Protein C survival during replacement therapy in homozygous protein C deficiency. Homozygous protein C (PC) deficiency is a rare genetic defect that usually results in fatal thrombotic complications (purpura fulminans and DIC), but it can be successfully managed with oral anticoagulants or PC replacement. The successful use of PC replacement for two individuals is described. The activity and antigen levels of PC in fresh frozen plasma (FFP) and prothrombin complex concentrate (PCC) are also reported. The concentration of PC in FFP is 87 +/- 15 units/dl. PC is present in all PCC analyzed; however, a ten-fold difference between the various brands and/or lots is noted. The PC activity and antigen correlates well with no significant levels of APC. Upon infusion of FFP into two homozygous PC-deficient children, the PC levels obtained were less than or equal to 30 units/dl post-infusion and undetectable after 12-18 hr. With infusions of PCC, plasma levels of PC obtained were 100-145 units/dl and less than 10 units/dl after 48 hr. The percent recovery and half-lives of PC from FFP and PCC were 49.8% and 7.8 hr, and 84% and 7.4 hr, respectively. One infant was treated every 48 hr for 2 years without significant purpura fulminans or DIC complications. The levels of the other PC system components did not change during the infusion of the PC-rich material. Based on this information, a specific replacement protocol has been developed using a PC-rich concentrate. However, several problems may arise with the "less pure" PC-rich concentrates: catheter-tip thrombosis, related large vessel thrombosis and blood-transmitted diseases. With a specific PC concentrate, replacement therapy is a viable alternative for the long-term management/treatment of homozygous PC deficiency.


Allogeneic bone marrow transplantation for hematological malignancies following etoposide, cyclophosphamide, and fractionated total body irradiation. Forty-three patients received etoposide, cyclophosphamide, and fractionated total body irradiation before allogeneic marrow transplantation. Fifteen patients had chronic myelogenous leukemia in chronic phase or acute leukemia in first remission (standard risk) and twenty-eight patients with more advanced disease (high risk). All patients received etoposide 1,500 mg/m2 intravenously on day -8, cyclophosphamide 60 mg/kg/day intravenously on days -7 and -6, and total body irradiation at 170 cGy twice a day on days -3, -2, and -1. During the first 100 days 12 high risk patients (43%) died from causes unrelated to relapse while none of the standard risk patients died. Renal and hepatic dysfunction were also significantly increased during the first 14 days in the high risk group. The addition of 1,500 mg/m2 of etoposide to the cyclophosphamide and total body irradiation was well tolerated for patients with standard risk. However, the regimen was poorly tolerated with high mortality in patients with more advanced disease.


Recombinant interferon-alpha 2A as maintenance treatment for patients with advanced stage chronic lymphocytic leukemia responding to chemotherapy. Forty-five patients suffering from advanced B-CLL were randomized to receive interferon-alpha (IFN alpha) or no treatment after achieving complete remission or partial response, following a chemotherapy protocol called MiNa. The two groups were fully comparable in terms of clinical characteristics and level of response obtained by chemotherapy. IFN alpha was given at a dose of 3 megaunits three times a week intramuscularly for 1 year. The IFN-treated patient group showed a significantly longer duration of response and a less frequent incidence of infections as compared to the no treatment group. A minority of patients who had had partial response to chemotherapy obtained complete remission while on therapy with IFN alpha. Toxicity was mild and patient compliance was excellent. We conclude that IFN alpha may have a role as maintenance therapy in CLL for patients responding to chemotherapy.


Cyclosporine and prednisone therapy for pure red cell aplasia in patients with chronic lymphocytic leukemia. We describe the characteristics of response to treatment with cyclosporine (CYA) plus prednisone in seven episodes of pure red cell aplasia (PRCA) in four patients with B cell chronic lymphocytic leukemia (CLL). Fourteen episodes of PRCA occurred in four patients with CLL. Eleven episodes were treated with conventional therapies which included an alkylating agent and prednisone. Four episodes that failed to respond to conventional therapies and an additional three episodes were treated with CYA and prednisone. Six of the seven episodes, including three of four which had failed conventional therapies, responded to CYA plus prednisone compared with six of eleven episodes treated with conventional therapies. Response to CYA and prednisone occurred without a reduction in leukemic mass. In contrast, PRCA remission did not occur until after leukemic mass reduction in three of four patients treated successfully with conventional therapies. Time to response was shorter (14 +/- 3 days) with CYA plus prednisone than with conventional therapies (154 +/- 97 days) in three of four patients. These results indicate that CYA plus prednisone is an effective therapy for the induction of remission from PRCA in patients with CLL.


Coexistence of congenital afibrinogenemia and protein C deficiency in a patient. A rare association of congenital afibrinogenemia and hereditary protein C deficiency is described in a 37-year-old female who suffered from ischemic necrosis in the left first toe. The diagnosis of afibrinogenemia was assessed by the absence of fibrinogen in clotting and immunological assays. The diagnosis of hereditary heterozygous type I protein C deficiency was based on the evidence of proportional decreases of activity and antigen of plasma protein C in the propositus, her mother, and two maternal aunts.


Reduction in tissue iron stores with a new regimen of continuous ambulatory intravenous deferoxamine. A new regimen of 24-hr ambulatory continuous intravenous infusion of deferoxamine (CIV DFO) through central venous ports was instituted in nine patients aged (mean +/- SD) 22.4 +/- 5.8 years over a period of 15.7 +/- 7.3 months. Central venous infusion sites were changed weekly in the clinic, eliminating the necessity for reconstitution of DFO and needle insertion at home. Because CIV DFO could be interrupted only by medical personnel, patient compliance was documented accurately; patients administered 93.0% +/- 3.2% of CIV DFO prescribed. Mean urinary iron excretion on CIV DFO (66.8 +/- 50.4 mg/24 hr) was significantly greater than that quantitated during 12-hr equivalent-dose subcutaneous DFO infusions (23.4 +/- 18.3 mg/24 hr; P less than 0.025). Mean serum ferritin declined by 71% over the treatment period (P less than 0.005). This regimen confers the advantages of uninterrupted exposure to DFO, is associated with excellent patient compliance, and should be considered in any patient with severe iron overload and erratic compliance with DFO.


Clinical aspects of chronic myeloproliferative diseases. The nonleukemic chronic myeloproliferative disorders, polycythemia vera, essential thrombocytosis, and myeloid metaplasia with myelofibrosis, are clonal disorders with similar but distinct clinical and laboratory findings. This review will discuss the diagnostic criteria for each disease, the variable clinical picture, and the therapeutic modalities, actual and theoretical.


Clonality in myeloproliferative disorders. The myeloproliferative disorders are a group of hematologic diseases that are believed to arise from somatic mutations in an early hematopoietic stem cell. This statement is based on the demonstration of monoclonal involvement of terminally differentiated myeloid and lymphoid elements. The techniques for establishing clonal derivation of cells are discussed and the application of these techniques to myeloproliferative diseases is reviewed. The evidence for limited myeloid involvement, lineage heterogeneity, in some patients with myeloproliferative disorders is summarized.


Prospects for gene therapy in acute lung injury. Gene transfection is an extremely useful tool with which to explore mechanisms of gene regulation, to examine the molecular physiology of proteins in cultured cells, and to produce transgenic organisms. Several transfection techniques that employ viral and nonviral vectors have been used successfully to transfect functional genes into lung cells in vivo. This report reviews some of the gene transfection techniques that have been applied to the intact lung, an organ that offers unique challenges and opportunities. Results indicate that somatic cell gene therapy is feasible and that gene-based therapies can be developed for acute and chronic lung diseases.


Pulmonary endothelial cell pathobiology: implications for acute lung injury. Pulmonary endothelial cells form a continuous monolayer on the luminal surface of the lung vasculature. Until the mid-1970s, the pulmonary endothelium was felt to provide little more than a passive surface for the exchange of gases, water, macromolecules, and some cell traffic. Recent evidence indicates that the pulmonary endothelium is a metabolically active surface, which provides a regulatory interface for the continual processing of blood-borne vasoactive molecules, plays an active role in hemostasis and immunologic and inflammatory events, regulates vascular tone, and interacts with inflammatory cells and neighboring vascular cell types. These metabolic properties are both constitutive and capable of being induced in response to stimuli or injury. Virtually any agent that causes pulmonary endothelial cell injury will lead to impairments in the functional metabolic properties of these cells, resulting in alterations in hemodynamics, hemofluidity, permeability, gas exchange, and intercellular signaling. The net result in the lung is often the clinical picture of acute lung injury with respiratory distress, refractory hypoxemia, diffuse alveolar infiltrates, and respiratory failure.


The relationship of total lymphocyte count to CD4 lymphocyte counts in patients infected with human immunodeficiency virus. A simple, inexpensive alternative to CD4 counts would facilitate the management of asymptomatic and early symptomatic patients with HIV infection. In this report, a high correlation was found between CD4 counts and total lymphocyte counts calculated from complete blood counts in a cohort of ambulatory HIV-infected patients. Using these data, patients with CD4 counts above and below 500 cells/mm3, 200 cells/mm3, and those with and without symptoms can be identified with a high degree of predictive value. The availability and lower cost of lymphocyte counts make them an attractive alternative to CD4 counts in managing asymptomatic and early symptomatic patients with HIV infection.


Impact of hemodialysis on left and right ventricular Doppler diastolic filling indices. Hemodialysis is associated with acute reduction in intravascular volume. To assess the impact of volume reduction on left and right ventricular diastolic filling indexes obtained by Doppler echocardiography, 24 patients on chronic hemodialysis were consecutively studied before, during, and immediately after one hemodialysis session. Twenty four normal sex and age-matched volunteers served as a control group. Study patients had abnormal diastolic indexes when compared to controls. At 2 hours of dialysis (mid dialysis) there was a significant decrease in peak early mitral flow velocity (E), no change in peak atrial filling velocity (A), and a reduction in the E/A ratio. The deceleration time of the mitral E wave also was prolonged compared to baseline. Similar findings were observed with respect to right ventricular filling indices. These changes occurred during the first 2 hours of dialysis and remained unaltered at end dialysis. When patients were subdivided according to weight loss, only the group that lost 1 or more kilograms had significant changes in the Doppler parameters of the left and right ventricle, as well as reduction of the left ventricular dimensions. These findings suggest that preload reduction is the main mechanism that accounts for acute changes in Doppler diastolic indices observed during hemodialysis.


