Infection prevention and control measures in practices of the Swiss sentinel network during seasonal influenza epidemics.

BACKGROUND: There are limited data on the transmission of influenza in the context of primary care practices, despite the fact that a significant proportion of the population consult their primary care physician for an influenza-like illness every year. AIM: To describe the use of influenza prevention and control methods in private practices of the Swiss sentinel network. METHODS: This online cross-sectional survey collected data about infection prevention and control measures in the 166 private practices of the Swiss sentinel surveillance network during the 2018-2019 influenza season. Questions pertained to the practice setting, infection prevention and control recommendations, influenza vaccination status of the physicians and their staff, adhesion to hand hygiene, and mask wearing. FINDINGS: Among the 122 practices that answered (response rate 73.5%), 90.2% of the responding physicians had been vaccinated themselves, and 46.7% (56/120) estimated that their staff vaccination coverage was >60%, although it was offered to employees in all practices. Most practices (N=68, 55.7%) had no specific recommendations for their staff concerning mask wearing. Most physicians reported washing or disinfecting their hands before examining a patient (N=91, 74.6%), after examination (N=110, 90.2%) and before a medical procedure (N=112, 91.8%). However, this rate was lower for arrival at the practice (N=78, 63.9%) and leaving the practice (N=83, 68.0%). CONCLUSION: Most physicians in the Swiss sentinel surveillance network have been vaccinated themselves. However, the vaccination rates among their staff are low, despite vaccine availability. Hand hygiene measures were also suboptimal. These results warrant further efforts to implement infection prevention and control measures in the ambulatory setting.

Short- and long-term results of total vs subtotal thyroidectomies in the surgical treatment of Graves' disease.

OBJECTIVE: Approximately one out of five patients with Graves' disease (GD) undergoes a thyroidectomy after a mean period of 18 months of medical treatment. This retrospective and non-randomized study from a teaching hospital compares short- and long-term results of total (TT) and subtotal thyroidectomies (ST) for this disease. METHODS: From 1987 to 1997, 94 patients were operated for GD. Thirty-three patients underwent a TT (mostly since 1993) and 61 a ST (keeping 4 to 8 grams of thyroid tissue--mean 6 g). All patients had received propylthiouracil and/or neo-mercazole and were in a euthyroid state at the time of surgery; they also took potassium iodide (lugol) for ten days before surgery. RESULTS: There were no deaths. Transient hypocalcemia (< 3 months) occurred in 32 patients (15 TT and 17 ST) and persistent hypocalcemia in 8 having had TT. Two patients developed transient recurrent laryngeal nerve palsy after ST (< 3 months). After a median follow-up period of seven years (1-15) with five patients lost to follow-up, 41 patients having had a ST are in a hypothyroid state (73%), thirteen are euthyroid (23%), and two suffered recurrent hyperthyroidism, requiring completion of thyroidectomy. All 33 patients having had TT--with follow-ups averaging two years (0.5-8)--are receiving thyroxin substitution. CONCLUSIONS: There were no instances of persistent recurrent laryngeal nerve palsy in either group, but persistent hypoparathyroidism occurred more frequently after TT. Long after ST, hypothyroidism developed in nearly three of four cases, whereas euthyroidy was maintained in only one-fourth; recurrent hyperthyroidy was rare.

Stimulation of corticosteroid biosynthesis by angiotensin I [des-asp1]angiotensin I, angiotensin II and [des-asp1]-angiotensin II in bovine adrenal fasciculata cells.

The effect of angiotensin I (AI), angiotensin II (AII), [des-asp1]AI, [des-asp1]AII and [des-asp1-arg2]AII on corticosteroid production in isolated fasciculata cells from bovine adrenals has been studied. AII and [des-asp1]AII in concentrations ranging from 10(-9)M to 10(-6)M had a potent stimulatory effect on steroid biosynthesis. The dose-response curves for both peptides were identical. AI was about 3 times less potent than AII and [des-asp1]AII. The effect of AI was not due to its conversion to AII. [Des-asp1]AI was as active as AI. No significant conversion to [des-asp1]AII was observed. [Des-asp1-arg2]AII had only a minimal effect on steroidogenesis. The structural analog [sar1,-ala8]AII inhibited all angiotensins specifically and competitively. The affinity of the cellular binding site was higher for AII and [des-asp1]AII than for [sar1,ala8]ALL, but lower for AI and [des-asp1]AI than for the inhibitor. Combination of submaximal doses of AI and AII resulted in an additive effect on steroid production. By contrast, combination of maximal doses of both peptides had the same effect as AII alone. These data demonstrate a potent steroidogenic activity for AII as well as AI, [des-asp1]AI and [des-asp1]AII in bovine adrenal fasciculata cells. A common receptor site for all four peptides is suggested.

A simplified competitive protein-binding assay for 25-hydroxycalciferol.

