridine maleate) has been identified as a partial dopamine agonist and putative antipsychotic in in-vitro and in-vivo neurochemical, neurophysiological and behavioural tests. By use of microdialysis in conjunction with high-performance liquid chromatography (HPLC) with electrochemical detection, the effects of the drug on brain dopamine release, previously observed in anaesthetized animals, were shown to occur in awake animals also. Detection of peripherally administered CI-1007 in the brain, i.e. evidence of the drug's ability to penetrate the blood-brain barrier, was achieved by use of in-vivo brain microdialysis in awake, freely moving rats and capillary HPLC in combination with tandem mass spectrometry (HPLC/MS/MS). Intravenous administration of CI-1007 (40 mg kg-1) significantly inhibits dopamine release in the nucleus accumbens, a region associated with dopamine hyperactivity in schizophrenia, while having a non-significant impact on the striatal dopamine neurotransmission which is critical to regular motor function. The differential neurochemical profile of the drug indicates its potential usefulness in treating positive disease symptoms and implies that its extrapyramidal side effects are lower than those of typical antipsychotics.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1998

Risk factors for high-risk proliferative diabetic retinopathy and severe visual loss: Early Treatment Diabetic Retinopathy Study Report #18.

PURPOSE: To identify risk factors for the development of high-risk proliferative diabetic retinopathy (PDR) and for the development of severe visual loss or vitrectomy (SVLV) in eyes assigned to deferral of photocoagulation in the Early Treatment Diabetic Retinopathy Study (ETDRS). METHODS: Multivariable Cox models were constructed to evaluate the strength and statistical significance of baseline risk factors for development of high-risk PDR and of SVLV. RESULTS: The baseline characteristics identified as risk factors for high-risk PDR were increased severity of retinopathy, decreased visual acuity (or increased extent of macular edema), higher glycosylated hemoglobin, history of diabetic neuropathy, lower hematocrit, elevated triglycerides, lower serum albumin, and persons with mild to moderate nonproliferative retinopathy, younger age (or type 1 diabetes). The predominant risk factor for development of SVLV was the prior development of high-risk PDR. The only other clearly significant factor was decreased visual acuity at baseline. In the eyes that developed SVLV before high-risk proliferative retinopathy was observed, baseline risk factors were decreased visual acuity (or increased extent of macular edema), older age (or type 2 diabetes), and female gender. CONCLUSIONS: These analyses supported the view that the retinopathy-inhibiting effect of better glycemic control extends across all ages, both diabetes types, and all stages of retinopathy up to and including the severe nonproliferative and early proliferative stages and the possibility that reducing elevated blood lipids and treating anemia slow the progression of retinopathy.

Adolescent↗
PubMed1998

Clinicopathologic correlation of hypocomplementemic and normocomplementemic urticarial vasculitis.

BACKGROUND: Urticarial vasculitis is characterized by persistent urticarial lesions with histologic evidence of leukocytoclastic vasculitis. Hypocomplementemic urticarial vasculitis (HUV) is a distinct clinical entity in a subset of patients with urticarial vasculitis. OBJECTIVE: We examined presentation of urticarial vasculitis and factors predictive of connective tissue disease. METHODS: The clinical, histologic, and immunologic characteristics of 132 patients with urticarial vasculitis seen at the Mayo Clinic were examined, and features of the hypocomplementemic patients were compared with those of the normocomplementemic patients. RESULTS: Twenty-four patients (18%) had hypocomplementemia; all were female. Interstitial dermal neutrophilia was seen in 19 biopsy specimens (83%). On direct immunofluorescence (DIF) testing of lesional skin, 23 patients (96%) had a continuous strong granular deposition of immunoreactants along the basement membrane zone compatible with lupus erythematosus in addition to vascular fluorescence. Systemic lupus erythematosus (SLE) was present or occurred in 13 (54%). One hundred eight patients (82%) had normocomplementemia; 65 (60%) were female. Interstitial dermal neutrophilia was seen in 11 of 26 (42%) randomly selected biopsy specimens. On DIF, one patient (1%) had the lupus band. SLE occurred in three patients (3%). CONCLUSION: Patients with HUV were more likely to be female, to have diffuse neutrophilia on biopsy specimens stained with hematoxylin and eosin, to have continuous strong granular deposition of immunoreactants along the basement membrane zone on DIF, and to have SLE than normocomplementemic patients. We submit that HUV represents a subset of SLE with shared clinical, laboratory, and immunologic features.

