Chronicles of informal caregiving in cancer: using 'The Cancer Family Caregiving Experience' model as an explanatory framework.

BACKGROUND: Cancer caregiving has emerged as a dominant focus of research in recent years. A striking feature of this vast amount of literature is that it is static, examining certain points of the cancer trajectory, mostly the diagnosis and palliative care. Only The Cancer Caregiving Experience Model conceptualised the caregiving experience and explored the conceptual implications of cancer family caregiving research. AIM: The data from this paper aim to empirically support the Cancer Caregiving Experience model, by exploring the cancer caregiving experience longitudinally. METHODS: Semi-structured interviews with 53 caregivers were carried out at patient's diagnosis (T1), 3 months (T2), 6 months (T3) and 12 months (T4) post diagnosis. RESULTS: Analysis of 139 interviews generated four themes that reflected a complex and dynamic process. The themes that mapped those of the model were "Primary stressors", "Secondary stressors", "Appraisal", "Cognitive-Behavioural responses" and "Health and Well Being". CONCLUSIONS: The study adds empirical support to The Cancer Caregiving Experience Model and confirms that different primary and secondary stressors influence how the caregivers perceive the caregiving demands, the coping mechanisms they employ and their health and well being during the cancer trajectory. Access to support services should be offered to all the caregivers from as early as the diagnosis period and take into account their specific needs.

ß-Blockade in the perioperative management of the patient with cardiac disease undergoing non-cardiac surgery.

The cardiology literature has suggested for decades that ß-blockade protects patients with ischaemic heart disease. Extending this concept to perioperative patients initially produced promising results, with reductions in perioperative myocardial ischaemia and longer-term cardiovascular complications observed in several small randomized trials. However, subsequent larger trials have either shown no benefit or greater morbidity (especially stroke), despite reductions in cardiovascular events. Retrospective database analyses have confirmed or disputed these findings. Speciality societies, most importantly, the American Heart Association/American College of Cardiology Foundation, have promulgated guidelines for perioperative ß-blockade, which have been revised, as the evidence has changed. While the European guidelines continue to emphasize perioperative ß-blockade in high-risk patients, the American guidelines have reduced the strength and breadth of recommendations, focusing on haemodynamic titration. Future work will need to focus on identifying populations most likely to benefit or to be harmed, including pharmacogenetic analyses and distinctions between individual ß-blockers.

Activin signaling functions upstream of Gbb to regulate synaptic growth at the Drosophila neuromuscular junction.

Activins are members of the TGF-ss superfamily of secreted growth factors that control a diverse array of processes in vertebrates including endocrine function, cell proliferation, differentiation, immune response and wound repair. In Drosophila, the Activin ligand Dawdle (Daw) has been shown to regulate several aspects of neuronal development such as embryonic axonal pathfinding, neuroblast proliferation in the larval brain and growth cone motility in the visual system. Here we identify a novel role for Activin signaling in regulating synaptic growth at the larval neuromuscular junction (NMJ). Mutants for Daw, the Activin type I receptor Baboon (Babo), and the signal transducer dSmad2, display reduced NMJ size suggesting that Daw utilizes a canonical Activin signal-transduction pathway in this context. Additionally, loss of Daw/Babo activity affects microtubule stability, axonal transport and distribution of Futsch, the Drosophila microtubule associated protein 1B (MAP1B) homolog. We find that Babo signaling is required postsynaptically in the muscle, in contrast to the well-characterized retrograde BMP/Gbb signal that is required for synaptic growth and function in presynaptic cells. Finally, we show that the Daw/Babo pathway acts upstream of gbb, and is involved in maintenance of muscle gbb expression, suggesting that Activins regulate NMJ growth by modulating BMP activity through transcriptional regulation of ligand expression.

Origins and consequences of the elongation of the human menstrual cycle during the menopausal transition: the FREEDOM Study.

