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The sweating apparatus in growth hormone deficiency, following treatment with r-hGH and in acromegaly.

Adult growth hormone deficient patients are known to exhibit reduced sweating and their ability to thermoregulate is diminished. Treatment of these patients with recombinant human growth hormone (r-hGH) is claimed to reverse these abnormalities. We have investigated this claim, as well as the mechanism underlying these altered sweating responses in GH-deficient patients as part of a placebo-controlled study on the effects of 6-12 months r-hGH therapy. Skin biopsies were obtained from these subjects and changes in morphology and innervation parameters for the eccrine sweat glands were examined. These included histochemistry for acetylcholinesterase (AChE) and immunohistochemistry for the neuropeptide vasoactive intestinal polypeptide (VIP) and for PGP9.5, a general neuronal marker. Sweat gland acinar size and periacinar innervation were measured by computerised image analysis. The patients underwent pilocarpine iontophoresis sweat rate tests and their serum insulin-like growth factor 1 (IGF-1) levels were assessed. Since active acromegaly involves excess GH secretion and hyperhidrosis, skin biopsies and sweat tests were also carried out on a group of these patients, as well as on control subjects. We have demonstrated a sweating defect in adult GH-deficiency which is accompanied by a reduction in AChE and VIP levels in the nerve supply to sweat glands. Following r-hGH therapy, an increase in AChE and VIP staining is seen in the sudomotor nerves accompanied by restoration of sweat rates and serum IGF-1 levels. Hence, normalization of sweat gland function includes recovery of sudomotor synapse constituents. A trophic effect of GH on sweat gland epithelium and/or on the associated nerves is proposed, supported by the observation that in acromegaly the size of sweat gland acini and the density of innervation to the sweat glands was greater than in controls.

Acetylcholinesterase↗

A modified technique for measurement of nasal transepithelial potential difference in infants.

OBJECTIVE: To establish a method for measuring nasal transepithelial potential difference (PD) in infants. STUDY DESIGN: A modified infant method (smaller catheter size, reduced flow rates, and shorter protocol time) was compared with an established adult nasal PD method in 10 adult volunteers (4 with cystic fibrosis [CF]). Nasal PD was measured in 13 infants with a possible diagnosis of CF. RESULTS: Recordings were similar for the established and the modified methods in adult volunteers. An amiloride concentration of 10(-4) mol/L was necessary for full inhibition of amiloride-sensitive sodium ion (Na(+)) transport. Of the 13 infants, 2 had PD values suggestive of CF (mean baseline PD, -50.1 mV and -31.4 mV; maximum baseline PD, -61 mV and -49 mV; change in PD after perfusion with zero chloride solution with isoprenaline and amiloride [DeltazeroCl(-)/Iso], -1 mV and +3.5 mV), and 11 had normal values (mean +/- SEM baseline PD, -13.2 +/- 1.0 mV; maximum baseline PD, -21.4 +/- 2.0; DeltazeroCl(-)/Iso, -15.3 +/- 1.9 mV). These results correlated with subsequent sweat test data, mutation analysis, and clinical outcome. CONCLUSION: Nasal PD measured with this modified method is comparable to that measured with an established adult method. The measurements were well tolerated in 13 infants and discriminated bioelectric profiles characteristic of normal and CF respiratory epithelium. This study supports the use of this modified nasal PD technique as a diagnostic test for CF in newborn infants.

Adult↗

X-linked ichthyosis.

In the period 1962-1974, 36 patients with X-linked ichthyosis, belonging to 22 families, were selected for study. The frequency of this genodermatosis is higher in the province of Salamanca than in other countries. In most of the cases, the lesions were apparent at birth or shortly after. In 41% of the patients studied by slit-lamp microscopy, posterior embriotoxom was seen. Hyperkeratosis was seen in follicular and sweat duct orifices. Statistical analysis of the pedigrees showed a higher proportion of affected males among the offspring of carriers and also among the offspring of the ichthyotics' sisters. In addition, among the patients' descendants, the higher ratio of females is statistically significant, showing that there is likely to be selection in favour of the X chromosome.

Child↗

[Allergic bronchopulmonary aspergillosis disclosing mucoviscidosis].