Adolescent↗
PubMed1997

Treatment of cytomegalovirus retinitis with a sustained-release ganciclovir implant. The Ganciclovir Implant Study Group.

BACKGROUND: Sustained-release, intraocular implants that deliver ganciclovir are an alternative method for the treatment of cytomegalovirus retinitis in patients with the acquired immunodeficiency syndrome (AIDS). METHODS: We conducted a randomized study of 188 patients with AIDS and newly diagnosed cytomegalovirus retinitis. The patients were randomly assigned to treatment with an implant delivering 1 microg of ganciclovir per hour, an implant delivering 2 microg of ganciclovir per hour, or intravenous ganciclovir. The primary outcome we studied was progression of cytomegalovirus retinitis. RESULTS: The median time to progression of retinitis was 221 days with the 1-microg-per-hour implant (75 eyes), 191 days with the 2-microg-per-hour implant (71 eyes), and 71 days with ganciclovir administered intravenously (76 eyes; P<0.001). The risk of progression of retinitis was almost three times as great among patients treated with intravenous ganciclovir as among those treated with a ganciclovir implant (risk ratio, 2.8; P<0.001). However, the risk of disease in the initially uninvolved eye was lower with intravenous ganciclovir than with a ganciclovir implant (risk ratio, 0.5; P=0.19). Patients treated with intravenous ganciclovir were also less likely to have extraocular cytomegalovirus infections (0, vs. 10.3 percent in the two implant groups; P=0.04). CONCLUSIONS: For the treatment of cytomegalovirus retinitis, the sustained-release ganciclovir implant is more effective than intravenous ganciclovir, but patients treated with a ganciclovir implant alone remain at greater risk for the development of cytomegalovirus disease outside of the treated eye.

AIDS-Related Opportunistic Infections↗
PubMed1997

The role of phenylalanine in structure-function relationships of phenylalanine hydroxylase revealed by radiation target analysis.

The activity of rat liver phenylalanine hydroxylase (PAH; phenylalanine 4-monooxygenase, EC 1.14.16.1) is regulated by interaction with its substrate, phenylalanine, and its coenzyme, BH4 [tetrahydrobiopterin (6R-dihydroxypropyl-L-erythro-5,6,7,8-tetrahydropterin)]. The structural changes accompanying these interactions have been studied by radiation target analysis. PAH purified from rat liver was incubated with 2 mM phenylalanine to achieve complete activation of the enzyme. Frozen samples were irradiated with various doses of high energy electrons; samples were subsequently thawed, and several surviving properties of the enzyme were determined. Each parameter decreased as a single exponential function of radiation dose. Radiation target analysis of enzymatic activity yielded a dimeric target size. Similar radiation effects on subunit monomers and on tetrameric structure were observed. Together with results from unactivated enzyme, these data show that phenylalanine increases the interactions between the subunits in a dimer and weakens the interactions between dimers in a tetramer. These alterations prevent the natural cofactor, a tetrahydrobiopterin, from exerting a negative effect on activity.

Animals↗
PubMed1997

3-[[(4-Aryl-1-piperazinyl)alkyl]cyclohexyl]-1H-indoles as dopamine D2 partial agonists and autoreceptor agonists.

A series of arylpiperazines and tetrahydropyridines joined to indoles by semirigid cycloalkyl spacers were prepared. Target compounds were studied for their ability to bind to the DA D2 receptor in vitro and to inhibit dopamine synthesis and spontaneous locomotor activity in rats. Effects of tether length and relative stereochemistry were assessed for a series of 2-pyridylpiperazines. The cyclohexylethyl spacer was found to be the most active in the series. Further studies explored effects of changes in the arylpiperazine and indole portions of the molecule. From these studies trans-2-[[4-(1H-3-indolyl)cyclohexyl]ethyl]-4- (2-pyridinyl)piperazine (30a) was selected for further evaluation. It was characterized as a partial agonist of DA D2 receptors in vitro and caused decreases in dopamine synthesis and release as well as dopamine neuronal firing. Compound 30a was shown to be devoid of behavioral effects associated with postsynaptic DA D2 receptor activation. Furthermore, compound 30a was shown both to decrease DA synthesis and to inhibit Sidman avoidance responding in squirrel monkeys. These findings suggest that DA D2 partial agonists with the appropriate level of intrinsic activity can act to decrease dopamine synthesis and release and may have potential utility as antipsychotic agents.

