Elevated sweat chloride test: is it always cystic fibrosis?

BACKGROUND: The sweat chloride test (ST) is the gold standard for cystic fibrosis (CF) diagnosis in symptomatic patients, within the newborn screening and in the follow-up of CF patients during molecular therapies. However, false positives have been reported in patients with different diseases. We describe and discuss 4 cases due to different clinical conditions in which we recorded false positive ST, and the test remained altered for a period of varying length. CASES PRESENTATION: Case 1: Eight months old female child suffering from constipation, recurrent vomiting and failure to thrive, family history of recurrent pancreatitis without mutations in the PRSS1 and SPINK1 genes. Both ST and fecal elastase were altered although no CFTR gene mutations were found. Due to rapid clinical deterioration, celiac disease was suspected and diagnosed by laboratory tests and intestinal biopsy. After 2 weeks of gluten-free diet ST and fecal elastase normalized. Case 2: 14 months old male suffering from bilateral renal dysplasia, episodes of metabolic alkalosis, recurrent respiratory infections and recurrent vomiting. The child had more ST positives, but no CFTR mutations were found. During follow-up, he developed sensorineural hearing loss and an atrial septic defect was found. Finally, a diagnosis of Klinefelter was made, but the ST normalized several years later. Case 3 and 4: Two boys with stubborn constipation and fecal occlusion treated with Poly Ethylene Glycol (PEG) with salts showed pathological ST. The test returned normal a few days after stopping treatment. CONCLUSIONS: We hypotesized the possible causes of ST alteration in these conditions: in celiac disease it could be due to a transient dysregulation of the aquaporins, rapidly reversed by the diet; in Klinefelter, it may be due to stable pubertal hypoandrogenism; while, the PEG formulation itself contains salts that can temporarily alter ST.

A novel treatment of cystic fibrosis acting on-target: cysteamine plus epigallocatechin gallate for the autophagy-dependent rescue of class II-mutated CFTR.

This corrects the article DOI: 10.1038/cdd.2016.22.

A novel treatment of cystic fibrosis acting on-target: cysteamine plus epigallocatechin gallate for the autophagy-dependent rescue of class II-mutated CFTR.

We previously reported that the combination of two safe proteostasis regulators, cysteamine and epigallocatechin gallate (EGCG), can be used to improve deficient expression of the cystic fibrosis transmembrane conductance regulator (CFTR) in patients homozygous for the CFTR Phe508del mutation. Here we provide the proof-of-concept that this combination treatment restored CFTR function and reduced lung inflammation (P<0.001) in Phe508del/Phe508del or Phe508del/null-Cftr (but not in Cftr-null mice), provided that such mice were autophagy-competent. Primary nasal cells from patients bearing different class II CFTR mutations, either in homozygous or compound heterozygous form, responded to the treatment in vitro. We assessed individual responses to cysteamine plus EGCG in a single-centre, open-label phase-2 trial. The combination treatment decreased sweat chloride from baseline, increased both CFTR protein and function in nasal cells, restored autophagy in such cells, decreased CXCL8 and TNF-α in the sputum, and tended to improve respiratory function. These positive effects were particularly strong in patients carrying Phe508del CFTR mutations in homozygosity or heterozygosity. However, a fraction of patients bearing other CFTR mutations failed to respond to therapy. Importantly, the same patients whose primary nasal brushed cells did not respond to cysteamine plus EGCG in vitro also exhibited deficient therapeutic responses in vivo. Altogether, these results suggest that the combination treatment of cysteamine plus EGCG acts 'on-target' because it can only rescue CFTR function when autophagy is functional (in mice) and improves CFTR function when a rescuable protein is expressed (in mice and men). These results should spur the further clinical development of the combination treatment.

Deep neck infection: a present-day complication. A retrospective review of 83 cases (1998-2001).

Deep neck infections are less and less frequent today than in the past. Nevertheless, their complications are often life-threatening. The present study reviews the experience of the Department of Otolaryngology and Head and Neck Surgery of Padua with deep neck infections during the period from 1998 to 2001. Eighty-three patients (55 males and 28 females) were retrospectively considered. The site of origin of deep neck infection was identified in 76 patients (91%). The most common cause was dental infection, occurring in 35 cases (42%). In 12 cases (14%) deep neck infection was a complication of oropharyngeal infection. The relatively high incidence of Peptostreptococcus sp, Streptococcus viridans, Streptococcus intermedius and constellatus isolation was consistent with the high rate of odontogenic cases. Surgery was advocated as the treatment for any infection of the deep neck spaces. The recent series has demonstrated that medical treatment did not seem to increase complication rates or mortality. Our tailored approach (medical or medical and surgical) based on clinical and radiological evidence was successful in 97% of the patients.

