Effects of methyldopa on renal hemodynamics and tubular function.

To determine the effects of methyldopa on renal function, clearance studies were performed on hypertensive subjects during sustained steady-state water diuresis. The data reveal an acute fall in glomerular filtration rate and sodium clearance, whereas renal blood flow was unchanged. The antinatriuresis was the result of decreased filtration of sodium and possibly enhanced proximal tubular sodium reabsorption. These changes occurred before any demonstrable fall in systemic blood pressure; thus a direct effect of the drug on arteriolar resistance within the renal circulation is suggested. Chronic administration of methyldopa for 1 wk induced sustained reduction in blood pressure and resulted in the same changes in renal hemodynamics and sodium excretion noted after acute administration. These data suggest that methyldopa, like other antihypertensives, reduces glomerular filtration rate and increases sodium retention.

Cefazolin in chronic hemodialysis patients: a safe, effective alternative to vancomycin.

Vancomycin use is common in hemodialysis patients, due in part to the ease of dosing, but can lead to the development of resistant organisms, including vancomycin-resistant enterococcus. Alternate antibiotics may be equally effective and allow similar dosing in the chronic hemodialysis population. A retrospective review of culture results from a 217-patient, non-hospital-based outpatient hemodialysis center was performed over a 7-month period. Wound and blood culture sensitivity to cefazolin, vancomycin, cefazolin plus gentamicin, and vancomycin plus gentamicin was analyzed. Cefazolin was equivalent to vancomycin for empiric treatment of clinically significant infections in a population with a low rate of methicillin-resistant Staphylococcus aureus infection. Cefazolin plus gentamicin was superior to vancomycin alone. The vancomycin plus gentamicin combination did provide minimally broader coverage than the cefazolin plus gentamicin combination. A prospective pharmacokinetic analysis of postdialysis cefazolin dosing was performed in anuric chronic hemodialysis patients dialyzed with polysulfone dialyzers. Peak, predialysis, and postdialysis cefazolin levels were obtained. Nondialysis clearance of cefazolin was sufficiently low (k(e), 0.027; t(1/2), 26.4 hours) and dialysis clearance sufficiently high (k(e), 0.254; t(1/2), 3.19 hours) to provide for safe and effective peak and trough cefazolin levels with postdialysis dosing in anuric hemodialysis patients. In conclusion, cefazolin alone or with gentamicin in an appropriate empiric antibiotic choice in chronic hemodialysis patients dialyzed in a nonhospital setting with low methicillin-resistant S. aureus infection rates. For infections with documented sensitivity to cefazolin, a 1 g intravenous dose postdialysis (750 mg in patients weighing <50 kg) is safe and effective.

High interleukin-10 serum levels are associated with fatal outcome in patients after bone marrow transplantation.

IL-10 plays an important role in the control of immune reactions during systemic infection. Here, IL-10 serum levels were investigated in patients after BMT. The IL-10 levels correlated with the clinical course of the patients and with serum levels of C-reactive protein (CRP) and neopterin (NP). A total of 26 patients with AML (7), ALL (12), CML (2), NHL (3) and multifocal Ewing's sarcoma (2) had received autologous (10) or allogeneic (16) BMT from related (9) or unrelated donors (7). Routine serum samples were obtained prior to BMT and at days 46 and 100 after BMT. However, in patients with severe complications additional samples were drawn at individual points in time. Prior to BMT, IL-10 serum levels were not detectable in 24/24 patients. Post-BMT, 11 patients developed elevated IL-10 levels, of these eight died of complications (DOC), whereas only one of 15 patients with undetectable IL-10 died of complications, indicating that high IL-10 levels were significantly correlated with severe life-threatening complications (chi2, P < 0.01). To determine the pathomechanism and role of the increased IL-10 levels, they were correlated to the respective NP and CRP serum concentrations. CRP and NP concentrations were found significantly elevated in patients with detectable IL-10, indicating a severe acute phase reaction associated with macrophage activation. In conclusion, high IL-10 serum levels in patients after BMT were significantly associated with fatal outcome. Since IL-10 is a strong suppressor of T cell immunity, high IL-10 production in patients with severe complications such as septic shock or GVHD > grade II after BMT might lead to functional immunodeficiency contributing to the poor prognosis of these patients.

Measurement of treatment response to sertraline in depressed multiple sclerosis patients using the Carroll scale.

