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In order to document the frequency and causes of elevated sweat chlorides we reviewed all sweat chloride determinations performed over a 2-year period. Seven hundred and thirty-five quantitative tests were performed. Three hundred and three positive or borderline results were obtained from 133 patients. Thirty-three of these patients did not have clinical evidence of CF. Fourteen of them (42%) suffered from malnutrition or growth stunting when tested. The remaining patients who were normally nourished, represented a very heterogeneous group with no unifying diagnosis. Initial sweat chlorides in 11/14 malnourished children were in the abnormal range (greater than 60 mmol/l). These tended to revert to normal coincident with improvement in nutritional status. Less remarkable elevations in sweat chloride levels were noted in the normally nourished patients, since almost 50% (9/19) were in the intermediate range (50-60 mmol/l). We conclude that malnutrition can be the cause of elevated sweat chlorides, which may lead to an erroneous diagnosis of cystic fibrosis. Clinicians should be aware of this association and adhere to strict criteria for the diagnosis of cystic fibrosis. Also, repeated sweat chloride determinations should be obtained, preferably following re-nutrition.

Screening of sweat chloride in newborn infants with the Orion Skin Chloride Measuring System and incorporating some procedural innovations is described. The results indicate that while diagnostic screening for cystic fibrosis can be readily undertaken, the test with the chloride ion-selective electrode is best left at least to the second day of life or later because of insufficient sweating in very young babies. Measurements on 2 babies with cystic fibrosis are also discussed.

The measurement of sweat chloride concentration was investigated by using the Orion 417 skin chloride electrode. The effects of variation in pilocarpine concentration, iontophoresis period, and sweat collection period were also investigated. The results show that the sweat chloride concentration is directly related to the amount of sweat produced. When the amount of sweat collected falls below a certain level, there is an apparent increase in sweat chloride concentration. A procedure is recommended for the measurement of sweat chloride concentration which offers good precision (coefficient of variation 9.8%) and the minimum of inconvenience to the patient.

An absent vas deferens may be associated with unilateral renal agenesis or undiagnosed cystic fibrosis. Such patients should be further evaluated with a sweat chloride and intravenous pyelogram. The finding of absent vas deferens during exploration for an undescended testis does not provide absolute evidence for absence of the testis, since these structures have independent embryologic origins.

This article evaluates a recently developed qualitative sweat patch test (SPT). A battery- powered stimulator with polymer pad electrodes is used to stimulate sweating, followed by the application of a paper patch which collects the sweat and shows color change on sweat chloride levels above 40 to 50 mEq/l. Our data consist of 66 patients with cystic fibrosis, 75 control subjects, and 37 relatives of patients with cystic fibrosis, excluding 22 subjects (11%) with insuffacient sweat. There were no false-negative results among 66 patients with cystic fibrosis, and in the control group, 71 of 75 subjects gave negative results and the other four gave positive results. Of the 37 relatives, eight gave positive results; all of the eight subjects are parents of patients with cystic fibrosis. Our results indicate that SPT is useful and reliable when there is sufficient sweat. This portable and simple patch test may serve as an excellent screening test for cystic fibrosis.

Abnormally high concentrations of sodium and chloride in the sweat of patients with fibrocystic disease of the pancreas were first noted by Darling, di Sant'Agnese, Perera, and Andersen, in 1953.1Papers supporting and extending this observation * appearing since that time would indicate that a high chloride concentration in the sweat is the most constant of the numerous manifestations of cystic fibrosis of the pancreas. Because of the diagnostic importance of the determination of sweat chloride, an effort has been made to devise a simpler procedure for the collection of sweat than that commonly used. In the studies mentioned above, sweat for analysis was produced by thermal stress, either by placing the subject in a room at 90 F for one to two hours † or by encasing the trunk and extremities in a plastic bag.5The present communication describes a method for local production of sweat by intradermal

(1) The chief diagnostic clues observed in seven cases of adult cystic fibrosis were: A characteristic roentgen appearance associated with bronchographic signs of "bronchitis;" recurrent staphylococcal infection of the respiratory tract; and evidence of diffuse airway obstruction in the absence of bronchial asthma. (2) Symptoms of pancreatic insufficiency were mild or absent in four of five patients who had laboratory evidence of intestinal malabsorption. (3) Spontaneous prolonged remission of Symptoms and a relatively benign course occurred in one instance. (4) The inability of a fibrocystic patient to conserve sweat Chloride during administration of desoxycorticosterone or salt deprivation was confirmed, and provides another useful diagnostic test for disease.

