Psychosocial changes following retirement

This study was designed to: (a) identify the perceptions of retirees about changes in their life patterns during retirement; (b) investigate the kinds of adjustment problems occurring in retirement as a basis for developing prevention oriented pre-retirement programs; and (c) identify extant factors which could demonstrate underlying themes relating to retirement adjustment. A 72-item, multiple response questionnaire was used to gather demographic data, information on use of time, pre-retirement planning, health problems, changing life patterns, and adjustment to retirement. It is the latter which is reported in these findings. The population included 1565 retirees from a designated company living in the south-eastern United States of America, with a response of 764 subjects (48.82%). Findings suggest the respondents were generally healthy and well adjusted; however, numerous adjustment problem areas were identified within the six life patterns. Additional factor analysis (principal components) demonstrated four factors of particular importance: satisfaction with retirement, retirement concerns, spousal relationships, and pre-retirement preparation outcomes.     

(R,R)-2,2'-[1,2-ethanediylbis[imino(1-methyl-2,1-ethanediyl)]]- bis[5-nitro-1H-benz[de]isoquinoline-1,3-(2H)-dione] dimethanesulfonate (DMP 840), a novel bis-naphthalimide with potent nonselective tumoricidal activity in vitro

(R,R)-2,2'-[1,2-ethanediylbis[imino(1-methyl-2,1-ethanediyl)]]- bis[5-nitro-1H-benz[de]isoquinoline-1,3-(2H)-dione] dimethanesulfonate (DMP 840), is a bis-naphthalimide anticancer tumoricidal agent currently in phase I clinical trials. DMP 840 exhibits curative activity in human tumor xenografts, where it shows selectivity for human solid tumors over murine leukemias. In contrast to the selectivity found for DMP 840 in vivo, DMP 840 exhibits potent antiproliferative activity in vitro against a variety of human and murine leukemia and solid tumor cell lines in culture, with inhibitory doses that reduce the number of treated cells to one half (IC50) values ranging from 2.3 to 53 nM. DMP 840 was growth inhibitory to three doxorubicin-resistant cell lines with IC50 values also in the nanomolar range. Clonogenic survival experiments showed that DMP 840 was equally cytotoxic to both exponentially growing and quiescent human clone A colon carcinoma cells. A 1-h incubation of DMP 840 (1.22-12 microM) caused 5-log cell kill in KB-3-1 human epidermoid carcinoma, clone A human colon carcinoma, and L1210 murine leukemia cell lines. The rapid cell killing by DMP 840 in clonogenic survival experiments and initial mechanism of action studies was consistent with a DNA-interactive mechanism for DMP 840 cytotoxicity. Mechanism of action studies in L1210 leukemia cells demonstrated that DMP 840 inhibited the incorporation of thymidine and uridine into DNA and RNA with IC50 values of 0.55 and 0.08 microM, respectively. DMP 840 produced DNA single-strand breaks in a dose-dependent manner. Double-strand breaks were not observed with DMP 840 treatment, even at higher concentrations of compound. Chinese hamster ovary (CHO) and P388 cells resistant to camptothecin and containing a mutant form of topoisomerase I were also used to evaluate whether DMP 840 was cross-resistant with agents active against topoisomerase I. While the CHOR line was 163-fold resistant to camptothecin, the CHOR line was only 1.7-fold resistant to DMP 840. In summary, DMP 840 is a DNA-interactive agent that demonstrates excellent antiproliferative activity in vitro against cultured tumor cells from both human and murine sources. Its mechanism of tumoricidal activity may be novel.     

Synthesis of corneal keratan sulfate proteoglycans by bovine keratocytes in vitro

Keratan sulfate proteoglycans (KSPGs) are the major proteoglycans of the cornea and are secreted by keratocytes in the corneal stroma. Previous studies have been able to show only transient secretion of KSPG in cell culture. In this study, cultures of bovine keratocytes were found to secrete the three previously characterized KSPG proteins into culture medium. Reactivity with monoclonal antibody I22 demonstrated substitution of these proteins with keratan sulfate chains. KSPG constituted 15% of the proteoglycan metabolically labeled with [35S]sulfate in keratocyte culture medium. This labeled KSPG contained keratan sulfate chains of 4700 Da compared to 21,000 Da for bovine corneal keratan sulfate. Labeled keratan sulfate from cultures contained nonsulfated, monosulfated, and disulfated disaccharides that were released by digestion with endo-beta-galactosidase or keratanase II. Nonsulfated disaccharides were relatively more abundant in keratan sulfate from culture than in corneal keratan sulfate. These results show that cultured bovine keratocytes maintain the ability to express all three of the known KSPG proteins, modified with keratan sulfate chains and sulfated on both N-acetylglucosamine and galactose moieties. KSPG made in vitro differs from that found in vivo in the length and sulfation of its keratan sulfate chains. The availability of cell cultures secreting corneal keratan sulfate proteoglycans provides an opportunity to examine biosynthesis and control of this important class of molecules.     