We studied 11 patients with stable multiple sclerosis (MS) with major depression in terms of response to Sertraline at 100 mg q.d. in an open label trial. Patients were evaluated with self assessment measurements (Carroll scale) prior to and during treatment. Only one patient discontinued the drug during the three month treatment trial, and this was due to perceived lack of efficacy by the patient. The remainder of the patients completed at least three months of treatment and had significant improvement in depressive symptoms by self assessment measurements. No patients experienced side effects. Sertraline appears to be well tolerated and effective in treatment of major depression in MS. The Carroll scale is an easily administered means of assessing treatment response, and correlated highly with our clinical impressions.

A schizophrenic patient with an arrhythmic circadian rest-activity cycle.

A haloperidol-treated patient with chronic schizophrenia had a near-arrhythmic circadian rest-activity cycle, whereas rhythms of 6-sulphatoxy-melatonin and core body temperature were of normal amplitude and phase-advanced. Sleep electroencephalography measured throughout a 31-h 'constant-bedrest' protocol revealed a phase-delayed sleep-wake propensity cycle, low sleep continuity (ultradian 'bouts'), and very little slow-wave sleep and slow-wave activity (0.75-4.5 Hz). Switching treatment to the atypical neuroleptic clozapine improved both the circadian organization of the rest-activity cycle and the patient's clinical state. This observation can be conceptualized in terms of the two-process model of sleep regulation. High-dose haloperidol treatment may have lowered the circadian alertness threshold, whereas clozapine augmented circadian amplitude (perhaps through its high affinity to dopamine D4 and serotonin 5HT7 receptors in the suprachiasmatic nuclei). Measurement of the circadian rest-activity cycle may be a useful non-invasive method to follow functional consequences of neuroleptic treatment.

Stability and change in functional assessment of patients with geropsychiatric disorders.

OBJECTIVES: Functional assessments of patients with geropsychiatric disorders accomplished by self-rating, informant rating, and performance test were compared. METHOD: Fifty-eight inpatients with major depression or progressive dementia were evaluated on three occasions over 6 months with informant and patient versions of the Activities of Daily Living Scale of the Older Americans Resources and Services Multidimensional Functional Assessment (OARS-ADL) and with the Performance Assessment of Self-Care Skills (PASS). RESULTS: Patients' scores became significantly worse (p < .01) on the informant version of the OARS-ADL and the PASS. Self-ratings with the OARS-ADL did not worsen significantly (p > .05). CONCLUSION: Agreement between informant rating and performance test concerning functional status of patients with dementia was good. Elderly patients with depression may experience subtle deterioration that only becomes apparent on performance tests.

Pseudodementia: a slow death.

The clinical term "pseudodementia" has remained a permanent nosological entity in the literature for over 100 years. Indeed, recognition of the fact that clinical symptoms associated with reversible neuropsychiatric conditions can mimic irreversible disorders was known as early as the middle of the 19th century. The importance of the term lies in the inherent assumption that the presenting dementia is not real, or is at least reversible, and therefore treatable. Nonetheless, there continues to be controversy regarding the validity and appropriate clinical use of the term. This article reviews the evolution and clinical utility of the term pseudodementia and attempts to redirect investigative efforts toward an understanding of the neuroanatomical substrates that underlie depression and cognitive impairment in the elderly. Based on a critical analysis of the relevant literatures, a subcortical-frontal neuroanatomical substrate of late-life depression is supported. Further, the presence of leukoaraiosis, as measured by magnetic resonance imaging, is proposed as a potential neurobiological marker that contributes to the depressed mood, cognitive impairment, and later cognitive deterioration of some elderly depressed.

[A 10-year follow-up of cases with anorexia first hospitalized in the Canton of Zürich]. / 10-Jahres-Katamnese der 1973-1975 im Kanton Zürich erstmals hospitalisierten Anorexie-Fälle.

Out of all 38 anorexia nervosa patients hospitalized for the first time in a private or state hospital for pediatrics, internal medicine or psychiatry in the Canton of Zurich during the period 1973-1975, 28 cases could be assessed 10 years later using a semistructured interview. Catamnestic data were categorized according to Morgan and Russel (1975) in a general outcome score and an average outcome score. Regarding somatic and psychosocial dimensions, 11% of the patients examined can be considered symptom-free, 71% improved and 14% unchanged. One patient (4%) had died from the sequelae of anorexia. 64% increased in weight, nevertheless more than half of the patients had disturbed eating behavior at the time of this catamnestic study. An equally frequent finding was considerable impairment of psychologic well-being chiefly reflected in anxiety and depression. The time necessary to attain the normal weight range had varied between a few months and 11 years. Of 8 variables often claimed to be prognostic in the literature on the course of anorexia nervosa, only a short duration of illness before hospitalization was shown to be relevant. The patients with good or medium outcome most often consider psychotherapy or a partner relationship a decisive factor in the favorable course of their eating problem.

