Incremental patterns in the amount of informal and formal care among non-demented and demented elderly persons: results from a 3-year follow-up population-based study.

OBJECTIVE: Elderly care includes complex interactions between formal services, informal care, morbidity and disabilities. Studies of the incremental effects of formal and informal care are rare and thus the objective was to describe the longitudinal patterns in formal and informal care given to non-demented and demented persons living in a rural area in Sweden. METHODS: Transitions in the Kungsholmen-Nordanstig Project (n=919) was followed up 3 years later (n=579), presented as different combinations of informal and formal care, institutionalization and mortality. Number of hours spent on care was examined by the Resource Utilization in Dementia instrument (RUD). Bootstrapped descriptive statistics and regression models were applied. RESULTS: The overall mortality during follow-up was 34%, and 15% had been institutionalized. Of those who lived at home, those receiving only formal care had been institutionalized to the greatest extent (29%; p<0.05). In terms of hours, informal care decreased amongst demented. The ratio between demented and non-demented was greater at baseline, both regarding informal care (10:1 and 3:1, respectively) and formal care (5:1 and 4:1, respectively). People with mild cognitive decline and no home support at baseline had a great risk of being receiver of care (formal or informal) or dead at follow-up. CONCLUSIONS: The amount of informal care was lower for demented persons still living at home at follow-up than at baseline, probably due to selection effects (institutionalization and mortality). Mild cognitive decline of non-users of care at baseline was strongly associated with receiving care or being dead at follow-up.

The amount of informal and formal care among non-demented and demented elderly persons-results from a Swedish population-based study.

BACKGROUND: Developed countries are experiencing a dramatic increase in the proportion of elderly persons, as well as a progressive aging of the elderly population itself. Knowledge regarding the amount of formal and informal care and its interaction at population-based level is limited. OBJECTIVES: To describe the amount of formal and informal care for non-demented and demented persons living at home in a population-based sample. METHODS: The population consisted of all inhabitants, 75 + years, living in a rural community (n = 740). They were clinically examined by physicians and interviewed by nurses. Dementia severity was measured according to Washington University Clinical Dementia Rating Scale (CDR). Informal and formal care was examined with the RUD (Resource Utilization in Dementia) instrument. RESULTS: The amount of informal care was much greater than formal care and also greater among demented than non-demented. There was a relationship between the severity of the cognitive decline and the amount of informal care while this pattern was weaker regarding formal care. Tobit regression analyses showed a clear association between the number of hours of informal and formal care and cognitive decline although this pattern was much stronger for informal than formal care. CONCLUSIONS: Informal care substitutes rather than compliments formal care and highlights the importance of future studies in order to truly estimate the amount of informal and formal care and the interaction between them. This knowledge will be of importance when planning the use of limited resources, and when supporting informal carers in their effort to care for their intimates.

Biomarkers of cadmium and arsenic interactions.

Advances in proteomics have led to the identification of sensitive urinary biomarkers of renal dysfunction that are increasingly used in toxicology and epidemiology. Recent animal data show that combined exposure to inorganic arsenic (As) and cadmium (Cd) gives rise to more pronounced renal toxicity than exposure to each of the agents alone. In order to examine if similar interaction occurs in humans, renal dysfunction was studied in population groups (619 persons in total) residing in two metal contaminated areas in China: mainly a Cd contaminated area in Zhejiang province (Z-area) and mainly a As contaminated area in Guizhou province (G-area). Nearby control areas without excessive metal exposure were also included. Measurements of urinary beta(2)-microglobulin (UB2MG), N-acetyl-beta-glucosaminidase (UNAG), retinol binding protein (URBP) and albumin (UALB) were used as markers of renal dysfunction. Urinary Cd (UCd) and total As (UTAs) were analyzed by graphite-furnace atomic absorption spectrometry. Urinary inorganic As and its mono- and di-methylated metabolites (UIAs) were determined by Hydride generation. Results. As expected, the highest UCd values occurred in Z-area (Geometric mean, GM 11.6 microg/g crea) while the highest UTAs values occurred in G-area (GM = 288 microg/g crea). Statistically significant increases compared to the respective control area were present both for UTAs, UCd and for UB2MG, UNAG and UALB in Z-area as well as in G-area. UIAs was determined only in Z area. In G-area, there was a clear dose-response pattern both in relation to UTAs and UCd for each of the biomarkers of renal dysfunction. An interaction effect between As and Cd was demonstrated at higher levels of a combined exposure to As and Cd enhancing the effect on the kidney. In Z-area an increased prevalence of B2MG-uria, NAG-uria and ALB-uria was found in relation to UCd, but no relationship to UTAs was found. A statistically significant relationship between UIAs and UB2MG was found among women in this area and an interaction between As and Cd was indicated for B2MG. Conclusion. The present studies, which employed sensitive biomarkers of renal dysfunction, give support to the idea that human co-exposure to Cd and inorganic arsenic gives rise to more pronounced renal damage than exposure to each of the elements alone, but further studies are needed to establish and clarify this interaction.

