Protracted phencyclidine coma from an intestinal deposit.

Phencyclidine is a common drug of abuse that can be taken orally, intravenously, or by inhalation. We describe a massive overdose of phencyclidine in a patient who swallowed a plastic bag containing the drug. Quantitative serum phencyclidine levels remained persistently elevated for several weeks. On hospital day 20, a plastic bag was passed via the rectum. Subsequently, the patient's serum phencyclidine levels fell in accordance with previously described pharmacokinetics. The patient rapidly recovered neurologic function. Persistently elevated serum drug levels should suggest continued drug absorption from a gastrointestinal deposit. We propose that colonoscopy and esophagogastroduodenoscopy be performed early in this setting.

Clinical and metabolic features of thyrotoxic periodic paralysis in 24 episodes.

BACKGROUND: Hypokalemia is a well-known, consistent finding in thyrotoxic periodic paralysis (TPP). It is less well known that hypophosphatemia and mild hypomagnesemia are often present in TPP and that rebound hyperkalemia can occur as a result of potassium therapy. OBJECTIVE: To report the prevalence of these electrolyte abnormalities in 24 episodes of TPP in 19 patients admitted to a single university-affiliated public hospital during a 15-year period. METHODS: The medical records of all patients admitted to the Santa Clara Valley Medical Center in San Jose, Calif, between August 1, 1982, and June 1, 1997, with any type of hypokalemic periodic paralysis were reviewed. In patients with TPP, serum potassium, phosphorus, and magnesium levels were evaluated during and after episodes of paralysis. The administered dose of potassium chloride, recovery time from hypokalemia, and prevalence of rebound hyperkalemia after recovery were also ascertained. Data are presented as mean +/- SD. RESULTS: Hypokalemia was present in all 24 initial episodes of TPP, with serum potassium levels ranging from 1.1 to 3.4 mmol/L (mean, 1.9+/-0.5 mmol/L). After recovery from hypokalemia, the maximum serum potassium level significantly increased, ranging from 4.0 to 6.6 mmol/L (mean, 4.9+/-0.5 mmol/L; P<.001). In 10 (42%) of 24 episodes, rebound hyperkalemia (serum potassium level >5.0 mmol/L) was present. Recovery time did not correlate with the potassium chloride dose administered (r = 0.17). Initial serum phosphorus levels ranged from 0.36 to 0.97 mmol/L (mean, 0.61+/-0.23 mmol/L) (1.1-3.0 mg/dL [mean, 1.9+/-0.7 mg/dL]), with hypophosphatemia present in 12 (80%) of 15 episodes. Serum phosphorus levels significantly increased (P<.01), to 1.26 to 1.74 mmol/L (mean, 1.48+/-0.16 mmol/L) (3.9-5.4 mg/dL [mean, 4.6+/-0.5 mg/dL]), with or without phosphorus replacement therapy. A slight increase in serum magnesium levels after paralysis resolved was observed in all patients (P<.07). No further episodes of paralysis occurred in any patients after they became euthyroid. CONCLUSIONS: Hypokalemia, hypophosphatemia, and mild hypomagnesemia are characteristic features of TPP. Hypokalemia occurred in 100% and hypophosphatemia in 80% of the episodes in our study. Rebound hyperkalemia is a potential hazard of potassium administration and occurred in 42% of 24 episodes.

The nature of androgen action on male sexuality: a combined laboratory-self-report study on hypogonadal men.

Sexual function and the effects thereon of testosterone enanthate were studied in six hypogonadal men with the objective of delineating the specific components of male sexuality affected by androgen. To obtain a detailed picture of these components, prospective self-report data (from daily logs) of sexual activity and feelings, recordings of all night penile tumescence, and laboratory psychophysiological data were assessed. Double blind placebo experiments with cross-over design were used to compare the effects of placebo and 200- and 400-mg doses of testosterone enanthate. Erectile responses to erotic film and fantasy were not lower in the hypogonadal patients than in normal men and, in fact, were higher on some parameters, especially prolongation of detumescence time after exposure to film or fantasy. Three subjects who kept consistent daily logs had increased frequencies of sexual acts and feelings, orgasms, and spontaneous erections after testosterone administration. Nocturnal penile tumescence and spontaneous daytime erections were reduced in untreated hypogonadal men and were significantly increased after testosterone treatment, but the laboratory-tested erectile responses to film and fantasy were not affected by testosterone. These data and previous findings lead to the conclusion that the major androgen action on male sexuality involves libido factors (i.e. sexual motivation/interest). Though stimulus-bound erections elicited in the laboratory were not reduced in hypogonadal men, spontaneous (sleep or waking) erections were clearly testosterone dependent.

