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CD30 is a member of the tumor necrosis factor receptor superfamily, which can transduce signals for proliferation, death, or nuclear factor kappa B (NF-kappa B) activation. Investigation of CD30 signaling pathways using a yeast two-hybrid interaction system trapped a cDNA encoding the tumor necrosis factor receptor-associated factor (TRAF)-2 TRAF homology domain. TRAF-1 and TRAF-3 also interacted with CD30, and > 90% of in vitro-translated TRAF-1 or -2, or 50% of TRAF-3, bound to the CD30 cytoplasmic domain. TRAF-1, -2, and -3 bound mostly, but not exclusively, to the carboxyl-terminal 36 residues of CD30. The binding was strongly inhibited by a CD30 oligopeptide centered around a PXQXT (where X is any amino acid) motif shared with CD40 and the Epstein-Barr virus transforming protein LMP1, indicating that this motif in CD30 is an important determinant of TRAF-1, -2 or -3 interaction. At least 15% of TRAF-1, -2, or -3 associated with CD30 when coexpressed in 293 cells. The association was not affected by CD30 cross-linking. However, cross-linking of CD30 activated NF-kappa B. NF-kappa B activation was dependent on the carboxyl-terminal 36 amino acids of CD30 that mediate TRAF association. TRAF-2 has been previously shown to have a unique role in TRAF-mediated NF-kappa B activation, and NF-kappa B activation following CD30 cross-linking was blocked by a dominant negative TRAF-2 mutant. These data indicate that CD30 cross-linking-induced NF-kappa B activation is predominantly TRAF-2-mediated.

Fluconazole is effective in the therapy of cryptococcal meningitis in patients with AIDS. The optimal dosage of fluconazole and the impact of combination with flucytosine are not known. In this study, rabbits with experimental cryptococcal meningitis were given fluconazole at low, intermediate, or high dose or in combination with a low or intermediate dose of flucytosine. Serial cerebrospinal fluid (CSF) examinations showed that all three doses of fluconazole and low-dose fluconazole in combination with intermediate-dose flucytosine were effective in reducing CSF cryptococcal titer, lactate, white blood cell count, and cryptococcal antigen (CRAG) titers. The intermediate and high doses of fluconazole reduced CSF fungal (P < .05) and CRAG (P < .001) titers earlier than low-dose fluconazole alone or in combination with flucytosine. Only the highest dose of fluconazole reduced brain edema after 7 days. In this model of cryptococcal meningitis, there was evidence of a dose response with fluconazole but no in vivo synergism with flucytosine.

Among the elderly, measures of general cognitive ability are not consistently related to the capacity for independent functioning. Some elder patients perform well on global tests of cognition, yet demonstrate behavior that is disruptive to their lives and those of their families. The genesis of these behavior problems is poorly understood, and caregivers, both professional and non-professional, frequently attribute their behavior to wilful misconduct. We propose that there are sufficient data concerning the so-called executive functions of the brain and their impairment in both normal aging and various types of dementia, to support the hypothesis that many behavioral disturbances among demented older adults are a function of different degrees of loss of the capacity to engage in purposeful, goal-directed activity. The executive functions are complex, and include the capacities for planning, organization and active problem solving, and the ability to engage in purposeful, goal-directed behavior. Impaired executive functioning is common in dementia, but also may be present in the context of an age-related decline in the speed and capacity of information processing and varying levels of general cognitive impairment. We review data in support of this model, and discuss a patient whose case illustrates deficits in the independent regulation of behavior, an important executive function mediated primarily by the prefrontal area. In the discussion we address several hypotheses suggested by this perspective.

Alphanumeric Sequencing involves the alternating recitation of counting and the alphabet. We report data on the use of this measure among 112 VA patients ranging in age from 61 to 100 years who were administered the Alphanumeric Sequencing, Trail Making Test, Digits Forward and Backward, the Mini-Mental State Examination, and the Behavioral Dyscontrol Scale. Persons who obtained scores < 27 on the Mini-Mental State Examination or < 14 on the Behavioral Dyscontrol Scale performed significantly more poorly than those who scored higher. Both the time and errors were correlated (.11 to -.49) with measures of information processing and short-term memory.

