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At least 415 records · Page 23Linked to original sources
PubMed1989

Prenatal diagnosis of cystic fibrosis by using linked DNA markers in 138 pregnancies at 1-in-4 risk.

Prenatal diagnosis was carried out in 138 pregnancies at 1-in-4 risk for cystic fibrosis (CF) by using closely linked DNA markers, including XV-2c and KM-19. In fully informative families, 25 of 123 (20%) fetuses were predicted to be affected; 16 of these 25 pregnancies were terminated and 9 were continued. Postnatal sweat tests are completed in 42 cases; the diagnoses were confirmed in 4 of 4 infants predicted to be affected and in 37 of 38 infants predicted to be unaffected. One infant predicted to be a carrier had an abnormal sweat test after birth, but the mother also had an abnormal sweat test, and there was no evidence of an error in linkage analysis. The data indicate that prenatal diagnosis using linkage analysis is fully informative in most families and is highly reliable with either chorionic villus sampling or amniocentesis. Although outcome data are available on only 42 pregnancies, based on our experience, on general principles of linkage analysis, and on the tight linkage of the known DNA markers with CF, we recommend that DNA analysis replace microvillar intestinal enzyme analysis for 1-in-4 risk pregnancies when DNA is available from the propositus.

Cystic Fibrosis↗
PubMed1982

In vivo and in vitro characteristics of eccrine sweating in patas and rhesus monkeys.

Biopsy specimens from the chest, palm, back, and lateral calf were obtained from three patas (4-6 kg) and two rhesus monkeys (6 and 8 kg) tranquilized with ketamine hydrochloride (10 mg/kg). The eccrine sweat glands of the specimens were subsequently isolated under a stereomicroscope and prepared for analysis. In both palmar and hairy skin (chest, lateral calf) patas eccrine glands were larger than those isolated from corresponding sites obtained from the rhesus specimens. In vitro stimulation of the patas' glands with methacholine (MCH) chloride produced a dose-dependent increase in sweating rate that was blocked by atropine. Maximal palmar sweating was comparable between the two species of monkey. Mean maximal in vitro sweating rates on the chest and lateral calf of the three patas monkeys were 3.79 and 4.6 nl. gl-1.min-1, respectively. In contrast, the in vitro sweating rate of the rhesus chest glands was negligibly small, i.e., 0.05 nl.gl-1. min-1. Maximal in vivo sweating rates measured by resistance hygrometry during exercise in a hot (40 degrees C) environment were usually synchronous, cyclic, and only slightly below maximal in vitro rates. When the monkey (patas) was already sweating, the onset and cessation of exercise produced an immediate rise and decline in sweating, respectively. At any given rectal or mean skin temperature, sweating was two- to sixfold higher in the patas compared with that of the rhesus monkey. These results indicate that the patas monkey is an excellent model for studying the physiology of sweating in humans.

Animals↗
PubMed1990

Biologically active interleukin 1 in human eccrine sweat: site-dependent variations in alpha/beta ratios and stress-induced increased excretion.

Human eccrine sweat devoid of epidermal protein contamination was collected from palms, soles, and different sites on the trunk. Interleukin 1 alpha (IL 1 alpha) and interleukin 1 beta (IL 1 beta) content were analyzed for immunoreactivity by enzymo-immunoassay and immunoblotting and for bioactivity by the stimulation of prostaglandin E2 (PGE2) production in human dermal fibroblasts. The bioassay was validated by using blocking antibodies against IL 1 alpha and beta. All sweat samples were found to contain significant amounts of immunoreactive and biologically active IL 1. The immunoreactive forms were at 17 kDa as shown by immunoblotting analysis, indicating that they were mature (secreted), undegraded IL 1 peptides. Whereas IL 1 alpha was detectable in sweat samples obtained from both truncal and palmo-plantar regions, IL 1 beta was only detectable in the sweat of palms and soles (IL 1 alpha/beta ratio greater than 700 in trunk and 5.4 in palms and soles) indicating a site-dependent difference in the excretion of the two IL 1 molecules. IL 1 concentration was high in spontaneous (IL 1 alpha, 3.7; IL 1 beta, 0.3 ng/mL) and pilocarpine induced sweat (IL 1 alpha, 3.9; IL 1 beta, 1.2 ng/mL), and it was much increased during jogging and sauna (IL 1 alpha, 22.6; IL 1 beta, 3.3 ng/mL). This does not appear to represent an excretory process aimed at clearing blood IL 1, but rather a stress-induced increased production of IL 1 by sweat gland cells.

