Trends in service time of pacemakers in the Netherlands: a long-term nationwide follow-up study

Aims

After decades of experience and strongly improved technology, service time of pacemaker generators is expected to increase. To test this hypothesis, we conducted a retrospective review of a large cohort of patients with a pacemaker.

Methods

We reviewed data collected between 1984 and 2006 in the first national Dutch pacemaker registry. This registry covered 96% of all generators implanted. We analysed the time of and reason for explantation of pacemaker generators. A 7-year follow-up interval after first implantation and following replacements was used to analyse changes over time.

Results

During 22 years of data collection, nearly 97,000 first pacemaker generators were implanted. A total of 27,937 (22.4%) generators were explanted within a mean of 6.3 (standard deviation 3.3) years. Reasons for approximately 60% of these explantations were ‘end of life’ of the pacemaker generator or elective system change. Complications or failures such as infections and recalls accounted for approximately 20% of the explantations. For the remaining 20%, the reasons for explantation had not been registered.

Conclusion

Despite progress in technology, a substantial proportion of pacemaker generators is explanted before its expected service time, with one in five generators being replaced due to technical failures, infections or other complications. Furthermore, the time interval between pacemaker implantation and explantation due to normal ‘end of life’ (battery EOL) decreased. Infections continue to rank highly as a cause for pacing system replacement, despite all current preventive measures.

     

Comparison of virulence and activity of some enzymes ofListeria monocytogenes

The virulence of microorganisms and the activity of some enzymes were compared on 17 strains ofListeria monocytogenes, including 5 Patterson's strains, 4 strains maintained for longer periods on nutrient media and 8 strains freshly or recently isolated from animals in our field material. The LD₅₀ and invasivity index were determined as indicators of virulence. The activity of catalase, glucose and lactic acid dehydrogenases and glutamic-oxalo-acetic transaminase were determined quantitatively. Close agreement was found between the values of both indicators of virulence and the activity of catalase. The quantitative assay of catalase and to some extent of some dehydrogenases, as well as glutamic-oxaloacetic transaminase thus represents a simple and satisfactory method of assessing the virulence ofListeria monocytogenes.     

Pro-collagenase-1 (matrix metalloproteinase-1) binds the alpha(2)beta(1) integrin upon release from keratinocytes migrating on type I collagen

In injured skin, collagenase-1 (matrix metalloproteinase-1 (MMP-1)) is induced in migrating keratinocytes. This site-specific expression is regulated by binding of the alpha(2)beta(1) integrin with dermal type I collagen, and the catalytic activity of MMP-1 is required for keratinocyte migration. Because of this functional association among substrate/ligand, receptor, and proteinase, we assessed whether the integrin also directs the compartmentalization of MMP-1 to its matrix target. Indeed, pro-MMP-1 co-localized to sites of alpha(2)beta(1) contacts in migrating keratinocytes. Furthermore, pro-MMP-1 co-immunoprecipitated with alpha(2)beta(1) from keratinocytes, and alpha(2)beta(1) co-immunoprecipitated with pro-MMP-1. No other MMPs bound alpha(2)beta(1), and no other integrins interacted with MMP-1. Pro-MMP-1 also provided a substrate for alpha(2)beta(1)-dependent adhesion of platelets. Complex formation on keratinocytes was most efficient on native type I collagen and reduced or ablated on denatured or cleaved collagen. Competition studies suggested that the alpha(2) I domain interacts with the linker and hemopexin domains of pro-MMP-1, not with the pro-domain. These data indicate that the interaction of pro-MMP-1 with alpha(2)beta(1) confines this proteinase to points of cell contact with collagen and that the ternary complex of integrin, enzyme, and substrate function together to drive and regulate keratinocyte migration.     

Fluorescent detection of Zn(2+)-rich vesicles with Zinquin: mechanism of action in lipid environments