In recent years, fine-needle-aspiration biopsies (FNA) have been widely used in the evaluation of renal masses, with false-positive FNA data being very uncommon. We present a case report of a 76-yr-old man with a 16-cm renal cyst and what was interpreted as an isolated calcified mural nodule. Following drainage of the main cyst fluid, FNA biopsy showed atypical cell clusters thought to be positive for malignancy. Subsequent surgery failed to disclose either a residual mural nodule or evidence of malignancy. Immunoperoxidase studies performed on both the cell block and actual cyst wall suggested that the abnormal cells were histiocytes. The diagnostic pitfalls of this case, along with a review of pertinent literature, are discussed.

We report here on the application of lot quality assessment (LQA) techniques by managers of a Save the Children (SC) Child Survival Project in Mbalachanda, Malawi, to evaluate data contained in a community-based health information system. By defining 'lots' as the health records for all households with children under 5 years old which were listed on the rosters of village health promoters supervised by a given community health supervisor, and by establishing criteria for 'acceptability' of samples drawn from these lots, we were able to identify and offer additional supervision to health workers (supervisors as well as village health promoters) who were not performing adequately. As LQA sampling procedures require that only a small sample be drawn from each lot, the assessment could be conducted easily and quickly. Health workers were found to have the greatest need for help in updating demographic data and information about home-based oral rehydration therapy (ORT) training sessions, and the least for help in recording children's immunization status. We conclude that LQA can be a useful supervisory tool for health programme managers.

Alphanumeric Sequencing involves the alternating recitation of counting and the alphabet. We report data on the use of this measure with two clinical samples of persons with multiple sclerosis, having either the chronic progressive (n = 23) or relapsing-remitting form (n = 52) of the disease. Patients were administered Alphanumeric Sequencing and several other tests of information-processing speed/capacity and short-term memory. Chronic progressive MS patients performed worse than 23 healthy controls on both the speed and error components of the test, while relapsing-remitting patients were worse than 35 controls only on the total time to complete the task. The time score was correlated with several measures of information processing and short-term memory.

This first section in a two-part study of health indices and practices among residents living in a Jakarta slum describes the use of public and private primary health care services in relation to socioeconomic and health status. As problems associated with urban poverty rapidly increase in developing countries, it is important to study the ethnic and economic diversity which exists in slums and shanty towns: results of such studies should inform the development of effective strategies for outreach and service delivery. Through a survey of 690 mothers and 593 children, we found that 1) poorer residents were more likely than relatively affluent ones to rely on local government clinics (posyandus) for primary health care; 2) regular posyandu users were more likely than non-users to be fully immunized and to use ORT correctly; 3) delivery in hospital was common among all residents, but especially among the more affluent; and 4) prevalence of contraception was high and not associated with socioeconomic status or type of primary health care service used. Strengthening primary health care services at the government's local health posts could benefit all groups in the community if wealthier residents participated more in the posyandus. Standards of care in the private sector should also be improved.

This second section in a two-part study of health indices and practices among a poor urban population in Indonesia focuses on problems related to immunization, nutrition, and incidence of diarrhea. Through a survey of 690 mothers and 593 children in two slum communities in Jakarta, we found that 1) 65% of the children were mildly to severely malnourished according to Gomez criteria, with malnutrition most prevalent among the poorest; 2) 75% of the mothers reported exclusive breastfeeding of their infants during the first four months after birth, but breastfeeding decreased sharply with increasing socioeconomic status; 3) of the 19% of one- to three-year-old children who were incompletely immunized, most were likely to be missing their measles and DPT3 immunizations; and 4) 28% of the mothers reported that at least one of their under-three-year-old children had diarrhea in the last month, with frequency of reporting highest among poor mothers and those using water from vendors. We concluded that selective interventions should be accompanied by development of a comprehensive health infrastructure that permits uninterrupted service delivery and follow up of those identified as high risk. Such a comprehensive primary health care system should be part of a multisectoral development strategy.