Clara cell protein as a biomarker for ozone-induced lung injury in humans.

Exposure to ozone (O3) impairs lung function, induces airway inflammation and alters epithelial permeability. Whilst impaired lung function and neutrophilia have been observed at relatively low concentrations, altered lung epithelial permeability is only seen after high-dose challenges. The appearance of Clara cell protein (CC16) in serum has been proposed as a sensitive marker of lung epithelial injury. Here, the use of CC16 as an injury biomarker was evaluated under a controlled exposure to O3 and the relationship between this marker of lung injury and early lung function decrements was investigated. Subjects (n=22) were exposed on two separate occasions to 0.2 parts per million O3 and filtered air for 2 h. Blood samples were drawn and lung function assessed at 2 h pre-exposure, immediately before and immediately after exposure as well as 2 and 4 h postexposure. O3 increased CC16 serum concentrations at 2 h (12.0+/-4.5 versus 8.4+/-3.1 microg x L(-1)) and 4 h postexposure (11.7+/-5.0 versus 7.9+/-2.6 microg x L(-1)) compared with air concentrations. Archived samples from O3 studies utilising the same design indicated that this increase was sustained for up to 6 h postexposure (9.1+/-2.6 versus 7.1+/-1.7 microg x L(-1)) with concentrations returning to baseline by 18 h (7.7+/-2.9 versus 6.6+/-1.7 microg x L(-1)). In these studies, the increased plasma CC16 concentration was noted in the absence of increases in traditional markers of epithelial permeability. No association was observed between increased CC16 concentrations and lung function changes. To conclude, Clara cell protein represents a sensitive and noninvasive biomarker for ozone-induced lung epithelial damage that may have important uses in assessing the health effects of air pollutants in future epidemiological and field studies.

Metallothionein gene expression in peripheral lymphocytes from cadmium-exposed workers.

Metallothionein (MT) plays an important role in the detoxification of cadmium. To investigate the usefulness of MT gene expression in peripheral blood lymphocytes (PBLs) as a biomarker of cadmium exposure and susceptibility, reverse transcriptase-polymerase chain reaction was used to measure the MT gene expression in PBLs from cadmium-exposed workers. Both basal and induced MT expressions were found to increase with increased blood cadmium (BCd) and urinary cadmium (UCd) levels. Both basal and induced MT expression levels were significantly correlated with the logarithm of BCd and the logarithm of UCd levels. The dose-response relationship between internal dose of cadmium and MT expression suggested the validity of MT expression in PBLs as a biomarker of cadmium exposure. In vitro induced MT expression level in PBLs was found to be inversely related to the level of renal dysfunction indicator, urinary N-acetyl-beta-D-glucosaminidase (UNAG). The latter finding indicates that MT expression in PBLs may be a useful biomarker of susceptibility to renal toxicity of cadmium.

Urinary calcium as a biomarker of renal dysfunction in a general population exposed to cadmium.