Adult↗
PubMed2003

Arithmetic calculation, deep inspiration or handgrip exercise-mediated pre-operational active palmar sweating responses in humans.

We examined the effects of repetitive mental stimulation such as arithmetic calculations with sequential subtraction or physical tasks such as handgrip exercise and deep breathing on active palmar sweating responses in humans. Thirty-three healthy, male and female volunteer students (20.4+/-2.1 years) participated in the present study. The responses of active palmar sweating were evaluated by using the newly developed ratemeter. The galvanic skin response (GSR) was also recorded in 10 out of 33 subjects. The oral explanation of the stimulation or tasks caused a rapid and wavy active palmar sweating response. The pre-operational responses of active palmar sweating to the stimulation or tasks were also observed by the GSR recording. The mental stimulation- and physical tasks-mediated pre-operational responses were significantly reduced by the trials. The mental stimulation or physical tasks also caused a rapid and oscillatory response of active palmar sweating during operation of the stimulation or tasks. The operation-mediated responses to physical tasks were observed ipsilaterally and contralaterally. The physical task-mediated responses were also reproducible, resulting in no habituation. In contrast, the operation-mediated responses to mental stimulation were reduced significantly by the trials, resulting in a marked habituation. The findings suggest that the mental stimulation- and physical tasks-mediated pre-operational responses of active palmar sweating obtained by using the newly developed ratemeter will make useful tests for evaluating neuronal activity of limbic system including amygdala, sympathetic sudomotor activity in the palmar skin and functional properties of the palmar sweat glands.

Adult↗
PubMed2002

Negative sweat test in hypertrypsinaemic infants with cystic fibrosis carrying rare CFTR mutations.

UNLABELLED: Persistent hypertrypsinaemia in newborn screening for cystic fibrosis (CF) recognises subjects at high risk to be affected. Diagnosis is confirmed by a positive sweat test and/or by the presence of two mutations in the cystic fibrosis transmembrane regulator gene. The aim of the present study was to evaluate the occurrence of a negative sweat test (chloride < 60 mmol/l) during the first months of life, in hypertrypsinaemic infants, which would lead to a delayed diagnosis. We reviewed clinical charts of CF patients born between January 1993 and September 1998, when the neonatal screening programme consisted of an immunoreactive trypsinogen (IRT)/DNA (F508del) + IRT strategy. Laboratory and clinical data were collected for patients diagnosed after 12 months of life. Out of 446,492 newborns, 104 CF patients were diagnosed giving an overall incidence of 1:4293. Of these, six had a blood IRT level above the cut off value (99th percentile) and a negative sweat test in the first trimester of life. At a mean age of 3.5years, the patients were again referred to our CF Centre for re-evaluation in order to confirm or exclude the disorder. Molecular analysis identified the following genotypes: F508del/A309D, F508del/3849 + 10kbC-->T, F508del/R117H (in two patients), R117H/ L997F, and F508del/R117L. CONCLUSION: Infants with cystic fibrosis bearing a spectrum of mild cystic fibrosis transmembrane regulator gene mutations may present as hypertrypsinaemic newborns with a sweat chloride within the normal range. Reference values for normal sweat test during the first months of life should be revised. A wide molecular genetic analysis is recommended for newborns presenting persistent hypertrypsinaemia and a sweat test result > 30 mmol/l in order to diagnose atypical forms of the disease.

Child↗
PubMed1993

Application of DNA analysis in a population-screening program for neonatal diagnosis of cystic fibrosis (CF): comparison of screening protocols.