Primary focal segmental glomerulosclerosis: clinical course and response to therapy

Primary focal segmental glomerulosclerosis (FSGS) is a lesion associated with a poor prognosis and results in end-stage renal disease after 5 to 10 years. Based on past experience, many nephrologists have considered primary FSGS a lesion that is steroid resistant and therefore are reluctant to offer steroids as treatment. Recent data, however, have demonstrated that patients with primary FSGS have a response to steroid therapy that is considerably better than had been described. Thus, it may be that nephrologists have been more "steroid reluctant" than the lesion is steroid resistant. To better understand this issue we review the clinical course and response to therapy in patients with primary FSGS.     

Prosthetic valve endocarditis: superiority of surgical valve replacement versus medical therapy only

The objective of our study was to assess the long-term outcome of patients with prosthetic valve endocarditis. We used a multicenter, prospective, observational study design. Six university teaching hospitals with high volume cardiothoracic surgery participated. Seventy-four patients with prosthetic valve endocarditis as defined by explicit, objective criteria were selected for participation. All patients were followed up prospectively for 1 year. Thirty-one percent and 69% had development of endocarditis within 60 days of valve insertion ("early") and after 60 days ("late"), respectively. The most common causes were Staphylococcus epidermidis (40%), Staphylococcus aureus (20%), streptococcal species (18%), and aerobic gram-negative bacilli (11%). Physical signs of endocarditis (new or changing murmur, stigmata, emboli) were seen in 58%. At 6 months and 12 months, mortality was 46% and 47%, respectively. Surgical replacement of the infected valve led to significantly lower mortality (23%) as compared with medical therapy alone (56%), as assessed by both univariate and multivariate analyses (p < 0.05). Improved outcome was seen for the surgical group even when controlling for severity of illness at time of diagnosis. From these findings we conclude that accurate assessment of outcome in prosthetic valve endocarditis requires long-term follow-up of at least 6 months following diagnosis. Surgical therapy warrants greater scrutiny; evaluation in controlled clinical trials is appropriate.     

Net interaction between different forms of short-term synaptic plasticity and slow-IPSPs in the hippocampus and auditory cortex

Paired-pulse plasticity is typically used to study the mechanisms underlying synaptic transmission and modulation. An important question relates to whether, under physiological conditions in which various opposing synaptic properties are acting in parallel, the net effect is facilitatory or depressive, that is, whether cells further or closer to threshold. For example, does the net sum of paired-pulse facilitation (PPF) of excitatory postsynaptic potentials (EPSPs), paired-pulse depression (PPD) of inhibitory postsynaptic potentials (IPSPs), and the hyperpolarizing slow IPSP result in depression or facilitation? Here we examine how different time-dependent properties act in parallel and examine the contribution of gamma-aminobutyric acid-B (GABAB) receptors that mediate two opposing processes, the slow IPSP and PPD of the fast IPSP. Using intracellular recordings from rat CA3 hippocampal neurons and L-II/III auditory cortex neurons, we examined the postsynaptic responses to paired-pulse stimulation (with intervals between 50 and 400 ms) of the Schaffer collaterals and white matter, respectively. Changes in the amplitude, time-to-peak (TTP), and slope of each EPSP were analyzed before and after application of the GABAB antagonist CGP-55845. In both CA3 and L-II/III neurons the peak amplitude of the second EPSP was generally depressed (further from threshold) compared with the first at the longer intervals; however, these EPSPs were generally broader and exhibited a longer TTP that could result in facilitation by enhancing temporal summation. At the short intervals CA3 neurons exhibited facilitation of the peak EPSP amplitude in the absence and presence of CGP-55845. In contrast, on average L-II/III cells did not exhibit facilitation at any interval, in the absence or presence of CGP-55845. CGP-55845 generally "erased" short-term plasticity, equalizing the peak amplitude and TTP of the first and second EPSPs at longer intervals in the hippocampus and auditory cortex. These results show that it is necessary to consider all time-dependent properties to determine whether facilitation or depression will dominate under intact pharmacological conditions. Furthermore our results suggest that GABAB-dependent properties may be the major contributor to short-term plasticity on the time scale of a few hundred milliseconds and are consistent with the hypothesis that the balance of different time-dependent processes can modulate the state of networks in a complex manner and could contribute to the generation of temporally sensitive neural responses.     