Animals↗
PubMed1997

Subretinal fibrosis in diabetic macular edema. ETDRS report 23. Early Treatment Diabetic Retinopathy Study Research Group.

OBJECTIVE: To describe the characteristics of and risk factors for subretinal fibrosis (SRF) in patients with diabetic macular edema. PATIENTS AND METHODS: A total of 109 eyes (in 96 persons) with SRF, defined as a mound or sheet of gray to white tissue beneath the retina at or near the center of the macula, were identified during the Early Treatment Diabetic Retinopathy Study, which is a randomized clinical trial of photocoagulation and aspirin treatment in patients with mild to severe nonproliferative or early proliferative diabetic retinopathy. The patients and the ocular characteristics of these 109 eyes, all of which had clinically significant macular edema, were compared with those of 5653 eyes in which clinically significant macular edema, but not SRF, was observed during the trial. RESULTS: In 9 of 109 eyes, the development of SRF may have been directly related to focal photocoagulation. Seventy-four percent of the eyes in which SRF developed had very severe hard exudates in the macula prior to the development of SRF, while this level of hard exudates was seen in only 2.5% of the eyes with clinically significant macular edema in which SRF did not develop (P < .001). Of the 264 eyes with this level of hard exudates at baseline (n = 29) or during follow-up (n = 235), SRF developed in 30.7% of the eyes, while this complication developed in only 0.05% of 5498 eyes with clinically significant macular edema without this level of hard exudates. CONCLUSIONS: Subretinal fibrosis is an infrequent complication of diabetic macular edema. Although it has been reported to be associated with photocoagulation burn intensity, in only 9 of 109 eyes in which SRF developed was it located adjacent to a photocoagulation-related scar (among 4823 eyes that received focal photocoagulation for treatment of macular edema). The strongest risk factor for the development of SRF is very severe hard exudate.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1997

Ganciclovir implant exchange. Timing, surgical procedure, and complications.

BACKGROUND: The ganciclovir implant is effective for the treatment of cytomegalovirus (CMV) retinitis. The device eventually runs out of drug, however, and must be replaced. We report our experience with exchanging ganciclovir implants during the course of a randomized clinical trial. METHODS: During our study, patients with newly diagnosed peripheral CMV retinitis were treated with a ganciclovir implant. The implant was scheduled for exchange at 32 weeks. It was exchanged earlier if progression of CMV retinitis occurred. Patient examinations and standard fundus photography were performed at 2-week intervals after the exchange procedure. RESULTS: Twenty-six exchange procedures were performed. Twenty-two eyes in 15 patients received a second implant and 4 eyes in 4 patients later received a third implant. Cytomegalovirus retinitis was rendered or maintained inactive in 22 of 23 cases with more than 1 month of follow-up after the second or third implants. Complications after the second implant procedure included transient vitreous hemorrhage in 5 eyes, postoperative inflammation in 1 eye, and retinal detachment in 1 eye. Median visual acuity returned to 20/25 by 28 days and to 20/20 by 42 days. Complications after the third implant procedure included dense vitreous hemorrhage in 3 of 4 eyes. Median survival time after a second implant procedure was 89 days. CONCLUSIONS: The initial ganciclovir implant exchange procedure is well tolerated with continued long-term control of CMV retinitis. Multiple reentries through the same wound may be associated with an increased risk for vitreous hemorrhage.

Antiviral Agents↗
PubMed1997

A new syndrome of Crohn's disease and pachydermoperiostosis in a family.

Few syndromic associations with Crohn's disease are described. The aim of this study was to characterize a new syndrome of Crohn's disease associated with pachydermoperiostosis in 3 brothers. Three probands, 6 siblings, both parents, 20 of 21 third-generation relatives, and 9 spousal controls were evaluated. Serological evaluation for antineutrophil cytoplasmic antibodies and human leukocyte antigens as well as genetic testing for tumor necrosis factor microsatellites, intercellular adhesion molecule 1 polymorphisms, the interleukin 1 receptor antagonist gene, and the interleukin 1 beta gene were performed. Only the 3 probands were affected and developed pachydermoperiostosis between ages 14 and 17 years. Pachydermoperiostosis preceded Crohn's ileocolitis by 6 and 20 years in two probands, excluding secondary hypertrophic osteoarthropathy. Two probands were antineutrophil cytoplasmic antibody positive vs. 1 of 27 unaffected relatives (P < 0.001, chi 2). Haplotypes for human leukocyte antigen and tumor necrosis factor microsatellites were discordant. The probands' generation was homozygous for the common allele 1 of the interleukin 1 receptor antagonist and interleukin 1 beta genes. Two probands carried a rare polymorphism of the intercellular adhesion molecule 1 gene. A new syndrome of Crohn's disease and pachydermoperiostosis associated with antineutrophil cytoplasmic antibodies is described. Inheritance is most likely autosomal recessive by pedigree. No clear association was found between this syndrome and the gene regions evaluated.

