Sweat tests to diagnose cystic fibrosis in adults

Twenty five patients with cystic fibrosis and 25 controls were studied to define a sweat sodium concentration in adults that could be taken as diagnostic of cystic fibrosis. Some of the controls had a sweat sodium concentration of over 50 mmol(mEq)/l, and thus cystic fibrosis should be diagnosed in an adult only when two measurements of sweat sodium concentration are above 70 mmol/l. In cases in which the sweat sodium concentration was borderline a suppression test using fludrocortisone improved the accuracy of diagnosis; this test entails recording the lowest concentration reached after administration of the drug. A scatter diagram of the baseline sweat sodium concentrations plotted against the lowest concentration attained after suppression with fludrocortisone may aid the diagnosis further.     

Sweat Chlorides in Salt-Deprived Cystic Fibrosis Heterozygotes

Sweat chlorides of 10 sets of parents of children with cystic fibrosis and 11 controls were studied in an attempt to develop a test for the diagnosis of cystic fibrosis heterozygotes by subjecting both the parents and controls to a low sodium diet and comparing sweat chloride values as the diet progressed. It was hoped that the sweat chloride levels of the parents, the heterozygotes, would remain stationary throughout the diet, since their children, the homozygotes, reveal this finding under similar conditions of salt deprivation. The sweat chloride levels of the controls, because of effects of aldosterone, were expected to decrease steadily from the commencement of the diet to its termination.

A decrease in sweat chloride values of similar magnitude was found in both parents and controls as the diet continued. It is concluded that the study of sweat electrolyte levels in salt-deprived subjects is of no value in the diagnosis of cystic fibrosis heterozygotes.

     

Cystic fibrosis in adults: the unsuspected pulmonary diagnosis.

The clinical spectrum of cystic fibrosis is insufficiently appreciated. This disease may occur in adolescents or adults who had minimal or no symptoms in childhood. In three patients the diagnosis was made on the basis of respiratory disease (including bronchiectasis, pneumonia and chronic bronchitis), a family history of respiratory disease, and elevated concentrations of electrolytes in the sweat. Two of the patients had pancreatic insufficiency, but this feature was not considered necessary for the diagnosis. It is important to make the diagnosis of cystic fibrosis in affected adults in order to prescribe appropriate therapy, avoid unnecessary operations, anticipate complications that are not common to other respiratory diseases, provide genetic counselling and initiate appropriate screening procedures to detect the disease in close relatives.     

Cystic fibrosis in Malaysian children

Cystic fibrosis (CF) is an autosomal recessive disease commonly found among the Caucasian population. The availability of sweat test and with increasing experience have made it possible to diagnose more cases of CF. Our first case of CF was diagnosed 16 years ago and to date we have managed sixteen cases of CF. Sixteen children were diagnosed with CF in our units at the Paediatric Institute and University Malaya Medical Centre (UMMC). They were referred with either one or all of the following symptoms: i) recurrent pneumonia, ii) bronchiectasis, iii) failure to thrive, iii) malabsorption or iv) history of meconium ileus obstruction during the neonatal period. When the clinical features suggested strongly of CF, sweat tests will be performed in duplicates and considered positive when the sweat chloride or sweat sodium was more than 60 mmol/l for both results. Seventy- two hours fecal fat excretion or stool for fat globule was performed to document malabsorption. From the year 1987 to 2003, 16 patients were confirmed to have cystic fibrosis in Malaysia by positive sweat tests. Thirteen patients were diagnosed in Paediatric Institute while the remaining three were diagnosed in UMMC. On follow-up two patients died due to severe bronchopneumonia at the age of two years old. Although once considered rare, CF should now be considered in any children with clinical presentations of recurrent chest infections, bronchiectasis, in the presence or absence of malabsoption stmptoms and in neonates with meconium ileus obstruction.     

