Social support, social selection and self-assessed health status: results from the veterans health study in the United States

This study provided a comprehensive assessment of the association between social support and health using longitudinal data from the Veterans Health Study. Unlike previous studies which examined the relationship between one single domain of social support with either mental or physical health, the present study assessed the effects of three different domains of social support on multiple measures of health. The findings of the study indicated that social support tended to mediate the deleterious effects of non-military traumatic events; whereas the adverse consequences of traumatic events experienced in the military were not affected by social support, suggesting that stressors associated with combat had a long lasting effect on the health status of veterans. The study results revealed that compared with those with better health, respondents with poor health were more likely to have lower levels of social support, suggesting that poor health might be a barrier to a person's ability to participate and/or maintain social relationships. The study also showed that different types of social support had varying beneficial effects on different measures of health. While perceived support had a strong effect on all the measures of health (except alcoholism) included in the study, living arrangement had a significant effect on post-traumatic stress disorder or physical health and participation in group activities had a strong effect only on physical functioning. The results of the study highlight the need for future research to determine whether particular types of social support affect various aspects of health differently. This simultaneous focus on multiple support functions and health outcomes is important because it provides insight into the mechanisms linking social support to health.     

Murine transgenic cells lacking DNA topoisomerase IIbeta are resistant to acridines and mitoxantrone: analysis of cytotoxicity and cleavable complex formation

Murine transgenic cell lines lacking DNA topoisomerase II (topo II)beta have been used to assess the importance of topo IIbeta as a drug target. Western blot analysis confirmed that the topo IIbeta -/- cell lines did not contain topo IIbeta protein. In addition, both the topo IIbeta +/+ and topo IIbeta -/- cell lines contained similar levels of topo IIalpha protein. The trapped in agarose DNA immunostaining assay (TARDIS) was used to detect topo IIalpha and beta cleavable complexes in topo IIbeta -/- and topo IIbeta +/+ cells. These results show that both topo IIalpha and beta are in vivo targets for etoposide, mitoxantrone, and amsacrine (mAMSA) in topo IIbeta +/+ cells. As expected, only the alpha-isoform was targeted in topo IIbeta -/- cells. Clonogenic assays comparing the survival of topo IIbeta -/- and topo IIbeta +/+ cells were carried out to establish whether the absence of topo IIbeta caused drug resistance. Increased survival of topo IIbeta -/- cells compared with topo IIbeta +/+ cells was observed after treatment with amsacrine (mAMSA), methyl N-(4'-[9-acridinylamino]-2-methoxyphenyl) carbamate hydrochloride (AMCA), methyl N-(4'-[9-acridinylamino]-2-methoxyphenyl)carbamate hydrochloride (mAMCA), mitoxantrone, and etoposide. These studies showed that topo IIbeta -/- cells were significantly more resistant to mAMSA, AMCA, mAMCA, and mitoxantrone, than topo IIbeta +/+ cells, indicating that topo IIbeta is an important target for the cytotoxic effects of these compounds.     

Primary infiltrating signet ring carcinoma of the eyelids

A 61-year old man presented with a five-year history of a swelling initially developing in his right lower lid that progressed to involve the lateral canthal skin and eventually the upper lid and anterior orbit. He was discovered to have an infiltrating, poorly differentiated, mucin-producing carcinoma. Systemic work-up failed to disclose a visceral malignancy, and it was concluded that his tumor was primary in the lids, arising from an adnexal sweat gland. Three other reports in the literature also share almost identical clinical and pathologic features, in that all of the earlier reports dealt with middle-aged or elderly men who had diffusely indurated lids. Histopathologically, the tumor cells grow diffusely in a sclerotic stroma, and resemble the "histiocytoid" variant of metastatic breast carcinoma to the lids in women. Ultrastructural studies in our case point toward an apocrine origin, although earlier authors have favored an eccrine origin. Despite its indolent clinical course, the tumor is capable of producing regional and distant metastases on long-term follow-up. Complete local excision, possibly necessitating radical surgery, is probably the preferred method of treatment, but local radiotherapy may have a beneficial effect in retarding spread of the disease.     

Dietary manipulation of plasma albumin concentration

The variation in plasma albumin concentrations of rats fed a wide range of protein- and energy-deficient diets has been investigated. These changes have been correlated with simultaneous effects of the diets on growth rate, carcass composition, protein and energy balance, and plasma concentration of insulin corticosterone and triiodothyronine (T3). Although rats eating diets of low protein content and libitum developed hypoalbuminemia, those fed equivalent amounts of protein at low energy intakes had plasma albumin concentrations nearer, or equal to control values. Data from the balance study showed that for hypoalbuminemia to occur, not only had dietary protein to be inadequate, it was also necessary for energy consumption to be in excess of requirements. It is suggested that in protein-deficient animals, energy consumed in excess of the amount required for maintenance and the protein-limited growth rate initiates a metabolic response which results in inappropriate use of the meagre protein intake. This "dysadapted" state, in the rat, appears to be indicated by elevated plasma T3 values. The implication that kwashiorkor-like symptoms can be generated by a relative as opposed to a total energy excess is discussed in relation to the appearance of this disease in humans.     

