Restructuring ENT out-patient services during the coronavirus disease 2019 pandemic - an iterative approach.

BACKGROUND: Coronavirus disease 2019 has demanded enormous adjustments to National Health Service provisions. Non-urgent out-patient work was initially postponed or performed virtually, but is now being re-established. In ENT surgery, aerosol-generating procedures pose a particular challenge in out-patient settings. OBJECTIVE: A rapid restructuring of ENT out-patient services is required, to safely accommodate aerosol-generating procedures and increase in-person attendances, whilst coronavirus disease 2019 persists. METHODS: Data were collected prospectively over four consecutive cycles. Two surveys were conducted. Results were analysed and disseminated, with recommendations for service restructuring implemented at cycle end-points. RESULTS: Out-patient activity increased four-fold, associated with a significant rise in aerosol-generating procedures during the study period. Mean aerosol-generating procedure duration dropped weekly, implying a learning curve. Service restructuring occurred at cycle end-points. CONCLUSION: Iterative data gathering, results analysis and outcome dissemination enabled a swift, data-driven approach to the restructuring of ENT out-patient services. Patient and staff safety was ensured, whilst out-patient capacity was optimised.

Drug therapy for nocturnal enuresis. Current treatment recommendations.

It is estimated that enuresis occurs in 5 to 7 million children in the United States. The treatment approach for enuresis is controversial, in large part due to a lack of consensus as to the exact cause of enuresis. Several factors either alone or together may contribute to this syndrome. In addition, there is strong evidence of a genetic component to enuresis. Pharmacotherapy continues to be the preferred treatment for both physicians and families. The most widely used drugs include antidepressants, anticholinergics, and desmopressin. The tricyclic antidepressant imipramine has been used extensively since the 1960s. The exact mechanism of action in enuresis is unknown although it appears to be related to the anticholinergic and antispasmodic effects of the drug. The most common adverse effects reported with imipramine include personality changes, insomnia, anorexia and anxiety. There has been renewed interest in antidiuretic treatment of enuresis. Researchers have found that enuretic children do not have the ability to reduce urine volume at night or concentrate the urine they produce during the night. Clinical trials with desmopressin administered by nasal inhalation report a marked reduction in enuretic episodes. Adverse effects were limited to nasal complaints, rhinitis, or epistaxis. Additional long term studies are needed to delineate desmopressin's role in therapy. Although the number of options for treatment of enuresis is expanding, criteria to predict patient response need to be defined.

Cytokeratin reorganization induced by adenosine diphosphate in kidney epithelial cells.

Exogenous adenosine diphosphate (ADP), the most potent mitogen for nontransformed African green monkey kidney epithelial cells of the BSC-1 line, rapidly alters the appearance of the cell monolayer. Examination of the cells with indirect immunofluorescence using monoclonal antibodies reveals a considerable reorganization of cytokeratin filaments without a major change in the pattern of microtubules or microfilaments. In untreated confluent cells, cytokeratin filaments are predominantly confined to a star-like spot in the perinuclear area, but these can be seen to begin to spread within 2 min after addition of ADP. The effect is particularly notable using anti-cytokeratin 8 antibodies. At 6 h this process is complete and produces a well-developed filamentous network throughout the cell. By 12 h, the network appears to collapse, so that the filaments again form a spot in the perinuclear area, a process that is complete by 24 h. Immunoblotting of total cellular proteins reveals no apparent alterations in the amounts of several species of cytokeratins, including cytokeratin 8 and 18, at 3 or 24 h after exposure to ADP. Other purine and pyrimidine nucleotides which do not stimulate DNA synthesis in these cells fail to alter cytokeratin organization, and there is no apparent alteration in the distribution of vimentin, another intermediate filament protein. The rapid ADP-induced cytokeratin reorganization appears to coincide with the induction of early growth-response gene transcription in these cells and may be correlated with the capacity of ADP to subsequently initiate DNA synthesis. This dramatic and reversible cytokeratin reorganization immediately after exposure to ADP may be an important step in the mitogenic signal transduction pathway.

Macula densa cells of mouse kidney do not synthesize epidermal growth factor precursor mRNA.

Epidermal growth factor (EGF) has previously been found in cells of the thick ascending limb of Henle's loop (TALH) and the first part of the distal convoluted tubule (DCT) of mouse kidney. To define the cellular localization of the mRNA that encodes the protein precursor of EGF, we used high-resolution in situ hybridization. EGF precursor cDNA was hybridized to both paraffin-embedded and frozen sections of mouse kidney. EGF precursor mRNA was detected in cells comprising the TALH and the first part of the DCT. In contrast, tubular cells in the macula densa did not express this specific mRNA. The results indicate that expression of the EGF precursor gene is restricted to specific types of cells in the distal nephron.

Enalapril: a well-tolerated and efficacious agent for the pediatric hypertensive patient.

Enalapril either alone or with a diuretic was administered to 15 children with various renal diseases and hypertension. Five were transplant recipients on multiple immunosuppressive agents. No adverse clinical or laboratory experiences were encountered except for mild proteinuria in two children, one of whom has evidence of chronic rejection. Enalapril effectively controlled blood pressure in all 15 patients when given once daily with or without food. Renal function improved in seven children. Six children are under excellent blood pressure control despite a reduction in the dose of enalapril. Two are currently on no medication, five require a diuretic, while one child is on an increased dose of enalapril.