The menopausal transition is characterized by the appearance of elongated cycles, which become longer and more frequent as menopause approaches. Several endocrine abnormalities have been attributed to these cycles; however, no quantitative studies of their causes and consequences exist to date. This study is based on sequential daily urinary concentrations of FSH, LH, estrone 3-glucuronide (E1G), and pregnanediol 3-glucuronide (PdG) from 34 women with perimenopausal menstrual irregularity (total of 289 cycles). The timing of ovarian response was determined as the day of E1G take-off (ETO). Other parameters measured were the mean FSH concentration before ETO (FSH(ETO)) and the midluteal levels of PdG, E1G, and LH. There was a strong parallelism between ETO and cycle length variability. FSH(ETO) levels increased gradually with ETO. Both ETO and FSH(ETO) were inversely related to luteal PdG and directly related to E1G. PdG and LH levels were inversely related. All comparisons were highly significant (P < 0.0001). We conclude that delayed ovarian response underlies the elongation of the menstrual cycle in the menopausal transition, which is likely to be caused by a temporary lack of ovarian responsiveness to FSH. A progressive decline in luteal PdG with increased E1G occurs in association with these trends.

Relationship between follicle-stimulating hormone levels at the beginning of the human menstrual cycle, length of the follicular phase and excreted estrogens: the FREEDOM study.

Although reproductive aging has been separately related to elevated FSH and shorter follicular phase (FP), the direct association between both parameters has not been investigated. Also, the exact effects of increased FSH on estrogen production are yet to be established.A large database of daily urinary concentrations of FSH, LH, and estrone 3-glucuronide (E1G) from 37 regularly menstruating women (median 11 cycles per patient) was used. Initial FSH levels (iFSH) were estimated as the mean value of d 1-5. The day of E1G take-off (ETO) was determined by an algorithm, and accordingly, the FP was divided into early (d 1 to ETO) and late (ETO+1 to LH peak). FP maximum and integrated E1G were calculated. Subjects were distributed according to their mean iFSH into three categories (5 to 10, and >10 IU/liter). There was a gradual decrease in FP length with increasing category (15.2 +/- 3.8, 14.1 +/- 3.6, and 13 +/- 2.6 d, respectively; P < 0.0001). A similar effect occurred in early FP (7.5 +/- 4, 6.4 +/- 3.7, and 5.4 +/- 2.7; P < 0.0001); in contrast, late FP was unaffected (7.7 +/- 2.1, 7.7 +/- 2.1, and 7.6 +/- 2.4; P = 0.86). No consistent increase in E1G was found with advancing iFSH category; however, women with mean initial LH higher than 6 IU/liter had significantly elevated maximum (P < 0.0001) and integrated (P = 0.002) E1G.FP length decreases in parallel with increasing iFSH, with a selective effect on the early FP. Increased FSH does not affect E1G; however, elevated initial LH level was related to higher E1G.

Synthesis, isolation, and characterization of trisodium tricarbonyliridate (3-), Na3[Ir(CO)3]. Initial studies on its derivative chemistry and structural characterizations of trans-[Ir(CO)3(EPh3)2](-), E = Ge, Sn, and trans-[Co(CO)3(SnPh3)2](-1).

Reduction of Na[Ir(CO)4] by sodium metal in (Me2N)3PO, followed by treatment with liquid ammonia, provided high yields (ca. 90%) of unsolvated Na3[Ir(CO)3], a thermally stable, pyrophoric orange solid. This substance contains iridium in its lowest known formal oxidation state of -3 and has been characterized by IR spectroscopy, elemental analyses, and derivative chemistry, i.e., by its conversion to the triphenylgermyl and triphenylstannyl complexes, trans-[Ir(CO)3(EPh3)2](-), E = Ge, Sn. Single-crystal X-ray structures of the tetraethylammonium salts of these species, as well as [Co(CO)3(SnPh3)2](-), confirm the trigonal bipyramidal nature of the anions, originally predicted on the basis of their IR spectra in the carbonyl stretching frequency region. These structural characterizations provide important additional evidence for the presence of metal tricarbonyl units in Na3[M(CO)3], M = Co, Ir.

High body mass index does not predict mortality in older people: analysis of the Longitudinal Study of Aging.