The role of surgical treatment in colon diverticulitis: indications and results.

PURPOSE: Colon diverticulitis is a common illness with affects 37-45% of western populations. Indications regarding therapy guidelines, operative timing and which surgical procedure to perform are still controversial. MATERIAL AND METHOD: Between January 1977 and December 1997, 239 patients, diagnosed with diverticulitis, have been admitted, on emergency, to our Department of General Surgery; 135 males (56%) and 104 females (44%), (mean age of 63 years). RESULTS AND DISCUSSION: Forty-two patients (18%), clearly diagnosed with diffuse or local peritonitis, underwent delayed emergency surgical procedure; 44 (22%) out of 197 patients, treated with medical therapy and subsequently underwent elective surgery procedures for complications (fistulas or stenosis). Among the 42 patients treated in emergency, 26 cases (62%) underwent to resection with immediate reconstruction. Among the elective surgery group 39 (89%) out of 44 underwent to resection with immediate reconstruction. Complications reached 40% in the group of emergency patients (mortality rate 12%) and 16% in the elective surgery group (mortality rate 2%). Several features possible influencing mortality rate have been analysed; age > 70 years, acute associated diseases, generalised peritonitis and surgical timing show a statistical significance. CONCLUSION: Therefore, a careful evaluation of the patients, an appropriate pre and post-operative medical treatment, with a wider use of the most recent techniques such as CT scan guided drain, intra-operative wash-out and peritoneal lavage are recommended in order to reduce morbidity and mortality.

Psychological distress in patients with tinnitus.

OBJECTIVE: This study was conducted to evaluate the psychological distress in patients with tinnitus that is often correlated with sleeping disorders, difficulties in concentration, and compromized social relations. METHODS: Eighty-four patients were studied using preliminary clinical and audiologic evaluations, and successive psychological tests. RESULTS: The cluster analysis indicated two essential groups composed of 45 patients (CLST-1) and 38 patients (CLST-2), respectively. The CLST-1 group had higher scores for depression, anxiety, and neuroticism. The IBQ CLST-1 revealed a greater degree hypochondria, conviction of disease dysphoria, and irritability. CONCLUSIONS: Our results indicate that the relationship between the intensity of the tinnitus and the extent of the distress is supported by the larger number of patients with more intense tinnitus in the first cluster. The CLST-2 with its normal psychological test results, apart from marked denial, would support the hypothesis of a somatic expression of the distress.

Group A streptococcus-liposome ELISA antibody titers to group A polysaccharide and opsonophagocytic capabilities of the antibodies.

Antibodies reactive with group A streptococci (GAS) carbohydrate were studied by ELISA and in an indirect bactericidal assay. The ELISA used GAS carbohydrate covalently bound to phosphatidylethanolamine incorporated into liposomes so that both precipitating and nonprecipitating antibodies were measured. Sera from children from different geographic areas exhibited marked differences in levels of anti-GAS carbohydrate antibody, which increased with age. The antibodies were predominantly of IgG. In bactericidal assays, most of these sera promoted phagocytosis of several type-specific M-positive strains. Opsonization was also related to serum levels of anti-GAS carbohydrate antibodies. These opsonizing antibodies were depleted from the serum by absorption of the sera on an N-acetyl-D-glucosamine affinity column. Antibody eluted from this column could partially restore opsonization of GAS. Anti-GAS carbohydrate antibodies play a major role in these opsonophagocytosis assays.

Bone-cement interface: a histological study of aseptic loosening in twelve prosthetic implants.

The histology of bone-cement interfaces was studied by using new fixation techniques that preserve the cement, as well as sectioning the samples without decalcification. This permits histological study of the unaltered morphology, and the precise topographical distribution of fibrous tissue, bone necrosis and cellular anomalies in relation to the cement. Twelve cases of implant loosening over an average 7 year follow-up period were examined. By dynamic studies with sequential fluorescent bone labelling it was possible to evaluate precisely the extent of bone damage after the application of cement. The characteristic findings were: fibrous tissue at the bone-cement interface; bone necrosis or reduced remodelling in proximity to the cement; away from the cement, normal bone remodelling is clearly demonstrated by fluorescent labelling.

Osteochondritis dissecans of the femoral condyles. A histological study with pre-operative fluorescent bone labelling and microradiography.

A review of the literature in osteochondritis dissecans of the femoral condyles reveals that the aetiopathology is still unclear and that relatively few histopathological studies have been carried out. The authors describe a method of study based on microradiography and on preoperative fluorescent labelling of the osteogenetic area followed by examination of the bone remodelling under ultraviolet light microscopy. The results in 12 adult cases are reported in relation to a topographical scheme which divides the lesions into four separate zones.