A single and reliable, competitive, protein-binding assay for plasma 25-hydroxycalciferol (25-OH-D), based on a previously described method which omits the chromatographic step, has been tested without the use of beta-lipoproteins. The accuracy is similar in the absence of beta-lipoproteins and in their presence, the recoveries being respectively 110-136% and 74-85%. The intraassay coefficient of variation is 7.23% in the absence versus 12.56% in the presence of beta-lipoproteins. The sensitivity of the described assay is 0.01 ng per assay tube and 1 mug/1 plasma. The mean plasma 25-OH-D level in eighteen normal Swiss volunteers aged 20 to 40 years is 39.5 +/- S.D. 9.3 mug/l. This level is similar to those found in Western Europe and U.S.A. subjects. Ten alcoholic patients without cirrhosis have significantly lower 25-OH-D plasma levels (13.0 +/- S.D. 8.9 mug/l) than appropriate age controls. This precise and accurate method is convenient for clinical studies since both chromatographic and beta-lipoproteins steps are avoided.

Stimulating effects of angiotensin I, angiotensin II and des-Asp1-angiotensin II on steroid production in vitro and its inhibition by Sar1-Ala8-angiotensin II.

Two of the agents known to block the renin-angiotensin-aldosterone system, namely Sar1-Ala8-angiotensin II and the nonapeptide SQ 20881, have been used to clarify the role of angiotensin II (AII) and its cogeners upon the steroidogenesis in isolated fasciculata cells from bovine adrenal tissue. It could be concluded that: (1) des-Asp1-angiotensin II is as active as AII on steroidogenesis from bovine fasciculata cells; (2) angiotensin I, although less potent, stimulates steroid production without being converted to AII or des-Asp1-AII, and (3) Sar1-Ala8-AII inhibits all three peptides in a competitive manner. The presence of a common receptor for all these three peptides is suggested.

Metabolism and biological activity of parathyroid hormone in renal cortical membranes.

Recent studies from several laboratories have documented the presence of fragments of parathyroid hormone in blood or peripheral tissues or in both. Inasmuch as amino-terminal fragments are known to be biologically active, it has been suggested that fragments, rather than the intact polypeptide of 84 amino acids, might be the active molecular species in tissue fluids. Accordingly, the metabolism of native bovine parathyroid hormone, bPTH-(1-84), was studied in purified renal cortical membranes from several species and correlated with hormonal stimulation of adenylyl cyclase in these membranes in vitro. Analysis of whole incubation mixtures or membrane-bound hormone by gel electrophoresis and gel chromatography after incubation of [3H]bPTH-(1-84) or 125-I-labeled bPTH-(1-84) or unlabeled biologically active bPTH-(1-84) with purified canine renal cortical membranes revealed no evidence of proteolysis, and yet the uncleaved hormone readily stimulated adenylyl cyclase. Kinetic studies of hormone-stimulated adenylyl cyclase activity revealed no difference in rate of onset of activity between bPTH-(1-84) And the active synthetic amino-terminal tetratriacontapeptide bPTH-(1-34), and hence there was no evidence of precursor-product relationship between the native hormone and an active amino-terminal fragment. The results suggest, insofar as the activity detected in these membranes reflects the biological response of the hormone in vivo, that the native hormone is indeed biologically active at the receptor level directly without the requirement for cleavage into active fragments.

Metabolism and biological activity of proparathyroid hormone and synthetic analogues in renal cortical membranes.

The metabolism of natural and synthetic analogues of bovine proparathyroid hormone (Pro-bPTH) and the biological activity of the synthetic fragments were evaluated in an in vitro assay employing renal cortical membranes (adenylyl cyclase bioassay). Apparent biological activity of the prohormone analogue was correlated with the cleavage of prohormone to hormone by the membranes. Analysis by electrophoresis on polyacrylamide gels and by ion-exchange chromatography on carboxymethyl cellulose (CMC) of the synthetic analogue Pro-bPTH-(-6 leads to +34) labelled with 125I, after incubation with renal cortical membranes, revealed conversion of the analogue to a fragment co-migrating or co-eluting with bPTH (1-34). Similar electrophoretic analyses using biosynthetic Pro-bPTH-(-6 leads to +84) internally labelled with [3H] leucine revealed degradation of Pro-bPTH-(-6 leads to +84) to smaller fragments. Proteolysis of both native prohormone and prohormone analogue was markedly reduced in incubations performed in the presence of benzamidine, a competitive inhibitor of trypsin and trypsin-like enzymes. Inclusion of benzamidine in incubations with purified renal cortical membranes from rat or dog in the in vitro renal adenylyl cyclase bioassay resulted in a ten-fold lowering of the potency of the fragment Pro-bPTH-(-6 leads to +34) relative to that of bPTH-(1-34); the potency of Pro-bPTH-(-6 leads to +34) was reduced from 5.4-3.6% to 0.5-0.3%, on a molar basis, of the potency of bPTH-(1-34). There was no effect of benzamidine on the intrinsic activity of bPTH-(1-34). These studies indicate that most if not all of the apparent biological activity of Pro-bPTH-(-6 leads to +34), at least in vitro, is dependent upon prior enzymic conversion to bPTH-(1-34).