We compare two protocols for newborn screening for cystic fibrosis (CF). The first uses the immunoreactive trypsinogen (IRT) assay with a cutoff of > or = 180 ng/ml and a sweat test to identify CF patients. The second uses the IRT assay with a 100 ng/ml cutoff in conjunction with direct analysis for the delta F508 CF transmembrane conductance regulator (CFTR) mutation in a two-tiered (i.e., IRT/DNA) protocol, followed by a sweat test. We screened 220,865 newborns from Wisconsin for CF, using the IRT protocol identifying 369 infants with an elevated IRT, of whom 46 were found to have CF. Another 7 CF patients were identified who had a false-negative IRT level. The CF incidence in the white population was 1 in 3,431 (carrier incidence of 1 in 30). The IRT protocol had a sensitivity of 87% and a positive predictive value of 12.5%. We subsequently used the IRT/DNA protocol to screen 21,258 infants. Of 518 infants with an IRT level > or = 100 ng/ml, 24 carried at least one copy of the delta F508 CFTR mutation, and 4 of these infants were found to have CF, yielding a positive predictive value for this protocol of 16.7%. Direct comparison of the positive predictive value of the two protocols is not valid, because of the different populations screened. However, had the IRT protocol been used on the IRT/DNA cohort, 50 infants, including the 4 with CF, would have received sweat tests, yielding a positive predictive value of 8%. Because of the small sample size, this positive predictive value is not significantly different from that obtained for the IRT/DNA test. However, from a practical point of view the IRT/DNA approach does decrease considerably the number of sweat tests that must be undertaken. The number of false positives for the IRT protocol (46 in 21,258) is increased significantly compared with that for the IRT/DNA approach (20 in 21,258; P < .001). The incidence of delta F508 carriers detected in cohorts with an elevated IRT level was increased compared with the incidence in the general population. The direct costs for the IRT/DNA approach (100 ng/ml) were $11,374 per CF patient detected, compared with $10,187 per CF patient detected for the IRT protocol. Therefore, we conclude that the IRT/DNA approach to CF newborn screening decreases the number of false-positive subjects contacted, without a significant increase in cost.

Analysis of Variance↗
PubMed2003

Serum CA 19-9 levels as a diagnostic marker in cystic fibrosis patients with borderline sweat tests.

Patients with normal or borderline sweat tests present a diagnostic challenge. In spite of the availability of genetic analysis and measurement of nasal potential difference, there is still uncertainty in diagnosing cystic fibrosis in some patients. CA 19-9 is a tumor-associated antigen whose levels were previously found to be elevated in some cystic fibrosis patients. We investigated whether serum CA 19-9 levels can contribute to establishing the diagnosis of cystic fibrosis in patients with a borderline sweat test, and evaluated the influence of different clinical variables on CA 19-9 levels. Serum CA 19-9 levels were measured in 82 cystic fibrosis patients grouped according to their genotype and in 38 healthy individuals. Group A included 50 patients who carried two mutations previously found to be associated with a pathological sweat test and pancreatic insufficiency (DeltaF508, W1282X, G542X, N1303K, and S549R). Group B included 13 compound heterozygote cystic fibrosis patients who carried one mutation known to cause mild disease with a borderline or normal sweat test and pancreatic sufficiency (3849+10kb C-->T, 5T). Group C included 38 normal controls. Nineteen cystic fibrosis patients carried at least one unidentified mutation. An association between CA 19-9 levels and age, pulmonary function, pancreatic status, sweat chloride, previous pancreatitis, serum lipase, meconium ileus, distal intestinal obstruction, liver disease, and diabetes was investigated. The distribution of CA 19-9 levels was significantly different between the three groups ( p<0.01); high CA 19-9 levels were found in 60% (30/50) of group Apatients and in 46.6% (6/13) of group B patients, but in only 5.2% (2/38) of the controls. CA 19-9 levels were inversely related to forced expiratory volume in 1 s, while no association was found with the other clinical parameters examined. Our findings suggest that the serum CA 19-9 in cystic fibrosis patients originates in the respiratory system, and has a useful ancillary role, particularly when diagnostic uncertainty exists. Hence, the diagnosis of cystic fibrosis should be considered in patients with borderline sweat tests and high CA 19-9 levels, but normal levels do not exclude cystic fibrosis.