Review of the records of 135 patients with cystic fibrosis of the pancreas revealed that nineteen had evidence of atopic allergy. The diagnosis of cystic fibrosis was easily overlooked in patients with classical manifestations of atopic allergy, such as asthma, nasal polyps, hay fever, urticaria, eczema, positive skin tests, and familial allergy. Optimal therapy for many of these patients included treatment of the allergic problem as well as the usual regiment for cystic fibrosis. Forty-seven patients with atopic bronchial asthma had no evidence of the sweat chloride abnormality characteristic of cystic fibrosis of the pancreas. The nature of the relationship between cystic fibrosis of the pancreas and atopic allergy is not clear.

To the Editor .—In the light of the interesting report of Zollar and Mufson on acute parotitis associated with parainfluenza 3 virus infection, 1 we would like to report the following case. We believe that it may be the third case illustrating the association of this virus with the mumps syndrome. Report of a Case .—An 11-year-old Italian-American girl was admitted to the National Jewish Hospital in Denver on April 14, 1971, for diagnosis and therapy of a chronic cough. A diagnosis of cystic fibrosis was made in the hospital on the basis of an increased sweat chloride concentration, fatty stools, and malabsorption. On May 3, 1971, she complained of pain in the left jaw, and over the course of the next 24 hours she developed obvious unilateral parotitis, without fever and without respiratory symptoms. The parotid fluid was clear and nonpurulent and was sent for bacterial and viral cultures

Multiple sweat tests were performed on 183 individuals—patients with cystic fibrosis,their parents and siblings, and control adults and children. The mean (M) and variance (V) of the set of tests on each individual were used to calculate the quadratic discriminant function between the known heterozygotes (parents) and the two control groups. The discriminant between control children and parents is: L=14 (M−7) 2 +(V−42) 2 −10,000. The discriminant between parents and control adults is: L=83 (M−11) 2 +(V−80) 2 −60,600. With a set of four tests, 84 per cent of parents and 83 per cent of the expected number of siblings could be identified as heterozygotes. In addition, repeated sets of 4 tests identified heterozygotes with low expressivity.

Aquagenic wrinkling of the palms (AWP) is an unusual and rare dermatological condition characterized by excessive palmar wrinkling, occurring within a few minutes of water exposure. Cystic fibrosis (CF) or CF carrier state associated forms, drug induced cases, and idiopathic forms have been described. We report the case of a 27-year-old woman with a 7-year history of transient excessive wrinkling of her palms after brief exposure to water. We present also a comprehensive review of the literature. We believe that AWP has been underdiagnosed thus far and we would like to encourage investigations such as sweat chloride test or genetic studies in these patients because of the association with CF or CF carrier state, particularly when AWP appears in younger ages.

Objective Sweat chloride measurement is considered a standard diagnostic tool for cystic fibrosis (CF). This study was performed to compare sweat chloride values obtained by quantitative pilocarpine iontophoresis (classic test) with sweat crystallization detected by direct observation of a drop of perspiration under light microscopy in patients with and without CF. Methods The tests using both techniques were performed simultaneously in patients with and without CF. Cutoff values of ≥60 mmol/L of chloride concentration for the classic sweat test was considered for diagnosis of CF. In crystallization method, observation of typical dendritic forms of salt crystals under light microscopy was interpreted positive. Findings Sixty patients suspected to CF (31 males and 29 females) with age range of 9 months to 2 years underwent the sweat test using both techniques. Median sweat chloride values was 26.13+10.85 in group with negative and 72.76+12.78 mmol/L in group with positive sweat test, respectively. All the patients who had positive sweat test in classic method showed typical dendritic forms of salt crystal in sweat crystallization test, which provided the test with 100% sensitivity (95%CI: 93.1–100). Only one of the 31 subjects with negative results for classic sweat test had positive result for crystallization sweat test, which provided the test with 96.7% specificity (95%CI: 92.9–100). Time spent to perform the crystallization test was significantly shorter than the classic method whereas its cost was also lower than the second method. Conclusion There was a good correspondence between two studied methods of sweat test. These results suggested the sweat crystallization test as an alternative test for detecting CF disease with high sensitivity and specificity.

On April 1, 2007, Alberta became the first province in Canada to introduce cystic fibrosis (CF) to its newborn screening program. The Alberta protocol involves a two-tier algorithm involving an immunoreactive trypsinogen measurement followed by molecular analysis using a CF panel for 39 mutations. Positive screens are followed up with sweat chloride testing and an assessment by a CF specialist. Of the 99,408 newborns screened in Alberta during the first two years of the program, 221 had a positive CF newborn screen. The program subsequently identified and initiated treatment in 31 newborns with CF. A relatively high frequency of the R117H mutation and the M1101K mutation was noted. The M1101K mutation is common in the Hutterite population. The presence of the R117H mutation has created both counselling and management dilemmas. The ability to offer CF transmembrane regulator full sequencing may help resolve diagnostic dilemmas. Counselling and management challenges are created when mutations are mild or of unknown clinical significance.

