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Plasma, oral fluid and sweat wipe ecstasy concentrations in controlled and real life conditions.

In a double-blind placebo controlled study on psychomotor skills important for car driving (Study 1), a 75 mg dose of +/- 3,4-methylenedioxymethamphetamine (MDMA) was administered orally to 12 healthy volunteers who were known to be recreational MDMA-users. Toxicokinetic data were gathered by analysis of blood, urine, oral fluid and sweat wipes collected during the first 5h after administration. Resultant plasma concentrations varied from 21 to 295 ng/ml, with an average peak concentration of 178 ng/ml observed between 2 and 4h after administration. MDA concentrations never exceeded 20 ng/ml. Corresponding MDMA concentrations in oral fluid, as measured with a specific LC-MS/MS method (which required only 50 microl of oral fluid), generally exceeded those in plasma and peaked at an average concentration of 1215 ng/ml. A substantial intra- and inter-subject variability was observed with this matrix, and values ranged from 50 to 6982 ng/ml MDMA. Somewhat surprisingly, even 4-5h after ingestion, the MDMA levels in sweat only averaged 25 ng/wipe. In addition to this controlled study, data were collected from 19 MDMA-users who participated in a driving simulator study (Study 2), comparing sober non-drug conditions with MDMA-only and multiple drug use conditions. In this particular study, urine samples were used for general drug screening and oral fluid was collected as an alternative to blood sampling. Analysis of oral fluid samples by LC-MS/MS revealed an average MDMA/MDEA concentration of 1121 ng/ml in the MDMA-only condition, with large inter-subject variability. This was also the case in the multiple drug condition, where generally, significantly higher concentrations of MDMA, MDEA and/or amphetamine were detected in the oral fluid samples. Urine screening revealed the presence of combinations such as MDMA, MDEA, amph, cannabis, cocaine, LSD and psilocine in the multiple-drug condition.

Adult↗

Comparison of daily urine, sweat, and skin swabs among cocaine users.

This study (1) compares urine, skin swabs, and PharmChek sweat patches for monitoring drug use; (2) measures possible environmental contamination in recent cocaine (COC) users; and (3) evaluates various immunoassays (IA) for screening COC in diverse matrices. Unique aspects include daily urine monitoring of 10 participants for 4 weeks, multiple monitoring methods, analysis for all specimens by IA and gas chromatography (GC)/mass spectrometry (MS), and the potential for continued illicit drug use by participants. Urine served as the "gold standard" specimen for determining drug use. Only cocaine and related substances were detected. Trace amounts of drugs were found on the skin (<50 ng per swab) of urine-negative participants' hands or forehead. In contrast, larger quantities of COC were found on the skin of individuals with BE-positive urines or individuals living with drug users (up to 20 microg per swab). Patch COC amounts among the three regular users (250-9000, 0-240, 160-22,000 ng per patch) exceeded BE (50-950, none, 30-2200 ng per patch). Pre-swabs, valuable for interpreting the source or time frame of positive patch results, contained substantial COC (38-1160, 0-152, 34-762 ng per swab) prior to patch application; therefore, patch results may represent current use, prior use, contamination, or a combination. In three individuals with no indication of cocaine use, false positives (defined as sweat patch positive when urine specimens were <300ng BE/ml) occurred at a 7% rate. Proposed cut-off concentrations of 75 ng cocaine per patch and 300 ng BE/ml urine curtail the incidence of false positives in this limited population. Three immunoassays were compared to screen specimens for cocaine: a modified, manual Microgenics CEDIA; a Cozart ELISA; and an OraSure ELISA. CEDIA's limit of detection (LOD) was 81ng/ml, compared with LODs of 4 ng/ml for the Cozart ELISA and 1.5 ng/ml for the OraSure ELISA. Cozart correlated with OraSure results for COC concentrations <2000 ng per swab (n=117), r(2)=0.79.

Adult↗

Fever and sweats in the patient with advanced cancer.

Fever and sweats are common complications of cancer and its treatment. This article reviews potential causes and pathophysiologic mechanisms of fever and sweat. Management recommendations, consisting of primary interventions directed at contributing causes and pathophysiologic mechanisms, and non-specific palliative measures are discussed. Optimal management is contingent on the physician's integration of medical expertise with patient-derived goals of care.

Analgesics, Non-Narcotic↗

Genetic changes in sweat gland carcinomas.

