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A collection method and high-sensitivity enzyme immunoassay for sweat pyridinoline and deoxypyridinoline cross-links.

BACKGROUND: Collagen cross-link molecules such as pyridinoline (PYD), deoxypyridinoline (DPD), and N-terminal cross-linked peptides (NTX) have been measured in urine as indices of bone resorption. However, very little is known regarding the excretion of pyridinolines into other biological fluids. We report a collection device, normalizing analyte, and high-sensitivity immunoassay for quantitative analysis of free pyridinoline cross-links in sweat. METHODS: Flame atomic emission and ion-selective electrode techniques were used to measure potassium as a sweat volume marker. The Pyrilinks immunoassay for urine free pyridinolines was optimized to increase sensitivity for measurements in sweat. The precision, accuracy, and detection limit of this assay were characterized. To assess values and variability of sweat pyridinolines in human subjects, a nonocclusive skin patch was used to collect sweat samples from a reference group and from a mixed group experiencing accelerated bone resorption, postmenopausal women and men receiving gonadotropin-releasing hormone for prostate cancer. RESULTS: The immunoassay intra- and interassay variations were </=10% and <16%, respectively, with a detection limit of 309 pmol/L. Linearity upon dilution and analytical recovery ranged from 93% to 109% and 85% to 122%, respectively. Sweat PYD values normalized to potassium output yielded a weekly intraindividual biological variability of 14.7%. The mean increase in the population experiencing increased bone resorption vs the reference group was 36% (P <0.05) for sweat PYD/K vs 23-40% (P <0.05) for urinary PYD/Cr, DPD/Cr, and NTX/Cr. CONCLUSION: We conclude that this new platform sweat collection technology and PYD immunoassay show potential as an indicator of bone resorption.

Amino Acids↗

EEMCO guidance for the efficacy assessment of antiperspirants and deodorants.

Overproduction of sweat, sweaty skin and body odours are unpleasant for many social groups. Body cleansing products are designed to combat these undesirable features of skin. In addition, antiperspirant and deodorant products are more specifically used in the underarm site by a large part of the adult population. Antiperspirants are offered to control emotionally triggered sweating in the armpit. Deodorants are designed to combat malodour generated from bacteria-modified sweat. This review summarizes the physiology of eccrine, apocrine and apoeccrine sweat glands. The mechanisms of action of antiperspirants and deodorants are described as well as the factors influencing their efficacies. A series of tests using various measurement methods can be used to demonstrate the efficacy of antiperspirants. These include the gravimetric method, water evaporation quantification, electrodermal measurements, staining procedures, dye injections and cyanoacrylate skin surface strippings and casting replicas. Deodorant efficacy can be evaluated by sensory assessments performed by an expert panel. Indirect support is provided by visualization of apocrine gland excretion and collection of sweat and volatile compounds. Microbiological assessments and chromatographic analysis also provide indirect information.

Apocrine Glands↗

Skin nerve fibres and their contacts with mast cells in patients with palmoplantar pustulosis.

Patients with palmoplantar pustulosis (PPP) frequently report that stress worsens their condition. A study was therefore made of the distribution and number of nerve fibres positive for protein gene product (PGP) 9.5 (a general nerve marker) and nerve fibres with substance P- and calcitonin gene-related peptide-like immunoreactivity in involved skin from patients with PPP and in skin from healthy controls. The number of mast cells in the papillary dermis was larger (P = 0.0003) in lesional palmar PPP skin than in control skin, and the number of contacts between mast cells and nerve fibres was significantly larger (P = 0.02) in PPP skin than in control skin. Image analysis of the nerve fibres around the sweat glands showed that the positively stained area as a percentage of the total area of the sweat gland (coil + surrounding nerves) was significantly lower in PPP skin (P = 0.0006). Furthermore, the nerves seemed to be fragmented. Neutrophils within and below the pustules and in the papillary dermis showed positive substance P staining. The increased number of contacts between nerves and mast cells in PPP skin and the intense substance P-like immunoreactivity of the neutrophils indicate that neuromediation may influence the inflammation in PPP, whereas the destruction of the nerve fibres around the sweat glands might be a result of the inflammation.

Adult↗

Cribriform tumors of the skin: CD38 expression distinguishes from histologic mimics in a multi-institutional series.