Urinary beta 2-microglobulin and N-acetyl-beta-D-glucosaminidase have been recommended as sensitive indicators of renal dysfunction induced by cadmium. However, an increase in urinary calcium in early renal damage induced by cadmium has been reported both in humans and in animal experiments. To investigate the feasibility of using urinary calcium as a biomarker of renal dysfunction induced by cadmium, two areas were selected in this study, namely, a polluted area with a 3.71 mg/kg cadmium concentration in rice and a control area with a 0.07 mg/kg cadmium concentration. The total number of participants was 499, made up of 252 in the control group and 247 from the cadmium-polluted area. Urinary cadmium, urinary calcium, and zinc concentrations were measured by atomic absorption spectrometry, and beta 2-microglobulin and N-acetyl-beta-D-glucosaminidase in urine were analyzed. The levels of urinary cadmium and urinary calcium in persons from the exposed area were significantly higher (P < 0.05) than those in the control area for both men and women, but there was no significant difference regarding urinary zinc between the two areas. A significant dose-response relationship between the prevalence of hypercalciuria and the excretion of urinary cadmium was observed, and a significantly increased prevalence of calciuria was found when excretion of urinary cadmium exceeded 2 micrograms/g creatinine. The findings were similar to those for excess urinary secretion of beta 2-microglobulin and N-acetyl-beta-D-glucosaminidase. Because cadmium can affect Ca2+ uptake by tubular cells, with decreased renal Ca2+ reabsorption, calciuria may reflect tubular cell damage caused by cadmium. It was concluded that cadmium exposure can result in increased excretion of urinary calcium in a general population and that there is a significant dose-response relationship. Urinary calcium can therefore be used as a biomarker of renal dysfunction induced by cadmium.

Patterns of elderly spousal caregiving in dementia care: an observational study.

AIM: The aim of this study was to describe which caring activities eight spouses performed when caring for a partner with dementia, and in what way these activities were carried out. BACKGROUND: Family caregivers are recognized as being the primary source of care for the community's older people. The largest group is comprised of spouses, with wives as the predominant caregivers. This informal care seems to be more or less invisible and performed in silence within the family. Despite the wealth of studies, the essence of family caregiving is not well understood. METHODS: Data collection was conducted by observing the dyads in their homes. A qualitative approach inspired by grounded theory was chosen to discover qualities and describe patterns of spousal caregiving in dementia care. RESULTS: The analysis yielded four broad themes, which included nine categories. Findings from the study shed some light on the invisible aspects besides the traditional hands-on caregiving. CONCLUSION: The elderly carers were engaged in demanding and time-consuming care ranging from supervision to heavy physical responsibility. They were caring for as well as about their partners. The study also showed that spouses were successful in managing their situation in different ways. The results reported in this article are unique as they come from direct observations in family home settings where a spouse cared for a partner with dementia. Knowledge about family caregiving is valuable for nurses as there is an emphasis on collaboration between family caregivers and professionals.

Lung cancer risks among lead smelter workers also exposed to arsenic.

Recent publications indicate an increased incidence of lung cancer in non-ferrous smelter workers exposed to lead. The present study provides further data on selected subgroups in one such cohort. The cohort was based on 3979 smelter workers employed for at least 1 year between 1928 and 1979, and also exposed to lead and included in the Blood Lead Register that was started at the smelter in 1950. Two subcohorts were formed from the original cohort. One consists of 710 workers employed at the lead departments (Lead subcohort 1), and the other of 383 workers employed at the lead departments (Lead subcohort 2), but never at other works where an excess lung cancer risk was previously identified. Standardized Cancer Incidence Rates (SIR) 1958-1987 were calculated relative to county rates. In the subcohorts, arsenic exposure in lung cancer cases was assessed in detail based on occupational hygiene information from the company. Lung cancer incidence was raised in both subcohorts (Lead subcohort 1: SIR 2.4; 95% CI 1.2-4.5; Lead subcohort 2: SIR 3.6; 95% CI 1.2-8.3). Total cancer incidence in the cohorts was not increased. A detailed study of arsenic exposure in the 10 lung cancer cases in these two subcohorts revealed that all but one of these cases had a significant exposure also to arsenic. An elevated incidence of lung cancer was observed in smelter workers exposed to lead. However, considerable arsenic exposure also occurred in a majority of the lung cancer cases in the investigated subcohorts. In this multifactorial exposure situation it has not been possible to separate the carcinogenic effects of lead and arsenic, but a possible interaction between these metals may be involved in explaining the carcinogenic risks.

Toxicological aspects of metallothionein.

