High-dose continuous infusion plus pulse interleukin-2 and famotidine in metastatic kidney cancer

High-dose continuous infusion interleukin-2 (IL-2) regimens generate a higher degree of lymphokine activated killer cell (LAK) cytotoxicity when tested against tumor cells in vitro and a higher rebound lymphocytosis in vivo than do bolus IL-2 regimens. Lymphocytes initially activated by continuous infusion IL-2 have increased cytotoxicity against cancer cells when they are subsequently pulsed with additional IL-2. Famotidine may enhance LAK cytolytic ability. Six patients with kidney cancer have been treated with a combination of famotidine 20 mg intravenous bid and continuous infusion IL-2 (18 MIU/sq m/24 hours) for 72 hours, followed by a 24-hour rest, then IL-2 18 MIU/sq m over 15-30 minutes. The most common metastatic sites were the lung, lymph node, and bone. Median number of cycles received = 5 (range, 3-8). The most common toxicities were fever, rigors, nausea/emesis, hypophosphatemia, hypotension, elevated creatinine, and metabolic acidosis. There were no treatment-related deaths, and no patients required intensive care admission. Two partial responses (33% response rate) have been seen. Median survival has not been reached at greater than 8 months. The combination of high-dose continuous infusion plus pulse IL-2 and famotidine is active in metastatic kidney cancer. An accrual of additional patients is needed to better assess the response rate.     

The beneficial effects of recipient-derived vascular endothelial growth factor on graft survival after kidney transplantation

BACKGROUND: Vascular endothelial growth factor (VEGF) is crucial for preservation of microvasculature and contributes to cytoprotection of the graft after kidney transplantation. METHODS: The authors investigated the influence of VEGF single-nucleotide polymorphism (SNP) on graft survival after renal transplantation. The SNP at positions -2578, -1154, and, -7 were analyzed in 306 donors and 387 recipients of renal transplants. RESULTS: The authors observed no effect of those recipient or donor SNP on acute rejection. However, graft survival was associated with recipient SNP at position -2578 C/A. Recipients with a genetic basis for high production of VEGF had significantly better graft survival compared with recipients with low production of VEGF. Homozygotes for the A allele (low producers of VEGF) had worse graft survival compared with high producers, the heterozygotes and homozygotes for C allele (P=0.03). Multivariate analysis in which the effects of donor age, recipient race, cold ischemia time, donor origin, and number of human leukocyte antigen mismatches were included showed that the status of noncarriers of -2578 C allele of recipients was an independent factor for graft failure (odds ratio, 1.8; 95% confidence interval, 1.0-3.0; P=0.03). CONCLUSIONS: The authors conclude that homozygote recipients for the -2578 A allele, the low producers of VEGF, are more vulnerable to tissue injury, resulting in worse graft survival.     

Anti-CD2 monoclonal antibody and tacrolimus in adult liver transplantation

BACKGROUND: Blockade of costimulation and adhesion signaling is an attractive approach to interfere with graft rejection METHODS: Between January 1997 and May 1999, forty adults having benign liver diseases were included in a prospective, randomized study comparing tacrolimus plus low-dose short-term steroids without (n=20, TAC group) or with a 10-day course of antihuman CD2 monoclonal antibody (n=20, BTI group). RESULTS: At day 7, histological rejection expressed by mean Banff scores (2.3+/-1.6 vs. 5.4+/-1.6 in the TAC group; P<0.0001) and incidence of moderate to severe rejection (score>or=6) (0 vs. 10 [50%] in the TAC group; P<0.001) were significantly lower in the BTI group. Rejection was treated in 10% (two patients) of BTI patients during the first 3 months and in 15% during the whole follow-up and in 25% (five patients) of TAC patients (P=NS). None of the BTI-patients presented with an adverse event. Three-month, 1-year, and 5-year actual patient survival rates were 100%, 95%, and 95% in the BTI group and 100%, 100%, and 85% in the TAC group. Graft survival rates were 100%, 90%, and 90% in the BTI group and 95%, 95%, and 80% in the TAC group (P=NS). The mAb had no negative impact on infectious or tumor events. CONCLUSIONS: Antihuman CD2 monoclonal antibody is a safe immunosuppressive drug which has a favorable impact on early immunological follow-up of liver transplanted patients. The antibody had no impact on late patient and graft survival.     

