Biochemical characteristics and increased tetraglucoside excretion in patients with phosphorylase kinase deficiency

Summary Patients with glycogen storage disease type IXa present with infantile hepatomegaly and a specific growth pattern, and variable biochemical alterations in blood. We studied the clinical and biochemical characteristics including the urinary oligosaccharide excretion of seven unrelated children. The urinary tetraglucoside excretion was increased in four children, three of whom had persistently high cholesterol and triglyceride concentrations. We propose screening for urine tetraglucoside excretion and the measurement of serum cholesterol in patients with growth delay and/or hepatomegaly to assess a possible glycogenosis.     

Treatment of acute gouty arthritis: One physician’s approach and where this management stands relative to developments in the field

An attack of acute gouty arthritis is one the most painful episodes that can be experienced by humans. Fortunately, there are three classes of agents that can effectively terminate the acute attack. These include colchicine, nonsteroidal anti-inflammatory drugs, and glucocorticoids. If therapy with any one of these is initiated promptly after the onset of symptoms, relief should occur quickly. Recent observations have increased the knowledge of crystal-induced acute inflammatory responses. These observations allow a better understanding of the mechanisms of action of these agents and provide the rationale for using them in combination in severe or refractory cases.     

Trovafloxacin-induced weakness due to a demyelinating polyneuropathy

Fluoroquinolones have been associated with peripheral sensory disorders and weakness, especially in patients with underlying myasthenia gravis or myasthenia-like Eaton-Lambert syndrome. Trovafloxacin is a relatively new quinolone for which these side effects have not been described. We report a case of diffuse weakness due to a demyelinating polyneuropathy that began after initiation of trovafloxacin in a patient without an underlying neurologic disorder.     

Efficacy and safety of empagliflozin in glycogen storage disease type Ib: Data from an international questionnaire

PurposeThis paper aims to report collective information on safety and efficacy of empagliflozin drug repurposing in individuals with glycogen storage disease type Ib (GSD Ib).MethodsThis is an international retrospective questionnaire study on the safety and efficacy of empagliflozin use for management of neutropenia/neutrophil dysfunction in patients with GSD Ib, conducted among the respective health care providers from 24 countries across the globe.ResultsClinical data from 112 individuals with GSD Ib were evaluated, representing a total of 94 treatment years. The median age at start of empagliflozin treatment was 10.5 years (range = 0-38 years). Empagliflozin showed positive effects on all neutrophil dysfunction–related symptoms, including oral and urogenital mucosal lesions, recurrent infections, skin abscesses, inflammatory bowel disease, and anemia. Before initiating empagliflozin, most patients with GSD Ib were on G-CSF (94/112; 84%). At the time of the survey, 49 of 89 (55%) patients previously treated with G-CSF had completely stopped G-CSF, and another 15 (17%) were able to reduce the dose. The most common adverse event during empagliflozin treatment was hypoglycemia, occurring in 18% of individuals.ConclusionEmpagliflozin has a favorable effect on neutropenia/neutrophil dysfunction–related symptoms and safety profile in individuals with GSD Ib.     

Pyrophosphohydrolase activity and inorganic pyrophosphate content of cultured human skin fibroblasts. Elevated levels in some patients with calcium pyrophosphate dihydrate deposition disease.

In calcium pyrophosphate dihydrate (CPPD) crystal deposition disease, metabolic abnormalities favoring extracellular inorganic pyrophosphate (PPi) accumulation have been suspected. Elevations of intracellular PPi in cultured skin fibroblasts from a single French kindred with familial CPPD deposition (19) and elevated nucleoside triphosphate pyrophosphohydrolase activity (NTPPPH), which generates PPi in extracts of CPPD crystal-containing cartilages (14) favor this suspicion. To determine whether NTPPPH activity or PPi content of cells might be a disease marker expressed in extraarticular cells, human skin-derived fibroblasts were obtained from control donors and patients affected with the sporadic and familial varieties of CPPD (CPPD-S and CPPD-F) deposition. Intracellular PPi was elevated in both CPPD-S (P less than 0.05) and CPPD-F (P less than 0.01) fibroblasts compared with control fibroblasts. Ecto-NTPPPH activity was elevated in CPPD-S (P less than 0.01) but not CPPD-F. Intracellular PPi correlated with ecto-NTPPPH (P less than 0.01). Elevated PPi levels in skin fibroblasts may serve as a biochemical marker for patients with familial or sporadic CPPD crystal deposition disease; ecto-NTPPPH activity further separates the sporadic and familial disease types. Expression of these biochemical abnormalities in nonarticular cells implies a generalized metabolic abnormality.     

