Comparison of Ampicillin-Sulbactam and Ticarcillin-Clavulanic Acid in Patients With Chronic Renal Failure: Effects of Differential Pharmacokinetics on Serum Bactericidal Activity

Study Objectives . To evaluate the pharmacodynamic antibacterial activity of ticarcillin-clavulanic acid (T-C) and ampicillin-sulbactam (A-S) combinations against reference bacterial strains in patients with end-stage renal disease maintained on long-term hemodialysis. Design . Randomized, crossover, controlled study. Setting . National Institutes of Health-funded general clinical research unit in a Veterans Administration Medical Center. Patients . Nine adult men with end-stage renal disease maintained on long-term hemodialysis. Two subjects did not complete the study due to problems of vascular access, and another withdrew for personal reasons. Interventions . On a nondialysis day, each subject was randomly administered either T-C 3.1 g or A-S 3 g as a slow intravenous infusion over 30 minutes. Serial blood samples were collected for measurement of antibiotic serum concentrations and determination of serum bactericidal titers. Following a washout period, the study was repeated with the alternative antibiotic combination. Measurements and Main Results . The mean observed apparent β-half-life of clavulanic acid was substantially shorter than that for the other three drugs. The bactericidal activity of both A-S and T-C against non-β-lactamase-producing (Nβ-LP) strains of S. aureus and E. coli was consistently high, as indicated by geometric mean SBTs of at least 1:5 at 24 hours. Against β-lactamase-producing (β-LP) S. aureus, the geometric mean SBTs for A-S were at least 1:25 throughout the study period, while the geometric mean SBTs for T-C decreased over 24 hours from 1:29 to 1:6. Against β-LP E. coli, the bactericidal activities for both A-S and T-C were poor, with geometric mean peak SBTs of only 1:6 and 1:3, respectively. The geometric mean SBT for T-C against this E. coli strain had declined to 1:1 at 6 hrs. Conclusion . Increasing the dosing interval for T-C in patients with end-stage renal disease may lead to periods of insufficient clavulanic acid to protect ticarcillin from β-lactamase degradation.     

Flip side of synaptic plasticity: Long-term depression mechanisms in the hippocampus

There is growing interest in the phenomenon of long-term depression (LTD) of synaptic efficacy that, together with long-term potentiation (LTP), is a putative information storage mechanism in mammalian brain. In neural network models, multiple learning rules have been used for LTD induction. Similarly, in neurophysiological studies of hippocampal synaptic plasticity, a variety of activity patterns have been effective at inducing LTD, although experimental paradigms are still being optimized. In this review the authors summarize the major experimental paradigms and compare what is known about the mechanisms of LTD induction. Although all paradigms appear to initiate a cascade of events leading to an elevated level of Ca²⁺ postsynaptically, the extent to which these paradigms involve common expression mechanisms has not yet been tested. The authors discuss several critical experiments that would address this latter issue. Numerous questions about the properties and mechanisms of LTD(s) in the hippocampus remain to be answered, but it is clear that LTD has finally arrived, and will soon be attracting attention equal to its flip side, LTP. © 1994 Wiley-Liss, Inc.     

Geste antagonistes in idiopathic lower cranial dystonia.

Geste antagonistes, or sensory tricks, are well described in focal dystonia affecting the neck, hand, and face. Improvement in dystonic movements is typically maintained while the trick is performed, but disappears when the geste ends. We investigated the phenomenological features of geste antagoniste maneuvers in 19 patients with idiopathic lower cranial dystonia who were prospectively evaluated over a period of 6 years. Of the 19, 10 were men, mean age of onset was 49.8 years, and the most commonly involved lower cranial area was the jaw (10 patients). In most patients, dystonia was task-specific. Taking advantage of the improvement with a sensory geste, we manufactured oral appliances that mimicked the geste in 8 patients, and 3 continue to use it.     

Incorporating abbreviated EEGs in the initial workup of patients who present to the emergency room with mental status changes of unknown etiology.

Patients frequently present to the emergency room (ER) with mental status changes without obvious cause. The EEG is underused in this population. The authors investigated whether an abbreviated EEG (AbEEG) can be incorporated in the early evaluation of these patients to provide useful information. A 5-minute AbEEG was performed using a preformed electrode placement system on 25 patients who presented to the ER with mental status changes of unknown cause. AbEEG findings were categorized as normal, showing diffuse abnormalities, focal abnormalities, electrographic seizures, or uninterpretable. Using retrospective chart review, the authors determined if the cause of mental status change was a diffuse encephalopathy or a nonneurologic event (DENNE), a focal brain abnormality, nonconvulsive status epilepticus (NCSE), psychogenic, or unknown, and if particular AbEEG findings were associated with specific causes of altered sensorium. The AbEEG identified NCSE in two patients who presented with new-onset seizures. The presence of diffuse slowing on the AbEEG was highly suggestive of mental status changes due to DENNE. AbEEGs can be successfully incorporated in the early evaluation of patients who present to the ER with mental status changes of unknown cause and provide useful information in this setting.     

Suicide among social workers: a research note.

Occupations have been a relatively neglected risk factor in the etiology of suicide. Client-oriented occupations are often thought to contribute to suicide by increasing psychological stress. The present study tests this thesis for the case of social work. Data were collected from 21 reporting states in the year of 1990. Controls are introduced for possible covariates of social work including gender, race, region, age, and marital status. The results of a preliminary logistic regression analysis found that being a social worker increased the odds of death by suicide by 55.6%, compared to the rest of the working age population. However, when controls for other occupations were incorporated into the analysis, social workers were no longer at elevated odds of death by suicide relative to other professional-managerial occupations. The psychological resources and training of social workers may act as buffers against occupational stress. Being Caucasian, male, younger, and being non-married all increased the odds of death by suicide.     

A family decision to discontinue dialysis treatment for a parent: an advanced practice nurse (APN) guided process.

Nephrology APNs play a major role in every aspect of caring for dialysis patients and often assume a leadership role with respect to patient and/or family concerns. It is always difficult to witness individuals and families struggle with making end-of-life decisions for a loved one. The middle-range theory of caregiver stress offers a way to utilize the RAM in the context of family caregiver experiences with a chronically ill relative. Additionally, there are a number of tools, such as the RPA/ASN guidelines, available for the APN working in nephrology. These guidelines provide a structured, systematic pathway for creating a plan of action. In the case of A.G., the intended outcomes were achieved largely due to the leadership role of the CNS in ensuring that there was a coordinated, dedicated, and comprehensive renal team approach. There were open lines of communication evident between all disciplines and the family throughout A.G.'s illness. His family received the full benefit of all available resources, and was able to make an informed decision with regard to the care of their father. Support was provided for the patient and his family at the end of life, culminating in a good death.