Cribriform tumor of the skin (formerly primary cutaneous cribriform carcinoma/primary cutaneous cribriform apocrine carcinoma) is a rare adnexal neoplasm of uncertain malignant potential. Recent studies have identified recurrent co-deletion of the long arm of chromosomes 6 and 9 and CD38 overexpression as potential diagnostic features, but their sensitivity and specificity remain incompletely defined. We identified 11 cribriform tumors with classic morphologic features, including several previously reported molecular characterized cases and additional unpublished cases, from multiple institutions. CD38 immunohistochemistry was performed on all tumors and compared with a panel of morphologic mimics, including adenoid cystic carcinoma (n&#x2009;=&#x2009;8), digital papillary adenocarcinoma (n&#x2009;=&#x2009;8), eccrine/apocrine adenomas (n&#x2009;=&#x2009;7), hidradenoma (n&#x2009;=&#x2009;2), and endocrine mucin-producing sweat gland carcinoma (n&#x2009;=&#x2009;3). SNP array analysis was available in nine cases. Patients had a median age of 47 years with a slight female predominance (64%). Tumors commonly involved the extremities and ranged from 0.3 to 2.0 cm. Histologically, all cases demonstrated a well-circumscribed dermal neoplasm of bland epithelial cells arranged in cribriform architecture with characteristic thread-like intraluminal bridging, without high-grade features. CD38 expression was identified in 9/11 cases (82%), typically with moderate-to-strong diffuse cytoplasmic staining. All morphologic mimics (n&#x2009;=&#x2009;28) were CD38 negative. Recurrent chromosomal deletions involving 6q and/or 9q were identified in 7/8 (88%) successfully tested cases. Two morphologically classic cribriform tumors lacked CD38 expression, including one with confirmed 6q/9q codeletion, while one CD38-positive case lacked detectable genomic copy number alterations. These findings further support cribriform tumors as a molecularly distinct, low-grade adnexal neoplasm characterized by recurrent 6q/9q deletions and frequent CD38 expression. CD38 appears to be a useful adjunctive diagnostic marker with high specificity among the selected mimics tested, although its sensitivity is incomplete, and absence of staining does not exclude the diagnosis.

Adnexal tumors↗

Thermal interaction between animal and microclimate: a comprehensive model.

An equation based on heat transfer theory is developed to predict the rate of heat loss from a homeothermic vertebrate to the environment, specified by the air temperature, humidity, windspeed and radiation receipt. The analysis incorporates the animal's thermoregulatory responses--sweating ability, vasomotor action, and regulation of body-core temperature, metabolic and respiratory rate. The loss of heat and water vapour from cattle is used as an illustration, and particular attention is given to their heat balance in hot environments. The predicted rates of heat loss from cattle indoors at various air temperatures and humidities are consistent with experiments. Outdoors, intercepted solar radiation can reduce substantially heat loss through the body tissue when the air temperature is low. In contrast, at high air temperatures the heat dissipation may not be sensitive to the radiation load, although body-core temperature is. Increased rates of air movement can aggravate strain at low air temperatures, but mitigate strain in a hot environment.

Air↗

Pokeweed poisoning.

A 68-year-old man who ingested an improperly prepared extract of pokeweed had sweating, confusion, tremor, weakness, incontinence, and syncope. Analysis of the symptoms from this and similar patients previously reported suggests that the pokeweed plant contains an agent that produces peripheral and central cholinergic stimulation.

Aged↗

Associations between night sweats and other sleep disturbances: An OKPRN study.

PURPOSE: Surprisingly little is known about the causes and implications of night sweats. This study was designed to clarify further the associations between night sweats and sleep-related symptoms. METHODS: We undertook a cross-sectional study of consecutive adult patients seen in 10 primary care physicians' offices. Data were collected and transmitted by a personal digital assistant. Information included demographic variables; height, weight, and blood pressure; occurrence of a variety of sleep-related symptoms; and occurrence and severity of night sweats, day sweats, and hot flashes in the past month. For women, information about menstrual status was also obtained. RESULTS: Thirty-four percent of the 363 patients interviewed reported night sweats, one half of whom reported saturating their bedclothes. In the multivariate model, night sweats were associated with daytime tiredness (OR = 1.99; 95% CI, 1.12-3.53), waking up with a bitter taste in the mouth (OR = 1.94; 95% CI, 1.19-3.18), legs jerking during sleep (OR = 1.78; 95% CI, 1.05-3.00), and awakening with pain in the night (OR = 1.87; 95% CI, 1.16-2.99). CONCLUSIONS: Night sweats are associated with several sleep symptoms. Both night sweats and sleep disturbances are commonly experienced by adult primary care patients. When their patients report night sweats, clinicians should consider asking about sleep quality and sleep-related symptoms.

Adolescent↗

Selective loss of cholinergic sudomotor fibers causes anhidrosis in Ross syndrome.

Ross syndrome consists of segmental hyperhidrosis with widespread anhidrosis, Adie syndrome, and areflexia. The cause of this disorder is unknown. Selective degeneration of cholinergic fibers or of neural crest-derived structures has been suggested. We present clinical and skin biopsy data of 4 patients, providing evidence of reduced cholinergic sweat gland innervation in hypohidrotic skin by morphometric analysis. These findings indicate a selective degenerative process of the cholinergic sudomotor neurons.