Analysis of sweat chloride levels in cystic fibrosis (CF) patients is essential not only for diagnosis but also for the monitoring of therapeutic responses to new drugs, such as cystic fibrosis transmembrane conductance regulator (CFTR) modulators and potentiators. Using iontophoresis as the gold standard can cause complications like burns, is uncomfortable, and requires repetitive hospital visits, which can be particularly problematic during a pandemic, where distancing and hygiene requirements are increased; therefore, it is necessary to develop fast and simple measures for the diagnosis and monitoring of CF. A screen-printed, low-cost chloride sensor was developed to remotely monitor CF patients. Using potentiometric measurements, the performance of the sensor was tested. It showed good sensitivity and a detection limit of 2.7 × 10−5 mol/L, which covered more than the complete concentration range of interest for CF diagnosis. Due to its fast response of 30 s, it competes well with standard sensor systems. It also offers significantly reduced costs and can be used as a portable device. The analysis of real sweat samples from healthy subjects, as well as CF patients, demonstrates a proper distinction using the screen-printed sensor. This approach presents an attractive remote measurement alternative for fast, simple, and low-cost CF diagnosis and monitoring

Background The classic sweat test (CST) is the golden standard for cystic fibrosis (CF) diagnosis. Then, our aim was compare the production and volume of sweat, and side effects caused by pulsed direct current (PDC) and constant direct current (CDC). To determine the optimal stimulation time (ST) for the sweat collection. To verify the PDC as CF diagnosis option. Methods Prospective study with cross-sectional experimental intervention. Experiment 1 (right arm): PDC and CDC. ST at 10 min and sweat collected at 30 min. Currents of 0.5; 0.75; 1.0 and 1.5 mA and frequencies of 0, 200, 1,000 and 5,000 Hz applied. Experiment 2 (left arm): current of 1.0 mA, ST at 5 and 10 min and sweat collected at 15 and 30 min with frequencies of 0; 200; 1,000 and 5,000 Hz applied Experiments 1 and 2 were performed with current density (CD) from 0.07 to 0.21 mA/cm2. Experiment 3: PDC was used in typical CF patients with two CFTR mutations screened and or with CF diagnosis by rectal biopsy and patients with atypical CF. Results 48 subjects (79.16% female) with average of 29.54 ± 8.87 years old were enrolled. There was no statistical difference between the interaction of frequency and current in the sweat weight (p = 0.7488). Individually, positive association was achieved between weight sweat and stimulation frequency (p = 0.0088); and current (p = 0.0025). The sweat production was higher for 10 min of stimulation (p = 0.0023). The sweat collection was better for 30 min (p = 0.0019). The skin impedance was not influenced by ST and sweat collection (p > 0.05). The current frequency was inversely associated with the skin impedance (p

5. Hung W, Wright JC, Finkelstein JW, Blizzard RM: Salivary:serum ratios of I TM in cretinism. J Clin Endocrinol Metab 22:1151, 1962. 6. Spencer RP, Karimeddini MK: Decreased salivary gland accumulation of pertecbnetate in neonatal hypothyroidism. J Nucl Med 22:96, 1981. 7. McKusick VA: Mendelian inheritance in man, ed 6. Baltimore, 1983, Johns Hopkins University Press, p 663. 8. Stanbury JB, Chapman EM: Congenital hypothyroidism with goitre. Lancet 1:1162, 1960. 9. Gilboa Y, Ber A, Lewitus Z, Hasenfratz J, Tikva P: Goitrous myxedema due to .iodide trapping defect. Arch Intern Med 112:212, 1963. 10. Wolff J, Thompson RH, Robbins J: Congenital goitrous cretinism due to the absence of iodide-concentrating ability. J Clin Endocrinol Metab 24:699, 1964.

Insulin and its vehicle without insulin were administered separately by iontophoresis to patients with cystic fibrosis (CF), obligate heterozygotes, and healthy controls. The resultant sweat chloride concentration after treatment with both preparations was compared in each individual. No difference after the two treatments was found in the control sample. A decrease in sweat chloride concentration after insulin iontophoresis in comparison with the vehicle was observed in both the CF (P smaller than 0.005) and heterozygote (P smaller than 0.01) samples. These observations suggest an involvement of insulin in CF and a possible role of insulin in sweat gland function.

We describe a method for direct potentiometric measurement of sweat chloride by use of a chloride-selective electrode, with strip-chart recording of the measurement to facilitate interpretation of the measurement. Comparison of this method and the Gibson and Cooke method [Pediatrics 23, 545 (1959)] gave a correlation coefficient of 0.86. Recording of the same test at various pressures showed that different pressures had little effect if they were kept constant.