OBJECTIVE: To determine the excess mortality associated with obesity (defined by body mass index (BMI)) in older people, with and without adjustment for other risk factors associated with mortality and for demographic factors. DESIGN: Retrospective cohort analysis of the Longitudinal Study of Aging (LSOA). SETTING: Nationally representative sample of community-dwelling older people. PARTICIPANTS: Seven thousand five hundred and twenty-seven participants age 70 and older in 1984. MEASUREMENTS: We used Cox regression to calculate proportional hazards ratios for mortality over 96 months. We tested the hypothesis that increased BMI (top 15%) increased mortality rates in older people. RESULTS: Death occurred in 38% of the cohort: 54% of the thin (lowest 10% of the population, BMI <19.4 kg/m(2)), 33% of the obese (highest 15%, BMI> 28.5 kg/m(2)), and 37% of the remaining participants (normal) died. Adjustment for demographic factors, health services utilization, and functional status still demonstrated reduced mortality in obese older people (hazard ratio 0.86, 95% confidence interval (CI) = 0.77-0.97) compared with normal. After adjustment, thin older people remained more likely to die (hazard ratio 1.46, 95% CI = 1.30-1.64) than normal older people. Sensitivity analyses for income, mortality during the first two years of follow-up, and medical comorbidities did not substantively alter the conclusions. CONCLUSION: Obesity may be protective compared with thinness or normal weight in older community-dwelling Americans.

Fetal development in rhesus monkeys exposed prenatally to cocaine.

Using a timed-breeding protocol, one group of female rhesus monkeys was implanted subcutaneously with osmotic minipumps containing 0.3 mg/kg/h cocaine (N=18) or saline (N=18) from day 24 postconception through gestation. Another group received cocaine (N=12) or saline (N=8) from conception through day 42 of gestation. Mean levels of cocaine in maternal serum were approximately 150 ng/ml during pregnancy. A total of 56 pregnancies were documented in 42 adult monkeys, and 39 pregnancies completed full-term. Maternal food consumption and body weight increased during pregnancy, and there were no significant differences among experimental groups. Although both groups with a history of cocaine exposure had lower survival rates compared to pair-fed controls, of the fetuses that survived, fetal heart rate, fetal biparietal diameter, and mean gestational length were in the normal range for all experimental groups. Similarly, body weight, biparietal diameter, body length, and modified Apgar scores at birth did not differ significantly among experimental groups. The results indicate that surviving fetuses exhibited normal growth.

Use of electronic mail for postoperative follow-up after ambulatory surgery.

The authors report on a patient who used electronic mail to report satisfactory recovery from ambulatory surgery and anesthesia. The potential benefits and pitfalls of using electronic mail for patient follow-up and communication, as well as research purposes, are reviewed. Potential benefits include cost savings, ease in collecting quality improvement data, and the potential for increased reporting of unpleasant events. Potential pitfalls include lack of universal access (with racial and socioeconomic differentials), privacy and security concerns, and potential slow responses to messages that might require emergent responses or actions.

Premedication with clonidine does not attenuate suppression of certain lymphocyte subsets after surgery.

UNLABELLED: Sixty-four patients undergoing elective major surgery were randomly assigned into a double-blinded, placebo-controlled, clinical trial to test the hypothesis that premedication with clonidine would attenuate postoperative reductions in circulating lymphocytes. The treatment group (n = 28) received a clonidine skin patch (0.3 mg/d) and a 0.6-mg oral loading dose 60-90 min before surgery. The control group (n = 36) received placebo patches and pills. Absolute blood levels of the following lymphocyte subsets were measured before induction of a standardized general anesthetic (baseline) and the morning after surgery: CD2, CD3, CD4, CD8, CD20, CD56, and the CD4:CD8 ratio. Significant decreases in lymphocyte subsets CD2, CD3, and CD4 were found in both groups; CD56 was significantly decreased only in the placebo group. However, the extent of lymphocyte depletion from baseline to Postoperative Day 1 between the clonidine and placebo groups was not different. Plasma concentrations of epinephrine, norepinephrine, and cortisol were measured from blood samples drawn at 8:00 AM on Postoperative Day 1. Plasma norepinephrine levels were significantly lower among patients who received clonidine. However, no significant differences were found in plasma epinephrine or cortisol levels between the clonidine and placebo groups. With a clinical dose, clonidine did not prevent postoperative lymphocyte depletion. alpha2-Agonists may not suppress adrenocortical stress responses sufficiently to prevent postoperative immune suppression. IMPLICATIONS: Lymphocyte (white blood cell) counts often decrease after major surgery. We hypothesized that clonidine would reduce hormonal stress and blunt reductions in lymphocytes after major surgery. In a randomized trial, we found no differences from placebo in cortisol levels or lymphocyte changes. Lymphocyte levels did not predict infectious complications.