The molecular pathogenesis of malignant appendageal tumors is poorly understood. Immunohistochemical staining, polymerase chain reaction (PCR)-based loss of heterozygosity (LOH) and sequencing analyses were performed in a mixed group of 21 sweat gland carcinomas. LOH was mostly confined to the chromosome arm 17p. None of the remaining 17 tumors showed LOH at any loci. Nuclear accumulation of p53 protein was observed in 3 tumors, all of which also showed LOH of 17p. One eccrine gland adenocarcinoma showed allelic loss of 17p and a Cys 176 Arg mutation in the p53 gene. The other three tumors that showed LOH of 17p, however, had wild-type p53 genes. A clear transition from benign eccrine poroma to porocarcinoma that was associated with p53 protein stabilization and allelic loss was observed in one tumor. One eccrine porocarcinoma/undifferentiated adnexal carcinoma showed prominent microsatellite instability, probably reflecting an underlying defect in DNA mismatch repair. Overexpression of erbB-2 was observed in three tumors. The low frequencies of LOH and p53 alterations in sweat gland carcinomas contrasted with the multiple genetic defects normally observed in cutaneous squamous cell carcinomas, and may be partly explained by the relative protection of cutaneous appendages from ultraviolet light and other environmental mutagens.

Adenocarcinoma↗

Mislocalization of delta F508 CFTR in cystic fibrosis sweat gland.

Misprocessing and mislocalization of the cystic fibrosis (CF) transmembrane conductance regulator (CFTR) has been described for the major CF-causing mutation (delta F508) in heterologous expression systems in vitro. We have generated monoclonal antibodies (mAbs) to CFTR with the aim of localizing the protein and its CF variants in vivo. Of the tissues where CFTR was observed, only the sweat gland is readily available and does not undergo secondary changes due to CF disease pathology. Sweat ducts from CF patients homozygous for delta F508 did not show the typical apical membrane staining seen in control biopsies. This demonstrates that the biosynthetic arrest and intracellular retention of delta F508 CFTR initially observed in vitro does occur in vivo and emphasizes the need to focus efforts on understanding the mislocalization.

Amino Acid Sequence↗

Determination of extractable perfluorooctanoic acid (PFOA) in water, sweat simulant, saliva simulant, and methanol from textile and carpet samples by LC/MS/MS.

Methods were developed to quantify the amount of perfluorooctanoic acid (PFOA) extracted from textile and carpet samples through contact with water, methanol, and sweat and saliva simulants using LC/MS/MS. The limit of quantitation (LOQ) for samples extracted in water and sweat simulant is 1 ppb (ng PFOA (g sample)(-1)) while the limits of quantitation for samples extracted in saliva simulant and methanol were 3 ppb and 2.5 ppb, respectively. Method validation results are provided for a polyester control textile sample that was extracted in water on two different days by different analysts, which gave an overall recovery of 103% and standard deviation of 5.3% for 30 analyses. However, for routine application of these methods to a large number of sample sets differing in chemical and physical compositions, a complete validation for each sample type is not practical or possible since control samples for fortifications are often not available. Instead, suitable analytical methods and acceptance criteria are described which ensure accurate PFOA quantitation in each of the solvent extract types. During routine use of these methods, post-extraction spike recoveries for the different sample types and solvents are 100 +/- 15% using a dual isotopically labeled (13)C-PFOA internal standard to correct for matrix effects. A comparison of extraction solvent versus time using a wrist action shaker for textile and carpet samples demonstrates that the total extractable amount of PFOA is similar for each of the solvent types. However, as expected the rate of extraction in water and simulants is significantly less than that of methanol. Finally, a comparison of 2 h and 24 h wrist action shaker extractions with a 1.5 h pressurized fluid extraction (PFE) in methanol reveals that the 24 h wrist action shaker yields the highest results. The 2 h wrist action shaker results are similar to those of the 1.5 h PFE extraction.

Caprylates↗

Isolation and characterization of latherin, a surface-active protein from horse sweat.