Using the criteria of the Structured Clinical Interview for DSM-III-R Dissociative Disorders (SCID-D), we assessed the incidence of feelings of unreality among a sample of 70 persons who had sustained head injuries. Among those whose head trauma could be classified as mild, more than 60% complained of a depersonalization syndrome. Among those with a significant period of unconsciousness, only 11% had similar complaints. There was a high comorbidity with post-traumatic stress disorder and vertigo. Feelings of unreality were not associated with cognitive impairment or elevated personality test scores, nor were there significant relationships with gender or involvement in litigation. A conservative estimate of incidence of depersonalization among persons with minor head trauma is 13%, while, at the upper end, as many as 67% of persons who sustain mild head injury may experience feelings of unreality.

Objective: To measure the prevalence of cobalamin (vitamin B12) deficiency in geriatric outpatients as documented by both low serum cobalamin levels and elevations of serum methylmalonic acid and homocysteine and to determine the response to cobalamin treatment., Design: Prospective study screening elderly subjects for cobalamin deficiency using radiodilution cobalamin assays as well as stable isotope dilution gas chromatography-mass spectrometry methylmalonic acid and homocysteine assays. In patients with serum cobalamin levels < or = 300 pg/mL, the response to cobalamin treatment in the group with levels of methylmalonic acid and/or homocysteine > 3 standard deviations (SD) above the mean for normals was compared with that of those without such elevations., Setting: Outpatient geriatric clinics at the VA Medical Center and University Health Sciences Center, Denver, CO., Patients: One-hundred and fifty-two consecutive outpatients, ages 65 to 99, were screened. Twenty-nine subjects with serum cobalamin levels < or = 300 pg/mL were prospectively evaluated and treated with cobalamin., Main Outcome Measures: Cobalamin, methylmalonic acid, homocysteine, complete blood counts, neurologic examination, and neuropsychological testing., Results: The prevalence of cobalamin deficiency as defined by a serum cobalamin level < or = 300 pg/mL and levels of serum methylmalonic acid and/or homocysteine elevated to > 3 SD was 14.5% of the screened outpatients. A similar proportion of patients with low normal serum cobalamin levels (between 201 and 300 pg/mL) demonstrated elevated metabolites > 3 SD (56%) compared with patients with low serum cobalamin levels (< or = 200 pg/mL) (62%). Cobalamin therapy caused a marked fall or complete correction of the elevated methylmalonic acid and homocysteine levels in each patient who was treated prospectively. Results for complete blood count, lactate dehydrogenase, bilirubin, baseline neurologic score, and baseline neuropsychologic scores did not differ in the group of patients with elevated metabolites compared with those with normal metabolites. The mean red cell volume fell significantly in the patients with elevated metabolites after 6 months of cobalamin treatment. One patient with elevated metabolites had marked improvement in his neurologic abnormalities after 6 months of cobalamin treatment., Conclusion: There was a high (14.5%) prevalence of cobalamin deficiency as demonstrated by elevations in serum methylmalonic acid and homocysteine in addition to low or low normal serum cobalamin levels in elderly outpatients. The serum cobalamin level was insensitive for screening since similar numbers of patients with low normal serum cobalamin levels of 201-300 pg/mL compared with patients with low cobalamin levels (< or = 200 pg/mL) had markedly elevated metabolites which fell with cobalamin treatment. Additional studies will be required to define the full clinical benefit from treatment with Cbl in elderly subjects.

This is a report on the statistical properties of a research and clinical measure of cognitive and behavioral functioning, which has so far demonstrated utility among elderly persons. This instrument, the Behavioral Dyscontrol Scale, is adapted from Luria's approach to the assessment of frontal lobe dysfunction. The scale shows high internal consistency and very good interrater reliability. In a clinically stable, elderly population, test-retest reliability is high. Normative data are presented for three different samples: 47 young adults, 141 cognitively normal elderly persons, and our total elderly sample of 229. A principal components analysis yielded 3 factors consistent with Luria's theory.