In predisposed patients, allergic bronchopulmonary aspergillosis (ABPA) can arise from aspergillus bronchial colonization. We report the case of a young woman who presented with a right basal pneumonia, ground glass opacities and mediastinal adenopathies on CT scan. Biological, radiological and clinical criteria, as well as an history of childhood asthma, allowed the initial diagnosis of ABPA. However, the unusual coexistence of an additional infection with Pseudomonas Aeruginosa evoked the diagnosis of cystic fibrosis, confirmed by a sweat test and genetic analysis. Under corticosteroid and antifungal therapy and antibiotics, the clinical and radiological evolution was favourable but immuno-allergic sensitisation persisted. The ABPA-cystic fibrosis association is not rare with an estimated prevalence of 2% to 11% according to previous studies. This variability is partly explained by the difficulty of the diagnosis due to confounding clinical, radiological, and biological signs between ABPA and cystic fibrosis. Many predictive development factors of ABPA in the context of cystic fibrosis have been reported, including respiratory function, personal or familial atopy, colonization with Pseudomonas Aeruginosa and age. As in non cystic fibrosis patients, the treatment requires systemic corticotherapy and itraconazole. ABPA is still often under diagnosed and should be evoked in the context of cystic fibrosis.

Adult↗

[Multilocular eyelid hidrocystoma: an anatomical and clinical observation].

A cystic cutaneous mass was observed on the lateral canthus of the left eyelid in a 25-year-old woman, 2 years after being operated on for a lesion that had existed in the same area several years before, but the patient could not identify its nature. The present mass appeared as a well-circumscribed bluish cystic lesion. A surgical resection was performed; pathological analysis disclosed a cystic sweat tumor composed of several contiguous cysts. One year of follow-up has revealed no complications.

Adult↗

[Pathogenesis and novel possibilities of diagnosis of cystic fibrosis].

Cystic fibrosis (CF) is an autosomal recessive disease caused by mutations in cystic fibrosis transport regulator (CFTR) gene. The clinical picture is characterized mainly by: bronchopulmonary disease (BPD), exocrine pancreatic insufficiency, hepatobiliary disease, meconium ileus, malnutrition and congenital bilateral absence of vas deferens. Life-span is closely related to respiratory system status, thus making the treatment of the BPD the key element of the management of CF. BPD is characterized by progressive destruction of bronchopulmonary tissues. It is due to chronic inflammation which, in turn, is caused chronic colonization/infection by typical pathogens, such as Pseudomonas aeruginosa, Staphylococcus aureus and Burkholderia cepacia. The end stage of the BPD is respiratory insufficiency and death. The diagnosis of cystic fibrosis is based on the clinical picture, sweat chloride test, molecular analysis and measurement of nasal potential difference.

Bacterial Infections↗

[Mucoviscidosis: in children and adults].

Because the lifespan of patients with cystic fibrosis is now longer, both pediatricians and adult care physicians are involved in the health care strategy. Respiratory manifestations occur due to bronchial dilatation and chronic bronchial infection, mainly due to Staphylococcus aureus and Pseudomonas. Episodes of adult infection are frequent and death usually results from respiratory failure. Characteristically, the disease also involves exocrine pancreas insufficiency. Other intestinal tract manifestations include meconial ileus and liver disease which may reach the stage of biliary cirrhosis. Nutritional disorders are frequent. Clinically there are respiratory and digestive tract disorders, pansinusitis and frequent nasal polyposis, sometimes associated with diabetes mellitus or joint pain. Male sterility results from bilateral agenesia of the vas deferens and in the female, fertility is decreased although pregnancy is possible. Clinical presentation suggests the diagnosis which is confirmed by a sweat test and genetic analysis. Care should be provided by a centre specialized in cystic fibrosis. The main treatments rely on respiratory physical therapy, antibiotics and gastroprotected pancrease extracts.

Adolescent↗

Use of in vitro systems for X-ray microanalysis.

The use of X-ray microanalysis in human pathology may require the use of cryoprepared tissue. Often it is impossible to carry out freezing of the tissue in an optimal way, and in addition, it is difficult to carry out experiments in living patients. The use of in vitro systems and cell cultures allows separation of the process of tissue removal and the freezing procedure, and also makes testing of pharmacological or toxic substances possible. In experiments with animal tissue it was shown that incubation in a physiological buffer induced significant changes in the concentrations of Na, K, and Cl. In general, the concentrations of Na and Cl increased, those of K decreased. Prolonged incubation of brain tissue (cortex and hippocampus) and of liver resulted in further changes of the cellular ion contents in the same direction. Incubation of pancreas and submandibular gland resulted in a limited reversal of the changes induced by dissection. The submandibular gland in vitro showed the same response to cholinergic stimulation as the gland in situ. The use of cell cultures for X-ray microanalysis is briefly reviewed and illustrated by an example of analysis of an immortalized sweat gland cell line. It was shown that these cells respond to stimulation by cAMP with loss of Cl and that this response was unaffected by the type of substrate the cells were grown on.