A point of view: why point-of-care places are not free marketplaces

Current wisdom holds that health care is a business and "as such must abide by market principles." Most nurses are not well enough versed in economic theories to credibly critique health care delivery decisions based on economic theories. The relationship of market principles to health care realities is described in basic terms to encourage nurses to "optimize patient care and influence health care policy." Physicians, who control all access points to the health care system, have enjoyed a 40-year market dominance that is "rapidly being replaced by insurance companies and for-profit investors." Providers' decisions to treat or not to treat are strongly influenced by whether the patient is in a fee-for-service or capitated payment environment.     

Ristocetin- and thrombin-induced platelet aggregation at physiological shear rates: differential roles for GPIb and GPIIb-IIIa receptor

We recently reported that washed platelets (WP) activated with ADP and expressing surface-bound vWF aggregated in flow through small tubes or in a cylindrical couette device at physiological shear rates of G = 300 s(-1)-1000 s(-1) in the absence of exogenous ligands, with GPIb-vWF partially, and activated GPIIb-IIIa totally required for the aggregation. We have now extended these studies to aggregation of platelets "activated" with ristocetin or thrombin. Washed platelet suspensions with added soluble vWF and ristocetin (0.3-0.75 mg/ml), or activated with thrombin (0.01-0.5 U/ml) but no added ligand, were sheared in a coaxial cylinder device at uniform shear rate, G = 1000 s(-1). The collision capture efficiency (alphaG) with which small aggregates form (= experimental/calculated initial rates of aggregation) was correlated with vWF platelet binding assessed by flow cytometry. The vWF-GPIb interaction was exclusively able to support ristocetin-mediated shear aggregation of metabolically active platelets, with very few vWF monomer equivalents bound per platelet (representing < or = 10 molecules of 10 million Da) required to yield high capture efficiencies (alphaG = 0.38+/-.02; n = 11), suggesting rapid and stable bond formations between vWF and GPIb. However, platelet surface-expressed vWF, generated by addition of thrombin to washed platelets, was found to mediate platelet aggregation with alphaG = 0.08+/-.01 (n = 6), surprisingly comparable to that previously reported for WP and ADP activation. Blocking the GPIIb-Illa receptor decreased alphaG by 95+/-3% (n =3), while a monoclonal antibody to the vWF site on GPIb caused a 49+/-7% (n = 8) decrease in alphaG. The partial role for GPIb thus appears to reflect a facilitative function for increasing contact time between flowing platelets, and allowing engagement of the GPIIb-IIa receptor to yield stable attachment.     

Hernia survey of the Section on Surgery of the American Academy of Pediatrics

The members of the Section on Surgery of the American Academy of Pediatrics were surveyed to determine the practice of North American pediatric surgeons in infants with inguinal hernia (IH). Case-scenario multiple-choice-design questionnaires regarding hernias and hydroceles were sent to all members of the Surgical Section, and responses were received from 292 (50%). In healthy full-term infant boys with asymptomatic reducible IH, 82% of responders perform repair electively, no matter what the age or weight. In full-term girls with a reducible ovary, 59% perform surgery at the next available time; if the ovary is nonreducible but asymptomatic, 44% operate emergently or urgently and 42% at the next elective slot. In former preemies, the pattern of repair is as follows. (1) For those recently discharged after 2 months in the neonatal intensive care unit (NICU) with reducible IH, 65% perform the repair when convenient. (2) A general anesthetic is used in 70%; 15% use spinal anesthesia, and 11% use caudal block with sedation. (3) If the repair is done in the hospital outpatient (same-day) unit, 36% wait until 50 weeks postconception (PC) and 33% wait until 60 weeks PC. (4) if the baby's weight is at least 1,000 g. 71% perform the repair before discharge. The pain control choice after childhood IH repair is Tylenol for 30%, local infiltration biquivacaine for 30%, caudal block for 22%, regional block for 11%, and Tylenol/codeine combined for 7%. In 6-week-old full-term infants with communicating hydroceles without definite "hernia," two thirds treat as an IH with elective repair as soon as possible. With respect to contralateral exploration in infants with unilateral IH, 65% perform it in males if they are < or = 2 years of age and 84% use it in females of up to 4 years of age. This approach is not influenced by presenting side, presence of hydrocele, or history of prematurity. Laparoscopic evaluation of the contralateral IH is performed by only 6% of responders, 40% of whom use the open ipsilateral sac for laparoscope introduction.