Spermatic vein occlusion by means of selective injection of boiling contrast material into the spermatic vein was attempted in 175 men with symptomatic varicoceles or infertility. Seventy-six patients (43%) returned for follow-up venography. Of 115 veins injected, 96 (83%) were totally occluded on the follow-up venogram obtained at 6 weeks to 2 years after injection. In the latter portion of the study, the technique was changed slightly, with injection of larger volumes of hot contrast material, resulting in a 91% occlusion rate. Each vein that was found patent on the follow-up venogram (19 of 115 [16%]) was assessed radiographically, and results were categorized as grade 1, a complete failure in which there was no change from the presclerotherapy appearance (nine of 19 [47%]); grade 2, a failure in which the treated vein was smaller but patent (five of 19 [26%]); or grade 3, a failure in which the treated vein was occluded with newly developed collateral vessels (five of 19 [26%]). The pretreatment size of the spermatic vein and the quantity of hot contrast material injected were both statistically significant factors in the treatment outcome.

Most granulomas of the prostate are nonspecific; infectious, post-operative, and allergic lesions are much less common. Fine-needle aspiration findings in the typical case are distinctive and easily recognized. Several series have been reported, but few have included histologic follow-up. We describe three cases of granulomatous prostatitis (GP) which showed a spectrum of findings confirmed by histologic sections. In all cases, carcinoma was suspected clinically. Case 1 represents typical nonspecific GP with epithelioid and multinucleated histiocytes. In case 2, aggregates of epithelioid histiocytes alternated with areas of necrosis and neutrophils. Histologically, the granulomas showed purulent centers. Silver stains revealed budding yeast in smears and sections. Cultures of FNA material subsequently revealed Cryptococcus. In case 3, the histiocytes were predominantly spindled and occurred singly and in groups. The differential diagnosis included reactive and neoplastic spindle cell lesions. Histologic sections showed GP with spindled histiocytes. Appreciation of the broad cytologic spectrum of GP will facilitate accurate cytologic diagnosis.

Folstein's Mini Mental State Exam, a test assessing the capacity to perform novel and/or repetitive motor tasks (Behavioral Dyscontrol Scale) and a brief measure of working memory were used in a sample of 50 male Veterans Affairs geriatric clinic patients who ranged in age from 63 to 105 (mean, 80.1). The purpose of this study was to attempt to predict the patients' capacity to regulate their behavior independently. We hypothesized that frontal lobe disorders often impair a patient's ability to function autonomously and that the Behavioral Dyscontrol Scale, a measure of frontal lobe impairment, would best predict the capacity for independent regulation of purposeful behavior. Therefore, we examined the relationship of the Behavioral Dyscontrol Scale with spouses' and caregivers' ratings of patients' independent living skills, and with behaviors that interfere with independent functioning. The results of hierarchial regression analyses indicated that the Behavioral Dyscontrol Scale was the only predictor of functional autonomy and was the best predictor of both impulsivity and apathy among geriatric patients. The Behavioral Dyscontrol Scale appears to assess a different functional domain than do the MMSE and similar measures, which rely heavily on the evaluation of orientation and gross cognitive status.

New York City trends in maternal drug abuse during pregnancy and in mortality rates for infants with in utero drug exposure are reported; causes of death among drug-exposed infants are studied, as is the association between maternal drug abuse and other factors that contribute to infant mortality (e.g., low birthweight, lack of prenatal care). Data for this study are derived from the linked files of New York City birth and infant death certificates. Reports of infants born to drug abusing mothers increased from 6.7 per 1000 live births in 1981 to 20.3 per 1000 live births in 1987, with abuse of cocaine accounting for most of the rise. When standardized for race and ethnicity, the mortality rate for drug-exposed infants born from 1978 through 1986 was 35.9, or 2.4 times that for infants in New York City in general. Drug-exposed infants were over three times as likely as infants in the general population to be of low birthweight. The association of both opiates and cocaine with increased mortality and low birthweight was similar. Death rates from SIDS and AIDS were especially higher for drug-exposed infants than for those in the general population, and were similar for opiate- and cocaine-exposed infants. The impact of drug abuse on infant mortality rates in selected low socioeconomic health districts is discussed.

