Effects of hyperglycemia, hyperinsulinemia, and hyperosmolarity on neutrophil apoptosis

BACKGROUND: Hyperglycemia is an independent risk factor for increased mortality of critically ill surgical patients, but despite the recognized clinical benefits of early insulin treatment, there is a lack of understanding of the cellular and molecular mechanisms behind this phenomenon. We hypothesized that polymorphonuclear neutrophils, the first line of the innate immune defense system, suffer from altered apoptotic turnover when exposed to hyperglycemic conditions, ultimately decreasing the number of viable cells active at a site of infection. METHODS: Venous blood samples were drawn from 10 volunteers and incubated for 0.5 or 24 h in a 1:10 dilution with RPMI 1640 medium at various glucose and insulin concentrations. Mannitol was used to control for increased osmolarity. In addition, all samples were incubated either with low-dose lipopolysaccharide (LPS) (1 ng/mL) or without LPS. Neutrophils were extracted using Ficoll-Hypaque density centrifugation and stained with annexin V and propidium iodide. Fluorescence was detected by flow cytometry and analyzed using CellQuest software. RESULTS: The mean percentage of apoptotic neutrophils after 24 h of incubation at physiologic glucose concentrations (100 mg/dL) was 42.2 +/- 4.1%; exposure to low-dose LPS decreased this number to 18.4 +/- 2.5% (p < 0.01). Neither the exposure to low (10 mg/dL) nor increasingly high (200 or 400 mg/dL) glucose concentrations altered these percentages significantly. Exposing whole blood to increasing osmolarity (addition of 5.5 mM and 16.5 mM mannitol to simulate 200 and 400 mg/dL glucose) led to a mean absolute reduction of the percentage of apoptotic neutrophils to 34.6 +/- 3.6% (+5.5 mOsm; p < 0.05) and 32.3 +/- 4.5% (16.5 mOsm; p < 0.01), respectively. CONCLUSIONS: The ability of neutrophils to enter their apoptotic program in cultured whole blood withstands short-term changes in glucose and insulin concentrations. Neither hyperglycemia nor hypoglycemia led to a significant alteration of the apoptotic turnover of these cells, suggesting that the increased rate of infectious complications in short-term hyperglycemic critically ill patients may not be traced to increased apoptosis of neutrophils. However, isolated hyperosmolarity reduces neutrophil apoptosis, an observation that may warrant future investigation.     

Validation of a brief screening test for depression in the elderly

This paper describes the clinical validation of the 10-question Short Zung Interviewer-assisted Depression Rating Scale (Short Zung I.D.S.) which has been derived from the 20-question Zung Self-rating Depression Scale (Zung S.D.S) for use in the elderly. The Short Zung I.D.S. was administered to 104 elderly volunteers from the community and to 33 elderly depressed patients assessed by a psychiatrist. The mean scores (41.3 and 81.0, respectively) were significantly different (P less than 0.0001). The Short Zung I.D.S. has proved to be a useful brief screening test for depression in the elderly and should be of value in measuring changes in mood.     

Guardianship: A medicolegal review for clinicians

Guardianship may pose an ethical dilemma for physicians, who must balance protecting vulnerable patients from potential safety concerns with respecting their autonomy. Older adults with dementia are particularly susceptible to loss of independence and the ability to participate in medical decision making. To have the capacity for medical decision making, individuals must understand relevant information, appreciate their circumstances, demonstrate reasoning, and express a consistent choice free from coercion. Although capacity assessments are usually task-specific, geriatricians and other specialists may be asked to comment on capacity more globally. These determinations may be used to support a Petition for the Appointment of a Guardian of a Legally Incapacitated Adult, the legal process of pursuing guardianship in probate court. Assigned guardians may be known to the incapacitated individual (e.g., a family member or friend) or may be professional guardians with no prior relationship to the ward. Guardians are encouraged to use substituted decision-making, taking into account the ward's previously expressed values and preferences. Although a number of viable alternatives to guardianship exist, numerous systemic barriers may prevent these from being fully explored. The ongoing need for guardianship should be periodically revisited and reassessed. Data about guardians and wards is shockingly sparse, as there are no centralized databases. Laws and regulations for guardianships vary significantly between states. Physicians can serve as important allies and advocates for patients with cognitive impairment at risk of incapacity, can help preserve their autonomy for as long as possible, and ensure appropriate protections are in place if the patient does lose their decision-making ability.     

Usefulness of adenosine in augmenting ventricular preexcitation for noninvasive localization of accessory pathways.

Adenosine was administered to test the hypothesis that it would maximize preexcitation and facilitate noninvasive localization of accessory pathways in 22 patients with suspected accessory pathway-mediated tachycardias. Twelve-lead electrocardiograms and 2-dimensional echocardiograms were recorded at baseline and during adenosine-augmented ventricular preexcitation to localize the accessory pathway. Phase analysis was performed on digitized 4-chamber and short-axis views using a first harmonic Fourier transformation. At baseline, 15 patients had manifest preexcitation. In 14 of these patients (93.3%), preexcitation became more prominent after adenosine. Four patients without preexcitation at baseline clearly had it after adenosine. In patients who had preexcitation in response to adenosine, the electrocardiogram correctly identified the accessory pathway locations in 18 of 19 patients at a regional level and was incorrect in 1 of 19 patients. Echocardiographic phase analysis correctly identified the accessory pathway location in all 17 patients, who had technically adequate studies, at a regional level. In conclusion, administration of adenosine accentuates preexcitation, allowing for more accurate electrocardiographic and echocardiographic accessory pathway localization.     

The interaction between electrosurgical generators, endoscopic electrodes, and tissue.

Endoscopic monopolar and bipolar devices were compared during cutting and coagulation. It was observed on appropriate animal models that the initial resistance (impedance) values recorded correspond to the normal tissue impedance at the electrode. The subsequent impedance values increase 25 to 50 ohms for the coagulator which relates to tissue desiccation and for the cutting electrodes the impedance increases greater than 1000 ohms during the arcing process. At similar power settings, typical monopolar generators produce maximum power at 300 to 500 ohms while typical bipolar generators produce maximum power at 25 to 100 ohms. With impedances greater than 1000 ohms, monopolar generators are capable of higher power output than are bipolar generators. Since cutting is a high impedance process, bipolar cutting electrodes do not perform as intended with typical bipolar generators. Therefore, bipolar cutting electrodes should be employed with a monopolar generator or a generator designed specifically for their use.