Sex differences and similarities in the management and outcome of stroke patients

BACKGROUND AND PURPOSE: Previous studies have documented sex differences in the management and outcome of patients with cardiovascular disease. However, little data exist on whether similar sex differences exist in stroke patients. We conducted a study to determine whether sex differences exist in patients with acute stroke admitted to Ontario hospitals. METHODS: Using linked administrative databases, we performed a population-based cohort study. The databases contained information on all 44 832 patients discharged from acute-care hospitals in Ontario between April 1993 and March 1996 with a most responsible diagnosis of acute stroke. The main outcomes measured consisted of sex differences in comorbidities, the use of rehabilitative services, the use of antiplatelet therapy and anticoagulants (in elderly stroke survivors aged > or =65 years only), discharge destination, and mortality. RESULTS: Male stroke patients were more likely than female stroke patients to have a history of ischemic heart disease (18.1% versus 15.3%, respectively; P<0.001) and diabetes mellitus (20.1% versus 18. 7%, respectively; P<0.001), whereas female patients were more likely than male patients to have hypertension (33.8% versus 30.0%, respectively; P<0.001) and atrial fibrillation (12.9% versus 10.2%, respectively; P<0.001). There were no sex differences in the usage of in-hospital rehabilitative services. The overall 90-day postdischarge use of aspirin and ticlopidine was similar in stroke survivors aged 65 to 84 years. However, among stroke survivors aged > or =85 years, men were more likely than women to receive aspirin (36. 0% versus 30.7%, respectively; P<0.001) and ticlopidine (9.2% versus 6.8%, respectively; P=0.007). Use of warfarin was similar for the two sexes. Men were more likely than women to be discharged home (50. 6% versus 40.9%, respectively; P<0.001) and less likely to be discharged to chronic care facilities (16.8% versus 25.2%, respectively; P<0.001). The risk of death 1 year after stroke was somewhat lower in women than men (adjusted odds ratio 0.939, 95% CI 0.899 to 0.980; P=0.004). The mortality differences were greatest among elderly stroke patients. CONCLUSIONS: Elderly men are more likely than elderly women to receive aspirin and ticlopidine and equally like to receive warfarin after a stroke. Despite these differences, elderly women have a better 1-year survival after a stroke.     

Rate of stroke recurrence in patients with primary intracerebral hemorrhage

BACKGROUND AND PURPOSE: Primary intracerebral hemorrhage (PICH) is a devastating illness with high early mortality. Hypertension is a major risk factor both for ischemic cerebrovascular disease and for intracranial hemorrhage. Survivors of PICH are at risk for both recurrent hemorrhage and ischemic cerebrovascular disease. We sought to determine the rate of recurrence of ICH or cerebral ischemia in a cohort of PICH patients at the Toronto Hospital, Toronto, Canada. METHODS: A retrospective search of computerized hospital records from 1986 to 1996 for patients with a discharge diagnosis of intracerebral hemorrhage (International Classification of Diseases, Ninth Revision-Clinical Modification [ICD-9-CM] code 431) was conducted to identify the index cases. Charts were abstracted for demographic and clinical characteristics. CT scans, MR scans, or radiologist reports were reviewed. To determine recurrence, the database was linked to the Ontario Provincial Government Vital Statistics Registry and to the Canadian Institute for Health Information database of hospital discharge abstracts. Logistic regression analysis was used to identify predictive factors for mortality after PICH. A Cox proportional hazards model was fitted to identify predictive factors for recurrent ICH or stroke. RESULTS: A total of 746 charts were identified by computer search. After abstraction, 423 index patients with PICH were identified. Of these, 27.4% died in the first 30 days of their admission. Predictors of death were age, intraventricular rupture of hemorrhage, and trilobar hemorrhage. The recurrence rate for PICH was 2.4% (95% CI 1.4% to 3. 9%) per year, whereas the recurrence rate for ischemic cerebrovascular disease was 3.0% (95% CI 1.8% to 4.7%) per year. The only significant predictor of readmission for ICH was lobar location of the index hemorrhage, with a hazard ratio of 3.8 (95% CI 1.2 to 12.0). CONCLUSIONS: PICH has a high 30-day mortality rate. Survival from the initial insult portends a moderate risk of recurrence of 2. 4% per year for PICH and 3.0% per year for ischemic cerebrovascular disease. Patients with PICH are at risk for both ischemic stroke or TIA and recurrent hemorrhage; thus, PICH may be a marker for ischemic stroke. Patients with lobar hemorrhage have a 3.8-fold increased risk of recurrent ICH.     

Previous exposure to VTA amphetamine enhances cocaine self-administration under a progressive ratio schedule in an NMDA, AMPA/kainate, and metabotropic glutamate receptor-dependent manner.