Two hundred fifty clinical isolates of anaerobic bacteria were tested for suceptibility to cefoperazone, cefamandole, cefoxitin, carbenicillin, clindamycin, and chloramphenicol. Anaerobic gram-positive cocci were susceptible to all of the antibiotics tested. Clindamycin was the most active agent against Bacteroides species, followed by chloramphenicol and then cefoxitin. Cefoperazone was less active than cefoxitin and equal in activity to carbenicillin. Cefamandole was the least active antibiotic against Bacteroides. B. distasonis, B. vulgatus, B. thetaiotaomicron, and B. ovatus were more resistant to the antibiotics than B. melaninogenicus, B. oralis, or B. bivius. Clindamycin was the most active agent against Clostridium species, followed by chloramphenicol; the three cephalosporins and carbenicillin were about equal in activity. Clindamycin was the most active antibiotic against Fusobacterium species, followed by chloramphenicol, carbenicillin, and cefoperazone (which were about equally active) and then cefamandole.

Aortic valve vegetation were studied in rabbits before and after intravenous injection of streptococcus mitis. Uninfected vegetation sections revealed compact eosinophilic masses with smooth-appearing edges and scattered polymorphonuclear leukocytes inside and on the surface. Scanning electron microscopic views demonstrated erythrocytes, small leukocytes, and platelets; the surface was markedly irregular. Fifteen minutes after injection of 10(10) streptococci, large mononuclear cells and polymorphonuclear leukocytes lined the vegetation edge; scanning electron microscopy showed large and small leukocytes. One and six hours after infection, there were more polymorphonuclear leukocytes inside the vegetation but few superficially. Bacteria were first seen at six hours as microcolonies inside the vegetation. Twenty-four-hour sections showed large bacterial colonies inside with few bacteria at the edges. Despite the smooth appearance of the vegetation edges, all electron microscopic views revealed very rough surfaces.

Birthweight, gestational age, and Apgar scores of drug-exposed infants were compared to those of drug-free infants using data collected from birth certificates. Infants born to abusers of opiates and cocaine as well as opiates and cocaine together were also compared to one another. The presence of adverse neurologic signs, need for intensive care, and length of hospitalization after delivery were compared among different types of drug-exposed infants using data collected in a program for infants at risk for developmental delay. Infants of all drug abusers weighed an average of 423 g less than controls; mean gestational age for infants in the different drug groups ranged from four to ten days less than for controls. Opiate-exposed infants were significantly more likely to show adverse neurologic signs than were those with exposure only to cocaine, and were more likely to need intensive care. Infants of polydrug (cocaine + opiate) abusers fared worse than infants born to abusers of single drugs with respect to birthweight, gestational age, and length of hospital stay. Outcomes for infants of "crack" abusers were worse than those for infants exposed to other forms of cocaine with respect to birthweight and adverse neurologic signs. Our findings suggest that special outreach and follow-up efforts may be needed to facilitate the optimal development of these infants.

Thirty cancer out-patients, 28 out-patients with cardiac disease, and 24 controls matched for age, sex, race, religion, and marital status were administered a 38-item questionnaire on sleep habits. Patients with cardiac disease perceived that they had more difficulty falling asleep, awakened earlier than planned, and felt sleepy during the day more often than the other two groups. Patients with cancer differed from controls only in feeling that they had more difficulty staying asleep. The findings demonstrate that while patients with two different chronic diseases have altered sleep patterns, the patterns are disturbed in different ways. This has important implications for therapy as a different approach is needed for the patient who has difficulty falling asleep as compared with the patient who has difficulty staying asleep.

We previously showed that the reovirus type 3 hemagglutinin (HA) has distinct functional domains. For example, we identified one group of anti-HA monoclonal antibodies which only inhibited virus-mediated hemagglutination and another group which exclusively neutralized reovirus infectivity. Using competition radioimmunoassays, we now report that these functionally discrete domains on the reovirus type 3 HA correspond to discrete antigenic regions of the protein.