Adolescent↗
PubMed1995

Gender differences in physiological reactions to thermal stress.

Following an extensive anthropometric evaluation, thermoregulatory responses were studied in nine men and nine women who performed immersed exercise with post-exercise rest in 28 degrees C water. During the post-exercise period esophageal temperature (Tes), oxygen consumption, heat flux and skin blood perfusion were monitored at 10 s intervals, with average minute values used for calculations. The delta Tes (relative to resting Tes) at which sweating abated and shivering commenced were defined as the delta Tes thresholds for the cessation of sweating and onset of shivering, respectively. No significant gender differences were evident in the sweating and shivering threshold delta Tes values, or the magnitude of the null-zone. Using z-tests for parallelism the rates of core cooling across the null-zone were not found to differ significantly between genders, nor were the slopes of the perfusion: delta Tes responses across the null-zone or the post-threshold shivering responses (ml.kg-1.min-1.degrees C-1). The slope of the sweating response (measured from immersion until sweat cessation; g.m-2.min-1 degree C-1) was, however, significantly lower in the female than in the male samples (z = 3.93; P < 0.01). Despite the gender-related dimorphic distribution of adipose tissue, both men and women lost equal proportions of their total heat flux from central and peripheral measurement sites.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1998

Homologous carcinomas of the breasts, skin, and salivary glands. A histologic and immunohistochemical comparison of ductal mammary carcinoma, ductal sweat gland carcinoma, and salivary duct carcinoma.

Morphologic mimicry among human malignant neoplasms is a well-known phenomenon in surgical pathology; both undifferentiated and "committed" neoplasms may exhibit this trait. One particularly common group of histologic simulants includes ductal carcinomas of the breasts, the cutaneous appendages, and the salivary glands. One hundred three tumors in this structural cluster were analyzed microscopically and immunohistologically to codify points of potential pathologic similarity and difference. All the lesions were typified by irregularly permeative clusters and cords of atypical polygonal cells with variable luminal differentiation. A proportion of primary neoplasms in each site demonstrated in situ ductal components; in the absence of the latter elements, however, it was not possible to make topography-related morphologic distinctions among them. Immunostains for gross cystic disease fluid protein-15 (GCDFP-15), carcinoembryonic antigen, S100 protein, c-erbB-2 oncoprotein, estrogen receptor protein, and progesterone receptor protein also showed largely overlapping phenotypes in each of the three tumor categories, with selected exceptions. These differences were elucidated through paired chi 2 analysis and included a statistically significant infrequency of GCDFP-15 in eccrine sweat gland carcinomas, a paucity of carcinoembryonic antigen in breast cancers, and an absence of estrogen receptor protein in salivary duct carcinomas. Such findings may be useful in predefined differential diagnostic settings involving the distinction between primary and metastatic ductal cancers of the breasts, skin, and salivary glands. Nevertheless, because of the striking homologies between such tumors at structural and protein-synthetic levels of comparison, it is mandatory that all available clinicopathologic information be used in this context.

Adenocarcinoma↗
PubMed2005

Generalised anhidrosis: different lesion sites demonstrated by microneurography and skin biopsy.

Generalised anhidrosis (GA) shows a uniform clinical picture whether the pathogenesis involves intrinsic abnormalities of sweat glands or postganglionic sympathetic cholinergic nerve dysfunction. We describe two patients who presented intolerance to heat and anhidrosis. In the first patient, symptoms started at 33 years of age, and were associated with absent tendon reflexes and a mydriatic right pupil unreactive to light. The other patient had been unable to sweat since birth. GA was diagnosed on the basis of clinical findings and thermoregulatory tests. Microneurography and morphological analysis of the skin and its innervation disclosed a different lesion site underlying GA in the two patients, and distinguished between a postganglionic autonomic nerve fibre lesion and sweat gland dysfunction.

Adult↗
PubMed1993

Correlation between genotype and phenotype in patients with cystic fibrosis.