Laboratory reengineering facilitates cost management.

In 1993, The Medical University of South Carolina (MUSC) in Charleston undertook a change management initiative to achieve a more cost-competitive position in its market and become a more attractive partner for a possible future affiliation with another provider organization. A key element of this change process was a reorganization of the medical center's laboratory department. Through consolidation of MUSC's separate laboratories and the introduction of a new, more efficient chemistry analyzer system, the medical center realized annual laboratory savings of approximately $1.3 million.

Characterizations of neutral lipid fatty acids and cis-9,10-epoxy octadecanoic acid in Pneumocystis carinii carinii.

Pneumocystis carinii causes pneumonitis in immunodeficient individuals and is a prevalent opportunistic infection of patients with AIDS. This pathogen resides extracellularly in the hypophase lining the alveolar epithelium, which is highly enriched in lung surfactant lipids. Procedures yielding highly pure organism preparations that enable reliable biochemical analyses of organisms isolated from the lungs of infected laboratory animals have been developed. The results of the present study revealed that the fatty acid profiles of total lipids, the neutral lipid traction, and individual neutral lipid classes of lungs from normal and immunosuppressed rats as well as P. carinii were grossly similar, although some quantitative differences were detected. One qualitative exception found was the detection in P. carinii of the rare fatty acid cis-9,10-epoxy stearic acid, which was not detected in the lipids of rat lungs. The detection of this fatty acid in P. carinii may also have important taxonomic implications. Unlike phospholipids, many of the fatty acids of nonmembrane neutral lipids may be utilized by P. carinii for other cellular functions, such as stored reserves for energy production and precursors for organism-specific membrane lipids. The present study represents the first report of detailed fatty acid analyses of individual neutral lipid classes of this important opportunistic pathogen.

Changes in lipid composition during in vitro encystation and fatty acid desaturase activity of Giardia lamblia.

Lipids of axenically-cultured Giardia lamblia trophozoites were compared with those of cells undergoing in vitro encystation. Although the lipid composition of the organisms grossly resembled those of low-bile or high-bile culture media, differences were clearly detected. Encysting trophozoites incubated in a high-bile medium for 24 h had a higher concentration of unsaturated fatty acids in the total cellular lipids than did nonencysting trophozoites. The organism, but not the medium, contained linoleate and linolenate, suggesting that G. lamblia desaturates oleate. The presence of a fatty acid desaturase activity in the organism was demonstrated by the conversion of a radiolabeled monounsaturated fatty acid (oleate) to radiolabeled polyunsaturated fatty acids. Triglycerides, a common form of storage lipids, were unusually low in G. lamblia, but steryl esters (which can also serve as reserves) were abundant. Steryl esters increased during encystation of G. lamblia. The changes observed in G. lamblia lipids (increased fatty acid unsaturation and the accumulation of storage lipids) are consistent with parasite differentiation into a cyst stage that is able to survive outside the host at reduced temperatures and reduced available nutrient resources. This study also demonstrated that G. lamblia not only has the capacity to de novo synthesize isoprenoid lipids (ubiquinone, prenylated proteins), but it can also metabolize fatty acids by the addition of double bonds.

Composition of Pneumocystis carinii neutral lipids and identification of coenzyme Q10 as the major ubiquinone homolog.

The lipids of purified preparations of Pneumocystis carinii carinii freshly isolated from infected rats were analyzed and compared with those of whole lungs from normal and methylprednisolone-immunosuppressed uninfected rats. In this study, the neutral lipid fraction was examined in detail; the relative concentrations of individual classes making up this fraction were quantified. Of particular interest was the nature of the organism's ubiquinone (coenzyme Q, CoQ) fraction because atovaquone, a hydroxynaphtho-quinone (566C80) analog of ubiquinone, is efficacious in the treatment of P. carinii pneumonia. The ubiquinone concentration in both P. carinii and lung tissues was relatively low compared to that present in rat heart and liver tissues. Two homologs were identified in the organism: CoQ10 was the predominant homolog with lesser amounts of CoQ9 present. In contrast, the lungs of normal and immunosuppressed uninfected rats had CoQ9 and lesser amounts of CoQ8, but no detectable CoQ10. Furthermore, radiolabeled mevalonic acid was incorporated in vitro into the ubiquinone fraction of P. carinii indicating that the organism has the de novo branch of the isoprenoid biosynthetic pathway leading to polyprenyl formation. Hence, it was concluded that CoQ10 (if not both CoQ10 and CoQ9) in P. carinii was not scavenged from the host but was synthesized by the organism. Although lung tissues contained substantial free fatty acids, the organism was enriched in these lipids. The high concentration of free fatty acids and relatively low level of triglycerides in P. carinii suggest that fatty acids may represent major carbon sources for ATP production by the organism.