Serum pancreatic lipase activity in cystic fibrosis

Patients with cystic fibrosis have been found to have abnormal serum concentrations of immunoreactive trypsin and abnormal activities of pancreatic isoamylase. A study was undertaken to discover whether activity of pancreatic lipase is also altered in cystic fibrosis. Serum from 23 patients with cystic fibrosis was assayed for immunoreactive trypsin and pancreatic lipase. Median serum pancreatic lipase activity was significantly lower in patients with cystic fibrosis than in controls, as was immunoreactive trypsin concentration (p less than 0.0001). Some patients had supranormal lipase concentrations but these were not always associated with absence of malabsorption. Serum pancreatic lipase activity is considerably changed in cystic fibrosis.     

Intermediate-range sweat chloride concentration and Pseudomonas bronchitis. A cystic fibrosis variant with preservation of exocrine pancreatic function

We studied the clinical and laboratory characteristics of seven patients with sweat chloride concentration consistently between 40 and 60 mEq/liter. Each has chronic Pseudomonas bronchitis, and all lack digestive symptoms. Laboratory findings indicate the preservation of exocrine pancreatic function. The patients include two of five children in one family and two of four in another. In a third family, one of five siblings has an intermediate sweat chloride concentration, but another has a typical fibrosis value (105 mEq/liter). One patient died of respiratory failure; results of an autopsy showed bronchiolectasis typical of cystic fibrosis, but minimal pancreatic changes. The data suggest a genetic basis for this variant of cystic fibrosis. These patients may be homozygous for a portion of a closely linked multigene cystic fibrosis locus or may have modifier genes that ameliorate the pancreatic and sweat lesions.     

Acute presentation of cystic fibrosis in an adult

The case history of a female patient presenting at the age of 25 with cystic fibrosis is described. Despite longstanding significant respiratory symptoms, she did not attend hospital until she was 23 and then failed to appear for further investigations and treatment. At the age of 25, she was admitted with a severe lower respiratory tract infection and respiratory failure. Within 5 days, acute intestinal obstruction developed which was unresponsive to conservative therapy. At laparotomy the small bowel was obstructed just proximally to the ileocaecal valve by solid faecal material. Post-operatively, the diagnosis of cystic fibrosis was confirmed by quantitative pilocarpine iontophoresis tests. The literature is reviewed regarding the adult presentations of cystic fibrosis and the recommended treatment for distal intestinal obstruction syndrome. The presence of adult cystic patients within the community is emphasized.     

Inflammatory joint disease and human immunodeficiency virus infection

Nine men positive for antibody to human immunodeficiency virus (HIV) who developed peripheral, non-erosive arthritis were followed up. The clinical features were compatible with reactive arthritis but were atypical in several respects: the joint symptoms were generally severe, persistent, and unresponsive to non-steroidal anti-inflammatory drugs. The onset of arthritis was associated with various infections, none of which are known to be associated with the development of reactive arthritis. HLA typing was performed for three patients, all of whom were positive for HLA-B27. HIV was isolated from the synovial fluid of one patient. No patient had AIDS before developing arthritis, but four progressed to having AIDS after a mean of 7.5 months, and two died. Arthritis resolved in only one patient. The possibility of HIV infection should be considered in all patients with conditions suggesting reactive arthritis. Synovitis in patients with severe immunodeficiency has important pathogenetic implications.     

Cystic fibrosis in a Bangladeshi child

Cystic fibrosis is one of the common lives limiting inherited diseases in Caucasians population. Recent reports suggest that the diagnosis of cystic fibrosis in this part of the world is missed or delayed due to low index of suspicion. A case of cystic fibrosis is reported here who is a Bangladeshi girl of nine-month-old who presented with the complaints of persistent cough, respiratory distress and failure to thrive. Diagnosis was made on the basis of sweat chloride estimation and mutation analysis, both of which were done, from abroad. She was put on pancreatic enzyme supplementation and nebulized bronchodilators. Cystic fibrosis though rare in Bangladesh its possibility is to be kept in mind in appropriate clinical circumstances     

Cystic fibrosis: present status and future prospects in detection of patients and carriers.