BACKGROUND: Cystic fibrosis is the most common lethal autosomal recessive disorder among whites. Seventy-two percent of patients with this disease are homozygotes or compound heterozygotes for eight mutations of the cystic fibrosis transmembrane conductance regulator gene on chromosome 7: delta F508, G542X, R553X, W1282X, N1303K, 621 + 1G-->T, 1717-1G-->A, and R117H. We studied the relation between genotype and phenotype in patients from 14 countries. METHODS: Each of 399 patients who were compound heterozygotes for delta F508 and one other mutation was matched with the delta F508 homozygote of the same sex who was the closest in age from the same center. A paired analysis was performed of the following outcome variables: age at diagnosis, sweat chloride concentration, growth percentiles, pulmonary-function values, chest-film score, pseudomonas colonization, nasal polyps, pancreatic sufficiency, pancreatitis, diabetes mellitus, meconium ileus, distal intestinal obstruction syndrome, rectal prolapse, cirrhosis, and gallbladder disease. RESULTS: The compound heterozygotes having the genotype R117H/delta F508 clearly differed from the age- and sex-matched delta F508 homozygotes: they more often had pancreatic sufficiency (87 percent vs. 4 percent, P < 0.001), were older when the diagnosis was first made (mean [+/- SD] age, 10.2 +/- 10.5 vs. 2.5 +/- 4.3 years; P = 0.002), and had lower sweat chloride concentrations (80 +/- 18 vs. 108 +/- 14 mmol per liter, P < 0.001). There were no statistically significant differences between delta F508 homozygotes and other compound heterozygotes with regard to any variable tested. CONCLUSIONS: Prenatal and prognostic counseling for patients with the R117H/delta F508 genotype should include the likelihood that they will have long-term pancreatic sufficiency. Patients with the other genotypes should expect the early onset of pancreatic insufficiency. For none of the genotypes studied can predictions be made about the occurrence of common complications or the severity or course of pulmonary disease.

Adolescent↗
PubMed1996

Heat cramps during tennis: a case report.

A 17-year-old, nationally ranked, male tennis player (AH) had been experiencing heat cramps during tennis match play. His medical history and previous physical exams were unremarkable, and his in-office blood chemistry profiles were normal. On-court evaluation and an analysis of a 3-day dietary record revealed that AH's sweat rate was extensive (2.5 L.hr-1) and that his potential daily on-court sweat sodium losses (89.8 mmol.hr of play-1) could readily exceed his average daily intake of sodium (87.0-174.0 mmol.day-1). The combined effects of excessive and repeated fluid and sodium losses likely predisposed AH to heat cramps during play. AH was ultimately able to eliminate heat cramps during competition and training by increasing his daily dietary intake of sodium.

Adolescent↗
PubMed1992

Diffuse panbronchiolitis observed in an Italian male.

We describe a case of a 43 year old man who presented with productive cough, dyspnea, severe obstructive ventilatory failure and diffuse micronodular shadows on chest roentgenogram. Bronchoalveolar lavage fluid analysis showed an increased total cellularity sustained by a huge neutrophilia. Sweat test was negative. Transbronchial lung biopsy and autopsy showed unit lesion of diffuse panbronchiolitis. This report represents, to the best of our knowledge, the first case of diffuse panbronchiolitis observed in Europe.

Adult↗
PubMed1992

Cystic fibrosis patients bearing both the common missense mutation Gly----Asp at codon 551 and the delta F508 mutation are clinically indistinguishable from delta F508 homozygotes, except for decreased risk of meconium ileus.

The glycine-to-aspartic acid missense mutation at codon 551 (G551D), which is within the first nucleotide-binding fold of the cystic fibrosis transmembrane conductance regulator (CFTR), is the third most common cystic fibrosis (CF) mutation, with a worldwide frequency of 3.1% among CF chromosomes. Regions with a high frequency correspond to areas with large populations of Celtic descent. To determine whether G551D confers a different phenotype than does delta F508, the most common CF mutation, we studied 79 compound heterozygotes for G551D/delta F508, from nine centers in Europe and North America. Each subject was matched, by age and sex, with a delta F508 homozygote from the same center. A retrospective cohort analysis was performed on the following outcome parameters: age at diagnosis, sweat chloride, meconium ileus at birth, height, weight, weight for height, FVC, FEV1, chest X-ray score, pseudomonas colonization, pancreatic sufficiency, and Shwachman clinical score. There was less meconium ileus among the G551D/delta F508 compound heterozygotes (relative risk 0.33; 95% confidence interval .13-.86), as well as a trend toward later age at diagnosis of pancreatic insufficiency. No statistically significant difference was found between the groups for any other parameter. These results suggest that the CF genotype can be a predictor of pancreatic and intestinal phenotype. Prenatal counseling for the two genotype groups should differ only with respect to probability of meconium ileus. Clinical outcome (after survival of meconium ileus) for G551D/delta F508 compound heterozygotes and delta F508 homozygotes is indistinguishable; therefore, prognostic counseling should not differ.