Ischemic acute renal failure.

Ischemic acute renal failure. Underperfusion of the kidneys often results in the development of ischemic acute renal failure. This review summarizes the recent developments in the understanding of the pathophysiology, diagnosis, and treatment of this serious and costly disorder that affects almost 5% of hospitalized patients.


Systematics and body size: implications for feeding adaptations in New World monkeys. The relationship between body size and feeding ecology is well established for primates. It is argued that the evolutionary history of modern New World monkeys and, in particular, the path to attainment of current body size is significant in understanding the similarities and differences between dietary strategies and other ecological parameters of similar-sized monkeys. Current interpretations of New World monkey evolutionary relationships are reviewed. Based on a synthesis of available body weights and the assumption that the earliest New World monkeys weighed close to 1 kg, similar to modern Aotus and Callicebus, predicted patterns of body size change in each lineage are given. Restrictions on directions of body size change in primates are discussed, and it is shown that "Stanley's Rule" offers a good explanation for differing body size ranges in New and Old World anthropoids. Predicted ecological correlates to body size drawn from the mammalian literature are offered and tested using data on New World monkeys, which show some concurrence and several interesting departures from predicted patterns. Sexual dimorphism in body weight of New World monkey species is reviewed, based on the new summary of body weight data given.


Vertical clinging, small body size, and the evolution of feeding adaptations in the Callitrichinae. Primates of the subfamily Callitrichinae (Callimico, Callithrix, Leontopithecus, and Saguinus) are small-bodied New World monkeys (105-700 g) possessing clawlike nails on all manual and pedal digits excluding the hallux. Specialized nails in these genera serve a critical function in feeding by enabling tamarins and marmosets to cling to trunks and other large vertical supports while exploiting food resources. Within the subfamily, there is evidence of at least four distinct large-branch feeding patterns. These include (1) seasonal exudate feeding and occasional trunk foraging (many Saguinus spp.); (2) exploitation of bark surface insects and the use of trunks as a platform to locate terrestrial prey (Saguinus fuscicollis, S. nigricollis, and Callimico); (3) manipulative foraging and bark stripping to locate concealed insects and small vertebrates (Leontopithecus); and (4) tree gouging and year-round exudate feeding (many Callithrix). Large-branch feeding and the use of vertical clinging postures appear to be a primary adaptation among virtually all callitrichines, distinguishing them ecologically from other platyrrhine taxa. Given the anatomy and behavior of extant callitrichines, Saguinus appears to be the most ecologically generalized member of this subfamily, and species of this genus may provide useful models for reconstructing the feeding and foraging adaptations of early callitrichines.


Morphological and behavioral adaptations for foraging in generalist primates: the case of the cebines. In addition to being frugivorous, Cebus and Saimiri stand out among the New World primates of similar body size in being heavily dependent on animal matter for protein (faunivory). A detailed description of the morphology and behavior of the two genera is presented with the object of evaluating the interaction and respective contributions of morphological and behavioral adaptations to foraging patterns. Our conclusions include the following: First, body size is extremely important in explaining the observed variation in diet. Second, the emphasis on faunivory is facilitated more by behavioral than by morphological specialization. Third, whatever morphological specializations are present, particularly in Cebus, are probably favored by diet at the most food-depauperate time of year. Fourth, although morphology may well reveal what a primate may potentially eat, to map this potential onto actual diet requires a detailed knowledge of its natural ecosystem. Finally, we consider whether the behavioral data support the tenuous morphological evidence for grouping Cebus and Saimiri within the clade Cebinae.


Dietary and dental adaptations in the Pitheciinae. Since Mivart (1865), Cacajao, Chiropotes, and Pithecia have been grouped into a single taxon, which he called the subfamily Pitheciinae but which I, following Rosenberger (this issue), refer to as the living members of the tribe Pitheciini. While few today doubt the association of these three living genera, not all would place them together with Aotus and Callicebus in the subfamily Pitheciinae. This is an attempt to sort out the behavioral and morphological features of feeding and dental morphology in these taxa. Extant members of the tribe Pitheciini are adapted for sclerocarpic foraging, morphological evidence for which is found in the fossils of Soriacebus and Cebupithecia. Sclerocarpic foraging in living pitheciins is a two-stage process of seed predation involving 1) specialized features of the anterior dentition that allow removal of a hard pericarp that protects a seed or seeds, followed by 2) mastication by the posterior dentition having low cusp relief to triturate nutritious seeds of a relatively soft and uniformly pliable consistency. The dentitions of fossil pitheciins, Soriacebus and Cebupithecia, demonstrate that the hypertrophy of lower incisors plus the robustness and flaring of the canine precede development of low cusp relief on molars and premolars in the evolution of morphological features associated with sclerocarpic foraging. Features of sclerocarpic foraging are found less uniformly in the other two pitheciines, Callicebus and Aotus.


Atelinae adaptations: behavioral strategies and ecological constraints. Comparisons between the four genera that make up the Atelinae reveal two distinct behavioral patterns, one in which energy expenditure is minimized (Alouatta) and one in which energy intake is maximized (Lagothrix, Ateles, and Brachyteles). Among the atelins, Lagothrix and Ateles devote over 75% of their annual feeding time to fruit, while Brachyteles devotes between 50% and 67% of their feeding time to leaves. Pronounced seasonality in the Atlantic coastal forest inhabited by Brachyteles may be responsible for its more folivorous diet. Alouatta falls in the body size range of Lagothrix and is much smaller than Ateles and Brachyteles. Nonetheless, Alouatta is more folivorous than sympatric atelins. The atelins also share a rapid, suspensory mode of locomotion that appears to enable them to minimize travel time between widely dispersed fruit sources. Alouatta, by contrast, employs a slower, but more energetically efficient, quadrupedal locomotion. Ranging patterns among the Atelinae are consistent with both diet and locomotor abilities: Atelins travel daily distances up to 5,000 m; Alouatta ranges are much shorter. Further distinctions are evident in Atelinae grouping patterns. Alouatta remains in small cohesive groups that occupy home ranges less than 60 ha in size. Both Lagothrix and Ateles have large groups that fission to reduce the costs of intragroup feeding competition when preferred fruits occur in small patches within much larger community ranges. While greater reliance on low-energy foods such as leaves may release Brachyteles from similar competitive constraints, their tendency toward fluid grouping associations is consistent with the pursuit of a frugivorous diet.


Evolution of feeding niches in New World monkeys. The adaptive radiation of modern New World monkeys unfolded as the major lineages diversified within different dietary-adaptive zones predicated upon a fundamentally frugivorous habit. The broad outlines of this pattern can be seen in the fossil record, beginning in the early Miocene. Cebids are obligate frugivorous predators. The smallest forms (Cebuella, Callithrix) are specialized exudativores, and the largest (cebines) are seasonally flexible omnivores, feeding particularly on insects (Saimiri) or "hard" foods, such as pith and palm nuts (Cebus), when resources are scarce. The smaller-bodied atelids (Callicebus, Aotus) may use insects or leaves opportunistically, but pitheciins (saki-uakaris) specialize on seeds as their major protein source. The larger atelines (Alouatta, Brachyteles) depend on leaves or on ripe fruit (Ateles). Locomotion, body size, and dietary adaptations are linked: claws and small body size opened the canopy-subcanopy niche to callitrichines; climbing and hanging, the fine-branch setting to the atelines; large size and strength, semiprehensile tails, and grasping thumbs, the extractive insectivory of Cebus; deliberate quadrupedalism, the energy-saving transport of folivorous Alouatta. Body size increases and decreases occurred often and in parallel within guilds and lineages. Conventional dietary categories, particularly frugivory, are inadequate for organizing the behavioral and anatomical evidence pertinent to evolutionary adaptation. Related models of morphological evolution based on feeding frequencies tend to obfuscate the selective importance of "critical functions," responses to the biomechanically challenging components of diet that may be determined by a numerically small, or seasonal, dietary fraction. For fossils, body size is an unreliable indicator of diet in the absence of detailed morphological information. More attention needs to be given to developing techniques for identifying and quantifying mechanically significant aspects of dental form, the physical properties of primate foods, their mode of access, and the cycles of availability and nutritional value.


Judicial and legislative responses to cost containment. Cost containment through reduction of insurance benefits and aggressive utilization review is increasingly risking the sacrifice of good clinical care in the pursuit of financial objectives. This article provides examples of judicial and legislative responses to perceived fiscal intrusions into clinical practice. Principles for asserting clinical goals in the cost containment process are also provided to assist in the inevitable negotiations and battles ahead.


Association of beta-endorphin with specific clinical symptoms of depression. Abnormalities in plasma concentrations of beta-endorphin-like immunoreactivity (beta-endorphin) have been reported in depressed patients. This study was done to test the hypothesis that specific clinical characteristics of depression are associated with plasma beta-endorphin concentration. Plasma beta-endorphin was evaluated in 20 depressed patients diagnosed according to DSM-III-R and in 23 age- and sex-matched comparison subjects, and each was evaluated with the structured Schedule for Affective Disorders and Schizophrenia (SADS). Twelve SADS items involving dysphoric mood and related symptoms were chosen for analysis. Within the group of all 43 subjects and within the depressed group, beta-endorphin level correlated significantly with psychic anxiety and with phobia. In the depressed group only, beta-endorphin also correlated significantly with obsessions/compulsions. Concentration of beta-endorphin was not significantly correlated with score on the Hamilton Rating Scale for Depression or Beck Depression Inventory or with scores on other SADS symptom items, including somatic anxiety, insomnia, subjective anger, overt anger, agitation, psychomotor retardation, panic attacks, appetite loss, or total weight loss. In the group of 23 comparison subjects, beta-endorphin did not correlate with Beck or Hamilton depression score or with any of the SADS clinical variables. High levels of plasma beta-endorphin may be associated with more severe anxiety, phobia, and obsessions/compulsions in depressed patients.