Adolescent↗
PubMed1997

The effect of selenium on the central dopaminergic system: a microdialysis study.

The effects of Selenium (Se) on central dopaminergic function were examined in male Sprague-Dawley rats. In this experiment, animals were implanted with microdialysis probes and dialysates were analyzed for dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA). After reaching baseline values, sodium selenite was either injected intraperitoneally (i.p.) or directly infused into the striatum (ST) or nucleus accumbens (NA). Se administration of 3.0 mg/kg (i.p.) significantly increased (70%) DA overflow in the ST. Meanwhile direct Se perfusion (10 mM) also caused a significant elevation of synaptic DA concentrations in the ST and NA. Levels of DOPAC and HVA were minimally affected in all studies. In order to test for the effects of DA receptor activation, animals were pretreated with quinpirole (0.5 mg/kg, s.c.), an hour prior to Se (10 mM) infusion through the probe. It was found that quinpirole pre-treatment reduced Se-induced changes in DA concentrations. It was concluded from the present study that Se's central action might be related to its ability to potentiate DA function.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1997

Ovarian malignancy in patients with dermatomyositis and polymyositis: a retrospective analysis of fourteen cases.

BACKGROUND: Dermatomyositis and polymyositis can be associated with an underlying malignancy. OBJECTIVE: Our purpose was to describe a group of patients with dermatomyositis and polymyositis in whom ovarian carcinoma was diagnosed and to evaluate further the characteristics of the association between these diseases. METHODS: A cross-sectional retrospective review identified 14 patients in a 45-year period (1950 to 1995) with dermatomyositis and polymyositis in whom an underlying ovarian malignancy was diagnosed. Clinical and laboratory data of these patients were reviewed, and immunofluorescent and hematoxylin-eosin-stained skin sections were examined. RESULTS: The mean age at diagnosis of dermatomyositis and polymyositis was 59 years. Of the 14 patients, 11 had dermatomyositis, two had polymyositis, and one had an overlap disease. The 12 patients with dermatomyositis had distinctive cutaneous lesions. In eight, cutaneous biopsy specimens demonstrated variable histologic changes. Thirteen patients had signs of proximal muscle weakness, and myopathy was further demonstrated by electromyographic testing in 10. Creatine kinase levels were increased in 6 of the 10 patients tested. Dysphagia was present in five patients, but esophageal dysmotility was not demonstrated in three. Dermatomyositis and polymyositis preceded the ovarian malignancy in nine patients, were concomitant with it in four, and succeeded the ovarian disease in one. CONCLUSION: Physical examination and imaging techniques failed to detect early ovarian cancer in our patients with dermatomyositis and polymyositis. When detected (usually by abdominopelvic examination, in two by computed tomographic examination), it was advanced, and survival was poor.

Adenocarcinoma↗
PubMed1997

Cutaneous manifestations of Churg-Strauss syndrome: a clinicopathologic correlation.

BACKGROUND: Allergic granulomatosis of Churg-Strauss (Churg-Strauss syndrome) is a distinct clinical disease of multisystem vasculitis. OBJECTIVE: We characterize the clinical and histologic features of cutaneous findings in Churg-Strauss syndrome. METHODS: All patients with Churg-Strauss syndrome seen between 1976 and 1995 were retrospectively reviewed. RESULTS: Ninety patients with the diagnosis of Churg-Strauss syndrome were identified; 36 (40%) had cutaneous findings. Five patients (6%) had skin lesions as the initial manifestation. The most frequent cutaneous findings were purpura and petechiae on the lower extremities and cutaneous nodules and papules on the elbows. In 37 biopsy specimens from 29 patients, the most common findings were extravascular necrotizing granuloma (15 specimens) and leukocytoclastic vasculitis (16 specimens). CONCLUSION: Cutaneous lesions in Churg-Strauss syndrome are common. Their characteristic clinical and histologic pattern may help establish the diagnosis.

Adolescent↗
PubMed1997

Dopamine agonist-induced inhibition of neurotransmitter release from the awake squirrel monkey putamen as measured by microdialysis.