Metallothionein (MT) is expressed to a certain extent in almost all mammalian tissues. The biological significance of MT is related to its various forms MT-1, MT-2, MT-3 and MT4. For MT-1 several isoforms of the protein exist and it is likely that these isoforms are related to various functions involved in developmental processes occurring at various stages of gestation. Toxicokinetics and biochemistry of essential and toxic metals such as cadmium, zinc, mercury and copper in organs e.g. kidney, CNS, are often related to metallothionein. It is debated whether there is a relation or not for other metals e.g. selenium and bismuth. For the toxicokinetics of cadmium, MT plays an important role. By expanding techniques from experimental toxicology and biochemistry to include molecular biology methods, more specific and relevant studies can be performed of the actual role and biological function of MT. The present paper on toxicological aspects of metallothionein, presents an overview and evaluation of present knowledge concerning differences among organs and within organs of the expression of MT and how this affects tissue sensitivity to toxicity.

Differential calcium transport disturbances in renal membrane vesicles after cadmium-metallothionein injection in rats.

Cadmium-metallothionein (CdMT) induced calciuria may result from disturbed calcium (Ca) transport through the renal tubular epithelium. The present study aimed at defining time of onset and the degree of disturbed calcium transport. Kidneys were obtained from rats at 4, 12 and 24 h after a single injection of CdMT (dose 0.4 mg Cd/kg b.w.), and compared to saline injected controls. Rapid-filtration 45Ca-assays were performed on basolateral and luminal membrane vesicles, isolated from kidney cortex using a sequential ultracentrifugation procedure. Luminal 45Ca uptake was increased at 4 h and then declined to about 80% of controls, suggesting an early phase perturbation of Ca absorption. Basolateral 45Ca uptake was reduced to less than 50% of controls, starting already at 4 h while 45Ca binding was reduced at 8 h. This may reflect an inhibited basolateral Ca pump mechanism after the binding step. Since the Ca pump normally expels Ca from the cell, an accumulation of intracellular calcium was indicated. Metal analysis verified a four-fold increase of Ca in kidney cortex at 24 h. This suggests that Cd impact on tubular cells involves disturbances on cellular absorption as well as expulsion of Ca.

Excursions of intake above ADI: case study on cadmium.

High oral intake of cadmium via food or drink in a single dose by humans gives rise to vomiting, abdominal pain, and diarrhea. Concentrations of cadmium in drinks giving rise to such symptoms have been 16 mg/liter and higher corresponding to doses of 3 mg and higher. Longer term intakes of food (rice) with concentrations around 1 mg/kg corresponding to daily intakes of 600 micrograms have given rise to some less pronounced symptoms including signs of malabsorption. Reproductive and developmental effects have been observed in animal experiments at oral and other exposures. The present provisional tolerable weekly intake (PTWI) for Cd is 500 micrograms (a weekly intake of 7 micrograms/kg body wt), corresponding to a daily intake of 70 micrograms or 1 microgram per kg body wt. Recent data demonstrating renal dysfunction in humans at even lower lifelong oral exposures indicate that the PTWI needs to be lowered in the future. An estimated lowest-observed-adverse-effect level (LOAEL) for symptoms from the gastrointestinal tract in humans after intake of a single oral dose is 43 micrograms/kg body wt. If a safety factor of 3-10 is used based on LOAEL, a tolerable single dose would be 0.3-1 mg (4 to 14 micrograms/kg body wt). For longer time exposures (months-a few years) daily intakes of 200 micrograms (3 micrograms/kg body wt) may be tolerated without obvious gastrointestinal symptoms or signs. At present, there is no convincing human evidence that such doses can cause reproductive or developmental effects, but since such effects have been reported in animals, it may be advisable not to exceed a daily intake of 1 microgram/kg body wt for such potentially sensitive subsections of the population as children and women who are pregnant or lactating. Any excursions above the PTWI need to be compensated for by a corresponding period with intake below the PTWI in order for the cumulative dose to be low enough to avoid the long-term effects of cadmium on the kidney.

Urinary N-acetyl-beta-D-glucosaminidase isoenzymes as biomarker of renal dysfunction caused by cadmium in a general population.