Animals↗

Scarcity of mutations detected in families with X linked hypohidrotic ectodermal dysplasia: diagnostic implications.

Indirect molecular diagnosis of X linked hypohidrotic ectodermal dysplasia (XLHED), a congenital disorder of hair, teeth, and eccrine sweat glands, has been possible by linkage analysis. Direct mutation detection would enable carrier detection in female relatives of sporadic cases, as well as help distinguish XLHED from the rarer, clinically indistinguishable, autosomal recessive disorder ARHED. Recently, a candidate gene for XLHED has been identified. Genomic DNA from 162 affected males and 21 females, who were either obligate carriers or had manifestations of the disorder, were screened by SSCP analysis. A subset of the patients had been previously screened for large genomic deletions and had limited screening of a single exon by SSCP analysis. The two known exons were amplified using flanking primers. Approximately 7% of patients, all males, had putative mutations identified within exon 1, but no variants were found within exon 2. Ten different putative mutations and four probable polymorphisms were identified. Both of the known exons were sequenced in 10 patients who had no detectable SSCP changes, but no additional mutations were found. No correlation between phenotype and genotype was evident between either affected subjects or subjects with or without detectable mutations. The results of the study indicate that only a small minority of affected males can be diagnosed by direct mutation analysis, and that the remainder of the patients are likely to have mutations in as yet unidentified exons of the EDA gene. Linkage analysis, in informative situations, therefore remains the only practical diagnostic option available.

Cohort Studies↗

Development of capillary electrophoresis methods for quantitative determination of taurine in vehicle system and biological media.

CE methods have been developed for the determination of taurine in pharmaceutical formulation (microemulsion) and in biological media such as sweat. The CE system with end-column pulsed amperometric detection has been found to be an interesting method in comparison with UV and fluorescence detection for its simplicity and rapidity. A gold-disk electrode of 100 mm diameter was used as the working electrode. The effects of a field decoupler at the end of the capillary, separation voltage, injection and pressure times were investigated. A detection limit of 4 x 10(-5) mol/L was reached using integrated pulsed amperometric detection, a method successfully applied to taurine analysis of the biological samples such as sweat. For taurine analysis of oil-in-water microemulsion, fluorescence detector was the favored method, the detection limit of which was 4 x 10(-11) mol/L.

Electrodes↗

Quantification of the plant-derived hallucinogen Salvinorin A in conventional and non-conventional biological fluids by gas chromatography/mass spectrometry after Salvia divinorum smoking.

A gas chromatography method with mass spectrometric detection is described for the determination of Salvinorin A, the main active ingredient of the hallucinogenic mint Salvia divinorum. The method was validated in plasma, urine, saliva and sweat using 17-alpha-methyltestosterone as internal standard. The analytes were extracted from biological matrices with chloroform/isopropanol (9:1, v/v). Chromatography was performed on a 5% phenyl methyl silicone capillary column and analytes were determined in the selected ion monitoring mode. The method was validated over the concentration range 0.015-5 microg/mL plasma, urine and saliva and 0.01-5 microg/patch in the case of sweat. Mean recoveries ranged between 77.1 and 92.7% for Salvinorin A in different biological matrices, with precision and accuracy always better than 15%. The method was applied to the analysis of urine, saliva and sweat from two consumers after smoking 75 mg plant leaves to verify the presence of the active ingredient of S. divinorum in human biological fluids as a biomarker of plant consumption. Salvinorin A was detected in urine (2.4 and 10.9 ng/mL) and saliva (11.1 and 25.0 ng/mL), but not in sweat patches from consumers.

Body Fluids↗

Respirator fit factor performance while sweating.

The extent to which sweat accumulation inside respirators affects respirator fit has not been quantified. This study represents an attempt to measure facial sweating and to quantify its effects on fit factors of negative pressure, full-facepiece respirators. Respirator fit factor (FF) data were obtained while 14 subjects completed 30 minutes of treadmill walking at an intensity of 75% of age-predicted maximal heart rate in an aerosol test chamber under ambient environmental conditions. Subject facial and whole body sweat production were also measured. Statistical analysis of the treadmill FF results showed that respirator fit was significantly (p < 0.05) degraded after 14 minutes of exercise. Sweat accumulation inside the respirator facepiece averaged 30.9 +/- 15.5 g. However, no significant correlation of subject facial sweat production with overall FF values measured during exercise was found. The results of this study indicate that respirator FFs degrade significantly over time under moderate exercise and environmental conditions and suggest that facial sweat accumulation alone does not account for the reduced FF levels.