To the Editor.— All of us who care for patients with cystic fibrosis (CF) are well aware of the varying degrees of clinical involvement they have. Indeed, over the past several years our concept of this disease has broadened considerably. No longer do we think of it solely as a pulmonary or a gastrointestinal illness. In actuality it is a systemic disease characterized by exocrine gland dysfunction. The recent article by Stern et al, "Intermediate-Range Sweat Chloride Concentration and Pseudomonas Bronchitis" (239:2676, 1978), presents well-documented clinical material that strongly suggests a genetic basis for what might be called a variant of CF. The authors' patients all have pulmonary lesions classically associated with CF but without any pancreatic lesions. More important, sweat chloride concentrations were intermediate between the "normal" and "typical CF" range. It has long been known that whereas most patients have pulmonary involvement of one degree or another, approximately

To the Editor.— Both the letter of Harry Shwachman, MD (240:2731, 1978), and the defensive response of Jocelyn M. Hicks, PhD (241:2264, 1979), miss the issue in regard to sweat chloride testing. The major issue is not the "lack of interest of clinical chemists," as Dr Shwachman claims, but the actual performance of the test. 1 Neither the pathologist nor the clinical chemist, in all likelihood, actually performs the test. Rather, it is the medical technologist or technician who carries out the actual procedure. It is a major part of our roles as educators and laboratory administrators to ensure that these people are adequately trained for the task and that the test meets high enough performance standards to provide a clinically relevant answer.

Preliminary studies previously reported by our laboratory have suggested that quantitative and qualitative measurements of methylumbelliferylguanidinobenzoate (MUGB) reactive proteases in mid-trimester amniotic fluid may provide an approach to the antenatal detection of cystic fibrosis. During the past year, we have evaluated thirty additional amniotic fluids using a combination of quantitative measurements of MUGB, isoelectricfocusing, and gel filtration, bringing the total number of high risk pregnancies monitored to forty-three. Eighteen pregnancies have come to term, fifteen from obligate heterozygote parents. Sweat chloride analysis has confirmed our prediction of fifteen normal and three affected with cystic fibrosis. Three additional pregnancies, predicted to be affected, were electively terminated. Unfortunately, confirmation is not possible. There has been one spontaneous abortion and one stillbirth. The stillbirth, predicted in 1979 to be normal by only two tests, had evidence of meconium peritonitis on autopsy. This case, therefore, may represent a missed diagnosis. The remaining twenty pregnancies will come to term within the next five months. These data suggest that this approach may provide a clinically useful means for antenatal detection of cystic fibrosis.

Thirty children, ages 6 weeks to 7 years with persistent chronic diarrhea unresponsive to a variety of other therapeutic modalities were treated with food extract injections. Diagnosis was made by history, specific food challenges using in vivo C3 alteration as an indicator of sensitivity, and intradermal provocative food testing. Other possible causes were eliminated by stool and blood examinations, sweat chloride measurement, gastrointestinal radiography and when indicated, intestinal mucosal biopsy. In 13 patients there was significant failure to thrive. The number of foods tested ranged from 1 to 23. Sensitivity was demonstrated by wheal growth within a 10 minute period and or by induction of symptoms or physical reactions. All patients were found to be sensitive to one or more foods. A good to excellent therapeutic response as measured by cessation of diarrhea and in most improved growth occurred in 23 patients. In 3 patients food extract therapy was considered unsuccessful or marginally helpful; in two it was discontinued. Two patients did not return after a brief period of treatment. No serious reactions to the testing or treatment injections was observed.

The Clinical Guide to Laboratory Tests potentially provides valuable information in a condensed format, especially for the house officer or nurse needing a quick reference. Despite these advantages, it is a difficult book to review, particularly because its very strengths in presenting large amounts of information result in weaknesses. For example, explanations on serum glucose measurements and the glucose tolerance test are as complete as expected, including references from the National Diabetes Data Group. Conversely, descriptions of the sweat chloride test include only a mention of reference values established at the University of Kentucky Medical Center, Lexington, and a questionable comment on possible false-negative results caused by "excessive sweating during hot weather." In addition, there is no reference to the Cystic Fibrosis Report ( J Pediatr 1976; 88(II):711-750) or a similar report that might provide an authoritative source of information. Unfortunately many other test discussions also cite only textbooks or locally

THE DEMONSTRATION of an elevated chloride content in the sweat has become a cornerstone in the diagnosis of cystic fibrosis (CF) because of its technical simplicity and its high degree of reliability in identifying a disease with many diverse clinical manifestations. 1-3 Furthermore, the sweat test is independent of pancreatic function and enables a diagnosis of CF, even in patients without pancreatic involvement. 4 Interpretation of the sweat test in CF requires awareness and understanding of the variations in the amount of sweat and/or its chloride content which may occur in conditions other than CF, both physiologic and abnormal. The most important of these conditions as presently reported include the increase in sweat sodium and chloride concentrations which occur with increased rate of sweating 5,6 and in Addison's disease, 7 and increased sweat sodium associated with aging 8 and with intermittent occlusion of blood supply. 9 Furthermore, Hsia et al