Hormonal changes and sexual function in aging men.

A cross-sectional study on 220 men, aged 41-93 yr, was conducted to determine whether age-related changes in circulating pituitary and gonadal hormone levels are related to quantitatively assessed changes in sexuality over this age span. The conclusion of most previous studies, that total and free plasma testosterone (T) levels decline with advancing age as gonadotropins increase, was corroborated. These changes were found to roughly parallel a decline in sexual function affecting the level of sexual activity, libido, and potency measures. PRL and estradiol did not change with age, and the age-related decline in free T was greater than that in total T. Decreases in free T and increases in LH manifested significant, but small, correlations with sexual hypofunction. Behavioral variables were also clearly related to LH and to the ratio of free T to LH and estradiol. The data also suggested that aging and hormonal changes were more strongly related to sexual activity and nocturnal erections that to libido (enjoyment, drive, and thoughts). Partial correlation procedures demonstrated that diseases and drugs were not responsible for the hormone-behavior relationships. Declining androgen levels, reduced sexual activity, and decreased sexual interest thus appear to be related sequelae of the aging process in men. Hormonal factors do not completely account for age-related changes in sexuality, although the full explanation of these changes must include a consideration of hormonal factors.

Do automated calls with nurse follow-up improve self-care and glycemic control among vulnerable patients with diabetes?

PURPOSE: We sought to evaluate the effect of automated telephone assessment and self-care education calls with nurse follow-up on the management of diabetes. SUBJECTS AND METHODS: We enrolled 280 English- or Spanish-speaking adults with diabetes who were using hypoglycemic medications and who were treated in a county health care system. Patients were randomly assigned to usual care or to receive an intervention that consisted of usual care plus bi-weekly automated assessment and self-care education calls with telephone follow-up by a nurse educator. Outcomes measured at 12 months included survey-reported self-care, perceived glycemic control, and symptoms, as well as glycosylated hemoglobin (Hb A1c) and serum glucose levels. RESULTS: We collected follow-up data for 89% of enrollees (248 patients). Compared with usual care patients, intervention patients reported more frequent glucose monitoring, foot inspection, and weight monitoring, and fewer problems with medication adherence (all P -0.03). Follow-up Hb A,, levels were 0.3% lower in the intervention group (P = 0.1), and about twice as many intervention patients had Hb A1c levels within the normal range (P = 0.04). Serum glucose levels were 41 mg/dL lower among intervention patients than usual care patients (P = 0.002). Intervention patients also reported better glycemic control (P = 0.005) and fewer diabetic symptoms (P <0.0001 ), including fewer symptoms of hyperglycemia and hypoglycemia. CONCLUSIONS: Automated calls with telephone nurse follow-up may be an effective strategy for improving self-care behavior and glycemic control, and for decreasing symptoms among vulnerable patients with diabetes.

The epidemiology of thyroid disease and implications for screening.

The burden of thyroid disease in the general population is enormous. As many as 50% of people in the community have microscopic nodules, 3.5% have occult papillary carcinoma, 15% have palpable goiters, 10% demonstrate an abnormal thyroid-stimulating hormone level, and 5% of women have overt hypothyroidism or hyperthyroidism. Despite this high prevalence of thyroid disease, screening for these disorders is not recommended by any major health agency. This article explores the epidemiologic issues surrounding this complex problem by analyzing prevalence, incidence, and mortality data from a worldwide variety of sources.

Cushing's syndrome: a review of diagnostic tests.

This review presents an analysis and interpretation of the published experimental data that form the basis for laboratory tests commonly used for screening, definitive diagnosis, and differential diagnosis in Cushing's syndrome. The single-dose overnight dexamethasone suppression test is excellent for screening outpatients since this test has a very low incidence of false-negative results (1.9% of 154 patients with Cushing's syndrome). The definitive diagnosis of Cushing's syndrome is best established by combining basal state measurements of the daily urine-free cortisol excretion and late evening plasma cortisol levels with the 2-mg low-dose dexamethasone suppression test. The etiology of Cushing's syndrome is best determined by combining measurements of basal state plasma adrenocorticotropin (ACTH) levels with the 8-mg high-dose dexamethasone suppression test. Under certain conditions, the basal state daily urine excretion of 17-hydroxycorticosteroids and 17-ketogenic steroids, the insulin tolerance test, and the metyrapone test may be useful in the definitive or differential diagnosis of Cushing's syndrome.

Emotional bondedness, subjective well-being, and health in elderly medical patients.

