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PubMed1994

Cystic fibrosis screening in neonates--measurement of immunoreactive trypsin and direct genotype analysis for delta F508 mutation.

This study investigated the clinical usefulness of screening for cystic fibrosis (CF) in 19,992 newborns, over 39 months, in an Austrian population. Immunoreactive serum trypsin (IRT) determination was followed by sweat chloride analysis (sweat test) to establish diagnosis. In a retrospective analysis covering 6 months of the study period, individuals who were considered to be at risk after IRT estimation (n = 22) were analysed for delta F508 mutation, using a new method of DNA extraction from the initial dried blood specimens. A total of 119 infants (0.6%) had values greater than 750 ng trypsin/ml whole blood. In 88 babies sweat tests were performed, leading to the diagnosis of CF in 11 cases. One patient was not initially identified by screening but was later discovered due to his clinical status. Three infants were noted to carry the delta F508 mutation (1 homozygous, 2 heterozygous). Two of these babies already had CF. The second heterozygote was a carrier. A highly efficient three tier screening strategy is presented in which IRT estimation, determination of delta F508 status and sweat chloride testing could lead to a high sensitivity analysis of this population.

Cystic Fibrosis↗
PubMed1989

Radioimmunoassay detection limits for 19-OH F1 alpha/F2 alpha prostaglandin in normal, infertile and vasectomized semen stains. Analysis of saliva, sweat and urine for possible non-specific or matrix effects.

The sensitivity of a simple radioimmunoassay (RIA) for the detection of 19-OH prostaglandin F1 alpha/F2 alpha (PG F) has been evaluated on a number of semen samples from vasectomized, infertile and fertile donors. The specificity of the test has been examined by testing saliva, sweat and urine from a number of male and female donors. The assay technique could readily detect the PG in semen stains prepared from 0.2 microliter of semen from normal, infertile and vasectomized donors. The detection limit of the assay system, based on the observed displacement, was calculated to be approximately 0.05 microliter semen. The assay could be conducted over a pH range of 7.5-10.5 even after the PG has been heated to 100 degrees C. The 19-OH series of PG were absent from sweat, saliva and female urine using the normal assay protocol; volumes in excess of 100 microliters of some urines particularly from women in labour and those with acute urinary tract infection showed some displacement. Low levels of PG were detected in 50% of the male urine analysed. However, urine samples from men who had engaged in recent sexual activity contained relatively high concentrations of PG which could be readily detected in 10 microliters of urine. These results emphasise the potential of these compounds as specific and sensitive markers for the presence of human semen.

Dinoprost↗
PubMed2001

Assessment of sweat-testing practices for the diagnosis of cystic fibrosis.

OBJECTIVE: To describe the results of the College of American Pathologists survey questions assessing the current practice of sweat testing in North America and to identify areas in which improvement is needed. DATA SOURCE: Results of the supplemental questions to the SW-B 2000 survey. STUDY SELECTION: Supplemental questions were designed to assess variation in sweat collection, analysis, and interpretation. DATA EXTRACTION: Extractions of the data were made based on the relevance of the data to the objectives of the review. DATA SYNTHESIS: The majority of laboratories surveyed performed sweat testing according to the procedures described in the National Committee for Clinical Laboratory Standards' document. The study revealed that a number of laboratories have adopted poor practice standards and are potentially compromising patient care. Areas of concern include the number of laboratories performing few sweat tests per year, the persistence of unreliable methodology, misunderstanding of collection parameters, lack of patient education, and erroneous result reporting. CONCLUSIONS: The study identified areas of concern toward which educational efforts can be directed. Such efforts include the development of a College of American Pathologists accreditation checklist for sweat testing and targeted responses in the sweat analysis participant summary report.

Chemistry, Clinical↗
PubMed2005

Cystic fibrosis in Korean children:a case report identified by a quantitative pilocarpine iontophoresis sweat test and genetic analysis.

Cystic fibrosis (CF) is inherited as an autosomal recessive trait, and the mutations in cystic fibrosis transmembrane conductance regulator (CFTR) gene contributes to the CF syndrome. Although CF is common in Caucasians, it is known to be rare in Asians. Recently, we experienced two cases of CF in Korean children. The patients were girls with chronic productive cough since early infancy. Chest computed tomography showed the diffuse bronchiectasis in both lungs, and their diagnosis was confirmed by the repeated analysis of a quantitative pilocarpine iontophoresis test (QPIT). The sweat chloride concentrations of the first patient were 108.1 mM/L and 96.7 mM/L. The genetic analysis revealed that she was the compound heterozygote of Q1291X and IVS8 T5-M470V. In the second case, the sweat chloride concentrations were 95.0 mM/L and 77.5 mM/L. Although we performed a comprehensive search for the coding regions and exon-intron splicing junctions of CFTR gene, no obvious disease-related mutations were detected in the second case. To our knowledge, this is the first report of CF in Korean children identified by a QPIT and genetic analysis. The possibility of CF should be suspected in those patients with chronic respiratory symptoms even in Korea.