Prevalence of seasonal affective disorder in Alaska. The goals of this study are to provide estimates of the prevalence of seasonal affective disorder in Alaska, to examine sociodemographic correlates, and to evaluate the relation between seasonal affective disorder and general depression. A random sample of 283 residents of Fairbanks who had lived in Alaska for 3 years or more were interviewed with the Seasonal Pattern Assessment Questionnaire and the Center for Epidemiologic Studies Depression Scale (CES-D Scale). Twenty-six (9.2%) of the subjects met diagnostic criteria for seasonal affective disorder, one of the highest figures yet reported. These cyclic winter affective disorders occurred more often in women than men (ratio = 3:2) and were less prevalent among residents who were older than 40 years of age. Assessment of depression with the CES-D Scale supported the diagnostic classification of respondents and the differentiation of seasonal affective disorder from other depression. This study supports the conclusions that seasonal affective disorder is prevalent in northern populations and that sex and age may represent the major risk factors that differentiate it from the general experience of depression in northern communities.


Duration of psychosis and outcome in first-episode schizophrenia. This study was undertaken to assess the potential effect of duration of untreated illness on outcome in a group of first-episode schizophrenic patients. Seventy patients with schizophrenia diagnosed according to the Research Diagnostic Criteria entered the study and were followed for up to 3 years. All patients received standardized treatment and uniform assessments both during the acute phase of their illness and throughout the follow-up period. Outcome was measured in terms of time to remission of acute psychotic symptoms as well as degree of symptom remission. The mean duration of psychotic symptoms before initial treatment was 52 weeks, preceded by a substantial prepsychotic period. According to survival analysis, duration of illness before treatment was found to be significantly associated with time to remission as well as with level of remission. The effect of duration of illness on outcome remained significant when diagnosis and gender variables, themselves associated with outcome, were controlled in a regression analysis. Duration of illness was not correlated with age at onset, mode of onset, premorbid adjustment, or severity of illness at entry into the study. Duration of psychosis before treatment may be an important predictor of outcome in first-episode schizophrenia. Acute psychotic symptoms could reflect an active morbid process which, if not ameliorated by neuroleptic drug treatment, may result in lasting morbidity. Further implications of these findings are discussed.


Cigarette smoking in schizophrenia: relationship to psychopathology and medication side effects. The authors' goal was to study the relationship between smoking status and clinical characteristics in schizophrenic patients. Seventy-eight schizophrenic outpatients were assessed by a single rater using the Brief Psychiatric Rating Scale (BPRS), the Abnormal Involuntary Movement Scale, and the Simpson-Angus Scale for extrapyramidal symptoms. Current smokers (N = 58) were compared with nonsmokers (N = 20) on clinical variables by independent t tests and chi-square tests. Differences in outcome variables were tested by multiple analysis of covariance (ANCOVA) with smoking status and gender as factors and age, neuroleptic dose, and caffeine consumption as covariates. Seventy-four percent of patients were current smokers and reported a mean of 19 cigarettes smoked per day. Compared to nonsmokers, current smokers were significantly more likely to be men, to be younger, and to have had an earlier age at onset and a greater number of previous hospitalizations. Current smokers and nonsmokers received mean neuroleptic doses of 1160 and 542 mg/day (chlorpromazine equivalents); the difference was significant. Current smokers also displayed significantly less parkinsonism and more akathisia and had higher total scores on the BPRS. Overall multiple ANCOVA demonstrated a significant main effect for smoking status but not gender or the interaction between gender and smoking status. Univariate ANCOVAs demonstrated a significant main effect of smoking status only for the Simpson-Angus Scale score. Cigarette smokers receive significantly higher neuroleptic doses, in part because of a smoking-induced increase in neuroleptic metabolism. Smoking is also associated with significant reduction in levels of parkinsonism. Smoking status is a significant factor that should be considered in assessment of neuroleptic dose requirements and neuroleptic side effects.


Sylvian fissure size in schizophrenia measured with the magnetic resonance imaging rating protocol of the Consortium to Establish a Registry for Alzheimer's Disease. Since previous work indicated smaller than normal temporal lobe structures in schizophrenic patients, the authors tested the hypothesis that this abnormality might be reflected in abnormally large sylvian fissures. The subjects were 48 schizophrenic patients and 51 normal comparison subjects matched groupwise with regard to age and sex. CSF spaces (sylvian fissures, temporal lobe sulci, temporal horns, third ventricle, lateral ventricles, and superficial cerebral sulci) were visually assessed with the magnetic resonance imaging rating protocol of the Consortium to Establish a Registry for Alzheimer's Disease (CERAD). The sylvian fissures of the schizophrenic patients were found to be bilaterally wider than those of the comparison subjects. There were no other significant differences. Schizophrenic patients appear to have larger than normal sylvian fissures, which may reflect smaller superior temporal gyri.


Predicting feasibility of day treatment for unselected patients referred for inpatient psychiatric treatment: results of a randomized trial. Because previous studies of day treatment as an alternative to inpatient treatment had major disadvantages or methodological shortcomings, the authors conducted a randomized controlled trial to estimate and predict the extent to which day treatment is feasible for unselected patients referred for inpatient treatment. Of 160 patients, 57 were randomly assigned to the control condition and 103 were assigned to the experimental condition. Control patients received standard clinical care. In the experimental condition, day treatment was attempted as soon as the patient's condition permitted. The average number of nights per week that experimental patients spent away from the hospital was compared to the average number of nights away for patients under standard care. Day treatment was satisfactory for 40% of the experimental patients but was completely infeasible for another 40%. The level of surveillance needed in the first week, physical illness, number of previous admissions, depressive symptoms, and treatment by qualified psychiatrists versus registrars were variables predictive of these differences. In this unselected group of patients, no absolute contraindications against day treatment were found. This suggests that the selection criteria applied in nearly all other controlled studies on the subject were unwarranted. The approach used in this study facilitated treatment in the least restrictive environment possible.


An evaluation of the Cleveland criteria for inpatient treatment of substance abuse. This study examined the validity of the Cleveland Admission, Discharge, and Transfer Criteria, a comprehensive system for assigning alcohol- and drug-abusing patients to appropriate levels of care. The subjects were 143 alcoholic and cocaine-dependent male patients in an intensive Veterans Administration day treatment program for substance abusers. Patients who should have received inpatient treatment according to the Cleveland criteria were compared with those who were properly "matched" to day treatment according to the criteria. The outcome measures were treatment completion, results of urine toxicology screens, and self-reports of substance use and psychosocial functioning. Patients who met the criteria for inpatient care were not more likely to drop out of day hospital treatment, and there was no evidence that they were drinking or using cocaine more frequently during follow-up. Furthermore, they did not appear to be doing worse on any of the other outcome measures, with the exception of psychological status. The results suggest that for male substance abusers in the lower socioeconomic levels, the Cleveland criteria may not be effective in differentiating patients who can manage well with day hospital treatment and those who require inpatient treatment.


Mental health status and community adjustment after treatment in a residential treatment program for homeless veterans. An uncontrolled outcome study was conducted to examine clinical improvement and the relationship of psychiatric and substance abuse problems, community adjustment, and housing status among homeless veterans who participated in a multisite residential treatment program. The study was performed at three U.S. Department of Veterans Affairs medical centers in Florida, Ohio, and California. Baseline, discharge, and 3-month postdischarge follow-up data were collected for 255 veterans admitted to the Domiciliary Care for Homeless Veterans Program. Multiple dimensions of outcome were examined, including psychiatric symptoms, alcohol abuse, drug abuse, social contacts, income, employment, and housing. Program participation was found to be associated with improvement in all areas of mental health and community adjustment. Improvement in psychiatric symptoms was associated with superior housing outcomes and improvement in community adjustment. When correlates of improvement in alcohol and drug abuse were examined, only one of eight possible relationships was found to be significant: improvement in alcohol problems was positively associated with improvement in employment. Homeless mentally ill veterans derive clear benefits from participation in a multidimensional residential treatment program. Improvement in mental health problems, however, is weakly linked to improvement in other areas, suggesting that treatment programs may have to attend separately to multiple domains of life adjustment.


Sensitivity of psychiatric diagnosis based on the best estimate procedure. A "best estimate" diagnosis is one made by expert clinicians on the basis of diagnostic information from direct interview conducted by another clinician plus information from medical records and from reports of family members. The authors address the question of whether the best estimate procedure can enhance the classification of psychiatric diagnoses of subjects who are interviewed directly. Four hundred seventy-five subjects were interviewed directly: 201 opiate-addicted probands who sought treatment from a university-based clinic and 274 of their spouses and/or first-degree relatives. Subjects were interviewed by trained clinical assessors using the Schedule for Affective Disorders and Schizophrenia and classified according to Research Diagnostic Criteria. Two psychologists independently diagnosed the same subjects by applying the best estimate procedure. Lifetime rates of major and minor depressive disorder, antisocial personality, alcoholism, and drug abuse were calculated. The rates of diagnoses made on the basis of direct interviews alone were compared with the rates of diagnoses made according to the best estimate procedure. Higher rates of diagnoses of all four disorders were made when the best estimate procedure was applied than when direct interview alone was used; the best estimate procedure also resulted in a minimal rate of false positives. The higher rate of diagnoses based on the best estimate procedure may represent an enhancement in the accuracy of psychiatric diagnoses or an increase in erroneous diagnoses. The authors consider the second possibility less likely.