Measuring depressive symptomatology of patients referred to a behavioral medicine clinic: Concordance of self-report measures.

We measured depressive symptomatology of 134 outpatient veterans treated within a Behavioral Medicine Clinic utilizing three reliable instruments with depression subscales: Minnesota Multiphasic Personality Inventory (MMPI), Derogatis Stress Profile (DSP), and Symptom Checklist 90-Revised (SCL-90-R). Results indicate that although the instruments correlate significantly, they differ in sensitivity to depression and are clinically discordant. The MMPI classified a substantially higher number of patients as depressed than either the DSP or SCL-90-R. The present study argues that the discrepancy in clinical concordance and sensitivity of the three depression scales has considerable implications for psychologists concerned with the assessment and treatment of depression.

Activation of protein kinase C induces de novo synthesis of the soluble interleukin-6 receptor in human B cells.

The mechanism of protein kinase C (PKC) induced release of the soluble interleukin-6 receptor (sIL-6R) from human B cells was investigated. Phorbol myristat acetat (PMA)-induced activation of PKC significantly enhanced the release of sIL-6R from the human B-cell line SKW 6.4. The PMA effect was completely blocked by cycloheximide, whereas different inhibitors of proteases had no effect. In contrast to the effect on sIL-6R release, FACS analysis did not reveal any effect of PMA on the expression of IL-6R on the surface of SKW 6.4 cells. After 6 h of stimulation with PMA, analysis of mRNA expression using a polymerase chain reaction-(PCR)-assisted mRNA amplification assay, showed increased expression of a spliced mRNA encoding for a soluble form of IL-6R. Comparable to the results in SKW 6.4 cells, activation of purified human B cells with PMA induced a significant augmentation of sIL-6R release which was also sensitive to cycloheximide. In conclusion, a novel mechanism of sIL-6R release is reported involving de novo synthesis. Thus, sIL-6R release from human B cells is completely different compared with that described in hepatocytes, which involved rapid, proteolytic cleavage of the membrane-bound receptor but not de novo synthesis. The results of this study may help to understand the molecular control of sIL-6R release from human B cells.

Interferometric fabrication of modulated submicrometer gratings in photoresist.

Interferometric recording is applied to the fabrication of modulated submicrometer gratings in photoresist.High diffraction efficiency requires optimized recording conditions, which are obtained by the use of an on-axis continuous surface-relief grating for the generation of the object beam. The optimized phase function is copied into the resist layer by means of a self-aligned two-step recording process with an intermediate copy in a volume photopolymer hologram. As a result, we demonstrate high carrier frequency surface-relief off-axis fan-out gratings for illumination in transmission with visible light.

Differing effects of acid versus neutral phosphate therapy of hypercalciuria.

Studies were performed on 12 patients with idiopathic hypercalciuria to evaluate the hypothesis that the acid load accompanying potassium acid phosphate would adversely affect renal calcium reabsorption and citrate excretion compared to the neutral form of the phosphate salt. During acute clearance studies, neutral phosphate (NP) led to a fall in FECa (2.2 +/- 0.6% to 0.8 +/- 0.1%, P less than 0.02) and no change in titratable acidity (TA) or net acid excretion (NAE). Acid phosphate (AP) did not reduce FECa acutely, and led to a rise in TA (22 +/- 4 to 62 +/- 6 muEq/min, P less than 0.02) and NAE (46 +/- 6 to 6 89 +/- 7 muEq/min, P less than 0.02). During chronic administration, AP resulted in higher urinary calcium excretion in both absorptive (187 +/- 29 vs. 141 +/- 18 mg/day, P less than 0.02) and renal hypercalciuric patients (233 +/- 24 vs. 173 +/- 190.02 mg/day, P less than 0.02). Also, TA and NAE were higher following AP, whereas citrate excretion was lower (375.4 +/- 64.6 vs. 633.4 +/- 28.8 mg/day, P less than 0.01). These data suggest that the reported ineffectiveness of AP in the therapy of nephrolithiasis may be related to the deleterious effects of the acid load on calcium and citrate metabolism.

Assessment of treatment outcomes in neuropsychiatry: a report from the Committee on Research of the American Neuropsychiatric Association.

The ANPA Committee on Research conducted a survey of its members and those of the British Neuropsychiatry Association to determine the extent to which neuropsychiatrists employ formal measures of clinical outcome. Results revealed that although respondents endorsed the practice of outcome assessment, formal diagnostic evaluations and outcome measures were rarely applied consistently to the broad range of neuropsychiatric conditions encountered clinically. These findings have implications for clinical research and managed care in neuropsychiatry and will form the basis for future work by the Committee on Research.