Old world cutaneous leishmaniasis in Los Angeles: a case report,overview of the current literature,and guide for the treating dermatopathologist

We describe a case of cutaneous leishmaniasis in a Spanish patient visiting Los Angeles. Leishmania species cause both cutaneous and visceral disease; the majority of infections with Leishmania are of the cutaneous form. Although leishmaniasis is a relatively rare occurrence in the United States, travel by United States' citizens to endemic regions and increased United States military operations in the Middle East raise the chances of encountering cutaneous leishmaniasis. The following case report and overview of the current literature outlines the major morphologic findings and current diagnostic modalities available to diagnose cutaneous leishmaniasis.     

Glycaemic patterns of male professional athletes with type 1 diabetes during exercise,recovery and sleep: Retrospective,observational study over an entire competitive season

Aims

To analyse glycaemic patterns of professional athletes with type 1 diabetes during a competitive season.

Materials and Methods

We analysed continuous glucose monitoring data of 12 professional male cyclists with type 1 diabetes during exercise, recovery and sleep on days with competitive exercise (CE) and non-competitive exercise (NCE). We assessed whether differences exist between CE and NCE days and analysed associations between exercise and dysglycaemia.

Results

The mean glycated haemoglobin was 50 ± 5 mmol/mol (6.7 ± 0.5%). The athletes cycled on 280.8 ± 28.1 days (entire season 332.6 ± 18.8 days). Overall, time in range (3.9-10 mmol/L) was 70.0 ± 13.7%, time in hypoglycaemia (<3.9 mmol/L) was 6.4 ± 4.7% and time in hyperglycaemia (>10 mmol/L) was 23.6 ± 12.5%. During the nights of NCE days, athletes spent 10.1 ± 7.4% of time in hypoglycaemia, particularly after exercise in the endurance zones. The CE days were characterized by a higher time in hyperglycaemia compared with NCE days (25.2 ± 12.5% vs. 22.2 ± 12.1%, p = .012). This was driven by the CE phase, where time in range dropped to 60.4 ± 13.0% and time in hyperglycaemia was elevated (38.5 ± 12.9%). Mean glucose was higher during CE compared with NCE sessions (9.6 ± 0.9 mmol/L vs. 7.8 ± 1.1 mmol/L, p < .001). The probability of hyperglycaemia during exercise was particularly increased with longer duration, higher intensity and higher variability of exercise.

Conclusions

The analysis of glycaemic patterns of professional endurance athletes revealed that overall glycaemia was generally within targets. For further improvement, athletes, team staff and caregivers may focus on hyperglycaemia during competitions and nocturnal hypoglycaemia after NCE.     

Kawasaki syndrome

Kawasaki syndrome is an acute, self-limited illness of young children which is characterized by prolonged fever, mucositis, skin changes, and cervical lymphadenopathy. Most investigators favor a microbial agent or agents as the trigger of KS followed by an immune-mediated vasculitis with a predilection for the coronary arteries. Serious complications include coronary artery aneurysms, aneurysmal thrombosis, and death. Aspirin has been the conventional treatment for KS, but it has not been shown to alter the basic pathology. Recently intact intravenous gamma globulin has been shown to reduce the frequency of coronary artery abnormalities. Definitive therapy of KS, however, awaits the discovery of its cause and pathogenesis.