N-Acetyl-beta-D-glucosaminidase (NAG) and its isoenzymes in urine have been studied in a population group residing in a polluted area in China. The area studied was contaminated by industrial wastewater from a nearby smelter that discharged cadmium-polluted wastewater into a river used for the irrigation of rice fields. Cadmium concentrations in rice were 3.70, 0.51, and 0.07 mg/kg for the highly and moderately polluted areas and the control area, respectively. Cadmium concentrations in urine exceeded 5 microgram/liter in the majority of subjects in the most highly polluted area. There was a marked dose-dependent increase in NAG and NAG B content of urine related both to urinary cadmium and to the calculated cadmium uptake. It is concluded that urinary NAG and its isoenzymes could serve as a sensitive biomarker of renal dysfunction in cadmium-exposed populations. The mechanisms underlying the increase in NAG and its isoenzymes after cadmium exposure need to be studied further.

Apoptosis and p53 gene expression in male reproductive tissues of cadmium exposed rats.

Reverse transcription (RT) PCR technique was used to investigate the mechanism of apoptosis induced by Cd and the change of its related genes in testes and prostate of rats. Adult male rats were given a single (s.c.) injection of CdCl2 0, 2.5, 5.0, 10 mumol/kg. 48 h and 72 h after administration of Cd, animals were sacrificed. The results indicated that Cd can induce apoptosis in testes via p53-independent pathway. No apoptosis occurred in prostate in any of the Cd-exposed groups. There was a clearly negative relationship in testes between p53 gene expression and Cd exposure and this dose-response relationship was observed both at 48 h and 72 h. There was a very small increase of this gene expression in the dorsolateral lobe of the prostate in Cd exposed groups. The other apoptosis related gene, bcl-x, was not detectable in either control or Cd-exposed group in testes and dorsal prostate. Although the MT-I gene was expressed in testes or dorsal prostate both in control and exposed groups, no overexpression of MT-I gene was found after administration of Cd. The expression of MT-I in the ventral prostate was not detected in the control group, but a weak expression was found after Cd exposure. Since p53 is a tumor suppressor gene which can inhibit tumorigenesis, the consequence of a Cd-induced decrease of p53 in testes may have a relation to the known risk of Cd tumorigenesis in this tissue.

Cadmium-induced apoptosis and changes in expression of p53, c-jun and MT-I genes in testes and ventral prostate of rats.

Apoptosis and a change in the expression of p53, c-jun and MT-I genes occurred in rats exposed to cadmium in a way known to cause carcinogenesis in testes and ventral prostate. In situ end labelling (ISEL), DNA electrophoresis, and RT-PCR methods were used in present study. Adult male Wistar rats were given a single (s.c.) injection of 0, 5, 10, or 20 micromol/kg CdCl2. Then 12, 48 or 96 h after administration of cadmium, animals were sacrificed. It was observed that cadmium markedly induced apoptosis in the testes at the dose of 5 micromol/kg while 10 and 20 micromol/kg cadmium caused more necrosis than apoptosis. Apoptosis in the ventral prostate was markedly induced by all the doses of cadmium and there was an obvious time- and dose-dependent relationship between apoptotic index (AI) and cadmium treatment. Far fewer apoptotic cells appeared in liver, compared to the testes and ventral prostate. p53 mRNA expression was clearly enhanced in the ventral prostate but clearly suppressed in the testes by cadmium exposure, and the time- and dose-effect was very clear. The expression level of p53 in the liver was not affected by cadmium treatment. Cadmium-induced overexpression of c-jun gene appeared at 12 h in the liver, but not until 96 h in the testes and ventral prostate. Although the MT-I gene was found to be expressed in all tissues, marked induction by cadmium of the expression of MT-I gene was only observed in the liver. These results indicate: (1) that apoptosis is an early mechanism of acute tissue damage by cadmium in the testes and ventral prostate; (2) that p53 and c-jun genes may be involved in cadmium-induced cytotoxicity (apoptosis) and related carcinogenicity in male reproductive tissues; and (3) that the enhanced expression of MT-I in the liver could protect this organ from cadmium-induced cytotoxicity (apoptosis) and carcinogenicity.

The susceptibility to nephrotoxicity of streptozotocin-induced diabetic rats subchronically exposed to cadmium chloride in drinking water.

