Evaluating New and Traditional Methods for Aminoglycoside Dosing in Patients With Various Degrees of Renal Function

Aminoglycosides are widely used, and clinicians continue to seek newer and better methods for initial dosing of these agents. Recently, three new methods were introduced: Thomson, Reesor Nimmo, and dosing in Tenopathy by easy-to-use multipliers (DREM). In comparing them with older, traditional dosing methods in patients with various degrees of renal function, the pharmacokinetic variables of gentamicin were determined from steady-state peak (C_max) and trough (C_min) serum concentrations using individualized regimens in 88 patients. Dosages were determined in each patient using the method of Hull-Sarubbi, rule of eights, and the three new methods, and the resultant C_max and C_min values were calculated from dosages generated by each method. The daily doses and C_max values derived with the Hull-Sarubbi, Thomson, and Reesor Nimmo methods were not significantly different (p>0.05). The Hull-Sarubbi was the most precise (root mean squared prediction error 1.3) and least biased (mean prediction error −0.05) of the five methods in predicting target gentamicin serum peak concentrations (C_max 6.5 mg/L). The Hull-Sarubbi (69%), Thomson (86%), and Reesor Nimmo (70%) methods yielded therapeutic C_max (5–8 mg/L) in a significantly higher percentage of patients than did the rule of eights (32%) and DREM (35%), (p<0.05). Therefore, if gentamicin serum concentrations are not available, the first three appear to be reasonable methods for initiating gentamicin dosage regimens, but the last two may not be desirable to use in a clinical setting. These conclusions are based on the assumption that patients are adults with stable renal function and relatively stable clinical conditions.     

In vivo induction of Ia expression in murine cornea after intravitreal injection of interferon-gamma

Intravitreal injection of interferon gamma (IFN-gamma) induces increased expression of Class II major histocompatibility complex (Ia) antigen expression on corneal endothelial cells and stromal fibroblasts. In contrast, IFN-gamma has no detectable effect on Ia antigen expression in epithelium. Induction of Ia antigen expression was rapid with increases detectable as early as 6-12 hours after a single injection of 1 x 10(5) units. Expression peaked at 24-48 hours and decreased to background levels by 120 hours. The Ia antigen expression increased in a dose-dependent manner, and IFN-gamma treatment also induced the synthesis of increased amounts of a 65-kilodalton (kD) protein in the cornea. Increased levels of this 65-kd protein are seen as early as 12 hours after treatment and can be induced with as little as 1 x 10(2) units of IFN-gamma. The function of the 65-kd protein is unknown. This model should be useful in studies on in vivo modulation of Ia antigen expression.     

Health Behavior Correlates of Depression in a Sample of High School Students

Frequency of symptoms of depression and selected health-related practices and events were measured in a sample of 219 high school students. Students reported numerous symptoms of depression. Relative proportions of boys and girls reporting symptoms of depression were not significantly different. However, girls reported experiencing more severe depression than their male counterparts. Depression correlated significantly with several of the 22 health practices and states of affect examined. Both the determinants and manifestations of depression in adolescent cohorts require in-depth investigation. Possible implications for school health personnel are discussed.     

Radiographic manifestations of bronchiolitis obliterans with organizing pneumonia vs usual interstitial pneumonia

The radiographic findings in 24 cases of bronchiolitis obliterans with organizing pneumonia and 16 cases of usual interstitial pneumonia were reviewed and compared. Some cases of bronchiolitis obliterans with organizing pneumonia have been mistaken for usual interstitial pneumonia, although the two diseases have distinct pathologic findings. Clinically, the diseases often have different manifestations. Bronchiolitis obliterans with organizing pneumonia has a better prognosis and often responds well to steroids. This study shows that the radiologic findings of bronchiolitis obliterans include alveolar opacities without lung-volume loss. Patients with usual interstitial pneumonia, however, have bilateral diffuse interstitial opacities with occasional honeycomb changes, and there is loss of lung volume in most patients. These findings suggest that the chest radiograph can aid in distinguishing the two diseases.     