Adult↗

Mutation in the gene responsible for cystic fibrosis and predisposition to chronic rhinosinusitis in the general population.

CONTEXT: Chronic rhinosinusitis (CRS) is a common condition in the US general population, yet little is known about its underlying molecular cause. Chronic rhinosinusitis is a consistent feature of the autosomal recessive disorder cystic fibrosis (CF). OBJECTIVE: To determine whether mutations in the cystic fibrosis transmembrane regulator (CFTR) gene, which is responsible for CF, predispose to CRS. DESIGN: Case-control study conducted from 1996 to 1999 in which the DNA of CRS patients and controls was typed for 16 mutations that account for 85% of CF alleles in the general population. Chronic rhinosinusitis patients with 1 CF mutation were evaluated for a CF diagnosis by sweat chloride testing, nasal potential difference measurement, and DNA analysis for additional mutations. SETTING: Otolaryngology-head and neck clinic of a US teaching hospital. PARTICIPANTS: One hundred forty-seven consecutive adult white patients who met stringent diagnostic criteria for CRS and 123 CRS-free white control volunteers of similar age range, geographic region, and socioeconomic status. MAIN OUTCOME MEASURES: Presence of CF mutations by DNA analysis among CRS patients vs controls. RESULTS: Eleven CRS patients were found to have a CF mutation (DeltaF508, n = 9; G542X, n = 1; and N1303K, n = 1). Diagnostic testing excluded CF in 10 of these patients and led to CF diagnosis in 1. Excluding this patient from the analyses, the proportion of CRS patients who were found to have a CF mutation (7%) was significantly higher than in the control group (n = 2 [2%]; P =.04, both having DeltaF508 mutations). Furthermore, 9 of the 10 CF carriers had the polymorphism M470V, and M470V homozygotes were overrepresented in the remaining 136 CRS patients (P =.03). CONCLUSION: These data indicate that mutations in the gene responsible for CF may be associated with the development of CRS in the general population. JAMA. 2000;284:1814-1819.

Adult↗

Increased sweat sulfate concentrations in chronic renal failure.

Inorganic sulfate concentrations are markedly elevated in patients with chronic renal failure (CRF). During hemodialysis, sulfate is removed and circulating levels drop significantly, while chloride concentrations remain relatively constant. We measured sulfate and chloride in sweat from CRF patients collected by pilocarpine iontophoresis. Sweat sulfate concentrations in uremic patients were significantly increased (404 +/- 43 vs. 105 +/- 6 microM in 22 controls). The correlation between plasma and sweat SO4 concentrations in CRF patients was significant (r = 0.77, P less than 0.01). However, the fractional excretion of sulfate in sweat (the sweat/serum ratio) was close to that of chloride (0.26 +/- 0.01 vs. 0.19 +/- 0.02) and was essentially the same before and after dialysis (0.20 +/- 0.01 vs 0.23 +/- 0.01) despite the significant absolute change in the extracellular SO4 concentration (from 2,018 +/- 153 to 709 +/- 21 microM) and no change in chloride concentrations. In patients with CRF, we conclude that the handling of inorganic sulfate by the sweat gland is not significantly different from that for chloride. Hemodialysis reduces absolute sulfate excretion markedly and thus may reduce the likelihood of forming calcium sulfate complexes in the sweat secretions. This could be a significant factor in the dialysis-related pruritus that has been ascribed to excess calcium deposition in the skin.

Adolescent↗

Detection of mercury and other undetermined materials in skin biopsies of endemic pemphigus foliaceus.

A novel variant of endemic pemphigus foliaceus (EPF) was described among individuals in an area surrounding El Bagre, Colombia, South America. The population in this rural mining community is exposed to high environmental levels of mercury, used for gold extraction, as well as other minerals, metalloids, and trace elements (e.g., quartz, rutile, granite, magnetite, and almenite) and ultraviolet radiation. Fifty control subjects and fifty EPF patients in the endemic area were examined for the presence of mercury in skin biopsies and hair, using autometallographic and mass spectroscopic analyses, respectively. Simultaneously, serum levels of IgE were measured, and cutaneous tests for hypersensitivity reactions were performed. Using autometallography, mercuric sulfides/selenides were detected in 14 of 51 skin biopsies distributed similarly in the control and patient groups. However, significantly higher serum IgE levels and mercury concentrations in hair, urine, and nails were found in patients compared with controls. Microscopic analysis revealed mercuric sulfides/selenides concentrated within and around the sweat gland epithelium, as well as in dendritic cells. Five skin biopsies from EPF patients and five from controls that tested positive for the presence of mercuric sulfides/selenides by autometallography were randomly selected for electron microscopic analysis. This analysis revealed a mixed electron-dense and electron-light material closely associated with desmosomes in patients. However, there were intracellular vesicles containing an amalgam of electron-dense and electron-light materials only in the EPF patients. Thus, EPF-affected individuals are exposed to high levels of environmental mercuric sulfides/selenides and other elements. This is the first study reporting mercuric sulfides/selenides in skin biopsies from people living in a focus of EPF, and these compounds may play a role in the pathogenesis of autoimmunity.