The mechanism of ACTH stimulation of adrenal ornithine decarboxylase activity.

The mechanism of action of adrenocorticotrophin (ACTH) stimulation of rat adrenal orticotrophin (ACTH) stimulation of rat adrenal ornithine decarboxylase activity was investigated. ACTH induction or ornithine decarboxylase activity was not prevented by administration of drugs that inhibit adrenal steroid biosynthesis. A dose of ACTH that produced maximal levels of adrenal cyclic AMP did not induce ornthine decarboxylase activity. Ovine growth hormone, which caused no increase in adrenal cyclic AMP, stimulated adrenal ornithine decarboxyase activity. These observations suggest that the increase in adrenal ornithine decarboxylase activity stimulated by ACTH is not dependent upon steroidogenesis, nor is it dependent on the early peak of cyclic AMP, although it may be influenced by the sustained levels of tissue cyclic AMP that follow the administration of large doses of ACTH. Furthermore, it appears there may be a pathway of ornithine decarboxylase activation in the adrenal which is entirely independent of cyclic AMP mediation. The effects of hypophysectomy on adrenal ornithine decarboxylase response to ACTH were examined. In rats given ACTH 16 h after hypophysectomy, the increase in ornithine decarboxylase activity was delayed when compared with the response in animals given ACTH 1 h after hypophysectomy. Actinomycin D given during the first 3 h after ACTH in the 16 h hypophysectomized rat abolished the expected increase in ornithine decarboxylase activity. Thereafter, a progressive increase in ornithine decarboxylase activity was observed as the interval between ACTH and Actinomycin D administration was further increased. In contrast, Actinomycin D administered 15 min before ACTH in the 1 h hypophysectomized rat had no effect on the subsequent increase in ornithine decarboxylase activity, and actually progressively enhanced the response the longer its administration after ACTH was delayed. Cycloheximide abolished the response to ACTH in both the 1 h and the 16 h hypophysectomized rat. Thus, it appears that ACTH stimulates a post-transcriptional mechanism regulating ornithine decarboxylase activity in the acutely hypophysectomized animal, whereas, in the chronically hypophysectomized rat, ACTH must first stimulate transcription of new messenger RNA which is involved in regulation of adrenal ornithine decarboxylase synthesis.

Analysis of the requirements for parathyroid hormone action in renal membranes with the use of inhibiting analogues.

Two synthetic analogues of bovine parathyroid hormone (PTH) with NH2-terminal modifications, PTH-(3-34) and [desamino-Ala-1]PTH-(1-34), were found to lack agonist activity but to demonstrate antagonist properties when tested in the rat renal cortical adenylyl cyclase assay in vitro against the native hormone or against PTH-(1-34), the active synthetic NH2-terminal tetratriacontapeptide. The inhibition exhibited by these analogues was proportional in degree to the dose of inhibitor, abolished by oxidation of the analogue, reversible by addition of an excess of active hormone, and specific for parathyroid hormone-stimulated renal adenylyl cyclase. No inhibition of basal or sodium fluoride-stimulated renal adenylyl cyclase could be demonstrated. Two other synthetic bovine analogues, PTH-(13-34) and PTH-(1-26), were devoid of agonist and antagonist properties. The over-all results suggest that the requirements for receptor binding of parathyroid hormone are rather broad. Conformational factors or binding interactions involving specific residues, or both seem to require the entire sequence from residue 3 to residue 27 for receptor binding to occur. A dichotomy between receptor binding and adenylyl cyclase activation was demonstrated only by alterations or deletions involving the first 2 NH2-terminal residues of the hormone and emphasizes the importance of these residues in eliciting the biological activity of parathyroid hormone. The two antagonists, [desamino-Ala-1]PTH-(1-34) and PTH-(3-34), should be useful in further analysis of the initial steps in hormone action.

Comparative effects of angiotensin and ACTH on cyclic AMP and steroidogenesis in isolated bovine adrenal cells.

The comparative effects of angiotensin II and adrenocorticotropic hormone (ACTH) on cyclic AMP and steroidogenesis were investigated employing isolated bovine adrenal cells from the zona fasciculata. Like ACTH, angiotensin produced a prompt increase in cyclic AMP which preceded the increase in corticosteroid production. Although this increase in cyclic AMP was small when compared to that induced by ACTH, it correlated with the amount of steroidogenesis. This observation is consistent with the view that cyclic AMP is the intracellular mediator of the steroidogenic action of angiotensin. Angiotensin acted synergistically with ACTH on cyclic AMP levels. This synergism was not explained by inhibition of phosphodiesterase activity. Unlike ACTH, angiotensin failed to stimulate adenylate cyclase in broken cell preparations. The observations suggest that more than one mechanism may be involved in effects of ACTH and angiotensin on cyclic AMP levels.