Middle-Down Fragmentation for the Identification and Quantitation of Site-Specific Methionine Oxidation in an IgG1 Molecule

A middle-down LC/MS approach, for the rapid quantitation and characterization of site-specific methionine oxidation in a recombinant monoclonal IgG1 molecule, is described. An IgG1 antibody was digested with endoprotease LysC under limited proteolytic conditions to produce two major components; an antigen binding fragment (Fab) and a crystallizable fraction (Fc). These fractions were then reduced to produce three major species; light chain (LC), Fc/2 which is the C terminal region of the heavy chain (HC) and the N-terminal heavy chain region (Fd). These three fragments were separated by reversed-phase HPLC using a diphenyl column. The diphenyl column resolved site-specific methionine oxidation in all three subunits. Middle- down N-terminal sequencing with a LCT premier mass spectrometer was used to identify the sites of oxidation in the LC. Sites of oxidation in the Fc/2 were identified using middle-down collision-induced dissociation (CID) on a Qtof premier. This method allowed for the rapid quantitation and identification of oxidation on each methionine residue in an IgG1 molecule.     

Comparison of novel computer detectors and human performance for spike detection in intracranial EEG.

OBJECTIVE: Interictal spikes in intracranial EEG (iEEG) may correlate with epileptogenic cortex, but review of interictal iEEG is labor intensive. Accurate automated spike detectors are necessary for understanding the role of spikes in epileptogenesis. METHODS: The sensitivity, accuracy and reproducibility of three automated iEEG spike detectors were compared against two human EEG readers using iEEG segments from eight patients. A consensus set of detections was generated for detector calibration. Spike verification was calculated after both human EEG readers independently reviewed all detections. RESULTS: Humans and two of the three automated detectors demonstrated comparable accuracy. In four patients, automated spike detection sensitivity was >70% and accuracy was >50%. In the remaining four patients, EEG background morphology resulted in poorer performance. Blinded human verification accuracy was 76.7+/-6.6% for computer-detected spikes, and 84.5+/-4.1% for human-detected spikes. CONCLUSIONS: Automated iEEG spike detectors perform comparably to humans, but sensitivity and accuracy are patient dependent. Humans verified the majority of computer-detected spikes. SIGNIFICANCE: In some patients automated detectors may be used for mapping spike occurrences in epileptic networks. This may reveal associations between spike distribution, seizure onset, and pathology.     

Flexibility of technopolymer clasps compared with cobalt-chromium and titanium clasps.

Patients often cite lack of retention and poor aesthetics as reasons for not wearing their partial dentures. Traditional metal alloy clasps have been shown to exert forces on abutment teeth that exceed those capable of producing tooth movement. In addition, metal display on anterior teeth is often unacceptable. The technopolymer materials are purported to have superior flexibility and exert less force than the metals. This study compared the flexibility and forces produced by technopolymer clasps with those exerted by cobalt-chromium and titanium clasps. The results showed that the technopolymer clasps were up to ten times as flexible as the metal clasps, and they returned to their pretest dimensions after being stretched. In addition, they exerted forces on the abutment teeth that fall within the range of those considered safe for use. This coupled with their pleasing aesthetics makes them suitable for use on periodontally compromised teeth, those with deep undercuts and on anterior teeth.     

Becoming a Father: First-Time Fathers' Experience of Labor and Delivery

In this study, ethnographic interviews were used to identify first-time fathers' experiences of the birth of their first child. Fourteen fathers were interviewed, and prenatal expectations of the experience are compared with the fathers' perceptions after the birth. Although the fathers expected to be treated as part of a laboring couple, they found that they were relegated to a supporting role. Initially the fathers were confident of their ability to support their wives, but they found that labor was more work than they had anticipated. They became fearful of the outcome, but hid these fears from their partners. Later, they found that their focus moved from their wives to their babies at the time of birth. The men all completed the experience with an enhanced respect for their wives. Fathers should be included in labor management plans and need support for their role as coach, particularly when their wives experience pain. They also need to be encouraged to eat and take a break from their wives' labor when appropriate.     

A preliminary study of serotonergic antidepressants in treatment of dysthymia

Rosenthal, Jesse et al. A Preliminary Study of Serotonergic Antidepressants in the Treatment of Dysthymia. Prog. Neuro-Psychopharmacol. & Biol. Psychiat. 1992, 16(6): 933–941.

1. 1. There is increasing evidence that antidepressants may alleviate symptoms of dysthymia, but few prior studies on selective serotonergic agents.

2. 2. Twenty patients meeting criteria for dysthymia, but not meeting criteria for major depression, received open label trials of a serotonergic antidepressant, either fluoxetine or trazodone.

3. 3. Seventeen (85%) completed three-month medication trials, and of these, twelve (70.6% of completers) responded to treatment. Seven (41.2% of completers) were still in remission on followup at five months.

4. 4. Both fluoxetine and trazodone were well tolerated in dysthymics, and showed similar short-term effectiveness in treating dysthymic symptoms.