Choice of anesthesia and intraoperative monitoring for lower extremity revascularization.

The prevalence of significant coronary artery disease re-enforces the importance of careful preoperative and intraoperative management in patients undergoing lower extremity revascularization. This article presents a practical approach toward the evaluation of anesthetic risk and the proper use of anesthetic agents and monitoring devices to minimize morbidity. The role of general and regional anesthetic agents is discussed, and complications of both techniques are presented.

Premedication with oral and transdermal clonidine provides safe and efficacious postoperative sympatholysis.

We studied 61 patients undergoing elective major non-cardiac surgery in a randomized, double-blind, placebo-control clinical trial to test the hypothesis that the addition of clonidine to a standardized general anesthetic could safely provide postoperative sympatholysis for patients with known or suspected coronary artery disease. Patients were allocated randomly to receive either placebo (n = 31) or clonidine (n = 30). The treatment group received premedication with a transdermal clonidine system (0.2 mg/d) the night prior to surgery, which was left in place for 72 h, and 0.3 mg oral clonidine 60-90 min before surgery. Clonidine reduced enflurane requirements, intraoperative tachycardia, and myocardial ischemia (1/28 clonidine patients vs 5/24 placebo, P = 0.05). However, clonidine decreased heart rates only during the first five postoperative hours; the incidence of postoperative myocardial ischemia (6/28 clonidine vs 5/26 placebo) did not differ between the two groups. Patients who experienced postoperative myocardial ischemia tended to have higher heart rates after surgery. Clonidine significantly reduced the plasma levels of epinephrine (P = 0.009) and norepinephrine (P = 0.026) measured on the first postoperative morning. There were no differences in the need for intravenous fluid therapy or antihypertensive therapy after surgery. The number of hours spent in an intensive care setting and the number of days spent in hospital were not different between the two groups. These results suggest that larger doses of clonidine should be investigated for their ability to decrease postoperative tachycardia and myocardial ischemia.

Relative effectiveness of four preoperative tests for predicting adverse cardiac outcomes after vascular surgery: a meta-analysis.

Various noninvasive tests have been proposed to stratify perioperative cardiovascular risk, including dipyridamole thallium scintigraphy (DTS), ejection fraction estimation by radionuclide ventriculography (RNV), ischemia monitoring by ambulatory electrocardiography (AECG), and dobutamine stress echocardiography (DSE). Which of these tests is most effective for predicting adverse perioperative cardiac outcome? To answer this question, and also to stimulate future studies, we evaluated 56 studies examining one or more of the four tests. We conducted meta-analysis on 20 studies that met the inclusion criteria. Outcome measures evaluated were cardiac death or myocardial infarction occurring during hospital stay or within 1 mo after surgery. Relative risk (RR), which is the probability of adverse cardiac outcome when the test is positive divided by the probability of adverse outcome when the test is negative, was used to combine evidence from different studies. An empirical Bayes procedure with a normal-normal hierarchic model was then used to obtain a meta-analytic confidence interval for the overall median of the relative risks. The between-study variance was estimated using the method of moments approach described by DerSimonian and Laird (Controlled Clin Trials 1986;7:177-88). Combined (median) RR [95% confidence interval (CI)] and the number of studies included in our meta-analysis for different evaluative tests were as follows: DTS 4.6 (2.1-10.4) (n = 6); RNV 3.7 (1.6-8.3) (n = 5); AECG 2.7 (1.4-5.1) (n = 6), and DSE 6.2 (1.7-22.8) (n = 3). We conclude that while DTS, RNV, AECG, and DSE are effective (the 95% CIs are greater than 1.0) in predicting the cardiac outcome after vascular surgery, the data are not definitive in determining the optimal test (95% CIs for RR overlap). Future studies should include DSE, as this test shows great promise for predicting adverse cardiac events after vascular surgery.