Male squirrel monkeys (Saimiri sciureus) were surgically prepared with cranial guide cannulae for acute microdialysis sampling of the putamen nucleus, a dopamine (DA)-rich brain region. On the day of an experiment an animal was placed in a Plexiglas restraining chair and a microdialysis probe was inserted through the guide into the putamen. Perfusates of artificial cerebrospinal fluid were collected every 20 min over several hours and analyzed via HPLC with electrochemical detection. DA D2/ D3 agonist drugs were administered either orally (p.o.) or subcutaneously (s.c.), and changes in levels of DA in the dialysates were measured. All of the drugs tested, i.e., quinpirole (0.5 mg/kg p.o.), talipexole (0.75 mg/kg p.o. or s.c.), and PD 135222 (7 mg/kg p.o.), decreased spontaneous DA overflow by approximately 40-50% during the first 2 h following dosing. In animals that routinely underwent the microdialysis procedure up to 23 times over a 2-year period, there was neither an appreciable change in basal DA overflow nor a significant change in the magnitude of drug response. These data suggest that DA D2/D3 agonists attenuate DA neuronal overflow in the primate brain, similar to effects seen in rodents. Furthermore, these results also demonstrate the utility of repeated intracerebral microdialysis as a tool to monitor dynamic changes in neurochemical activity in monkeys over a prolonged period of time.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1996

Structure-function relationships of phenylalanine hydroxylase revealed by radiation target analysis.

Phenylalanine hydroxylase (PAH) purified from rat liver is an oligomeric protein (predominantly tetramers) composed of 52-kDa subunits that are identical in primary structure. We have used radiation target analysis to probe the subunit organization of the enzyme. When 6-methyltetrahydropterin was used as the cofactor, the loss of hydroxylase activity as a function of radiation dose was defined by a single exponential decay, yielding a target size of about 120 kDa. However, when the enzyme was assayed with the natural cofactor tetrahydrobiopterin (BH4), the inactivation curves were much more complex. In these cases, the activity first increased, then decreased, as a function of radiation dose. The inactivation profile at higher radiation doses implied a target size of approximately 100 kDa. Kinetic analysis of the enzyme was significantly activated relative to the nonirradiated sample. In addition, the irradiated enzyme was desensitized to substrate-level activation by phenylalanine. The initial increase in activity at low radiation doses is due to the destruction of a large inhibitor. Analysis of the irradiated samples by high-performance size-exclusion chromatography indicated that the hydroxylase tetramer was lost with a target size of 110 kDa. Our data indicate that the tetrameric form of purified PAH consists of two enzymatically active dimers and that BH4 interacts with a tetramer to inhibit or deactivate the enzymatic activity.

Animals↗
PubMed1996

Suppression of first pain and slow temporal summation of second pain in relation to age.

BACKGROUND: Thermal stimuli delivered to skin of the arms or legs can produce a sensation of two distinct pains. These pains have been associated with activity in A-delta (first pain) and C-fiber (second pain) nociceptive fibers, respectively. Under appropriate conditions first pain decreases in intensity (adaptation) while second pain increases in intensity (slow temporal summation). Change in first and second pain to repeated stimulation of skin has not been assessed in relation to age. METHODS: Ten younger (M = 25 years) and ten older (M = 65 years) subjects participated in a study of first and second pain intensity elicited by nociceptive range heat pulses (.7 second pulses; adapting temperature 39 degrees C to a stimulus temperature of 51 degrees C) delivered to skin of arms and legs. Response times to sensations of first and second pain were assessed to provide evidence that subjects were responding to first and second pain. RESULTS: Age groups did not differ on pain intensity ratings of initial stimuli to previously unstimulated skin for either first or second pain. Older subjects failed to evidence slow temporal summation of second pain at the leg. Response times to first, but not second pain from the leg were delayed in the elderly. Response times to first and second pain at the arm did not differ with age. Auditory response times were slower in the older group. CONCLUSIONS: Age did not influence pain intensity to unadapted and unsensitized skin. Slow temporal summation of second pain was not observed at the leg in the older group, suggesting that mechanisms subserving C-fiber mediated sensitization of second order nociceptive neurons may fail with age. Longer response times to first, but not second pain in older subjects may represent an age effect on myelinated (A-delta; first pain) and not unmyelinated (C-fiber; second pain) nociceptive afferents and may represent a type of small fiber peripheral neuropathy.

Acoustic Stimulation↗