Development of a sensitive, easily performed, reliable test would be an important advance in detecting cystic fibrosis, improving genetic counselling and providing early effective treatment. The sweat chloride test, which is reliable in diagnosis, is technically too difficult for a screening program, and only reliably detects homozygotes. In contrast, the meconium test for detecting homozygote newborns is simple, inexpensive, reasonably specific but its general application has yet to be evaluated. Detection of serum components is the basis of two new tests to distinguish patients with cystic fibrosis and carriers. The effect of these serum components on ciliary activity is the principle of one test, an extremely difficult procedure that is subjective and lacks sufficient specificity for routine use. The second test, in which serum components are separated by isoelectric focusing, may provide an objective biochemical means of detecting both homozygotes and heterozygotes.     

Recombinant human DNase inhalation in normal subjects and patients with cystic fibrosis. A phase 1 study.

OBJECTIVE--To evaluate the safety of recombinant human DNase (rhDNase) in normal subjects and in patients with cystic fibrosis. DESIGN--Nonrandomized trial in which individuals inhaled rhDNase three times a day Monday through Friday on two consecutive weeks. SETTING--The study was performed in the Clinical Research Center at the University of Washington, Seattle. Patients were recruited from the Cystic Fibrosis Center at the University of Washington. SUBJECTS AND PATIENTS--Twelve normal subjects and 14 patients with cystic fibrosis were studied (12 patients completed the protocol). The subjects and patients had to be aged 18 to 65 years and have a negative pregnancy test, if female. The normal subjects had to have a normal chest roentgenogram, be nonsmokers, and have normal pulmonary function testing. The patients with cystic fibrosis had to have a forced vital capacity greater than 40% predicted normal and have no recent exacerbation (within 2 weeks) of their lung infection or change in their medication. INTERVENTIONS--The study design was a repetitive dose escalation of aerosolized rhDNase. The subjects inhaled rhDNase three times a day, Monday through Friday, on 2 consecutive weeks and were rechallenged with a single dose 21 days after the last dose. Spirometry was measured before and 30 minutes after every rhDNase dose. MAIN OUTCOME MEASURES--Pulmonary function testing, serum DNase concentrations, and anti-DNase antibodies. Secondary outcome measures were dyspnea score and quantitative bacterial culture. MAIN RESULTS--Inhalation of rhDNase was well tolerated by all persons. There were no serious adverse reactions, and no allergic reactions were observed, even on rechallenge. No individual developed rhDNase antibodies. Improvement in both lung function and dyspnea score was observed in the adults with cystic fibrosis. Forced vital capacity was 3.2 +/- 0.3 L (mean +/- SE) on day 1 and was 3.5 +/- 0.3 L on day 12. Forced expiratory volume in 1 second was 2.1 +/- 0.2 L (mean +/- SE) on day 1 and was 2.3 +/- 0.3 L on day 12. CONCLUSIONS--Aerosolized rhDNase appears safe in normal subjects and in adults with cystic fibrosis and may improve lung function with short-term therapy.     

Ostraceous and inverse psoriasis with psoriatic arthritis as the presenting features of advanced HIV infection

Knowledge of both the common and atypical presentations of human immunodeficiency virus (HIV)-associated dermatoses may be helpful in arousing suspicion of HIV, especially in patients with no reported risk factors. Herein, we report the case of an otherwise healthy, nonpromiscuous 29-year-old man who presented to our institution with an eight-week history of plaques with oyster shell-like scales on the trunk, extremities and genital area. The plaques were associated with fever, and intermittent knee pain and swelling. Initial diagnostic tests were suggestive of drug hypersensitivity syndrome, and the patient’s condition improved with treatment using oral prednisone. However, the lesions recurred when the dose of prednisone was tapered, even after the culprit drug had long been discontinued. Repeat skin punch biopsy and arthrocentesis revealed a diagnosis of psoriasis vulgaris with psoriatic arthritis. Due to the atypical presentation of psoriasis, the patient was counselled to undergo HIV testing, which came back positive. Clinicians should be attuned to the skin signs heralding HIV/acquired immunodeficiency syndrome, in order to facilitate early diagnosis and treatment.     