Blood Pressure↗
PubMed1996

Sweat duct milia--immunohistological analysis of structure and three-dimensional reconstruction.

The fine structure of sweat duct milia and the pathomechanism in their aetiology are still unknown. To examine the relationship and connection of milia to the sweat ducts as well as to the overlying epidermis, nine sweat duct milia, six incomplete and three complete, were studied by three-dimensional reconstruction (3DR) analysis based on photomicrographs obtained after histological and immunohistochemical staining with antibodies against carcinoembryonic antigen (CEA), cancer antigen (CA 50) and human cytokeratin 19 (CK 19). In both incomplete and complete milia, an eccrine duct expressing the antigens penetrated into the cyst wall at the centre of its base, formed a circular path within the wall, and opened into the inner cavity. The eccrine duct was mature in eight milia and immature in one. In the cyst wall, CA 50 and CK 19 were detected throughout the entire cyst except for the most apical portion of incomplete milia, where the cyst wall fused with the overlying epidermis which did not express any of the antigens. CEA was distributed mainly in the basal half of the milia. The finding that the path of the eccrine duct within the cyst wall is circular conflicts with the currently accepted concept of simple penetration of the eccrine duct into the wall, suggesting an acrosyringeal origin of the milia. An incomplete milium is the result of fusion between cells derived from an eccrine duct and those derived from the surrounding epidermis, while the formation of a complete milium does not involve this fusion.

Aged↗
PubMed1992

Cytokeratin expression in mucinous sweat gland carcinomas: an immunohistochemical analysis of four cases.

Four mucinous sweat gland carcinomas were examined for the distribution of cytokeratin (CK) polypeptides using immunohistochemical techniques on paraffin-embedded sections. All the tumour specimens reacted with monoclonal antibodies to CK 7, CK 8, CK 18 and CK 19. Antibodies to CK 1, CK 1/2/10/14, CK 1/5/10/11, CK 13, CK 14 and CK 20 did not stain any of the carcinomas. The results add additional support to the notion that mucinous sweat gland carcinoma represents a tumour histogenetically related to the eccrine secretory coil. Furthermore, the absence of CK 20 might significantly contribute to the differentiation of this tumour from cutaneous metastases from gastrointestinal carcinomas.

Adenocarcinoma, Mucinous↗
PubMed1998

Enantioselective analysis of methadone in sweat as monitored by liquid chromatography/ion spray-mass spectrometry.

In recent years, remarkable advances in sensitive analytical techniques have enabled the analysis of drugs in unconventional samples, such as sweat. In a study conducted during a methadone maintenance program, PharmChek sweat patches were applied to 20 subjects. The subjects were orally administered methadone in 1 dosage/day, and doses ranged from 80 to 100 mg. The sweat patch was applied 10 minutes before administration and removed 72 hours later just before a new administration of methadone. The absorbent pad was stored at -20 degrees C until analysis in plastic tubes. Methadone was extracted in 5 ml methanol in presence of 200 ng of racemic methadone-d3, used as internal standard. After a 30-minute agitation, the methanol solution was evaporated to dryness. Enantioselective separation of methadone was obtained using an alpha-1-acid glycoprotein column (100 x 4 mm ID) and liquid chromatography/ion spray-mass spectrometry. In all 20 specimens obtained from subjects under racemic methadone treatment, R- (the active form) and S-enantiomers of methadone were identified with the following concentrations: 26 to 1118 ng/patch for R-methadone and 28 to 1114 ng/patch for S-methadone. The ratio between R- and S-methadone was in the range of 0.72 to 2.66 and was higher than 1.00 in 15 samples. No correlation between the doses of methadone administered and the concentrations of methadone in sweat was observed.

Chromatography, High Pressure Liquid↗
PubMed1997

Frey's syndrome after parotidectomy: a retrospective and prospective analysis.

Gustatory sweating is a well-known sequela after parotid surgery. In a retrospective and prospective study of patients undergoing parotid surgery, the onset, time course, extent, and treatment modalities of Frey's syndrome were analyzed. Twenty-two percent of the patients evaluated by questionnaires and 43% of the patients followed prospectively within 1 year were found to be symptomatic. Although the Minor starch-iodine test was positive in 38% of patients at 3 months, none of these patients experienced symptoms. Up to 12 months after surgery the rate of patients who tested positive increased to 96% and the total area of sweating expanded to a mean value of 18 cm2. Whereas most of the patients are not markedly disturbed, few patients (5% to 10%) suffer from severe gustatory sweating. These patients present a therapeutic challenge.