Previous exposure to amphetamine (AMPH) in the ventral tegmental area (VTA) enhances cocaine self-administration in a D(1) dopamine receptor-dependent manner. The present study examined the contribution of VTA NMDA, AMPA/kainate, and metabotropic glutamate (mGlu) receptors to this effect. Rats in different groups received three intra-VTA injections, one every third day, of either saline (0.5 microl/side), AMPH (2.5 microg/0.5 microl/side), AMPH+CPP (NMDA receptor antagonist; 10 microM or 100 microM/0.5 microl/side), AMPH+CNQX (AMPA/kainate receptor antagonist; 0.3 mM or 1 mM/0.5 microl/side), AMPH+MCPG (mGlu receptor antagonist; 0.5 mM or 50 mM/0.5 microl/side), or the glutamate receptor antagonists alone. Starting 7-10 days after the last pre-exposure injection, rats were trained to self-administer cocaine (0.3 mg/kg/infusion) and then tested under a progressive ratio (PR) schedule of reinforcement for 6 consecutive days. As reported previously, VTA AMPH pre-exposed rats worked more and obtained more infusions of cocaine than saline pre-exposed animals. Coadministration of CPP, CNQX, or MCPG with AMPH during pre-exposure dose-dependently blocked this enhancement of cocaine self-administration. Rats pre-exposed to the glutamate receptor antagonists alone did not differ on the test days from the saline pre-exposed controls. These results indicate that, in a manner paralleling the induction of sensitization of the locomotor stimulating effects of AMPH, activation of NMDA, AMPA/kainate, and mGlu receptors during pre-exposure to AMPH in the VTA is necessary for the enhancement of cocaine self-administration to develop.     

Otoacoustic emissions as a screening test for hearing impairment in children recovering from acute bacterial meningitis

OBJECTIVES: To study the efficacy of otoacoustic emissions (OAEs) as a screening test for hearing impairment in children with acute bacterial meningitis. Hearing tests were performed before discharge from the hospital in an attempt to improve coverage and avoid delays in the diagnosis of postmeningitic hearing loss. METHODS: Children with bacterial meningitis were recruited from 21 centers. In the 48 hours before discharge from the hospital, all patients underwent a thorough audiologic assessment consisting of transient evoked OAEs, auditory brainstem responses (ABRs), otoscopy, and tympanometry. Hearing loss was defined as ABR threshold >/=30 dB. The results of OAE screening were compared with the gold standard of ABR threshold. RESULTS: Of 124 children recruited, we were able to perform both OAEs and ABRs on 110 children. Seven (6.3%) of the 110 children had ABR threshold >/=30 dB; 2 had sensorineural hearing loss and 5 had conductive hearing loss. At follow-up, hearing loss persisted in both cases of sensorineural hearing loss and no new cases were identified. All 7 children with hearing loss failed the OAE screening test. Ninety-four children with normal hearing thresholds passed the test, and 9 failed. Thus, the screening test had a sensitivity of 1.00 (95% confidence interval, 0.59 to 1.00), a specificity of 0.91 (0.85 to 0.97), a positive predictive value of 0. 44 (0.20 to 0.70), and a negative predictive value of 1.00 (0.96 to 1.00). CONCLUSIONS: OAE screening in children recovering from meningitis was found to be feasible and effective. The test was highly sensitive and reasonably specific. Inpatient OAE screening should allow early diagnosis of postmeningitic hearing loss and prompt auditory rehabilitation.     

Iron-induced oxidative DNA damage and its repair in primary rat hepatocyte culture

Iron-overload diseases frequently develop hepatocellular carcinoma. The genotoxic mechanism whereby iron is involved in hepatocarcinogenesis might involve an oxidative process via the intermediate production of reactive oxygen species. This was presently investigated by examining kinetics of formation and repair of DNA base lesions in primary rat hepatocyte cultures supplemented with the iron chelate, ferric nitrilotriacetate Fe-NTA (10 and 100 microM). Seven DNA base oxidation products have been identified in DNA extracts by gas chromatography- mass spectrometry, which showed a predominance of oxidized-purines (8- oxo-guanine, xanthine, fapy-adenine, 2-oxo-adenine) above oxidized pyrimidines (5-OHMe-uracil, 5-OH-uracil, 5-OH-cytosine) in control cultures. All these DNA oxidation products revealed a significant dose- dependent increase at 4 to 48 h after Fe-NTA supplementation, among which fapy-adenine showed the highest increase and 5-OH-cytosine was the least prominent. Involvement of iron in this oxidative process was established by a correlation between extent in DNA oxidation and intracellular level of toxic low molecular weight iron. DNA excision- repair activity was estimated by release of DNA oxidation products in culture medium. All the seven DNA oxidation products were detected in the medium of control cultures and showed basal repair activity. This DNA repair activity was increased in a time- and dose-dependent fashion with Fe-NTA. Oxidized-pyrimidines, among which was 5-OHMe-Uracil, were preferentially repaired, which explains the low levels detected in oxidized DNA. Since oxidized bases substantially differed from one another in terms of excision rates from cellular DNA, specific excision- repair enzymes might be involved. Our findings, however, demonstrate that even though DNA repair pathways were activated in iron-loaded hepatocyte cultures, these processes were not stimulated enough to prevent an accumulation of highly mutagenic DNA oxidative products in genomic DNA. The resulting genotoxic effect of Fe-NTA might be relevant in understanding the hepatocarcinogenic evolution of iron-overload diseases.