乳腺囊性增生病60临床病理分析

目的探讨乳腺囊性增生病与乳腺癌发生的关系。方法通过免疫组化SP法对乳腺囊性增生病进行bcl-2和PCNA标记。结果60例乳腺囊性增生病中，导管上皮不典型增生24例，bcl-2和PCNA的阳性表达分别为66．7％和54．2％；伴导管乳头状瘤者25例，bcl-2和PCNA的阳性表达为16．0％和20．0％；伴大汗腺化生者52例，bcl-2和PCNA的阳性表达为5．8％和7．7％；伴囊肿形成者53例，bcl-2和PCNA无阳性表达。结论乳腺囊性增生病伴导管上皮不典型增生者与乳腺癌的发生关系密切，而导管乳头状瘤、大汗腺化生、囊肿与癌的发生关系不大。     

A novel CFTR mutation found in a Chinese patient with cystic fibrosis

Background Cystic fibrosis (CF) is rare in Chinese. We investigated the mutations in the gene of cystic fibrosis transmembrane conductance regulator ( CFTR ) in a Chinese CF patient and reviewed the clinical features, gene mutations in Chinese CF cases. Methods Blood samples were collected from a previously reported CF girl and her parents. The 24 coding exons of CFTR of the proband were amplified and sequenced. Results A Chinese girl of 16 years old was diagnosed as CF at the age of 14. She had recurrent productive cough with bronchiectasis in bilateral upper lobes, parasinusitis and otitis media, but without pancreatic involvement. Her sweat chloride was (108.9 ±3.3) mmol/L. A heterozygous novel missense mutation of 699 C → A which results in the amino acid change of N189K was identified in exon 5. In addition, a heterozygous 3821-3823 delT mutation in exon 19 was found in CFTR . The mutation 699C → A was inherited from her father, and the 3821-3823delT mutation was from her mother. Twenty patients with CF in Chinese reported from 1974 to 2004 were also reviewed. DelF508 mutation was not found in the nine cases whose CFTR mutations were analyzed. Conclusions The CF proband carries two heterozygous mutations (699C → A and 3821-3823delT) in CFTR . 699C → A mutation is a novel mutation which is not reported previously. Review of reported Chinese cases suggests that the genotype of Chinese CF may be different from those of white cases. More studies are needed to understand the spectra of CFTR and clinical CF features in Chinese.     

正常人与囊性纤维化病人汗腺细胞膜单离子通道对Forskolin的反应

本文报道用片膜钳技术研究正常人及囊性纤维化病人(CF)的汗腺上皮细胞膜单个离子通道活动的特性,并比较分析了它们对Forskolin的反应。在400多个膜片上找出了至少七种或七个状态的离子通道的特性。观察到正常人和CF的部分汗腺上皮细胞(包括腺细胞与管细胞)膜离子通道对Forskolin有兴奋反应。发现腺细胞的兴奋反应率在正常人明显高于CF病人,差异非常显著。而管细胞的兴奋反应率,两组问无明显差异。以上结果提示,用Forskolin可协助鉴定CF的缺损,但宜选用腺细胞,不宜选用管细胞。     

Cystic fibrosis: prenatal diagnosis and carrier detection by DNA analysis

The analysis of restriction fragment length polymorphism (RFLP)s was used to detect 11 polymorphisms that are linked to cystic fibrosis in 42 Australian families with at least one child with cystic fibrosis. The data from all the families were fully informative in regard to the gene for cystic fibrosis (CF). Prenatal assessment was performed for 24 of these families: seven fetuses were assessed to be homozygous for cystic fibrosis, 13 fetuses were heterozygous and three fetuses were free of the CF gene. Of the seven pregnancies in which it was predicted that the infant would be affected by cystic fibrosis, two were continued electively; both have come to term and the infants each were shown to have cystic fibrosis at birth. Of the 17 pregnancies in which it was predicted that the infant would not be affected by cystic fibrosis, 13 have come to term and all the infants but one (who has not yet been followed-up) have been shown to be unaffected by cystic fibrosis at birth. The polymerase chain reaction has been used to amplify the CS.7 and KM.19 loci close to the CF gene. This procedure allows a polymorphic site in each locus to be analysed in a much shorter time (one or two days rather than 10 days) and allows the use of very small test-samples, such as dried blood on filter paper ("Guthrie blood spots"). Our observations confirm the results of overseas studies and indicate that these techniques are eminently useful for prenatal diagnosis and the detection of carriers in the vast majority of Australian families with cystic fibrosis.     