High concentrations of free Zn2+ ions are found in certain glutamatergic synaptic vesicles in the mammalian brain. These terminals can be visualized histochemically with quinoline sulfonamide compounds that form fluorescent complexes with Zn2+. The present study was undertaken to examine the interaction of the water-soluble quinoline sulfonamide probe, Zinquin (2-methyl-8-(toluene-p-sulfonamido)-6-quinolyloxyacetic acid) with the complex heterogeneous cellular environment. Experiments on rat hippocampal and neocortical slices gave indications that Zinquin in its free acid form was able to diffuse across the plasma and synaptic vesicle membranes. Further experiments were undertaken on unilamellar liposomes to study the interaction of Zinquin and its metal complexes in membranes. These experiments confirmed that Zinquin is able to diffuse across lipid bilayers. Steady-state and time-resolved fluorimetric studies showed that Zinquin in aqueous solution mainly forms a 1:2 (metal:ligand) complex with small amounts of a 1:1 complex. Formation of the 1:1 complex was favored by the presence of lipid, suggesting that it partitions into membranes. Evidence is presented that Zinquin can act as a Zn(2+)-ionophore, exchanging Zn2+ for two protons. The presence of a pH gradient across vesicles traps the Zn(2+)-probe complex within the vesicles. Zinquin is useful as a qualitative probe for detecting the presence of vesicular Zn2+; however, its tendency to partition into membranes and to serve as an ionophore should be borne in mind.     

Early osmoregulatory stimulation of neurohypophyseal hormone secretion and thirst after gastric NaCl loads

Cerebral osmoreceptors mediate thirst and neurohypophyseal secretion stimulated by increases in the effective osmolality of plasma (P(osmol)). The present experiments determined whether an intragastric load of hypertonic saline (ig HS; 0.5 M NaCl, 4 ml) would potentiate these responses before induced increases in P(osmol) in the general circulation could be detected by cerebral osmoreceptors. Adult rats deprived of water overnight and then given intragastric HS consumed much more water in 15-30 min than rats given either pretreatment alone, even though systemic P(osmol) had not yet increased significantly because of the gastric load. In other rats pretreated with an intravenous infusion of 1 M NaCl (2 ml/h for 2 h), plasma levels of vasopressin and oxytocin were considerably elevated 15 and 25 min after intragastric HS treatment, whereas systemic P(osmol) was not increased further. These and other findings are consistent with previous reports that hepatic portal osmoreceptors (or Na(+) receptors) stimulate thirst and neurohypophyseal hormone secretion in euhydrated rats given gastric NaCl loads and indicate that these effects are potentiated when animals are dehydrated.     

The synpolydactyly homolog (spdh) mutation in the mouse -- a defect in patterning and growth of limb cartilage elements

We have investigated the recessive mouse mutant synpolydactyly homolog (spdh) as a model for human synpolydactyly (SPD). As in human SPD, the spdh phenotype consists of central polydactyly, syndactyly and brachydactyly and is caused by the expansion of a polyalanine encoding repeat in the 5' region of the Hoxd13 gene. We performed a detailed phenotypic and functional analysis of spdh/spdh embryos using skeletal preparations, histology, in situ hybridization, BrdU labeling of proliferating cells, and in vitro expression studies. The absence of normal phalangeal joints and the misexpression of genes involved in joint formation demonstrate a role for Hox-genes in joint patterning. The spdh mutation results in abnormal limb pattering, defective chondrocyte differentiation, and in a drastic reduction in proliferation. Abnormal chondrocyte differentiation and proliferation persisted after birth and correlated with the expression of the mutant Hoxd13 and other Hox-genes during late-embryonic and postnatal growth.     

Inhibition of NaCl appetite when DOCA-treated rats drink saline

Marked increases in the consumption of concentrated NaCl solution were elicited in rats by daily injection of the synthetic mineralocorticoid, deoxycorticosterone acetate (DOCA). DOCA-treated rats drank different volumes of NaCl solution depending on its concentration (between 0.15 M and 0.50 M), with less consumed (in milliliters) the more concentrated the fluid was. In consequence, total Na(+) intake (in milliequivalents) was roughly similar in all groups. Gastric emptying of Na(+) also diminished as the concentration of the ingested NaCl solution increased, and the delivery of Na(+) to the small intestine was remarkably similar in all groups. Cumulative volume of ingested fluid in the stomach and small intestine was very closely related to intake (in milliliters) of the concentrated NaCl solutions. Systemic plasma Na(+) levels did not increase until after rats stopped consuming concentrated NaCl solution, although they were elevated at the onset of water ingestion. The situation appeared to be different when 0.15 M NaCl was consumed. This isotonic solution emptied and was absorbed relatively rapidly, and DOCA-treated rats drank larger amounts of it throughout a 1-h test period than when they drank concentrated NaCl solutions. Collectively, these findings suggest that saline consumption by DOCA-treated rats may be inhibited by two presystemic factors, one related to the volume of ingested fluid (i.e., distension of the stomach and small intestine) and one related to its concentration (i.e., elevated osmolality of fluid in the small intestine and/or in adjacent visceral tissue).