Adult↗

Sweat gland carcinoma: an easily confused skin malignancy.

Sweat gland carcinoma is a rare malignancy of the skin appendage. Surgeons and pathologists have limited experience with such tumor. Various classifications and diagnostic identifications lead to easy confusion with other metastatic lesions. Eight cases of sweat gland carcinoma were collected from 1020 cases of primary skin malignancies seen at the Veterans General Hospital-Taipei over the past 20 years. After a careful review of the clinical history and histopathology files, as well as immunohistochemical stains of CEA and S-100 protein, only three cases were proved to be sweat gland carcinomas, accounting for less than 0.3% of the primary tumors of skin. All three cases were eccrine histology in type. Two cases were CEA positive, and one case was positive with S-100 protein stain. Five cases which were excluded were negative to CEA and S-100 protein analysis. Thus it is suggested that sweat gland carcinoma should receive more accurate differential diagnosis from other skin malignancies, particularly metastatic tumors. Immunohistochemical analysis could help differential diagnosis. Treatment modalities of sweat gland carcinoma base mainly upon adequate wide surgical excision.

Aged↗

Sympathetic sudomotor function in diabetic neuropathy.

Sympathetic nerve function was studied by the Silastic mold technique and by evaporimetry in the hand and the foot in 357 type I diabetic patients. The number of active sweat glands was below normal in 24% of patients in the hand and in 56% in the foot, while the sweat evaporation rate was low in 17% and 40% of patients, respectively. Computerized analysis of the molds, which allowed automatic sweat gland counts and estimations of the secretion volume of each sweat gland, detected abnormalities in 36% and 60% of patients. The Silastic imprint technique was found to be a sensitive test for detection of sympathetic nerve involvement, even in asymptomatic patients with normal clinical and nerve conduction examinations. Its sensitivity and accuracy has been enhanced by the computerized analysis of the molds.

Adolescent↗

Use of nasal potential difference and sweat chloride as outcome measures in multicenter clinical trials in subjects with cystic fibrosis.

One of the goals of current research in cystic fibrosis (CF) is to develop treatments that correct or compensate for defects in function of the cystic fibrosis transmembrane regulator (CFTR) gene. The use of outcome measures that assess CFTR function such as nasal potential difference (NPD) measurements and sweat chloride determinations will be required to evaluate the efficacy of such treatments in multicenter clinical trials. The purpose of this work was to identify the sources and magnitude of variability in NPD and sweat chloride measurements when performed at multiple centers. For the variance component analysis presented here, we used NPD and sweat chloride measurements from 37 subjects with CF participating in a phase I, four-center clinical trial of CPX (8-cyclopentyl-1,3-dipropylxanthine), a drug intended to enhance trafficking of Delta F508 CFTR to the cell membrane. The specific techniques used to measure these outcomes were not standardized, and varied between the four sites. Variability of both NPD measurements (baseline potential difference during infusion with Ringer's solution; change in response to addition of 0.1 mM amiloride; and subsequent change in response to perfusion with low chloride solution containing 0.1 mM amiloride and 0.01 mM isoproterenol) and sweat chloride measurements differed significantly between study sites. For change in NPD, one study site had significantly greater variability (lower reproducibility) of measurement than the other three sites. For sweat chloride measurements, reproducibility was lower at two of the sites relative to the other two sites. Sample size calculations showed that lower reproducibility at one or more sites can substantially reduce the power of studies using NPD or sweat chloride determinations as outcome measures. Standardization of measurement protocols, careful operator training and certification, and ongoing monitoring of individual operator performance may help to improve reliability in multicenter trials.

Adolescent↗

Uncertainty in the diagnosis of cystic fibrosis: possible role of in vivo nasal potential difference measurements.

The diagnosis of cystic fibrosis (CF) is not always certain, despite extensive clinical evaluation, multiple sweat chloride tests, and genotype analysis. We hypothesized that nasal transepithelial potential difference measurements have a useful role in this situation. In 11 patients without an established diagnosis of CF, results of simultaneous nasal potential difference (PD) and sweat chloride measurements were compared with those from control subjects, obligate CF heterozygotes, and patients with a confirmed diagnosis of CF. Two patients conformed to the PD profile for CF patients, whereas nine had values corresponding to those of the healthy control subjects. Subsequently the 5-thymidine (IVS8-5T) CF gene variant was identified in the two patients with abnormal PD measurements.

Adolescent↗