Adenoma, Pleomorphic↗
PubMed1998

Sweat gland carcinoma: a clinicopathologic analysis of an expanded series in a single institution.

Primary adenocarcinoma of sweat glands is a rare tumor; approximately 220 cases have been reported in the last 30 years. We reviewed the charts of patients with primary diagnosis of this tumor treated at the Mayo Clinic between 1935 and 1995. We included only cases with initial histology slides available for re-examination. Tumors were classified into five recognizable histologic patterns (solid, ductal, mucinous, microcystic adnexal, and adenocystic carcinoma) and graded by the Broder system. Statistical analysis consisted of Kaplan-Meier product limit method and Cox multiple regression test. In total, 55 patients were identified, and age ranged from 13 to 85 years (mean 59 years). Thirty-six patients (65 percent) presented to the Mayo Clinic for initial treatment; all except one had disease limited to the primary site. Microcystic adnexal carcinoma was the most frequent type, and more than 50 percent were grade 2 tumors. Among these 36 patients, 4 had some type of recurrence. Patients who developed metastasis had a high-grade tumor in the initial biopsy. Nineteen patients were referred with recurrence; 13 had local recurrence, 4 had regional diseases, and 2 had distant metastases. The histologic distribution showed 47 percent solid tumors, and 37 percent of them were grade 3. Multiple regression analysis did not show a difference in recurrence or survival when gender, age, tumor location, or histologic pattern was evaluated. In addition, there was no difference in the outcome between wide surgical resection and micrographic surgery. The only predictive factor for distant metastases and/or death (p < 0.003) was histologic grade. Overall 10-year survival rate was 86 and 60 percent for primary and referred patients, respectively. We conclude that histologic diagnosis of sweat gland carcinoma must be complemented by clinical examination to evaluate metastases. Clinical behavior depends on the histologic type of tumor, degree of differentiation, and clinical stage. On recurrence, the likelihood of further recurrences and mortality increases dramatically. Aggressive initial local ablation with tumor-free margins is recommended. In high-grade tumors, prophylactic regional lymph node dissection may further characterize tumor aggressiveness and may justify adjuvant radiotherapy as part of the primary treatment.

Adenocarcinoma↗
PubMed2005

The relevance of sweat testing for the diagnosis of cystic fibrosis in the genomic era.

Cystic fibrosis (CF) is the most common inherited disorder of childhood. The diagnosis of CF has traditionally been based on clinical features with confirmatory evidence by sweat electrolyte analysis. Since 1989 it has been possible to also use gene mutation analysis to aid the diagnosis. Cloning of the cystic fibrosis transmembrane conductance regulator (CFTR) gene has advanced our understanding of CF, in particular the molecular basis of an expanded CF phenotype. However, because there are over 1000 mutations and 200 polymorphisms, many without recognised effects on CFTR, the molecular diagnosis can be troublesome. This has necessitated measurement of CFTR function with renewed interest in the sweat test. This review provides an overview of the clinical features of CF, the diagnosis and complex genetics. We provide a detailed discussion of the structure and function of CFTR and the classification of CFTR mutations. Sweat electrolyte analysis is discussed, from the physiology of sweating to the rigours of a properly performed sweat test and its interpretation. With this information it is possible to understand the relevance of the sweat test in the genomic era.

Journal Article↗
PubMed1989

An analysis on the rates and regulation of insensible water loss through the eccrine sweat glands.

An analysis is presented on insensible water loss from the human body at rest through exposed skin surfaces into still air. Possible sites of moisture release are identified as the stratum corneum of the skin, free surfaces of dilute sweat liquids perpetually present in the microscopic ducts of a large population of eccrine sweat glands, and moist microvillous processes which line part of the periductal surfaces in the glands, particularly in the helical coils within the stratum spinosum of the epidermis. Water supply to the sites involves transepidermal migration across skin tissue layers, secretion and partial reabsorption of solutes and water within eccrine glands, and transport across periductal lining of eccrine glands from the surrounding connective tissues respectively. Evaporation and gas phase diffusion within eccrine ducts were modelled. Basal loss rates of water (as regulated by the ambient temperature and relative humidity and by aspects of the anatomy of and physiological factors for eccrine glands, the epidermis and the dermis) were calculated at between 1 and 20 g hr-1 at an ambient temperature of 25 degrees C and a relative humidity of 60% as an example. Such rates are significant fractions of experimental values for insensible water loss rates reported at between 4 and 35 g hr-1 in air at 22-30 degrees C and a relative humidity of 30-60%.