The relationship between social interaction, as measured by a new Emotional Bondedness Scale, health, and subjective well-being were examined in 205 ambulatory medical patients aged 65 to 98 (M = 71.2 years). Health was measured by a Self-Rated Health Scale, a Physician-Rated Health Scale, the Sickness Impact Profile, and the Zung Self-Rating Depression Scale. Subjective well-being was measured by the Life Satisfaction Index--A and the Affect Balance Scale. A significant correlation was found between emotional bondedness, health, and subjective well-being. Multiple regression analyses revealed that emotional bondedness is a significant predictor of subjective well-being and self-rated health. The variables age, marital status, type of residence, and income were not significantly correlated with either measure of subjective well-being. This study suggests that emotional bondedness has a direct impact on and is closely associated with health and subjective well-being in elderly medical patients.

Screening for thyroid disease.

PURPOSE: To evaluate the usefulness of screening for thyroid dysfunction in various clinical settings. DESIGN: Review and synthesis of the literature. MAIN RESULTS: Screening in the community detects new overt thyrotoxicosis or hypothyroidism in approximately 0.5% of the general population. The yield is best among women over 40 years of age (1%) and is lowest among young men (0%). Case-finding (testing clinic patients who are seeing a physician for unrelated reasons) has a better yield and is less expensive than screening in the community. Patients hospitalized with acute illnesses do not benefit from routine thyroid function testing. However, patients who are admitted to specialized geriatric units because of general disability, failure to thrive, and other indications may benefit. In various studies, from 2% to 5% of patients admitted to geriatric units have treatable thyroid disease. The serum total thyroxine, free thyroxine index, free thyroxine, and sensitive thyrotropin assay are all effective as initial tests for screening. The sensitive thyrotropin assay is less cost-effective than the other choices. RECOMMENDATIONS: Case-finding in some women over 40 years of age can be useful. Patients admitted to specialized geriatric units may also benefit from routine testing. Thyroid function tests are not indicated for community screening programs or for patients hospitalized with acute medical or psychiatric illnesses.

Optimal therapy for the geriatric patient: the challenge to clinical pharmacology.

The elderly are an increasing proportion of the population. Their median life span should rise to 85 years, although in later life organs of drug distribution and elimination may deteriorate in function and 100 years will remain the general maximum. Progressive containment of chronic diseases will still leave them at lethal risk from acute infectious diseases because of depleted homeostatic reserves of vital systems (cardiovascular, hepatic, immunological and renal). A decline in chronic disease should lengthen the period of well-being and reduce medical needs and perhaps drug needs of older persons. To estimate further therapeutic requirements of the elderly, information is needed on the epidemiology of drug use and rates of efficacy and toxicity in the elderly. Implicit in the data gathering is a true need for systematic post-marketing surveillance (PMS) of drugs with particular respect to drug efficacy and unanticipated adverse or beneficial reactions in this age group. Observational, non-experimental techniques can be devised and should be tested as appropriate methods of establishing the rates of anticipated efficacy and unwanted effects of drugs. The application of such techniques may be one of the only feasible ways to establish utility functions for drugs used in the elderly.

The Cushing syndrome: an update on diagnostic tests.

STUDY OBJECTIVE: Review and evaluation of diagnostic tests for the Cushing syndrome based on reports published since 1978. DATA IDENTIFICATION: Studies published in the English literature from 1978 through 1989 were identified using Index Medicus and cross searching of bibliographies. STUDY SELECTION AND DATA EXTRACTION: Studies of five or more patients for general analysis and smaller studies and case reports when pertinent. To develop criteria for the corticotropin-release hormone (CRH) stimulation test, only studies reporting individual patient data were analyzed. RESULTS: No new test is clearly better than existing tests in establishing a definitive diagnosis. Among tests to determine cause, the CRH stimulation test, by newly developed criteria, has a 91% sensitivity (95% CI, 85% to 95%) and a 95% specificity (CI, 82% to 99%), and the overnight high-dose dexamethasone suppression test has an 89% sensitivity (CI, 80% to 94%) and a 100% specificity (CI, 84% to 100%) for the pituitary Cushing syndrome. Magnetic resonance imaging has greater sensitivity for detecting adrenocorticotropin (ACTH)-producing pituitary adenomas than computed tomography. Inferior petrosal sinus sampling can correctly identify a pituitary cause in 88% (CI, 79% to 94%) of cases. CONCLUSIONS: Diagnosis is still best established by using 24-hour urine free cortisol measurements or low-dose dexamethasone suppression testing. The CRH stimulation test is an outpatient alternative to determine cause, and the over-night high-dose dexamethasone test may become the test of choice along with plasma ACTH measurements by radioimmunoassay in the initial evaluation of cause. Magnetic resonance imaging should be used to evaluate the pituitary Cushing syndrome, and inferior petrosal sinus sampling is most useful in problematic cases with uncertain cause.

