Intraoperative retinal light damage reflected in electrophysiologic data

In a series of 30 unilaterally pseudophakic patients, electroretinograms and electrooculograms were recorded 6 months postoperatively. The unoperated on fellow eyes served as controls High intraoperative retinal light exposure (3.4–7.3 mW/cm², Zeiss OPMI 6 operating microscope) caused a substantial reduction of electrophysiologic potentials. Light protection prevented deterioration of electroretinogram and electro-oculogram potentials; reducing the bulb voltage, tilting the axis of illumination, filtering short wavelengths and the use of light shields resulted in 4-log-unit lower intensities (0.8–3.7 W/cm²).Abbreviations ACL anterior chamber lens - ECCE extracapsular cataract extraction - ICCE intracapsular cataract extraction - PCL posterior chamber lens     

Depression by neuropeptide Y of noradrenergic inhibitory postsynaptic potentials of locus coeruleus neurones

Summary Intracellular recordings were performed in a pontine slice preparation of the rat brain containing the locus coeruleus (LC). The spontaneous firing of action potentials was prevented by passing continuous hyperpolarizing current via the recording electrode. Focal electrical stimulation evoked a synaptic depolarization (PSP) followed by a hyperpolarization (IPSP). Neuropeptide Y (NPY; 0.1 mol/l) inhibited the IPSP only. Pressure ejection of noradrenaline produced hyperpolarization which was potentiated in the presence of NPY (0.1 mol/l). Hence, NPY appears to inhibit the release of noradrenaline from dendrites or recurrent axon collaterals of LC neurones. Correspondence to: P. Illes at the above address     

G protein-mediated receptor-receptor interaction: studies with chemotactic receptors in membranes of human leukemia (HL 60) cells

Summary Differentiated human leukemia (HL 60) cells contain high numbers of receptors for the chemotactic factors, N-formylmethionyl-leucyl-phenylalanine (fMet-Leu-Phe) and complement component 5a (C5a), both coupled to pertussis toxin-sensitive guanine nucleotide-binding regulatory proteins (G proteins). Agonist activation of either receptor stimulated binding of the GTP analog, guanosine 5-[-thio]triphosphate (GTP[S]), to membrane G proteins and by a similar extent in a non-additive manner. The possible interaction of the two receptors was studied by measuring agonist binding to one receptor in the presence of the other receptor agonist. fMet-Leu-Phe and C5a had no effects on [¹²⁵I]C5a and fMet-Leu-[³H]Phe receptor binding, respectively, when studied in the absence of regulatory ligands. Similarly, the inhibitory effects of NaCl and GDP on agonist receptor binding were not altered in the presence of the other receptor agonist. In contrast, in the presence of the GTP analogs, GTP[S] and guanosine 5-[,-imino] triphosphate, fMet-Leu-Phe and C5a reduced the binding of [¹²⁵I]C5a and fMet-Leu-[³H]Phe, respectively, in a concentration-dependent manner. The potencies of the GTP analogs to inhibit binding of [¹²⁵I]C5a and fMet-Leu-[³H]Phe was increased about 3-fold by fMet-Leu-Phe and C5a, respectively. The data presented suggest that fMet-Leu-Phe and C5a receptors share the same G protein pool in membranes of HL 60 cells and that activation of these G proteins by one of the two receptors decreases the availability of G proteins for the other receptor. Correspondence to T. Wieland at the above address     

Phase I evaluation of 773U82-HCl in a two-hour infusion repeated daily for three days

One of a novel series of compounds (AMAPS or arylmethylaminopropanediols), 773U82-HCl has shown significant antitumor activity inin vitro and inin vivo tumor systems, but has less animal CNS toxicity than the lead compound in the same series (crisnatol). This study was designed to evaluate the pharmacokinetics, qualitative and quantitative toxicities of 773U82-HCl and to determine the recommended phase II dose (MTD) of 773U82-HCl given as a short infusion daily for 3 days every 3 weeks. Twenty-nine patients with refractory malignancies received 79 courses over 9 dose levels during this study. Doses ranged from 50 to 1060 mg/m²d×3 days. Due to the possibility of local hemolysis with concentrations > 1.5 mg/ml, drug was administered in solutions containing 1.5 mg/ml. Because large volumes were needed at the higher dose levels, the infusion duration was increased from 2 hours to 4 hours. Mild to moderate nausea, vomiting, fatigue, dizziness and headaches were observed. Myelosuppression was the dose limiting toxicity. The recommended phase II dose and schedule was determined to be 800 mg/m²d×3d every 3 weeks. 773U82-HCl plasma concentration-time data were analyzed using a two-compartment pharmacokinetic model. The t1/2 averaged 6 hours and the total body clearance was 75.9 L/hr/m². The volume of distribution (Vdss) was large, averaging 470 L/m².Abbreviations ECG electrocardiogram - t^1/2 half-life - Vdss volume of distribution - HPLC highperformance liquid chromatography - Vd_ss steady-state volume of distribution - AUC area under the concentration × time curve - CL total body clearance - C_max peak plasma level - V_c central volume of distribution     