氨基比林和亚硝酸钠诱发的肝内胆管癌动物模型

目的 用氨基比林和亚硝酸钠诱发叙利亚地鼠肝内胆管癌（ICC）动物模型,观察胆管癌发生的病理变化。方法 以800mg／L的氨基比林和亚硝酸钠溶液作为50只6周龄利亚地鼠的饮用水,每周饮用6d,连续饮用24周,定期分批处死动物,观察肝脏组织的病理学改变。结果 诱癌早期出现卵圆细胞增生、管六增生及小胆管的囊性增生,中期主要病变为肝内胆管上皮乳头状增生、化生、不典型增生和胆管纤维化,晚期可见肝内胆管腺瘤和腺癌。晚期肝内管癌的发生率达50．0％（10／20）。结论 该动物模型与人类肝内胆管癌发生发展的过程相似,方法简便、经济、可重复性好,具有良好的应用前景。肝内胆管的各种增生发生性病变与ICC密切相关,尤其是不典型增生和胆管腺瘤,应视为ICC的高危性癌前病变。     

Cystic fibrosis infant care challenges in diagnosis and management in the era of newborn screening

With newborn screening for cystic fibrosis (CF) now accessible in every state in the US, more infants are being diagnosed. Currently, no large-scale randomized studies are available to assist clinicians in providing evidence-based medical care for the youngest CF patients. We review the standard of diagnostic evaluation, the sweat test, showing a slightly altered range for infants less than 6 months of age. Cystic fibrosis transmembrane conductance regulator (CFTR) metabolic syndrome is an entity that can be clinically challenging for parents and caregivers. Simply indentifying infants with CF can be challenging. This review tries to clarify the CFTR gene and its expressions and the additional benefits that may be drawn from newborn screening. We searched literature to review guidelines for care of infants with CF, and we reviewed newborn screening methods and diagnosis. We focused on early nutritional intervention and lung protective strategies to improve growth and lung function outcomes.     

Ignorance is bliss? HIV and moral duties and legal duties to forewarn

In 1997, a court in Cyprus jailed Pavlos Georgiou for fifteen months for knowingly infecting a British woman, Janet Pink, with HIV-1 through unprotected sexual intercourse. Pink met Georgiou in January 1994 whilst on holiday. She discovered that she had contracted the virus from him in October 1994 but continued the relationship until July 1996 when she developed AIDS. She returned to the UK for treatment and reported Georgiou to the Cypriot authorities. There have been a number of legal cases involving deliberate transmission of HIV, but most have involved forced exposure to infected bodily fluids for example, rape or biting, and have been dealt with using the existing legislation for rape or assault. While it is often difficult to prove responsibility for transmission in cases of forced exposure to HIV, it is even more contentious in cases like those of Janet Pink where an individual has consented to sex but claims that he/she was not forewarned of his/her partner's HIV-positive status. At present there is no specific criminal offence of having unprotected sexual intercourse without disclosing one's HIV-positive status but a prosecution could possibly be brought under any one of a number of existing offences. Perhaps a change of policy needs to be considered. The Home Office has issued a consultation document which outlines a proposal that will allow the criminalization of intentional transmission of diseases, like HIV, that are likely to cause serious harm. This revised legislation would cover all other potentially fatal diseases (including salmonella and legionnaire's disease, for instance) but seems primarily to be targeted at HIV transmission. Should transmission of HIV through consensual sex, without the HIV-positive status of the individual being disclosed, be an offence? This question, and that of whether there is a moral obligation to disclose a positive HIV status prior to having a sexual relationship is the subject of this paper.