A protein, latherin, with unusual surface activity was isolated from horse sweat by gel filtration and ion-exchange chromatography. The protein has a Stokes radius, determined by gel filtration, of 2.47 nm, and in the ultracentrifuge sediments as a single species with S20,W 2.05 S, indicating an Mr of 24,400. On SDS/polyacrylamide-gel electrophoresis the molecule behaves as a single peptide chain of apparent Mr 20,000. Latherin contains a high proportion of hydrophobic amino acids (37.2%), and the leucine content (24.5%) is exceptionally high. The unusual composition of the protein may account for apparent anomalies in the Mr of latherin determined by empirical methods. Evidence indicating that latherin is responsible for much of the surface activity of horse sweat was obtained by a simple assay for surface tension and by contact-angle measurements. Latherin adsorbs very readily at hydrophobic surfaces, rendering them wettable. A possible role for latherin in thermoregulation is proposed.

Amino Acids↗

Effects of UTP on Na+, Cl- and K+ transport in primary cultures from human sweat gland coils.

Extracellular ATP and UTP can increase membrane permeability in the sweat gland, but the intracellular signalling regulating the response to these agonists is poorly understood. Stimulation of Cl- transport by nucleotides has been suggested as a pharmacological therapy to improve Cl- secretion in patients with cystic fibrosis. In the present study, regulation of Na+, Cl- and K+ transport in primary cultures of cells from the secretory coil of human sweat glands was investigated by electron probe X-ray microanalysis. Stimulation with 200 microM UTP for 2 min at room temperature caused a significant increase in intracellular Na but did not affect Cl and K. After 5 min, the Na concentration was still increased, but now also a significant decrease in Cl and K was observed, indicating an increase in Cl- and K+ permeability. The effect of UTP on Cl- secretion was enhanced in Mg2+-deficient buffer, indicating that the response is elicited by the extracellular fully ionized form of UTP (UTP4+), but not by MgUTP2+. The effects of UTP were abolished in Ca2+-deficient buffer supplemented with EGTA. Alloxan, an adenylate cyclase inhibitor, did not inhibit the response to UTP. These results indicate that the membrane Cl- and K+ permeability elicited by UTP in primary coil cell cultures is Ca2+-dependent. The response to UTP did not attenuate at 8 degrees C, suggesting that it could be activated, in part, via ligand-gated ion channels. The effect of UTP was not decreased in the presence of ouabain. Pre-treatment of the cells with pertussis toxin (24 h) had minor effects on Cl- secretion activated by UTP, indicating a role for G proteins in the UTP activation of Cl- secretion.

Adenylate Cyclase Toxin↗

Human sweat and 2-oxopentanoic acid elicit a landing response from Anopheles gambiae.

A wind tunnel bioassay and video to observe mosquitoes landing on heated glass cylinders were used to test sweat and some derivatives for responses of Anopheles gambiae Giles (Diptera: Culicidae), a highly anthropophilic African species of malaria vector. Filter papers impregnated with human sweat and a diethyl ether extract from the filter papers elicited significantly more landings than a water control (P<0.001). The concentration of lactic acid in the extract was determined by GLC assay, but bioassays of an equivalent dose of lactic acid (from a commercial supplier) did not elicit landings. Chemical analysis of the extract by combined GLC/mass spectrometry indicated the presence of 73 compounds, of which 40 were tentatively identified. The major components of the extract were aliphatic carboxylic acids. An artificial blend of 22 carboxylic acids did not elicit landings. Bioassays of 2-oxopentanoic acid elicited significantly more, landings (P<0.001). The possible importance of oxo-carboxylic acids for host-seeking by anthropophilic mosquitoes is discussed and their use for trapping is suggested.

Animals↗

Sweat gland and pupillary responsiveness in Horner's syndrome.

Eight patients with Horner's syndrome (five with a 1st neuron lesion and three with a 2nd neuron lesion) were examined for their pupillary responses to pharmacologic stimulation with tyramine (2%) and with phenylephrine (1%) eye drops. The same patients were also evaluated for their forehead sweating pattern on stimulation with body heating and pilocarpine injection, using the Evaporimeter. Five patients had a brain stem (1st sympathetic neuron) lesion, while three patients had had a traumatic C8-Th1 root avulsion and hence had a preganglionic neuron lesion. The average response with the phenylephrine eye test and the pilocarpine sweat test differed markedly between the two groups; only the central neuron lesion group had a supersensitivity reaction to both drugs. These procedures may be of diagnostic value in localizing the lesion in patients with a Horner's syndrome of unknown etiology. Patients with 3rd neuron lesion have not been examined with this combination of techniques.

Aged↗

Cystatin M/E expression is restricted to differentiated epidermal keratinocytes and sweat glands: a new skin-specific proteinase inhibitor that is a target for cross-linking by transglutaminase.