Subject Index to Volume 9 (1992)

Subject Index

Subject Index to Volume 9 (1992)     

Kinetic analysis of chloride conductance in frog skeletal muscle at pH 5

At pH 5 the steady-state chloride chord conductance in frog skeletal muscle rises to an asymptotic maximum at very negative voltages and approaches an asymptotic minimum at positive voltages. When a two-pulse test paradigm is used, the conductance computed from steady-state currents during the first (conditioning) voltage step are not duplicated by the conductance at the onset of a second (test) step. If the test step is to a more negative voltage than the conditioning step the steady-state conductance is overestimated; if it is to a less negative voltage the conductance is underestimated. In some fibres the initial currents accompanying steps from the resting potential are inwardly rectified. From this it was inferred that chloride channel conductance is voltage dependent: in those fibres in which no such initial inward rectification was observed it was inferred that at rest the voltage-dependent chloride channels are all closed. Time-dependent (gated) changes of conductance could be reasonably described by a first-order process, but the relaxations were not simple exponentials. Simulation of the experimental set-up predicted the type of deviation from exponentiality seen experimentally, although the observed deviations were often more pronounced than those predicted.     

Psychiatry Resident and Medical Student Perspectives on ECT: Influence of Exposure and Education

We surveyed medical students doing the required psychiatry clerkship at our hospital and first-year psychiatry residents in our residency training program for their attitudes, knowledge, and opinions about electroconvulsive therapy (ECT) before and after their inpatient rotations. The students' knowledge was lower and their attitudes more negative toward ECT than those of residents at baseline. Upon completion of the rotation, students and residents had more knowledge and highly positive attitudes about ECT and stated that they would undergo ECT if it were recommended. Willingness to undergo ECT if it were recommended correlated with the knowledge measures of ECT.     

Contribution of thallium-201-SPECT to the grading of tumorous alterations of the brain

Single photon emission computed tomography (SPECT) with thallium-201-chloride (²⁰¹TI) was used in 22 patients to assess the grade of malignancy of brain tumors.Low- and high-grade malignant gliomas could be well differentiated by calculating the Grade Index (GI), i.e., ²⁰¹TI uptake in the tumor area relative to a contralateral brain region. Low-grade gliomas (WHO-grade I–II) usually showed a GI of <1.5. Tumors classified histologically as high-grade malignant (WHO-grade III–IV) had GI values greater than 1.42 and a mean value of 1.89.Until labelled amino-acid tracers for gamma-cameras become commercially available, thallium-201 brain-SPECT can provide an independent and complementary method to CT/MRI for the differential diagnosis of grading of brain tumors. This simple technique can help to reduce sampling errors during needle biopsies of brain tumors, particularly of high-grade lesions incorrectly graded as low-grade tumors due to inadequate biopsy material. In addition, pre- and post-therapy studies can influence the strategy of therapy itself and allow an early detection of recurrences.     

The Rationale and Results of Gastroplasty/Distal Gastric Bypass

A recent review of the results of gastroplasties done at the University of Alberta Hospital showed that there was a high incidence of late weight loss failure. Therefore a new operation, gastroplasty/distal gastric bypass, has been performed on 263 patients. This operation results in a profound (mean greatest percentage excess weight loss of 87% at approximately 2 years) and lasting weight loss (mean final percentage excess weight loss of 78%) at 4 years, range 2-7.5 years post-operatively. Only 0.9% of patients failed to maintain at least a 40% excess weight loss. The operation achieves its effect through a moderate restriction that permits patients to eat normal table food from the time of discharge and with a mild malabsorption that is not ordinarily associated with diarrhea or notable deficiencies. Certain patients required debanding of the stoma and others developed staple-line eventration. Neither of these events after long-term follow-up resulted in weight loss failure nor in other serious side-effects. It is concluded that moderate failure of the gastroplasty stoma and staple line does not necessarily result in weight loss failure, because the malabsorptive portion of the operation remains intact. Low hemoglobin occurred in 16% of cases and deficiency of serum iron in 34%; a much smaller number of patients had chronic or intermittent deficiencies of these entities. Correction was easily achieved with oral replacement. Deficiencies in albumin, calcium, phosphorus and folate were rarely seen and minimal elevation of serum AST values occurred in just over 1% of patients. Chronic deficiencies or elevations were not seen in these patients. Stomal ulcer occurred in 6% of patients and bleeding associated with stomal ulcer in 1%. Half the patients with ulcer were managed with H₂ blockers, the other half with vagotomy. Both forms of treatment when individualized effectively prevent re-ulceration.     

Evaluation of facial fat distribution using magnetic resonance imaging

Magnetic resonance imaging (MRI) provides noninvasive images of facial and neck fat for a variety of conditions. It accurately maps the soft tissues pre- and postoperatively, enabling surgeons to precisely and objectively assess results of soft tissue facial contouring and fat transplantation. The risks of MRI are few. It has the potential to provide aesthetic surgeons with a more scientific means of comparing various techniques of fat contouring.