Food reinforcement, the dopamine D2 receptor genotype, and energy intake in obese and nonobese humans

The authors measured food reinforcement, polymorphisms of the dopamine D2 receptor (DRD2) and dopamine transporter (DAT1) genes, and laboratory energy intake in 29 obese and 45 nonobese humans 18-40 years old. Food reinforcement was greater in obese than in nonobese individuals, especially in obese individuals with the TaqI A1 allele. Energy intake was greater for individuals high in food reinforcement and greatest in those high in food reinforcement with the TaqI A1 allele. No effect of the DAT1 genotype was observed. These data show that individual differences in food reinforcement may be important for obesity and that the DRD2 genotype may interact with food reinforcement to influence energy intake.     

Th1 immune response promotes severe bone resorption caused by Porphyromonas gingivalis

Bacterial infections of the dental pulp result in soft tissue and alveolar bone destruction. It has been suggested that Th1 responses promote disease, whereas Th2 responses are protective. However, other studies have challenged this notion. To address this question, bone destruction was evaluated in mice immunized to develop strong and polarized Th1- or Th2-biased responses to the oral pathogen Porphyromonas gingivalis. Th1 bias was confirmed by the presence of high titers of serum IgG2a and the production of high levels of interferon (IFN)-gamma and no interleukin (IL)-4 by lymph node cells stimulated with P. gingivalis antigens. In contrast, Th2-biased animals had high titer IgG1 and no IgG2a, and their lymph node cells produced high levels of IL-4 but no IFN-gamma. Subsequent infection of the dental pulp with P. gingivalis caused extensive inflammation and alveolar bone destruction in Th1-biased mice, whereas Th2-biased mice and controls developed minimal lesions. Inflammatory granulomas in Th1-biased mice were heavily infiltrated with osteoclasts and had high local expression of IFN-gamma, IL-1alpha, and IL-1beta. Little or no IFN-gamma/IL-1alpha/IL-1beta and no obvious osteoclasts were detected in lesions of Th2-biased and control groups. These results directly demonstrate that specific Th1 responses promote severe infection-stimulated alveolar bone loss.     

Atherosclerosis and vascular aging as modifiers of tumor progression, angiogenesis, and responsiveness to therapy

It is rarely considered that age-related common vascular co-morbidities may affect therapeutic outcomes of antiangiogenic therapy in cancer. Indeed, the accepted model of human disease consists of 4- to 8-week-old (young) tumor-bearing, but otherwise healthy, experimental mice, yet human cancers are diagnosed and treated in later decades of life when atherosclerosis and vascular diseases are highly prevalent. Here we present evidence that tumor growth and angiogenesis are profoundly altered in mice affected by natural aging and with genetically induced atherosclerosis (in ApoE(-/-) mice). Thus, transplantable tumors (Lewis lung carcinoma and B16F1) grew at higher rates in young (4 to 8 weeks old) ApoE(+/+) and ApoE(-/-) nonatherosclerotic syngeneic recipients than in their old (12 to 18 months old) or atherosclerotic (old/ApoE(-/-)) counterparts. These age-related changes were paralleled by reduced tumor vascularity, lower expression of tumor endothelial marker 1, increased acute tumor hypoxia, depletion of circulating CD45(-)/VEGFR(+) cells, and impaired endothelial sprouting ex vivo. Exposure of tumor-bearing mice to metronomic therapy with cyclophosphamide exerted antimitotic effects on tumors in young hosts, but this effect was reduced in atherosclerotic mice. Collectively, our results suggest that vascular aging and disease may affect tumor progression, angiogenesis, and responses to therapy.     

Comparison of lactate values between point-of-care and central laboratory analyzers

Measurement of lactate levels is important in the care of critically ill adult and pediatric patients. We compared 3 whole blood lactate methods (Radiometer ABL 725, Radiometer Medical A/S, Bronshoj, Denmark; i-STAT, i-STAT, East Windsor, NJ; and Nova Lactate Plus, Nova Biomedical, Waltham, MA) with 2 plasma-based methods (Roche Integra, Roche Diagnostics, Indianapolis, IN; and Vitros, Ortho Clinical Diagnostics, Rochester, NY). The Vitros LAC slide assay was used as the reference method. Results were compared by least squares regression and Bland-Altmann plots and by comparing concordance within clinically relevant lactate ranges. Correlation between lactate methods was good with slopes between 0.87 and 1.06 and intercepts of 0.9 to 1.8 mg/dL (0.1-0.2 mmol/L) of lactate for all 4 methods compared with the Vitros. At high (>54.1 mg/dL [6 mmol/L]) lactate values, the Radiometer and i-STAT methods reported lower lactate results compared with the Vitros and Integra. The Nova analyzer reported higher lactate results than either the Vitros or Integra. The negative bias in i-STAT and Radiometer results may confound the interpretation of patient condition if multiple methods are used within the same institution.     