Using serial analysis of gene expression on cultured human keratinocytes we found high expression levels of genes putatively involved in host protection and defense, such as proteinase inhibitors and antimicrobial proteins. One of these expressed genes was the recently discovered cysteine proteinase inhibitor cystatin M/E that has not been characterized so far at the protein level with respect to tissue distribution and additional biologic properties. Here we report that cystatin M/E has a tissue-specific expression pattern in which high expression levels are restricted to the stratum granulosum of normal human skin, the stratum granulosum/spinosum of psoriatic skin, and the secretory coils of eccrine sweat glands. Low expression levels were found in the nasal cavity. The presence of cystatin M/E in skin and the lack of expression in a variety of other tissues was verified both at the protein level by immunohistochemistry or western blotting, and at the mRNA level by reverse transcriptase polymerase chain reaction or northern blotting. Using biotinylated hexapeptide probes we found that cystatin M/E is an efficient substrate for tissue type transglutaminase and for transglutaminases extracted from stratum corneum, and that it acts as an acyl acceptor but not as an acyl donor. Western blot analysis showed that recombinant cystatin M/E could be cross-linked to a variety of proteins extracted from stratum corneum. In vitro, we found that cystatin M/E expression in cultured keratinocytes is upregulated at the mRNA and protein level, upon induction of differentiation. We demonstrate that cystatin M/E, which has a putative signal peptide, is indeed a secreted protein and is found in vitro in culture supernatant and in vivo in human sweat by enzyme-linked immunosorbent assay or western blotting. Cystatin M/E showed moderate inhibition of cathepsin B but was not active against cathepsin C. We speculate that cystatin M/E is unlikely to be a physiologically relevant inhibitor of intracellular lysosomal cysteine proteinases but rather functions as an inhibitor of self and nonself cysteine proteinases that remain to be identified.

Cell Differentiation↗

[Parotid swelling with night sweat, fever and weight loss symptoms. A rare differential diagnosis].

HISTORY AND CLINICAL FINDINGS: A 29-year-old patient complained of recurrent swelling of the eyelids and cheeks, fever, diffuse headaches, night sweat and weight loss (8 kg during 8 weeks). Both parotid glands showed swelling which were solid, plain and non-painful to pressure. Palpation did not reveal enlarged lymph nodes. There were no other pathological findings except for anisocoria and disturbed motoric function of the right eye's pupil. INVESTIGATIONS: Laboratory findings, chest X-ray, abdominal sonography and ilium crest biopsy showed no signs of lymphoma or other tumour. MRT showed enlarged parotid glands and hypointensity of a few small (up to 2 cm) areas. Because of these findings Heerfordt syndrome with involvement of the third cranial nerve and the lacrimal glands was suspected and verified by parotid biopsy. TREATMENT AND COURSE: Under corticosteroid therapy started with 80 mg/d symptoms rapidly ceased. Therapy was continued for one year. 8 months after therapy had been stopped the patient had no complaints and investigations showed no signs of recurrence nor pulmonary or any other organ manifestation. CONCLUSION: If swelling of the parotid glands with night sweat, fever and weight loss occur, parotid biopsy should be performed early to exclude malignancy. With parotid gland biopsy also diagnosis of other diseases which have similar signs, such as Sjögren syndrome and parotid gland sarcoidosis, can be established early.

Adult↗

[Frey's syndrome (gustatory sweating) after fracture of the temporomandibular joint].

Damage of the auriculo-temporal nerve with consecutive Frey's syndrome (gustatory sweating) can occur with fractures of the temporomandibular joint (TMJ) as a result of the anatomic proximity. A case of marked gustatory sweating as a rare complication of a mandibular joint fracture and alternation of therapy are reported.

Fracture Fixation, Internal↗

Recurrent polymorphous sweat gland carcinoma of the skin.

Polymorphous sweat gland carcinoma is an unusual, recently described variant of low-grade malignant adnexal neoplasm of the skin characterized by a prolonged clinical course and predilection for the extremities. We describe a case of recurrent polymorphous sweat gland carcinoma in a 56-year-old man who presented with multiple large skin nodules distributed along the flexor surface of his left arm. The lesions were treated by surgical excision; multiple local recurrences, as well as the development of new lesions, were observed over a period of 5 years. No distant metastases have been observed so far. The clinical differential diagnosis and management of these unusual lesions are discussed.