Adolescent↗
PubMed2006

[Ocular findings in Fabry's disease].

INTRODUCTION: Fabry's disease is a recessive X-linked disorder that results from a deficiency of the lysosomal hydrolase a-galactosidase A (alpha-Gal A). The absence of alpha-Gal A enzyme activity leads to accumulation of glycosphingolipid globotryaosyl ceramide (GL-3) in the lysosomes of a variety of cell types. Subsequently, angiokeratoma and ocular signs develop until, in most cases after the third decade of life, severe renal dysfunction or cardiomyopathy becomes obvious. Corneal opacities (cornea verticillata) occur in 90% conjunctival vascular changes in 60%, retinal vessel tortuosity in 55%, and cataracts in 50% of cases. Recently, enzyme replacement therapy has been shown to be an effective treatment modality that can eliminate glycolipid stores and reverse the disease pathology. CASE REPORT: A male patient born in 1971 was admitted for clinical examination due to proteinuria and erythrocyturia. During further evaluation nephrologist suspected Fabry's disease, because patient had skin changes early referred as petechiae, and acroparesthesias. He had also low heat tolerance and virtually no sweat. Physical status: angiokeratoma on gluteat regions and upper arms. Urine analysis in several occasions 10-15 E in sediment, alb. positive. On ECG, 2-mm depression of ST in precordial region. Heart ultrasound: low mitral regurgitation angio stage 1, left ventricle hypertrophy. Abdomen ultrasound: both kidneys around 12 cm large, parapyelic cysts in both kidneys of 2.5 cm in diameter. Biomicroscopy of both eyes: cornea verticillata. Fundus of both eyes: papillae n. optici with poorly defined edges, but without prominence, very tortuotic retinal blood vessels. In March 2002, very low alpha GAL enzyme activity in blood (alpha-Gal A = 0.5 +/- 0.2 nmol of substrate hydrolyzed hourly per serum mL--normal serum enzyme level 8.5-18.9 nmol/mL/h). In May 2002, enzyme replacement therapy was started with recombinant alpha-Gal A enzyme (Fabrazyme) 1 mg/kg every 14 days. Control evaluation and examination showed good cardiac and renal function. The patient felt better and stronger with improved heat tolerance. CONCLUSION: Fabry's disease occurs in all ethnic groups. It is estimated that one in 200 people is a carrier, and one in 40,000-100,000 has the disease. Today in Croatia, Fabry's disease has been diagnosed in only one patient, and according to the usual prevalence there are still 45-100 unrecognized patients. The ophthalmologists are in excellent position to diagnose Fabry's disease in early stages. Therefore it is very important that the ophthalmologists in Croatia become aware of the importance of ocular findings in Fabry's disease, so they can participate in the identification of unrecognized patients.

Adult↗
PubMedDate not supplied

Evaluation of the dimethylglyoxime stick test for the detection of nickel.

The value of the dimethylglyoxime stick test for the detection of nickel was determined for 54 randomly purchased metal objects designed for prolonged skin contact, and for 15 metal alloys of known composition. Surface nickel content was determined by EDAX analysis (energy dispersive X-ray) and nickel release in synthetic sweat was measured by Zeemann atomic absorption spectrometry. The study confirmed that the dimethylglyoxime stick test will identify most nickel containing alloys. There are, however, important exceptions. In such cases provocative user tests or patch tests with the suspected alloy are indicated.

Electron Probe Microanalysis↗