Streptozotocin-induced diabetic rats and normal non-diabetic (ND) rats were exposed to cadmium chloride in drinking water in doses of 0, 50 and 100 ppm for 90 days. There was a dose-related increase in urinary protein and enzymes in the diabetic group, but an increase in proteinuria only in the high exposure subgroup of the ND group. It is suggested that diabetic rats induced by streptozotocin are more susceptible to cadmium nephrotoxicity than normal (ND) rats. Metallothionein synthesis in liver was estimated to be similar in both the diabetic and non-diabetic groups after exposure to cadmium. Less excretion of cadmium in urine and greater accumulation of cadmium in kidney were observed in the diabetic group, and this may be one of the mechanisms underlying the susceptibility of diabetic animals to the effects of cadmium. Further biochemical and histological studies are required in order to explain the detailed events involved in inducing such changes in the toxicokinetics of cadmium.

Pain and pulmonary function following laparoscopic and abdominal hysterectomy: a randomized study.

BACKGROUND: The aim of this study was to evaluate pain and pulmonary function the first two days after abdominal and laparoscopic hysterectomy. METHODS: Women scheduled for abdominal hysterectomy were prospectively randomized to either laparoscopic (n=20) or abdominal (n=20) hysterectomy. Analgesics were self-administered by the patients by means of a programable infusion pump containing morphine. Postoperative pain was evaluated using a visual analog scale. Oxygen saturation was measured with an oxymeter. Pulmonary function was assessed using a peak flow meter measuring peak expiratory flow and a vitalograph measuring forced vital capacity and forced expiratory volume in one second. RESULTS: Pain scores were lower after laparoscopic hysterectomy at the first (p<0.05) and second postoperative day (p<0.01). Lung function was impaired on days 1 and 2 postoperatively, measured as peak expiratory flow, forced vital capacity and forced expiratory volume in one second, in both groups compared to the preoperative values. The patients undergoing laparoscopic hysterectomy had less impairment of lung function measured by peak expiratory flow (p<0.01), forced vital capacity (p<0.05) and forced expiratory volume in one second (p<0.05) the first postoperative day compared to the patients undergoing abdominal hysterectomy. The second postoperative day differences between the groups remained for peak expiratory flow (p<0.05) and forced expiratory volume in one second (p<0.05). CONCLUSIONS: Laparoscopic hysterectomy results in less pain and less impairment of respiratory function compared to abdominal hysterectomy.

Epidural abscess after epidural analgesia treated successfully with antibiotics.

Spinal extradural abscess is an infrequent, but serious complication to extradural catheters. Early diagnosis is essential for successful treatment. An extradural abscess may develop slowly over days to several weeks and symptoms may be vague and unspecific, delaying correct diagnosis. Meticulous supervision of the patients is required and must continue as long as an epidural catheter is in place and for some time after the catheter has been withdrawn. This case report describes a patient undergoing extensive reconstructive plastic surgery after a leg trauma. For postoperative pain treatment a continuous epidural infusion of bupivacaine was given. After 10-14 days an extradural abscess developed with increasing low back pain but without any neurologic symptoms. With antibiotics a complete resolution of the extradural abscess occurred, documented by computerized tomography (CT).

Renal dysfunction from cadmium contamination of irrigation water: dose-response analysis in a Chinese population.

In a cadmium-contaminated area in China and a nearby non-contaminated area, 342 persons were selected for studies of a possible relationship between cadmium dose (i.e. total cadmium intake) and response in terms of renal dysfunction. An increase in urinary excretion of beta-2-microglobulin (UB2M), adjusted for age and sex, was used as an indicator of the response. A statistically significant relationship was found between measured cadmium concentrations in whole blood (range; < 3.5 to > 15 micrograms/l) and UB2M, and there was a statistically significant linear trend. Also, cadmium in urine (< 4 to > 16 micrograms/g creatinine) and UB2M displayed a statistically significant positive relationship when the total data set was analysed for males and females. The relationship between a dose index (obtained from calculated cumulative absorbed doses over a lifetime) and UB2M was statistically significant. The results of this first study on dose-response relationships in a Chinese population are similar to those observed in other populations.