Monitoring therapy in patients taking levothyroxine.

PURPOSE: To evaluate the use of thyroid function tests to monitor therapy in patients taking levothyroxine. DATA IDENTIFICATION: Studies published between 1966 and January 1990 were identified through computer searches and references of identified studies. STUDY SELECTION: Studies that included a careful description of the patients under study, well-defined interventions, and a meaningful criterion standard were emphasized. DATA EXTRACTION: Data from different studies were combined to estimate the probability of positive and negative test results in well-defined clinical situations. Informal methods of synthesizing evidence were used when combining data from different studies was not justified. RESULTS: The sensitive thyrotropin (TSH) test is the preferred method to monitor therapy because it agrees with physiologic measures of thyroid hormone effect. Among clinically euthyroid patients who take 100 to 150 micrograms/d of levothyroxine, the probability that the sensitive thyrotropin will be undetectable is close to 50%. These patients are most likely to benefit from testing. Patients who take over 250 micrograms/d are almost certain to have undetectable sensitive thyrotropin levels; in these patients, the dose may be lowered without testing. CONCLUSIONS: Adequate long-term studies are needed to determine the role of biochemical testing in monitoring therapy. Current evidence suggests that the sensitive thyrotropin test should be used to monitor therapy. Clinically euthyroid patients taking lower dosages of levothyroxine are most likely to benefit from testing.

Effects of a geriatric clinic on functional health and well-being of elders.

Using a prospective, randomized design, the effects on self-reported functional health and well being of 18 months of primary outpatient care in a geriatric clinic staffed by a multidisciplinary team with geriatric training were compared with traditional Veterans Administration care for 205 elders. Significantly less decline in functional health was found for the geriatric clinic participants on the total Sickness Impact Profile (SIP) (M = .18 vs. 3.12, p = .029) and its physical dimension (M = .28 vs. 4.39, p = .011), but not for the psychosocial dimension of the SIP, life satisfaction, depression, self-rated health, or affect balance. In addition, twice as many geriatrics clinic patients died (p = .10) during the study. Further clarification of the impact of a multidisciplinary geriatrics clinic on health outcomes and cost in VA and other settings are needed prior to recommending that this model of geriatric health care be adopted.

Regulation of plasma membrane protein phosphorylation in two mammalian cell types.

The appreciation of protein phosphorylation as a ubiquitous mechanism for the post-translational control of protein function has drawn our attention to the phosphorylation of plasma membrane proteins. We have studied this phenomenon in the human erythrocyte and rat adipocyte, and have observed several features, common to the two systems, which may be of general significance. In examining protein phosphorylation in intact cells incubated with 32Pi, it is evident that the 32P-polypeptides of the plasma membrane are among the most highly labelled species in the cell, despite their minor contribution to overall protein content. The addition of epinephrine (to adipocytes) or cAMP (to erythrocytes) increases the phosphorylation of certain peptides, whereas others are unaffected. The protein kinases mediating these phosphorylations are present in the plasma membrane as isolated, and can be divided into two groups--cAMP dependent and cAMP independent. These two classes of kinase differ markedly in their substrate specificity toward endogenous and exogenous polypeptide substrates. Two classes of protein kinases with similar properties can be detected in the cytoplasm. The relationship between the membrane-bound and cytoplasmic enzymes is uncertain. The potential roles of the plasma membrane cAMP dependent protein kinases are evident from the diverse effects of cAMP on surface properties; however, the prevalence of plasma membrane proteins phosphorylated via cAMP independent pathways is striking. Thus, elucidation of the regulatory properties of the plasma membrane cAMP independent protein kinases may give new insight into the control of a variety of surface phenomena not mediated by cAMP.

Insulin and the phosphorylation of intracellular proteins.

Protein phosphorylation is a ubiquitous form of posttranslational protein modification in mammalian cells which often serves to regulate protein function. Insulin alters the activity of a number of enzymes known to be regulated via phosphorylation. With the premise that altered protein phosphorylation might be an obligatory intermediate step in insulin action, we have examined the effects of insulin on the phosphorylation of the major phosphopeptides in adipocytes and hepatocytes. Insulin affects overall protein phosphorylation in two ways: 1) Insulin selectively stimulates the phosphorylation of a major peptide in adipose tissue (MW 123,000) and liver (MW 46,000) through a mechanism independent of cAMP and the cAMP-dependent protein kinase. Net dephosphorylation is not observed with insulin as the sole hormone. 2) Insulin antagonizes cAMP-directed protein phosphorylation. The mechanism of insulin-stimulated phosphorylation and the possible role of this phenomenon in overall insulin action is discussed.