Posttraumatic adaptation and distress among adult burn survivors. The purpose of this study was to examine the prevalence, natural history, and psychosocial impact of posttraumatic symptoms in adult burn survivors. Forty-three adult inpatients at a regional burn center were assessed at discharge with standardized instruments to determine the presence of psychiatric disorder, assess personality, and quantify depression. Thirty-one patients were evaluated 4 months after discharge. Posttraumatic stress disorder was diagnosed in 7% of patients at discharge and in over 22% of patients at follow-up. Symptoms of avoidance and emotional numbing (DSM-III-R criterion C symptoms) tended to emerge after discharge from the hospital. While posttraumatic symptoms were associated with symptoms of depression, they were not strongly associated with psychosocial adjustment to illness; psychosocial adjustment was more strongly related to aspects of personality, the injury itself, and its treatment. Since adult burn survivors often develop new symptoms of posttraumatic distress after leaving the hospital, longitudinal surveillance is required to detect new cases and provide appropriate treatment. Survivors at risk for poor psychosocial adjustment after discharge may be identifiable during hospitalization, and preventive treatment strategies should be developed and tested for this population.


The relationship between personality and DSM-III axis I disorders in the population: results from an epidemiological survey. The aim of this study was to assess the relationships between specific personality disorders and DSM-III axis I conditions in a community sample. A total of 810 subjects were examined by psychiatrists in the second stage of the Eastern Baltimore Mental Health Survey, part of the Epidemiological Catchment Area Program of the National Institute of Mental Health. A semistructured examination, the Standardized Psychiatric Examination, was employed to assess axis I and axis II conditions. Scales for compulsive and antisocial personality disorders were derived from DSM-III criteria. The relationships between scores on these personality disorder scales and the presence of generalized anxiety disorder, alcohol use disorders (alcohol abuse and alcohol dependence), and simple phobia were evaluated by using logistic regression. Higher compulsive personality scores were associated with a greater odds of generalized anxiety disorder and simple phobia but a smaller odds of alcohol use disorders. In contrast, higher antisocial personality scores were associated with a greater odds of alcohol use disorders but a smaller odds of generalized anxiety disorder. There was no relationship between antisocial personality scores and simple phobia. Personality disorders have specific relationships to axis I conditions, which suggests different vulnerabilities but also different protective influences.


Pubertal stage and panic attack history in sixth- and seventh-grade girls. Although the incidence of first panic attacks appears to peak during adolescence, little is known about which features of adolescence contribute to the risk of a first panic episode. The purpose of this study was to compare the relative importance of age and pubertal stage in explaining the occurrence of panic attacks in adolescents. From a school-based sample of sixth- and seventh-grade girls, 754 subjects completed both a structured clinical interview determining history of one or more panic episodes and a self-assessment of Tanner stages of pubertal development. A multiple logistic regression analysis was performed with panic attack history as the dependent variable and pubertal stage, age, and their interaction as the independent variables. A history of one or more four-symptom panic attacks was found in 5.3% of the girls (N = 40). After age was controlled for, pubertal stage was significantly related to panic attack history. At each age, higher rates of panic attacks were found in the more physically mature girls. Pubertal stage, after adjustment for the effects of age, appears to predict panic attack occurrence in young adolescent girls. Understanding the link between puberty and panic may offer clues regarding the onset and etiology of panic attacks.


Tics and Tourette's disorder: a 2- to 7-year follow-up of 54 obsessive-compulsive children. This study examined a hypothesized etiologic relationship between Tourette's disorder and obsessive-compulsive disorder. Fifty-four children who had initially participated in treatment protocols for obsessive-compulsive disorder (Tourette's disorder was an exclusionary criterion) were reevaluated 2-7 years later with a neurological examination and a structured interview to establish the presence or absence of tics and Tourette's disorder. The children's first-degree relatives (N = 171) were also screened for tic disorders. At baseline, 57% (N = 31) of the patients had lifetime histories of tics. At follow-up, 59% (N = 32) had lifetime histories of tics; eight of these (all males) met the criteria for Tourette's disorder (six had developed the disorder, and two, it could be argued in retrospect, might have met the criteria at baseline). The patients with lifetime histories of tics had greater anxiety, a higher ratio of CSF 5-hydroxyindoleacetic acid to homovanillic acid, and a younger age at onset of obsessive-compulsive disorder than those without tics. The patients with Tourette's disorder differed from other male patients only in having an earlier age at onset of obsessive-compulsive disorder. Of the first-degree relatives, 1.8% (N = 3) had Tourette's disorder, and 14% (N = 24) had a tic disorder. Except for their earlier age at onset of obsessive-compulsive disorder, the patients with Tourette's disorder were indistinguishable from those without. The apparent high rate of tics and Tourette's disorder in the subjects and their relatives is consistent with the hypothesis that in some cases, obsessive-compulsive disorder and Tourette's disorder may be alternative manifestations of the same underlying illness.


Differences in neuropsychological and academic achievement between adolescent delinquents and status offenders. This study sought to determine whether neurocognitive factors could discriminate delinquents brought before a juvenile court in a large urban area from nondelinquent status offenders brought before the same court. Psychological tests were administered to 216 adolescents, aged 13-15 years, presenting to a large urban juvenile court. One hundred ten delinquents (65 male and 45 female) were compared to 106 high-risk nondelinquents (65 male and 41 female) on the WISC-R subtests, the Wide Range Achievement Test, and the Memory for Designs Test. Discriminant analysis revealed that the male delinquents could not be discriminated from the comparison group of male status offenders on the basis of scores on any of the measures. Among the female subjects, scores on reading, arithmetic, digit span, and picture completion subtests and the Memory for Designs Test differed significantly between groups, with some of the findings favoring status offenders and others favoring delinquents. Overall, the findings did not support the hypothesis that inferior intelligence is an independent risk factor for delinquent behavior.


Intravenous versus intramuscular atropine in ECT. Twelve patients receiving ECT consented to random assignment to either intravenous or intramuscular administration of atropine for a total of 48 ECTs. There were no statistically significant differences between routes of administration in heart rate, blood pressures, or sialorrhea, but intravenous administration eliminated one injection per treatment and the development of dry mouth and tachycardia between the intramuscular injection and ECT. The authors recommend that atropine for ECT be administered intravenously.


Creating a healthy public.

Creating a healthy public. Significant change in thought and action will be required for our health system to become capable of serving all citizens effectively. Reliance on market forces and political expediency to shape health policy has focused attention inappropriately on finding ways to pay for illness care rather than maximizing health status. This misdirection of thought and effort has led many of us to search for ways to assure that health policy decisions are consistently based on both science and an ethic of humane concern. Courageous and disciplined local leadership will be needed to motivate policymakers to focus on the task of creating a healthy public. Linkage of academicians and practitioners with the public in a manner than empowers communities to assess and prioritize their own health problems could foster a strong community-based demand for ethical and humane decision making. Constituent demand for improved health status could provide the support politicians need if they are to legislate a national health program that emphasizes health promotion and disease prevention as well as illness care.


Communitywide smoking prevention: long-term outcomes of the Minnesota Heart Health Program and the Class of 1989 Study. The Class of 1989 Study is part of the Minnesota Heart Health Program (MHHP), a populationwide research and demonstration project designed to reduce cardiovascular disease in three educated communities from 1980 to 1993. This paper describes an intensive, school-based behavioral intervention on cigarette smoking, comparing long-term outcomes in one of the intervention communities with those in a matched reference community. Beginning in sixth grade (1983), seven annual waves of cohort and cross-sectional behavioral measurements were taken from one MHHP intervention community and its matched pair. All students in each community were eligible to participate (baseline n = 2401). Self-reported data collected at each period described prevalence and intensity of cigarette smoking. There were no differences at baseline for either weekly smoking prevalence or intensity of smoking. Throughout the follow-up period, however, smoking rates as determined by these measures were significantly lower in the intervention community: 14.6% of students were weekly smokers at the end of high school compared with 24.1% in the reference community. These results suggest that multiple intervention components such as behavioral education in schools, booster programs to sustain training, and complementary communitywide strategies may all be needed for lasting reductions in adolescent tobacco use.


Locking devices on cigarette vending machines: evaluation of a city ordinance. Policymakers, researchers, and citizens are beginning to recognize the need to limit minors' access to tobacco by restricting the sale of cigarettes through vending machines. One policy alternative that has been proposed by the tobacco industry is a requirement that vending machines be fitted with electronic locking devices. This study evaluates such a policy as enacted in St. Paul, Minn. A random sample of vending machine locations was selected for cigarette purchase attempts conducted before implementation and at 3 and 12 months postimplementation. The rate of noncompliance by merchants was 34% after 3 months and 30% after 1 year. The effect of the law was to reduce the ability of a minor to purchase cigarettes from locations originally selling cigarettes through vending machines from 86% at baseline to 36% at 3 months. The purchase rate at these locations rose to 48% at 1 year. Our results suggest that cigarette vending machine locking devices may not be as effective as vending machine bans and require additional enforcement to ensure compliance with the law.


Adolescents' multisubstance use patterns: the role of heavy alcohol and cigarette use. Knowledge about the roles that heavy alcohol and cigarette use play in patterns of concurrent substance use among adolescents is lacking despite studies showing that adolescent substance users are typically multisubstance users and that alcohol and cigarettes are commonly used heavily by those who use illicit substances. The roles of increasing use and heavy first-time use of alcohol and cigarettes in multisubstance use patterns were examined in a cohort of 4192 secondary students who were surveyed three times over a 4-year period. When subsequent use patterns were compared for students who increased their levels of alcohol or cigarette use and those who initiated use for the first time but at heavy frequencies, analyses indicated that the former group was more likely to initiate the subsequent use of other substances and to maintain and increase use already initiated. These results suggest that adolescents are likely to have been involved in a history of licit substance use characterized by increasing levels of use before progressing to and maintaining the use of other substances. Increasing frequencies of alcohol and cigarette use, therefore, may be markers for more serious patterns of substance use.


Determinants of passive smoking in children in Edinburgh, Scotland. Using saliva cotinine as a quantitative marker, we examined the contribution of factors other than parental smoking to children's passive exposure to tobacco smoke. Saliva specimens from a random sample of 734 7-year-old schoolchildren in Edinburgh, Scotland, were analyzed for cotinine. Their parents completed a questionnaire covering smoking habits and conditions in the home. A number of independent predictors of cotinine were identified in addition to the main one of smoking by household members. These predictors included home ownership, social class, day of the week, season of the year, number of parents present, crowding in the home, the number of children in the household, and sex. Cotinine was higher in children from less advantaged backgrounds, during winter, on Mondays, in girls, and when fewer other children were present. The effects were similar between children from nonsmoking and smoking homes. Questionnaire measures of parental smoking are insufficient to fully characterize young children's exposure to passive smoking. Because socioeconomic variables contribute to measured exposure, passive-smoking studies that treat class as a confounder and control for it may be overcontrolling.