Enalapril: a well-tolerated and efficacious agent for the paediatric hypertensive patient.

Enalapril, either alone or with a diuretic, was administered to 14 children with various renal diseases and hypertension. Five were transplant recipients on immunosuppressive agents. No adverse clinical or laboratory experiences were encountered. Renal function improved in seven children. Normal blood pressure for age was achieved in all 14 children. However, eight children required the addition of a diuretic. In four children blood pressure remained normal despite a reduction in the dose of enalapril. Enalapril was efficacious as a once per day agent. Concomitant ingestion of food did not attenuate the blood pressure-lowering effect of enalapril.

Carrier detection of pyruvate carboxylase deficiency in fibroblasts and lymphocytes.

Pyruvate carboxylase (E.C. 6.4.1.1) activity was determined in the circulating peripheral lymphocytes and cultured skin fibroblasts from the family of a patient with hepatic, cerebral, renal cortical, leukocyte, and fibroblast pyruvate carboxylase deficiency (PC Portland deficiency). Lymphocyte activities were: mother, 33--39%; father, 11--29%; brother, 82--103%; and sister, 38--48% of the lowest normal. Fibroblasts from the patient's mother and father had 42 and 34%, respectively, of the activity of the lowest normal. These data demonstrate that the disease is inherited in an autosomal recessive manner and that lymphocytes and fibroblasts can be used to detect carriers. Neither pyruvate carboxylase nor mitochondrial PEPCK activity in lymphocytes was increased by a 21-hr fast.

Pyruvate carboxylase deficiency and lactic acidosis in a retarded child without Leigh's disease.

A child with lactic acidosis, severe mental and developmental retardation, and proximal renal tubular acidosis is presented. Biopsy and autopsy studies show severe hepatic, renal cortical, and cerebral deficiencies in pyruvate carboxylase (EC 6.4.1.1) activity. The patient had 1.81 +/- 0.20 units/g fresh weight at biopsy and 0.75 +/- 0.07 units/g fresh weight hepatic pyruvate carboxylase activity at autopsy compared with 10.9, 11.3, and 9.5 units/g fresh weight in two autopsy and one biopsy controls, respectively. The patient's renal cortical pyruvate carboxylase activity at autopsy was 0.008 +/- 0.004 units/g fresh weight compared with 5.05 units/g in the autopsy control. The patient had no detectable (less than 0.018 units/g fresh weight) cerebral pyruvate carboxylase activity at autopsy compared with 0.44, 0.53, and 0.695 units/g in the autopsy cerebrum of one human and two rhesus monkeys, respectively. Pyruvate dehydrogenase complex, phosphoenolpyruvate carboxykinase (PEPCK, EC 4.1.1.32), and fructose-1,6-bisphosphatase (EC 3.1.3.11) activities were in the normal range. The patient's urine pH was above 7.9 when the total serum CO2 was greater than 7.8 mM. However, the patient was able to acidify the urine to pH 5.1 when the total serum CO2 was 1.6 mM. The neuropathologic examination of the brain at autopsy revealed no sign of Leigh's disease, although developmental and degenerative lesions were observed. This is the first reported patient with a primary deficiency in hepatic, renal, and cerebral pyruvate carboxylase deficiency in whom the neuropathologic lesions, distinct from those of Leigh's disease, and proximal renal tubular acidosis have both been documented.

Pyruvate carboxylase and phosphoenolpyruvate carboxykinase activity in leukocytes and fibroblasts from a patient with pyruvate carboxylase deficiency.

Normal values are given for the activities of pyruvate carboxylase (E.C.6.4.1.1), mitochondrial phosphoenolpyruvate carboxykinase (E.C. 4.1.1.32, PEPCK), and citrate synthase (E.C. 4.1.3.7) in fibroblasts, lymphocytes, and leukocytes. Also given are values for these enzymes in the leukocytes and fibroblasts from a severely mentally and developmentally retarded patient with proximal renal tubular acidosis and hepatic, cerebral, and renal cortical pyruvate carboxylase deficiency. In normals, virtually all of the mitochondrial PEPCK and pyruvate carboxylase activity was present in the mononuclear leukocyte fraction of whole venous blood. Cellular fractionation studies with human lymphocytes and fibroblasts demonstrated that all of the PEPCK activity in these cells is mitochondrial. Normal values for pyruvate carboxylase in leukocytes were 0.092 (0.070--0.208) mU/mg protein (n=5), in lymphocytes 0.154 (0.092--0.262) mU/mg protein (n=5), and in fibroblasts 1.36 (0.778--2.19) mU/mg protein (n=5). The patient with hepatic, renal, and cerebral pyruvate carboxylase deficiency had no detectable activity (less than 0.009 mU/mg protein) in his leukocytes and 0.018 mU/mg protein in his fibroblasts. Data from an assay for pyruvate carboxylase activity in the patient's fibroblasts show that the activity observed is significant but very close to the lower limits of the assay. Values for PEPCK in normal lymphocytes were 1.42 (0.824--1.88) mU/mg protein (n=5), in leukocytes 1.68 (1.64--1.72) mU/mg protein (n=2), and in fibroblasts 5.49 (3.94--6.33) mU/mg protein (n=6).