Health promotion and disease prevention for older adults: Intervention themes and strategies used in Quebec local community health centres and seniors' day centres

OBJECTIVE: Despite the considerable potential of disease prevention and health promotion (DPHP) among older adults, extant data suggest that this field of intervention is still underdeveloped. To shed further light on this issue, this paper presents the results of an inventory of DPHP interventions for older adults conducted in local community health centres (CLSCs) and seniors' day centres in the province of Quebec. METHODS: All CLSCs (N=147) and day centres (N=124) were invited to participate (response rates: 74% and 79%). Data were collected through telephone interviews. Interventions were coded according to type of intervention strategies and target themes. RESULTS: Awareness-raising and health education strategies emerged as the most frequently-cited type of intervention strategies, reported by 77% of CLSCs and 95% of day centres, respectively. The two themes reported by a majority of CLSCs were physical health (87%) and community issues (58%). Lifestyle habits (92%) and social issues (92%) were the two most frequently-cited themes in day centres. DISCUSSION: DPHP for older adults is substantially well developed in terms of intervention offerings in the two types of organizations under study. However, the range of available interventions requires expansion to increase the potential of DPHP programs to tackle the numerous challenges posed by the aging of the population.     

A positive correlation between occlusal trauma and peri-implant bone loss: literature support

The relationship between occlusal overload and peri-implant bone loss remains a controversial topic in implant dentistry. A causal relationship between the incidence of marginal bone loss next to an implant and occlusal overload implies a treatment plan and occlusal scheme would benefit from a force management approach. A MEDLINE-assisted and hand search of peer-reviewed English literature and relative textbooks were used for a selective review of articles addressing biomechanical stress and bone loss in cellular biomechanics, engineering principles, mechanical properties of bone, animal studies, clinical reports, bone physiology, and implant design biomechanics. These papers demonstrate occlusal overload on implants may increase the incidence of marginal bone loss.     

Regulation of synaptic plasticity in a schizophrenia model

The pathology of schizophrenia is characterized by increased hippocampal activity at baseline and during auditory hallucinations. Animal-model studies in which the flow of activity to the hippocampus is increased through decreased amygdalar GABAergic inhibition have shown alterations of hippocampal circuitry similar to schizophrenia, but the functional importance of this phenomenon remains unclear. We provide evidence of decreased hippocampal feed-forward and tonic GABA-mediated inhibition in this animal model, complementing increased hippocampal activity seen in neuroimaging and postmortem studies. We demonstrate that GABA dysfunction increases long-term potentiation through activation of the cholinergic system, offering a new mechanism for pharmacological strategies of this disorder.     

Fruit and vegetable consumption and cognitive decline in aging women

We prospectively examined fruit and vegetable intake in relation to cognitive function and decline among aging women. Participants were followed from in 1976 with biennial questionnaires, and food frequency questionnaires were administered in 1984, 1986, and every 4 years thereafter. From 1995 to 2001, we administered, by telephone, six cognitive tests measuring general cognition, verbal memory, category fluency, and working memory. We repeated assessments two years later for 13,388 women (>90% follow-up). We averaged dietary intakes from 1984 through the first cognitive assessment, and used linear regression to obtain multivariable-adjusted mean differences in performance and decline in performance across intake levels. Fruits were not associated with cognition or cognitive decline. However, total vegetable intake was significantly associated with less decline. Specifically, on a global score combining all tests, women in the highest quintile of cruciferous vegetables declined slower (by 0.04 unit; 95% confidence interval, 0.003, 0.07; p trend = 0.1) compared with the lowest quintile. Women consuming the most green leafy vegetables also experienced slower decline than women consuming the least amount (by 0.05 unit; 95% confidence interval, 0.02, 0.09; p trend < 0.001). These mean differences were equivalent to those observed for women about 1 to 2 years apart in age.     

Special education needs of children with newly diagnosed epilepsy

Children with epilepsy often experience poor social and educational outcomes. This study aimed to determine the timing of services with respect to the onset of seizures. It also aimed to identify the aspects of childhood epilepsy (type of epilepsy, etiology, seizure control, and treatment) that are associated with the use of special education services. As part of a prospective community-based study, 613 children were recruited when first diagnosed with epilepsy. Mean age at first seizure was 5 years 11 months (SD 4, range 1mo to 15y 8mo). Parents were interviewed 5 years after children were first diagnosed with epilepsy (n=542; 276 [51%] males). Children's mean age at time of interview was 11 years 10 months (SD 4y 1mo, range 5y 8mo to 21y 8mo). Etiology was classified as idiopathic (n=181, 33.4%), cryptogenic (n=261, 48.2%), and remote symptomatic (n=100, 18.5%). Service use was reported in 315 (58%) children. Compared with neurologically intact children (i.e. cryptogenic and idiopathic etiology; n=415, 77%), children with a remote symptomatic etiology and/or an epileptic encephalopathy (n=127, 23%) received services more frequently (88% vs 49%, p<0.001). In the former group, services were initiated for 66 (15%) children before their first seizure; according to age at onset, services were initiated before the first seizures in 12/164 (7.3%) if <5 years, 34/171 (19.9%) if 5-9 years, and 20/80 (25%) if >10 years. A large proportion of children with epilepsy, even if neurologically otherwise normal, receive special education services. Initiation of services often precedes onset of seizures even in neurologically intact children. This suggests that behavioral and cognitive abnormalities may predate the onset of epilepsy and are not necessarily the direct consequences of epilepsy.