Cigarette smoking and occupational status: 1977 to 1990. In this study we examined the relationship between occupational status and smoking habits in men and women during the period from 1977 to 1990. Cigarette smoking and occupational history were obtained from 8045 men and women who served as controls for a hospital-based study of tobacco-related diseases. There was an association between increasing occupational status and tobacco exposure in men, but not in women. The quit rate increased over time in all sex-occupational groups except for male laborers, whose quit rate remained constant. Nicotine-dependent smokers are likely to find it difficult to quit. Male nicotine-dependent smokers were consistently found in greater numbers among blue collar workers throughout the study period. Initially, female nicotine-dependent smokers were more often found among blue collar workers, but in recent years became more frequent among white collar workers. These trends provide clues to the future epidemiological distribution of lung cancer and other tobacco-related diseases. An understanding of gender differences in the occupational profile of cigarette smokers can provide guidelines for effective antismoking interventions.


Predictors of smoking relapse after noncardiac surgery. Study of Perioperative Ischemia (SPI) Research Group. We studied 235 smokers who were admitted for major noncardiac surgery and who survived hospitalization to determine the frequency and predictors of smoking relapse 1 year after hospitalization. We analyzed data collected prospectively from the Study of Perioperative Ischemia. We determined smoking status by self-report. At 12 months posthospitalization, 142 (76%) of the 186 surviving patients had resumed smoking. Significant independent predictors of relapse at 12 months were a history of alcohol abuse and a history of heavy cigarette smoking (P less than 0.01 and P less than 0.05, respectively). Since smokers commonly undergo surgery, the perioperative period provides a valuable window of opportunity for smoking cessation interventions designed to decrease the high rate of smoking relapse after surgery.


Smoking cessation in women concerned about weight. Weight gain after smoking cessation is often cited by women smokers as a primary reason for not attempting to quit smoking or for relapsing after a cessation attempt. A randomized trial of 417 women smokers was conducted to test the addition of two weight control strategies to a smoking cessation program. Participants received the standard smoking cessation program, the program plus nicotine gum, the program plus behavioral weight control, or the program plus both nicotine gum and behavioral weight control. Weight and smoking status were measured at the end of treatment and at 6 and 12 months posttreatment. Smoking cessation rates were highest in the group receiving the smoking cessation program plus nicotine gum. Weight gain did not vary by treatment condition, so its effect on relapse could not be examined by group. There was no significant relationship between weight gained and relapse in individuals. The added behavioral weight control program was attractive to the participants and did not reduce smoking cessation rates. However, it did not produce the expected effect on weight, thereby restricting our ability to examine the effect of weight control on smoking cessation and relapse.


How women's adopted low-fat diets affect their husbands. One way of promoting a reduction in dietary fat intake is by changing the diet of family members. This study investigated the long-term effects of a low-fat dietary intervention on husbands of women who participated in the Women's Health Trial (WHT). An average of 12 months after the end of the WHT, a randomly selected sample of participants' husbands was sent dietary and health questionnaires as part of a follow-up study of the maintenance of the low-fat diet among WHT participants. We found an absolute difference in fat intake between groups of 4 percentage points (32.9% energy from fat among intervention husbands [n = 188] vs 36.9% among control husbands [n = 180]). The wife's attitude and fat intake were among the most important predictors of her husband's fat intake, indicating that the effect of the WHT intervention on the husbands of participants was more likely due to their acceptance of lower-fat foods being served at home than to overt actions by the men. Our results suggest that a dietary intervention aimed at women can have an effect on their husbands and may be a cost-effective approach to healthy dietary change for both women and men.


Weight loss attempts in adults: goals, duration, and rate of weight loss. Although attempted weight loss is common, little is known about the goals and durations of weight loss attempts and the rates of achieved weight loss in the general population. Data were collected by telephone in 1989 from adults aged 18 years and older in 39 states and the District of Columbia. Analyses were carried out separately for the 6758 men and 14,915 women who reported currently trying to lose weight. Approximately 25% of the men respondents and 40% of the women respondents reported that they were currently trying to lose weight. Among men, a higher percentage of Hispanics (31%) than of Whites (25%) or Blacks (23%) reported trying to lose weight. Among women, however, there were no ethnic differences in prevalence. The average man wanted to lose 30 pounds and to weigh 178 pounds; the average woman wanted to lose 31 pounds and to weigh 133 pounds. Black women wanted to lose an average of 8 pounds more than did White women, but Black women's goal weight was 10 pounds heavier. The average rate of achieved weight loss was 1.4 pounds per week for men and 1.1 pounds per week for women; these averages, however, may reflect only the experience of those most successful at losing weight. Attempted weight loss is a common behavior, regardless of age, gender, or ethnicity, and weight loss goals are substantial; however, obesity remains a major public health problem in the United States.


Intestinal parasites among North Carolina migrant farmworkers. The public health significance of intestinal parasitism among migrant farmworkers has been poorly defined. We report a three-part study in which we attempted to provide population-based estimates and identify risk factors for infection. Parasite prevalence and incidence were estimated from two cross-sectional studies and a longitudinal study. We used questionnaires and clinical measurements such as hematocrits to examine risk factors and health effects. In the 1987 convenience sample (n = 265), parasite prevalence ranged from 28% among the US born to 86% among the Central American born, with no significant difference between the prevalence of pathogens among US-born (14%) and Mexican-born (24%) subjects (P = .12, chi 2 test). High prevalences were also found in the 1988 random sample. An annual incidence of 9.5% (n = 74) was demonstrated in 1988. Symptoms such as abdominal pain were associated with infection, and lower hematocrits were associated with hookworm infection (P = .02, t test). Infection with intestinal parasites appears to be an occupational hazard of farmwork, necessitating improved working and living conditions and greater clinical awareness.


Restricted activity days among older adults. The number of restricted activity days experienced by an individual in the course of a year is an important measure of functional well-being, particularly for older adults. We sought to determine multivariate associations between restricted activity days and various health conditions. We used data from the 1984 Supplement on Aging of the National Health Interview Survey to estimate the relationship between restricted activity days and age, gender, and the presence or absence of selected chronic conditions and falls for all noninstitutionalized people aged 65 years and over. Chronic conditions and falls accounted for most of the variance in the model. Of an annual average of 31 restricted activity days, 6 days were associated with falls; 4 days with heart disease; 4 days with arthritis and rheumatism; 2 days each with high blood pressure, cerebrovascular disease, and visual impairment; and 1 day each with atherosclerosis, diabetes, major malignancies, and osteoporosis. These results can be used in estimating the potential impact of health promotion programs on the health status of noninstitutionalized older adults.


Predictors of smoking cessation and relapse in older adults. We examined longitudinal changes in smoking behavior among older adults in three community cohorts of the Established Populations for Epidemiologic Studies of the Elderly. Smoking prevalence declined from 15% at baseline to 9% during 6 years of follow-up. Annual smoking cessation and relapse rates were 10% and less than 1%, respectively. Interval diagnosis of myocardial infarction, stroke, or cancer increased subsequent smoking cessation but not relapse. Although smoking cessation around diagnosis is increased, primary prevention could yield greater benefits.


The Tobacco Institute's "It's the Law" campaign: has it halted illegal sales of tobacco to children? A survey of tobacco retailers was conducted to evaluate the efficacy of the Tobacco Institute's "It's the Law" program, which has the goal of eliminating the illegal sale of tobacco to minors. Only 4.5% (7) of the 156 retailers surveyed were participating in the "It's the Law" program. Eighty-six percent of the retailers who were participating in the program were willing to illegally sell cigarettes to children, compared with 88% (131/149) of the retailers who were not participating.


Homosexual and bisexual men's perceptions of discrimination in health services. Questionnaires were distributed to homosexual and bisexual male participants in the Multicenter AIDS Cohort Study and to homosexual and bisexual male patients with acquired immunodeficiency syndrome (AIDS) to determine whether the men believed they had been refused medical or dental treatment because of their sexual orientation or a condition related to the human immunodeficiency virus (HIV). Men with AIDS were significantly more likely (18%) to report being refused treatment by a doctor or dentist on the basis of a known or suspected HIV-related condition than were men who were seropositive (5%) or seronegative (1%). Significantly more respondents reported refusal of dental care than of medical care.


Making human junk: child labor as a health issue in the Progressive Era. The adverse health effects of work on approximately 2 million employed children troubled many in the United States during the early 20th century. Advocates of reform initially built a rationale for protective legislation primarily from informal, lay observations of the broad developmental outcomes of premature employment. In this endeavor, they projected a dismal scenario of impending national deterioration. This argument received strong criticism for the inadequacy of its corroborating evidence. In response, Progressive reformers emphasized the specific, measurable consequences of particular occupations. Increasingly, liberal advocates of the exclusion of boys and girls from the work force drew upon statistical compilations of occupational injuries and illnesses diagnosed by physicians. Despite their turn toward scientism, Progressives remained somewhat ambivalent about the sufficiency of quantitative data alone to achieve their aims.