Arm↗

The influence of exercise intensity on sweating efficiency of the whole body in a mild thermal condition.

To investigate whether the exercise intensity affects sweating efficiency (eta sw) during exercise under mild environmental conditions, six healthy males, aged 22 +/- 2 years, performed three bicycle ergometer exercises at varying intensities (73W: Ex-1, 103W: Ex-2 and 133W: Ex-3) for 40 min under the conditions of 25 degrees C room temperature, 50% relative humidity and 0.3-0.4 m s-1 wind velocity. Heart rate, oxygen consumption, rectal temperature (Tre), mean skin temperature (Tsk; 4 skin sites) and total sweat rate were determined intermittently throughout the experiments. Moreover, heat loss by evaporation (E), radiation (R), convection (C) and eta sw were calculated using the heat balance equations. The findings concerning thermoregulatory parameters under the three experimental conditions were summarized as follows: (1) the higher the exercise intensity, the larger the values of Tre and Tsk at the end of exercise and E, R and C during exercise (2) the mean values +/- SE of eta sw were 55.4 +/- 5.1, 63.2 +/- 5.2 and 58.5 +/- 1.9% for Ex-1, Ex-2 and Ex-3, respectively. The results suggest that exercise intensity would have no effect on eta sw in this mild thermal environment.

Adult↗

An overview of the use of urine, hair, sweat and saliva to detect drug use.

This paper provides a brief overview of qualitative drug testing procedures using urine, hair, saliva and sweat specimens. Issues related to collection, analysis and interpretation of each specimen as well as their advantages and disadvantages are discussed. The biological detection of drug use involves a screening test which, if positive, is followed by a confirmatory test. Urine is the most widely used specimen in the detection of drugs. Urinalysis offers an intermediate window of detection (1-3 days). Hair analysis offers the largest window of detection (7-100+ days). Saliva analysis may be useful in determining very recent drug use (1-36 hours). The analysis of sweat may be useful for continuous monitoring of drug use (1-14 days). Drug testing has become a fast, convenient process with the development of point-of-collection drug testing devices.

Hair↗

Cold-induced sweating syndrome is caused by mutations in the CRLF1 gene.

In 1978, Sohar et al. described a strikingly peculiar syndrome in two Israeli sisters. These young women responded to environmental temperatures of 18 degrees C-7 degrees C with profuse sweating on large segments on their back and chest. Both had additional abnormalities, including a high-arched palate, nasal voice, depressed nasal bridge, inability to fully extend their elbows, and kyphoscoliosis. We have observed this disorder in two Norwegian brothers. Genome-wide screening in the two families, followed by saturation marker studies and linkage analysis, identified a 1.4-Mb homozygous candidate region on chromosome 19p12. The maximum multipoint LOD score was 4.22. In both families, DNA sequencing of 25 genes within the candidate region identified potentially deleterious CRLF1 sequence variants that were not found in unaffected control individuals. Our findings confirm that the cold-induced sweating syndrome is an autosomal recessive disorder that is probably caused by impaired function of the CRLF1 gene, and they suggest important developmental functions for human CRLF1.

Adolescent↗

Characterization of a monoclonal antibody against a mucin-type glycoprotein in human sweat.

We report the preparation and characterization of an IgG2 monoclonal antibody (MAb), HSMA, prepared against a human pooled sweat extract (HPSE). The major component of HPSE was a mucin-type molecule, as revealed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) stained with periodic acid-Schiff (PAS) reagent. By immunoblotting, HSMA revealed a smear in the high molecular weight range, typical of mucins. In enzyme-linked immunosorbent assay (ELISA), HSMA failed to react with HPSE fractions isolated after anionic exchange gel chromatography. Similarly, radio-immunobinding assays demonstrated no reactivity between HSMA and A, B, H, and Lewis blood group-related structures. The immunohistological labeling on normal skin showed that HSMA reacted with the cells of eccrine sweat glands, and to a lesser extent, with sebaceous glands and epidermal cells. Periodate treatment in situ abolished these reactions, thus suggesting the carbohydrate structure of the HSMA-epitope. In indirect immunofluorescence (IF) studies, HSMA also reacted with other exocrine glands, e.g. mammary glands, sublingual glands, mixed sero-mucous glands of the trachea, and in the pancreas. Sparse positive cells were also observed in the testis, kidney, thyroid and digestive tract.

Animals↗