Autoimmune Diseases↗

Steroid analysis of human apocrine secretion.

Analysis of the secretion of the human apocrine gland has shown the presence of dehydroepiandrosterone and androsterone sulfates, two androgen steroids previously identified in axillary sweat. These steroid sulfates were characterized by the gas chromatographic/mass spectrometric analysis of the odorous steroids formed on direct injection of the apocrine secretion into the host gas chromatographic injector. No spectral evidence was found for the presence of the delta16-androgen steroids which have axillary-like odors and have also been reported in axillary sweat. Cholesterol was the major steroid component of the secretion.

Adult↗

Transcutaneous chemical collection of caffeine in normal subjects: relationship to area under the plasma concentration-time curve and sweat production.

A novel transcutaneous chemical collection device (TCD) has been developed to study the phenomenon of outward transcutaneous chemical migration. The TCD is a Bandaid-like device containing an immobilized aqueous media and binding reservoir material to prevent back-transfer into the skin. This device, when placed against the skin, allows collection and quantitation of chemicals that diffuse directly through the skin from within the body. The relationship of the amount of drug collected in the TCD to the amount in the body available for collection (as represented by the area under the plasma-concentration time curve, AUC) and the effects of sweating, a potential confounding factor, on collection of drug in a TCD were studied, using caffeine as a model compound. TCD were placed on the skin of normal male volunteers. Twenty-four hours later subjects took caffeine by mouth. Blood samples were collected and TCD were removed at various times after drug intake and analyzed by HPLC for caffeine. Studies of the sweating effect were carried out in a similar manner, except that one arm of each subject was maintained at 40 degrees C to induce local sweating, the other arm acted as a non-sweating control. The amount of caffeine collected was linearly related to the AUC. Sweating seemed to have a large (40%) contribution to transdermal collection in the early period (5.5 h) of the study, but this difference was much less (14%) at longer collection times (10 h).

Adult↗

Quantitative sweat testing using acetylcholine for direct and axon reflex mediated stimulation with silicone mold recording; controls versus neuropathic diabetics.

Sweat glands were stimulated by iontophoresed acetylcholine (ACh). Using a two-chamber capsule, one group of sweat glands was stimulated directly by ACh, and another stimulated indirectly via axon reflexes. Sweat droplets were recorded with a silicone mold and counted by a dissecting microscope and a computerized scanner. Responses from 32 diabetics with generalized somatic peripheral neuropathy were compared with 32 controls. Counting sweat droplets by computerized scanning was more accurate than by microscope. The numbers of droplets, their total areas, and mean areas were all larger in the direct response. Counts of droplet numbers was more diagnostically useful than measuring the total area and the mean areas of the droplets. There was a high correlation between droplet numbers of the direct and the indirect sweat responses. Droplet number counts of the direct response had a slightly higher diagnostic yield than those of the technically more complicated indirect response: for a specificity of 95%, the direct response had a sensitivity of 55%, the indirect being 50%.

Acetylcholine↗

Sudomotor function in human poikilothermia.

Hypohidrosis predisposes to hyperthermia and may indicate generalized thermoregulatory failure. To assess the sweating capacity in human poikilothermia, we performed a quantitative analysis of the central and peripheral sudomotor pathways in four women with acquired poikilothermia (aged 29 to 38 years) and nine controls. Heat challenge in a climatic chamber (ambient temperature 40 degrees C, 50% relative humidity) for 180 minutes revealed that both sweat secretion and evaporative weight loss were significantly lower in the patients than in the controls (p < 0.01). Temperature thresholds for thermal sweating were markedly elevated in at least two patients, whereas a third patient showed no sweating response. Stimulation of the eccrine sweat glands by intradermally injected acetylcholine during reduced core temperature (34.9 +/- 0.7 degrees C) revealed a significantly reduced sweating response in all patients (p < 0.01); the sudomotor response to pilocarpine iontophoresis was reduced or absent in three patients. We conclude that the generalized thermoregulatory sudomotor failure in these patients was attributable primarily to disorders of the central sudomotor drive; the impaired postganglionic sudomotor response is temperature related and possibly secondary to (long-standing) poikilothermia. Quantification of heat-dissipating capacity is pivotal for diagnosing severe thermolability and may help to prevent serious heat illness.

Acetylcholine↗