Prevalence of human T cell lymphotropic virus types 1 and 2 (HTLV-1/2) in selected Tijuana subpopulations. To assess the prevalence of human T cell lymphotropic virus type 1 and 2 (HTLV-1/2) infections among potentially high-risk populations in the city of Tijuana, Mexico, the prevalence of specific antibodies was determined and information on risk behaviors was obtained between June and October 1988. The study involved 631 presumably healthy individuals, randomly selected from a study population recruited sequentially from prisoners, prostitutes, and injecting drug users (IDUs), and randomly from homosexual and bisexual men. The presence of HTLV-1/2 antibodies was determined by enzyme immunoassay and an immunofluorescence method, and positive reactions were confirmed by a radioimmunoprecipitation assay and Western blot. The prevalence of HTLV-1/2 was 2% (2 of 105) among prostitutes, 7% (29 of 410) among prisoners, 1% (1 of 105) among homosexual/bisexual men, and 21% (22 of 106) among IDUs. To properly identify the specific HTLV type, a subsequent sample of 41 imprisoned IDUs were voluntarily and anonymously recruited in June 1990 and asked to donate 20 ml of whole blood. Twenty-two percent (9 of 41) were serologically positive for HTLV-1/2, and polymerase chain reaction analysis performed on peripheral blood mononuclear cells identified HTLV-2 as the specific virus prevalent in this group. Two individuals were positive for human immunodeficiency virus type 1 (HIV-1). One of these individuals was coinfected with HTLV-2.(ABSTRACT TRUNCATED AT 250 WORDS)


The impact of human immunodeficiency virus infection on the epidemiology and treatment of Trypanosoma brucei gambiense sleeping sickness in Nioki, Zaire. To determine if there is an association between human immunodeficiency virus type 1 (HIV-1) infection and Trypanosoma brucei gambiense sleeping sickness, all incident cases of trypanosomiasis and a control group of blood donors presenting to the same rural hospital in Zaire were tested for anti-human immunodeficiency virus type 1 (anti-HIV-1) antibodies. There was no significant difference in the prevalence of HIV-1 infection between the two groups (7 of 220, [3.2%] for the incident cases and 8 of 388 [2.1%] for the blood donors; P = 0.56). Among the three HIV-1 seropositive incident cases of trypanosomiasis treated with difluoromethylornithine, two (67%) relapsed after treatment compared with four of 39 (10%) HIV-1 seronegative incident cases treated with the same drug (P = 0.05). These findings suggest that at the present time, HIV-1 infection is not having a significant impact on the incidence of T. brucei gambiense sleeping sickness in rural Zaire, but the possibility that incident cases of trypanosomiasis concurrently infected with HIV-1 may be at higher risk of treatment failure warrants further investigation.


Quantification of Rickettsia australis.

Quantification of Rickettsia australis. Several assay systems were compared for measuring the concentration of viable Rickettsia australis, including embryonated eggs, tissue cultures, and mouse inoculation. Direct rickettsial counts that included the enumeration of both viable and nonviable rickettsiae were used to obtain baseline values. Assays were conducted in parallel using serially diluted R. australis preparations to establish which assay displayed the greatest sensitivity and reproducibility. Overall, the plaque assay using buffalo green monkey kidney cells with centrifugation of the rickettsiae onto the monolayers was the most sensitive assay for detecting R. australis, while the embryonated egg assay and mouse lethality titrations were the least sensitive.


Microepidemiology of onchocerciasis in Guatemala: dispersal and survival of Simulium ochraceum. Wild Simulium ochraceum females, both blood engorged and non-blood engorged, were collected from human volunteers infected with Onchocerca volvulus, marked with fluorescent dyes, and released from the same locality as they were collected during February and March 1989. A small hyperendemic village located within 0.5 km of streams supporting large populations of S. ochraceum larvae served as the site for both collection and release of adult females. Fifteen sites for the recapture of flies were located within this same village, within two other villages located 1.0 and 3.7 km from it, and at other places spaced approximately 0.25-3.5 km within a coffee agroecosystem. Flies from both groups were recaptured at distances ranging to 3.5 km from the point of release. Non-blood-engorged flies, however, exhibited a greater tendency to disperse away from the release site. Of the total number of blood-engorged flies recaptured, 51.9% were collected at the release point, 25.7% at 1.0 km, and 1.6% at 3.3-3.5 km. The corresponding percentages for non-blood-engorged flies were 26.9%, 40.4%, and 4.4%, respectively. No flies from either group were recaptured at the most distant site, a large village that was 3.7 km away. Marked flies from both groups were recaptured 12-14 days after release, which was sufficient time for the development of infective O. volvulus larvae. A survival rate (4.7%) of marked, blood-engorged flies over the second and third gonotrophic cycles was estimated from the slope of the regression line of the log number of flies recaptured.(ABSTRACT TRUNCATED AT 250 WORDS)


Ivermectin: reduction in prevalence and infection intensity of Onchocerca volvulus following biannual treatments in five Guatemalan communities. Residents of five hyperendemic communities located in the central focus of onchocerciasis in Guatemala were treated with ivermectin (Mectizan) or placebo every six months for 30 months. The effects of treatment on prevalence and the intensity of skin infection (microfilarial skin density [MFD]) were evaluated. Significant and persistent reductions in both of these indices were achieved by coverage of 80.7% of the eligible populations. The highest proportionate reductions in both indicators of infection occurred after the first treatment, followed by more gradual decreases through the fourth treatment. In one community in which the mean coverage was 92.7%, prevalence decreased from 74.0% at pretreatment to 34.9% after four treatments, while the MFD decreased from 7.8 to 2.0; reductions of 52.8% and 74.3% from pretreatment values, respectively. In every ivermectin-treated community except one, in which drug acceptance was low, the mean community MFD values were reduced to the level associated with low infectiousness for the vector, Simulium ochraceum. Moreover, the category of MFD associated with high vector infectiousness was reduced at least ten-fold over the pretreatment level. One community had low participation during the first two treatments (32.8% and 22.7% of those eligible). This increased to 55.2% at the third treatment because of implementation of an educational program describing both the disease and the beneficial effects of ivermectin and because skin biopsies and nodulectomies were not performed. Secondary reaction rates for all communities were 29.5%, 9.9%, 10.3%, 8.2%, and 7.1% for the first through fifth treatments, respectively. Pruritus was the most common (34.0%) secondary reaction, followed by facial edema (31.8%). All reactions were classified as mild to moderate. Recommendations for mass distribution of ivermectin in Guatemala are given.


The effects of repetitive community-wide ivermectin treatment on transmission of Onchocerca volvulus in Guatemala. The effects of biannual ivermectin treatment at the community level on transmission of Onchocerca volvulus during the dry season were measured over a 30-month period in Guatemala. In the Los Tarrales Transmission Zone, an area encompassing three villages, significant changes occurred in both the prevalence and quantity of infection in the Simulium ochraceum vector population. These included a 76% reduction in females with infective stage larvae (L3S) and an 80% reduction in number of L3S per 1,000 parous flies. Significant reductions in both the mean infective biting density (IBD) and mean transmission potential (TP) also occurred. In Santa Emilia, the prevalence of infection with L3S in S. ochraceum was significantly reduced by 77% from the baseline value. The number of O. volvulus L3S per 1,000 parous flies was also reduced by 92%. Changes in both the IBD and TP were substantial but not significant due to the high degree of variance in the occurrence of O. volvulus L3S in the vector population. This was due, in part, to the movement of infected migrant workers into the finca (coffee farm). In Los Andes, four recurrent treatments successfully blocked transmission of infective stage larvae. Prevalence (flies with all stages of developing larvae) in the vector population was reduced by 89% over the two-year period; yearly reductions in both the IBD and TP were also highly significant, ultimately ending in zero values. This finding is particularly striking since prior to treatment, Los Andes exhibited the highest IBD of the three study locations and the second highest TP.


Nonvascular delivery of Rift Valley fever virus by infected mosquitoes. To determine whether virus-transmitting mosquitoes inoculate infectious particles extravascularly or directly into the vascular system, we permitted mosquitoes infected with Rift Valley fever virus to feed on the distal third of the tails of suckling mice. Amputation of the distal half of the tail within 5 min after their being bitten significantly increased mouse survival as compared with that of mice whose tails remained intact. Even when tails were amputated 10 or more min after mosquito feeding, the median time to death was significantly longer in the group with the amputated tails (53.5 hr) than in those mice with intact tails (46.0 hr). Mouse survival did not correlate with ingestion of blood by the infecting mosquito. We conclude that mosquitoes inoculate virus extravascularly, rather than directly into the vascular system, when feeding on a vertebrate host. Such extravascular delivery of virus by a transmitting mosquito may affect viral pathogenesis, antiviral activity, and vaccine efficacy.


Ingestion of Plasmodium falciparum sporozoites during transmission by anopheline mosquitoes. We investigated the process of sporozoite transmission during blood feeding for Anopheles gambiae and An. stephensi experimentally infected with Plasmodium falciparum. When infective mosquitoes were fed 22-25 days postinfection on an anesthetized rat, sporozoites were detected in the midgut of 96.5% of 57 An. gambiae (geometric mean [GM] = 32.5, range 3-374) and in 96.2% of 26 An. stephensi (GM = 19.5, range 1-345). There were no significant differences between species either in salivary gland sporozoite loads or in the number of ingested sporozoites. There was a significant linear relationship between sporozoite loads and the numbers of ingested sporozoites for both An. gambiae (r = 0.38) and An. stephensi (r = 0.69). Subsequently, An. gambiae were tested for sporozoite transmission by allowing them to feed individually on a suspended capillary tube containing 10 microliters of blood. A total of 83.3% of 18 infective mosquitoes transmitted a GM of 5.9 (range 1-36) sporozoites. The same mosquitoes contained a GM of 23.4 (range 2-165) ingested sporozoites. The number of ingested sporozoites was related to sporozoite loads (r = 0.42) but not to the number of sporozoites ejected into capillary tubes. Ingested sporozoites remained in the midgut up to 10 hr after feeding. The comparable numbers of sporozoites ingested by infective mosquitoes in both experiments indicates that the actual number of sporozoites transmitted to the vertebrate host during blood feeding is significantly reduced by the blood ingestion process.(ABSTRACT TRUNCATED AT 250 WORDS)