Neural coupling between the arms and legs during rhythmic locomotor-like cycling movement

Neuronal coupling between the arms and legs allowing coordinated rhythmic movement during locomotion is poorly understood. We used the modulation of cutaneous reflexes to probe this neuronal coupling between the arms and legs using a cycling paradigm. Participants performed rhythmic cycling with arms, legs, or arms and legs together. We hypothesized that any contributions from the arms would be functionally linked to locomotion and would thus be phase-dependent. Reflexes were evoked by electrical stimulation of the superficial peroneal nerve at the ankle, and electromyography (EMG) was recorded from muscles in the arms and legs. The main finding was that the relative contribution from the arms and legs was linked to the functional state of the legs. For example, in tibialis anterior, the largest contribution from arm movement [57% variance accounted for (VAF), P < 0.05] was during the leg power phase, whereas the largest from leg movement (71% VAF, P < 0.05) was during leg cycling recovery. Thus the contribution from the arms was functionally gated throughout the locomotor cycle in a manner that appears to support the action of the legs. Additionally, the effect of arm cycling on reflexes in leg muscles when the legs were not moving was relatively minor; full expression of the effect of rhythmic arm movement was only observed when both the arms and legs were moving. Our findings provide experimental support for the interaction of rhythmic arm and leg movement during human locomotion.     

Malignancy in Renal Transplant Recipients Exposed to Cyclophosphamide Prior to Transplantation for the Treatment of Native Glomerular Disease

Study Objective

To evaluate the risk of posttransplantation malignancy in renal transplant recipients exposed to pretransplantation cyclophosphamide for the treatment of glomerular nephropathy (GN).

Design

Retrospective cohort study.

Setting

Tertiary academic medical center.

Patients

Six hundred adult renal transplant recipients were transplanted between 1993 and 2014; 54 patients were exposed to pretransplantation cyclophosphamide for treatment of GN (GN‐CYC group), and 546 patients with polycystic kidney disease were not exposed to pretransplantation cyclophosphamide (PKD group).

Measurement and Main Results

Data were collected retrospectively from electronic medical records. The primary outcome was occurrence of posttransplantation malignancy. During a median follow‐up of 5.5 years, 130 patients developed malignancy (incidence rate 3.5 events per 100 person‐yrs). Exposure to cyclophosphamide before transplantation was significantly associated with malignancy after transplantation (adjusted hazard ratio [aHR] 2.20, 95% confidence interval [CI] 1.16–4.22, p=0.02), specifically skin cancer (aHR 2.24, 95% CI 1.09–4.60, p=0.03). Malignancy risk in the GN‐CYC group was higher in the setting of lymphocyte‐depleting induction (alemtuzumab; aHR 4.53, 95% CI 0.99–20.72, p=0.05) compared with basiliximab induction. Incidences of death‐censored graft loss and mortality were similar between the GN‐CYC and PKD groups.

Conclusion

In our observational study, renal transplant recipients exposed to pretransplantation cyclophosphamide appeared to have a higher risk of developing a malignancy compared with unexposed renal transplant recipients. Further investigation into the impact of pretransplantation immunosuppression on malignancy, particularly the compounded effect with lymphocyte‐depleting induction, is warranted.     

Initial presentation of older injured patients to high-volume hospitals is not associated with lower 30-day mortality in Medicare data

OBJECTIVE: To evaluate whether survival of older patients with severe injuries is positively associated with initial presentation to high-volume trauma hospitals. DESIGN: Historical cohort study. SETTING: We analyzed Medicare fee-for-service records. Cases were classified by maximum Abbreviated Injury Score (AISmax); those with isolated hip fractures or AISmax <3 were excluded. The initial hospital (emergency department or inpatient) for each case was classified by its number of included inpatient cases. PATIENTS: Patients aged >or=65 with principal injury diagnoses (ICD-9 800-959, excluding 905, 930-939, 958) admitted to hospitals or who died in emergency departments during 1999. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Thirty-day mortality was determined using Medicare denominator data and modeled as a function of hospital volume, AISmax, age, gender, and comorbidity. We found that 95,867 patients (74,894 AISmax = 3; 17,932 AISmax = 4; 3,041 AISmax = 5) were managed in 4,391 hospitals. More than 90% of the interhospital transfers were from emergency departments, mostly from low-volume to high-volume hospitals, and were more frequent with greater severity. Regression models showed no difference in 30-day survival between patients taken first to low-volume hospitals (and possibly transferred) vs. patients taken directly to high-volume hospitals. Prior studies showing a positive or negative effect of hospital volume on survival of older patients could be replicated but their findings could not be generalized. CONCLUSIONS: Existing systems of trauma care result in similar survival for older patients with serious injuries seen first at low-volume or high-volume hospitals.     

Common oral lesions: Part II. Masses and neoplasia

Certain common oral lesions appear as masses, prompting concern about oral carcinoma. Many are benign, although some (e.g., leukoplakia) may represent neoplasia or cancer. Palatal and mandibular tori are bony protuberances and are benign anomalies. Oral pyogenic granulomas may appear in response to local irritation, trauma, or hormonal changes of pregnancy. Mucoceles represent mucin spillage into the oral soft tissues resulting from rupture of a salivary gland duct. Oral fibromas form as a result of irritation or masticatory trauma, especially along the buccal occlusal line. Oral cancer may appear clinically as a subtle mucosal change or as an obvious mass. Oral leukoplakia is the most common premalignant oral lesion. For persistent white or erythematous oral lesions, biopsy should be performed to rule out neoplastic change or cancer. Most oral cancers are squamous cell carcinomas. Tobacco and heavy alcohol use are the principal risk factors for oral cancer. Family physicians should be able to recognize these lesions and make appropriate referrals for biopsy and treatment.