Affected Body Systems Research Articles

One–Two PM Punch: Gene Combination Increases Vulnerability to Air Pollutant

Numerous epidemiologic studies have found a link between exposure to fine particles (PM2.5) and increased morbidity and mortality. Other studies have found evidence of some of the specific pathways through which this damage occurs, but much remains unknown about the relative importance of these pathways in humans. An international team of researchers has taken a step toward filling that void through its discovery that the combination of two genetic traits—a deletion of one gene and a polymorphism of another—combine to significantly increase risk of oxidative stress and subsequent cardiovascular disease in some people exposed to PM2.5 [EHP 115:1617–1622; Chahine et al.]. One well-known indicator of potential cardiovascular problems is reduced heart rate variability (HRV). When the heart is less able to vary its beat, it can’t respond as nimbly to challenges such as pollutants, microbes, or emotional stresses. PM2.5 exposure has been linked with reduced HRV, possibly in part by triggering oxidative stress. Several genes are known to play a role in defending against oxidative stress. Two of these include glutathione S-transferase-M1 (GSTM1) and heme oxygenase-1 (HMOX-1). To determine whether these genes have a link with reduced HRV, the team studied 476 older Boston-area males, almost all white, for whom they had information on the two genes, as well as data for three established indicators of HRV: standard deviation of normal-to-normal intervals (SDNN), variation at high frequency (HF), and variation at low frequency (LF). Ambient PM2.5 data came from a central stationary monitor, which had sampled in the 48-hour period prior to HRV testing and had earlier been shown to be a good proxy for personal exposures in the area. The team accounted for confounders such as age, body mass index, smoking, and prescription drug use. Overall, they found that each 10-μg/m3 increase in PM2.5 was associated with a statistically significant decrease in two measures of HRV (6.8% for SDNN and 17.3% for HF). Decreases for all three indicators were greater in men with either a GSTM1 deletion or a particular polymorphism of HMOX-1. But the decreases were greatest in the men who had both the GSTM1 deletion and the HMOX-1 polymorphism, dropping 12.7% for SDNN, 27.8% for HF, and 20.1% for LF. This combination occurred in 48% of the subjects. The researchers acknowledge that much more work needs to be done addressing variables such as sex, age, race, geographic setting, pathway of damage, and affected body system. But their findings lead them to conclude that at least one combination of genetic traits increases vulnerability to oxidative stress and cardiovascular damage from PM2.5.

Clinical Management of the Organ Donor

There is a critical mismatch between available organs for transplant and acutely or critically ill patients with end-stage organ disease. Patients who may benefit from organ transplantation far outnumber available organs. The causes for this imbalance are multiple. One cause is family refusal to donate. A second cause is nonrecognition or delay in determination of brain death. A third cause is donor loss due to profound cardiopulmonary and metabolic instability consequent to brain-stem herniation and brain death. Family refusal may be addressed by education, public awareness, as well as close attention to social, cultural and ethical issues, and optimal communication with donor families. Brain death may be consequent to traumatic brain injury, ischemic versus hemorrhagic stroke, as well as massive cerebral anoxia/ischemic following cardiac arrest. Nonrecognition or delay in brain death determination may be addressed by clinician education and frequent clinical assessment to detect early stages of brain-stem herniation refractory to aggressive measures for control of intracranial pressure. Donor loss due to profound cardiopulmonary and metabolic instability may be addressed by aggressive, mechanism-based treatment for clinical instability based on affected body system, as well as measures to support metabolic activity at the cellular and tissue level in the brain-dead organ donor. This article explores cerebral physiology related to impending brain death and catastrophic intracranial pressure elevations. In addition, physiologic consequences of brain death are correlated with affected body systems and mechanism-based therapies to support organ function pending transplantation. Ethical/legal issues are explored as related to patient autonomy and optimal family outcomes. Effective family communication, astute clinical assessment, and optimal clinical management of the organ donor are illustrated using a case study approach, highlighting the role of the advanced practice nurse in donor management.

The Safety Profile of Fluvoxamine in Elderly Patients

The safety profile of fluvoxamine was assessed in 4843 elderly, mainly depressed patients (65 years or older; range 65 to 97 years) enrolled in worldwide post-marketing studies. This cohort of elderly patients was extracted from a population of 34 587 patients in whom the safety profile of fluvoxamine has been extensively assessed (Wagneret al., 1994). The daily dose of fluvoxamine ranged from less than 50 to 300 mg and the studies were conducted over periods of up to 1 year. The most conservative category was chosen throughout the analysis in situations where more than one category was applicable. Overall, 3250 patients (67·1 per cent) completed the full study period. At least one adverse event was reported by 2228 patients (46·0 per cent), the most frequently affected body systems being the ‘gastrointestinal’ and ‘nervous’ systems, followed by the ‘body as a whole’. Nausea was the most common adverse event. At least one serious adverse event was experienced by 135 patients (2·8 per cent), hospitalization being the most widespread classification (113 patients; 2·3 per cent). The incidence of overall suicidality with fluvoxamine was low. Thus, these findings indicate that fluvoxamine is a well tolerated drug in elderly patients.

The Safety Profile of Fluvoxamine in Elderly Patients

The safety profile of fluvoxamine was assessed in 4843 elderly, mainly depressed patients (65 years or older; range 65 to 97 years) enrolled in worldwide post-marketing studies. This cohort of elderly patients was extracted from a population of 34 587 patients in whom the safety profile of fluvoxamine has been extensively assessed (Wagneret al., 1994). The daily dose of fluvoxamine ranged from less than 50 to 300 mg and the studies were conducted over periods of up to 1 year. The most conservative category was chosen throughout the analysis in situations where more than one category was applicable. Overall, 3250 patients (67·1 per cent) completed the full study period. At least one adverse event was reported by 2228 patients (46·0 per cent), the most frequently affected body systems being the ‘gastrointestinal’ and ‘nervous’ systems, followed by the ‘body as a whole’. Nausea was the most common adverse event. At least one serious adverse event was experienced by 135 patients (2·8 per cent), hospitalization being the most widespread classification (113 patients; 2·3 per cent). The incidence of overall suicidality with fluvoxamine was low. Thus, these findings indicate that fluvoxamine is a well tolerated drug in elderly patients.

Examination of the Equine Patient with Gastrointestinal Emergency

Clinical examination of the equine patient with acute abdominal pain should identify the affected body system and yield a provisional diagnosis. Determination of signalment, history, physical examination, and basic laboratory tests should assist in classification of the gastrointestinal disorder and direct the therapeutic plan. Determination of the definitive diagnosis of abdominal pain based on clinical examination is not crucial. For a successful outcome, efforts should be directed toward early recognition of the need for surgery and treatment of cardiovascular compromise in horses with severe gastrointestinal disease.