Ultrasonographic changes of the liver in Schistosoma haematobium infection. Abdominal ultrasonographic examination was performed in 61 hospitalized patients with chronic liver diseases and 253 school children from a village endemic for Schistosoma haematobium and were compared with 142 urban children without exposure to Schistosoma. The prevalence of ultrasound-detectable hepatomegaly and splenomegaly and the degree of periportal fibrosis was compared between those with and without S. haematobium infection. Among 13 patients with biopsy-proven schistosomal hepatic fibrosis, three with coarse changes secondary to S. mansoni infection showed grade III periportal fibrosis, while 10 patients with fine schistosomal hepatic fibrosis due to S. haematobium had borderline (two) or grade I (eight) changes. Ultrasound evidence of periportal fibrosis was not detected in patients with hepatic cirrhosis, chronic active hepatitis, or fatty infiltration. However, three of 14 patients with chronic persistent hepatitis had grade I periportal fibrosis and two had borderline changes. The frequency of ultrasound-detected hepatomegaly and splenomegaly was greater among rural S. haematobium-infected children (35.2% and 22.4%, respectively) than among noninfected rural (21.1% and 13.3%) and urban (16.9% and 4.9%) children. Also, the frequency of grade I periportal fibrosis was significantly greater (P less than 0.01) in S. haematobium-infected children (22.4%) than in noninfected rural (11.7%) and urban (0.7%) children. No patients with S. haematobium infections, either in the hospital or the village, had grade II or III periportal fibrosis.(ABSTRACT TRUNCATED AT 250 WORDS)


Combined microautoradiographic and histopathologic analysis of the fate of challenge Schistosoma mansoni schistosomula in mice immunized with irradiated cercariae. Combined microautoradiographic and histopathologic methods were used to locate and examine schistosomula of Schistosoma mansoni in the lungs of irradiated cercaria-immunized mice 21 days after percutaneous challenge infection with 75Se-labeled cercariae. Of 75 schistosomula examined in serial sections, 53% were located in the pulmonary microvasculature, 23% in alveolar spaces, 3% with one end in a vessel and the other in an alveolar space, and the locations of 21% were not identified. Inflammatory reactions of variable intensity were observed around schistosomula in both vascular and alveolar sites, although the most intense category of reactions was associated almost entirely with alveolar larvae. All autoradiographic foci contained recognizable schistosomula. Although the concentration of reduced silver grains precluded cyto-structural analysis, observations on schistosomular contour and shape provided no evidence of larval damage. Our findings suggest that immune elimination of schistosomula in mice immunized with irradiated cercariae is partly or largely effected by a process of alveolar extrusion of viable parasites during their lung migration.


Evidence that both normal and immune elimination of Schistosoma mansoni take place at the lung stage of migration prior to parasite death. The number and distribution of autoradiographic foci observed in this and previous studies following percutaneous infection with 75Se-labeled Schistosoma mansoni cercariae indicate that the lungs are the principal site of worm elimination in both normal mice and mice immunized with irradiated cercariae. It was observed in the present study, however, that the intensities of the autoradiographic foci produced in the lungs during both the normal (early) and immune (late) phases of elimination were identical to those of foci produced in the livers of the same mice by larvae shown to be alive. In contrast, foci produced in the lungs by heat-killed, intravenously injected, lung schistosomula became smaller and fainter with time, disappearing completely between seven and 10 days after injection in normal mice and between four and six days in immunized mice. These results indicate that although the targets of both normal and immune elimination do not proceed beyond the lung stage of migration, they do not die in the lungs. A possible explanation for this paradoxical situation, for which there is some experimental evidence, is that unsuccessful migrators leave the blood stream, enter alveoli, pass up the trachea, and are eventually digested in the gastrointestinal tract or eliminated from the body intact.


Carditis in Lyme disease susceptible and resistant strains of laboratory mice infected with Borrelia burgdorferi. The clinical and pathologic evolution of cardiac Lyme disease was evaluated in four-week-old susceptible C3H/He (C3H) and resistant C57Bl/6 (B6) mice on days 3, 6, 10, 15, 30, 60, and 90 after intradermal inoculation with Borrelia burgdorferi strain N40. Culture, DNA polymerase chain reaction, in situ nucleic acid hybridization, immunoperoxidase histochemical analysis, and silver stain were used to detect spirochetes. Spirochetes were first detected by culture on day 6 in two of four C3H mice. The hearts of all mice of both genotypes were culture positive by day 10 and infection persisted through day 90. The spirochetes had a predilection for connective tissue in the heart base, especially around the aorta, epicardium of the upper ventricles and atria, myocardial interstitium, and endocardium. Carditis was first detectable on day 10, reaching a maximum severity on day 15, then resolved, except for persistence of periaortic lymphoplasmacytic infiltrates through day 90 in C3H mice and through day 60 in B6 mice. The C3H mice developed more severe disease than the B6 mice, and this was associated with the earlier appearance, greater numbers, and later clearance of spirochetes in C3H mice. Electrocardiographs of infected and control mice revealed bradycardia and tachycardia in many C3H mice, but in very few B6 mice. Serum creatinine phosphokinase levels did not become elevated at any interval.


Pathology of falciparum malaria in Vietnam. Autopsy samples from the brains of 20 patients who died of falciparum malaria were examined by light microscopy and by an immunohistologic method. Particular attention was paid to a comparison of the pathologic features of the white matter and the cortex. In the high-sequestration (greater than 50%) group (n = 8), the mean +/- SD percentage of cerebral microvessels that showed parasitized red blood cell (PRBC) sequestration was 71.2 +/- 8.1% in the cortex and 84.0 +/- 6.7% in the white matter. The difference in the PRBC sequestration rate between cortex and white matter was statistically significant (P less than 0.01). Perivascular and ring hemorrhages were seen more frequently in the white matter than in the cortex. Deposition of IgG and Plasmodium falciparum antigen in the cerebral microvessels was more highly significant in the white matter than in the cortex (P less than 0.01). Our study demonstrated that the localized concentration of PRBC sequestration in the brain correlated with the marked immunohistologic differences in the microvessels of cortex and white matter.


Cochlear microphonics recorded from fetal and newborn sheep. Sounds present within the uterus stimulate the fetal inner ear and central auditory pathway. This study was undertaken to determine the efficiency of transmission of exogenous airborne stimuli to the fetal inner ear. In this way, we may quantify the extent to which the fetal auditory system is isolated from sounds produced outside the mother. Cochlear microphonics were recorded from fetal and newborn sheep to evaluate the extent to which the fetus is isolated from sounds exogenous to the ewe. Electrodes were surgically placed in contact with the round window membrane in nine near-term fetal sheep. Cochlear microphonics were recorded in response to 1/3 octave-band noises (0.125 to 2.0 kHz) delivered through a loudspeaker 1.8 m from one side of the pregnant ewe. Sound pressure levels generated by the noises were simultaneously recorded ex utero with a microphone and in utero with a hydrophone previously sutured to the fetal neck. After cochlear microphonic amplitudes were recorded, the fetus was delivered through an abdominal incision. Recordings were repeated from the newborn lamb. Fetal sound isolation was calculated as the difference between the sound pressure levels that were necessary to evoke equal cochlear microphonic amplitudes from the fetus and from the newborn lamb. The sound attenuation observed was variable for all frequencies. The fetus was isolated from external sounds by 11.1 dB for 0.125 kHz, 19.8 dB for 0.25 kHz, 35.3 dB for 0.5 kHz, 38.2 dB for 1.0 kHz, and 45.0 dB for 2.0 kHz. Other investigators have demonstrated that the immature auditory system is more susceptible to damage produced by noise exposure than is the mature auditory system. Low-frequency noise produces damaged cells that later in life code higher frequencies. A possibility of fetal hearing loss produced by intense noise exposure needs more careful evaluation.


Bone conduction thresholds in patients with otosclerosis. Sensorineural hearing loss in patients with otosclerosis is commonly encountered. This study was conducted to determine if surgery on the otosclerotic ear had an effect on the sensorineural hearing. A cohort of 262 patients subjected to operation in 311 ears were evaluated. All patients had a minimum of 5 years follow-up and patients over 60 years of age were excluded. Audiograms obtained 1 day before surgery were compared with those obtained 1 year postoperatively and at the last follow-up examination in the study. Results were evaluated using the Student's t test for statistical analysis of hearing results. The mean follow-up was 9.6 years. Deterioration of bone conduction scores occurred in 6.4% of 311 operated ears. Deterioration of bone conduction threshold occurred in the speech frequency in 6 ears (1.9%). Bone conduction scores of operated ears remained quite stable compared with the otosclerotic ears not subjected to operation. Patients with bilateral otosclerosis may benefit from surgery performed on both ears when indicated.


Basal cell carcinoma with matrical differentiation. Three cases of basal cell carcinoma showing shadow cells within basaloid islands have been described using the term basal cell carcinoma with matrical differentiation for this histologic variant. We present four new cases of basal cell carcinoma with evidence of matrical differentiation. Unlike the cases previously published, these lesions showed nests of shadow cells either within the lobules of basaloid cells or forming nests in the stroma. We also noted the presence of a foreign body reaction and calcification. These neoplasms illustrate the capability of basal cell carcinoma to differentiate toward hair matrix cells. Basal cell carcinoma with matrical differentiation must be added to the uncommon variants of basal cell carcinoma showing adnexal differentiation. A parallel between the degrees of differentiation of the cutaneous sebaceous neoplasms with those showing matrical differentiation is proposed.


Bullous lesions in acrodermatitis enteropathica. Histopathologic findings regarding two patients. Acrodermatitis enteropathica (AE) is an autosomic recessive disorder affecting early infancy. Two cases of infantile AE with low plasma zinc levels are reported in which unusually prominent bullous and vesicobullous lesions were seen on the hands and feet, in addition to the more typical erythematous and scaly patches. Both psoriasiform and bullous lesions responded dramatically to oral zinc-sulfate supplementation. The histopathologic features of the bullous lesions of AE have not previously been fully examined. Histologically, the bullous lesions were characterized by intraepidermal vacuolar changes with massive ballooning, leading to intraepidermal vesiculation and blistering, with prominent epidermal necrosis and with no acantholysis. The bullous lesions did not arise on erythematous patchy lesions, but developed ex novo on unaffected skin. The histopathologic differential diagnosis with other bullous conditions is discussed.