Eccrine Glands↗
PubMed2004

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↗
PubMedDate not supplied

Screening for cystic fibrosis: the importance of using the correct tools.

BACKGROUND: Cystic Fibrosis (CF) is a potentially lethal genetic disorder. The most frequent mutation worldwide in the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) gene is designated as the Delta F508 mutation. This mutation was found in only 33% of Pakistani patients studied. Since the common Pakistani mutations remain to be identified, appropriate screening tools are required to identify disease. Sweat chloride determinations remain the gold standard for diagnosing CF. This study was done to emphasize the importance of using the correct tests. METHODS: The study was conducted at the Aga Khan University Hospital. The CFTR delta F508 mutation was tested on blood samples from patients suspected with CF. Sweat chloride analysis using pilocarpine iontopharesis was done with a positive value of greater than 60 meq/L. RESULTS: 57 pediatric samples were screened for the delta F508 mutation and were positive in only 10.6% of all patients tested. 12/57 (21%) had a preliminary sweat test. 6/12 (50%) of these patients had an abnormal sweat test and 3/6 patients with an abnormal sweat chloride (50%) had deltaF508 mutations-- 2/6 (33%) were homozygotes and 1 was a compound heterozygote. Since 79% did not have a sweat test, it was difficult to assess whether this subset of patients had cystic fibrosis with a CFTR mutation other than the delta F508 tested or no CF. CONCLUSION: Sweat chloride analysis is critical to distinguish CF from other causes of severe pulmonary and pancreatic insufficiencies and to define patients requiring further analysis.

Chlorides↗
PubMed1987

Cl- permeability of sweat duct cell membranes: intracellular microelectrode analysis.

Cl- permeability in the reabsorptive sweat duct (RSD) epithelium from normal subjects was studied using electrophysiological techniques. The average basolateral membrane potential (Vb) of normal ducts was -36.8 +/- 0.8 mV and the average apical membrane potential (Va) was -27.2 +/- 0.8 mV (n = 45). Amiloride in the lumen of microperfused sweat ducts hyperpolarized Va by 34.3 +/- 3.1 mV and Vb by 25.7 +/- 3.1 mV (n = 12) with a small but significant increase in voltage divider ratio (Ra/Rb) from 4.2 +/- 0.8 to 5.0 +/- 0.8 (n = 8). Cl- substitution in the lumen depolarized Va by +37 +/- 4.2 (n = 11) accompanied by a significantly larger increase in Ra/Rb from 4.8 +/- 2.6 (n = 8) to 7.0 +/- 3.1 (n = 8). Bath Cl- substitution depolarized Vb by +24.3 +/- 2.7 mV (n = 15) while decreasing Ra/Rb from 3.2 +/- 0.7 to 1.9 +/- 0.4 (n = 7). These results indicated a significant Cl- permeability in both apical and basolateral membranes. Removing Cl- from the lumen significantly decoupled Va and Vb and restricted the amiloride-induced hyperpolarization to the apical membrane. This result may suggest that intracellular Cl- might be responsible for coupling Va and Vb and that hyperpolarization of Va and Vb by amiloride may result in changes in intracellular Cl-. Alternatively, Va and Vb could be coupled through a Cl- sensitive paracellular shunt. These results are consistent with Cl- permeability in both apical and basolateral membranes of duct cells. However, the question of whether paracellular Cl- permeability is important in Cl- uptake cannot be determined from the present data.

Amiloride↗
PubMed1996

Enzymatic determination of sodium and chloride in sweat.

OBJECTIVE: To develop methods based on enzyme activation for the analysis of sweat sodium and chloride using beta-galactosidase and alpha-amylase, respectively. METHODS: Both were monitored kinetically on the Cobas Fara centrifugal analyzer. The sweat, collected with the Macroduct system, was diluted no more than five-fold for the volumes obtained of 16 to 80 mu L, median 32.5 mu L. The sodium assay utilized a sodium-binding cryptand to maximize linearity. RESULTS: Between-run coefficients of variation (%) at 10, 20, and 50 mmol/L were 3.6, 4.5, and 1.3 for sodium and 7.1, 6.1, and 6.0 for chloride, respectively. The sodium method showed excellent agreement with flame photometry (y = 0.997x + 0.742; r = 0.998), and chloride with a mercuric thiocyanate method (y = 0.995x + 0.485; r = 0.996), giving equivalent discrimination between patients with and without cystic fibrosis. CONCLUSIONS: The methods enable the rapid analysis on the same analyzer of both sodium and chloride in a single dilution of sweat collections of low volume.

Bridged Bicyclo Compounds, Heterocyclic↗