Segmental lentiginosis with "jentigo" histologic pattern. We report a case of segmental lentiginosis (unilateral lentiginosis), that is, asymmetric distribution of lentigines on one side of the body, in a 23-year-old woman. Lesions involved the right side of the face and the cervical region, mostly within the area of division of the trigeminal nerve. Histologic examination disclosed a lentiginous pattern as well as some nests of melanocytes at the dermal-epidermal junction (so-called jentigo pattern). Similar cases have been described in the literature under the term "zosteriform lentiginous nevus," which in our opinion makes for confusion since the same term has also been used to describe cases that fit the diagnostic criteria for speckled lentiginous nevus (nevus spilus).


Pigmented trichoblastoma.

Pigmented trichoblastoma. We report a case of trichogenic tumor with epithelial and mesenchymal components recapitulating the formation of hair germs. The epithelial lobules were highly pigmented and affected the full thickness of the dermis, extending into the subcutaneous fat. In addition, amyloid deposits were found within the epithelial lobules and in the stroma. The overall architecture was reminiscent of hair bulbs. Problems of differential diagnosis with other trichogenic tumors and pigmented tumors are discussed.


Making sense of the dysplastic nevus controversy. A unifying perspective. There is currently much confusion regarding the "dysplastic nevus." There is justification for this confusion, given the abundance of seemingly contradictory statements in the literature. This article proposes a unifying perspective that can help reconcile seemingly contradictory statements and decrease confusion regarding the "dysplastic nevus." The proposed unifying perspective suggests that the "dysplastic nevus" does not exist in nature as a distinct clinical-pathologic entity, but that there is probably legitimacy to the concept of a "dysplastic nevus."


Rapid whitening of the hair first reported in the Talmud. Possible mechanisms of this intriguing phenomenon. The first reported episode of rapid whitening of the hair is recorded in the Talmud. This intriguing phenomenon is explained on the basis of a two-step process. The first step involves the actual abrupt development of white hair due to vitiligo or alopecia areata. The second step involves the apparent sudden whitening of the scalp hair due to either simultaneous lengthening of the white hair or selective loss of the dark hair. In fact, the hair that is perceived as suddenly whitening was already white.


Temperature dependence of retention in reversed-phase liquid chromatography. 1. Stationary-phase considerations. The retention mechanism in reversed-phase liquid chromatography (RPLC) has been investigated by examining the temperature dependence of retention, with emphasis on the role of the stationary phase in the retention process. Both chromatographic temperature studies and differential scanning calorimetry were used to examine the role of alkyl chain bonding density on the retention mechanism in RPLC. Phase transitions of reversed-phase stationary phases were observed at bonding densities greater than 2.84 mumol/m2. Thermodynamic constants for the transfer of a solute from the mobile phase to the stationary phase (delta H degrees and delta S degrees) were calculated for low bonding density columns, and comparison of these values to previously reported values for the partitioning of a nonpolar solute from the bulk organic liquid to water indicated that the chromatographic retention process is not well-modeled by bulk-phase oil-water partitioning processes. In addition, this data showed that the entropic contribution to retention becomes more significant with respect to the enthalpic contribution as the stationary-phase bonding density is increased, providing additional support that partitioning, rather than adsorption, is the relevant model of retention.


Temperature dependence of retention in reversed-phase liquid chromatography. 2. Mobile-phase considerations. The retention mechanism in reversed-phase liquid chromatography (RPLC) has been examined over a wide temperature range with emphasis on the role of the mobile phase. van't Hoff plot shapes were used to assess the retention mechanism, and the data showed evidence of the hydrophobic effect when water-rich and/or hydrogen-bonded mobile phases such as methanol/water were used. However, different van't Hoff plot shape was observed with acetonitrile/water mobile phases, indicating a change in the retention mechanism. These data showed that the hydrophobic effect, which had previously been proposed as the driving force for retention, is not a satisfactory explanation for the retention process in all RPLC systems.


Experimental evaluation of the separation efficiency in capillary electrophoresis using open tubular and gel-filled columns. The band dispersion phenomena in capillary zone electrophoresis (CZE) using untreated and surface-treated open tubular and gel-filled capillaries were experimentally evaluated, with emphasis on small capillary diameters (10-100 microns). Laser-induced fluorescence detection was used for high-sensitivity detection of the isoindoles originated from model amino acids. The plots of plate height vs electric field strength were generated for different column radii and compared with a theoretical model for CZE. In addition to the diffusion-controlled band dispersion in the relatively low electric field range, adsorptive interactions between a solute and the capillary wall may play a certain role in band-broadening. The sorption-desorption kinetics become important with increasing electric field strength. Thermal effects appear to contribute little to band-broadening in relatively small capillaries (less than 50-microns i.d.) within normal operating voltages (less than 30 kV), but could become significant in capillaries with larger bores (greater than 75-microns i.d.). With gel-filled capillaries of small diameters (less than 50-microns i.d.), diffusion processes can be minimized. In addition, thermal effects do not appear critical in such columns at reasonable voltages.


Sequential injection immunoassay utilizing immunomagnetic beads. A novel sequential injection immunoassay (SIIA) method is described which utilizes immunomagnetic beads to investigate short-time antibody binding. The method is versatile and flexible and may therefore be adapted to many different applications. Initial results for a competitive assay are also presented. The immunomagnetic bead reactor is created within the flowing stream by retaining immunomagnetic beads with an electromagnet to form an open tube reactor. Thus, the spent beads may be discharged after each analysis. This eliminates the problems of instability of reaction surfaces and eliminates the need for additional time traditionally required for regeneration of the solid-reacting phase in order to not only save time and increase sampling frequency but also to provide each individual sampling cycle with a fresh, uniform portion of beads. The spent beads are collected off line and may be regenerated later. Short-time binding kinetic studies demonstrate linear initial binding under 1 min, which then begins to reach saturation in approximately 10 min. Competitive binding assays of monoclonal mouse IgG (MRC OX-19) to polyclonal sheep anti-mouse IgG immobilized to the immunomagnetic beads show reproducible linear displacement in 30-120-s reactions. Fluorescence detection is utilized with a detection limit of 155 ng/mL, and since the reaction time is typically 2 min or shorter, the sampling frequency is 30 samples/h.


Performance characteristics of a composite multivariate quality control system. We present the results of an evaluation of the performance characteristics of a composite multivariate quality control (CMQC) system that incorporates quality control rules for univariate, multivariate, and correlation conditions. The CMQC system evaluated is designed to help analysts detect unacceptable trends and systematic error in one or more variables, unacceptable random error in one or more variables, and unacceptable changes in the correlation structure of any pair of variables. It is also designed to be tolerant of missing data, to allow analysts to reject as few as one or as many as all variables in a run, and to provide analysts with control statistics and graphics that logically relate to sources of analytical error. We show that the various components of the CMQC system have adequate statistical power to detect systematic errors, random errors, and correlation changes under the conditions likely to be encountered with multivariate analytical measurement systems: (1) a single variable with increased systematic or random error; (2) all variables or a subgroup of variables affected by a common problem that increases systematic or random error; and (3) missing data for one or more variables in a run. We also show that the power of the multivariate component of the CMQC system to detect systematic and random errors is higher than the power of an alternative multivariate test criterion.


Multiwavelength thermal lens spectrophotometer based on an acousto-optic tunable filter. The instrumentation development of a novel, all solid-state, nonmoving parts, fast-scanning and wide-tuning range multiwavelength thermal lens spectrophotometer based on the acousto-optic tunable filter (AOTF) is described. Initially, the essential electronic driver was developed to facilitate the systematic characterization of the paratellurite (TeO2) AOTF and to demonstrate that this filter can be successfully and uniquely used as an all solid-state, nonmoving parts dispersive device to rapidly diffract white incident light into a selected color beam, to amplitude modulate the diffracted monochromatic light, and to keep its intensity constant. The multiwavelength thermal lens instrument was subsequently constructed using this AOTF, and preliminary results on advantages of this spectrophotometer such as its ability to characterize trace chemicals and to analyze multicomponent samples are delineated.


Liquid sample injection using an atmospheric pressure direct current glow discharge ionization source. An atmospheric pressure DC glow discharge in helium has been used as an ionization source for organic samples introduced by liquid injection into atmospheric pressure ionization mass spectrometry (API/MS). The glow source operates typically in the range up to 1 mA of current at less than 1 kV, although the source can be operated up to a discharge current of 10 mA. Even at the high current used in this work, the protonated molecule, MH+, is observed with little or no fragmentation for many of the samples studied. The detection limits achieved for API glow discharge detection are typically in the low femtomole region for small organic molecules including small biological neurotransmitters, drugs, pesticides, phenylthiohydantoin-substituted amino acids, and explosives. A detection limit of approximately 2 pg has been achieved for tyramine with linear quantitation over at least 3 orders of magnitude. The sensitivity in these experiments has been further improved by optimization of the skimmer-interface system and the liquid injection/nebulization design.


Characterization of N-linked oligosaccharides by electrospray and tandem mass spectrometry. Electrospray and tandem mass spectrometry are used to characterize underivatized oligosaccharides that have been digested from asparagine side chains of glycoproteins. Oligosaccharides that contain sialic acids were detected with the best sensitivity in the negative-ion detection mode whereas those that do not contain sialic acid were detected with the best sensitivity in the positive-ion detection mode. The positive-ion abundances of oligosaccharides were greatly enhanced in electrospray mass spectra by adding 10 mM sodium acetate or ammonium acetate to the sample solvent. Tandem mass spectrometry was used to determine primary structural features of the oligosaccharides. Methodology that has been developed on branched high-mannose, hybrid, and complex carbohydrate standards was applied to a mixture of oligosaccharides that were digested with N-glycanase from the glycoprotein, ovalbumin. The composition and relative abundances of individual oligosaccharides obtained from the electrospray mass spectrum compare favorably to those obtained by anion-exchange chromatography/pulsed amperometric detection and by gel permeation chromatography of the oligosaccharides after radiolabelling the reducing end of the carbohydrates. The oligosaccharide content of ovalbumin was independently determined from the heterogeneity observed in the electrospray mass spectrum of the intact 44-kDa glycoprotein. Comparison of the oligosaccharide compositions determined before and after enzymatic digestion shows a selective digestion of high-mannose and low molecular weight oligosaccharides by N-glycanase.