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Biomedical subjects

S Jacobs

Publications and source records attributed to S Jacobs.

At least 307 records · Page 17Linked to original sources
PubMedDate not supplied

Pharmacokinetics of interferon alpha-2b in healthy volunteers.

In a three-way crossover design, 12 healthy male volunteers received 5 X 10(6) IU/m2 body surface area interferon alpha-2b(IFN alpha-2b) by intravenous (IV) infusion over 30 minutes, intramuscular (IM) injections, and subcutaneous (SC) injections. Blood and urine samples were collected at specified times, and analysis of IFN alpha-2b concentrations was performed by immunoradiometric assay. "Flulike" symptoms were the most frequently reported adverse experiences and were independent of the route of administration. After a 30-minute IV infusion, IFN alpha-2b disappeared rapidly from serum, with distribution and elimination phase half-lives of 0.1 hour and 1.7 hours, respectively. Interferon alpha-2b was absorbed slowly after IM and SC administration, with similar absorption half-lives of 5.8 and 5.5 hours, respectively. The observed maximal concentrations after IM and SC administration were 42.1 IU/mL at six hours and 45.8 IU/mL at eight hours, respectively. Interferon alpha-2b was eliminated with half-lives of 2.2 hours after IM administration and 2.9 hours after SC administration. The areas under the serum concentration-time curves for the SC and IM doses were higher than those obtained for the IV infusion. Measurable amounts of IFN alpha-2b were not found in urine regardless of the route of administration.

Adult↗
PubMedDate not supplied

Isolation and characterization of a novel human bladder cancer cell line: BK10.

Molecular studies of bladder carcinomas have aided in determining causative genetic events and the prognosis of cancers endowed with certain abnormalities. In vitro bladder cancer characterization of key cytogenetic alterations is useful for study of molecular changes that may promote oncogenic events. In our laboratory, a novel human bladder cancer cell line, BK10, has been established in vitro and passaged for more than 20 mo. This new bladder cancer cell line (BK10) was derived from bladder tissue containing grade III-IV/IV transitional cell carcinoma. Bladder cancer tissue was obtained at the time of radical cystoprostatectomy extirpation. Cell cultures derived from this surgical sample exhibited an epithelial morphology and expressed epithelial cytokeratins. Immunostains of BK10 were negative for prostate specific antigen (PSA), fibronectin, smooth muscle actin alpha, and desmin. Karyotypic analysis revealed an aneuploid chromosomal content <4n> with many numerical and structural abnormalities previously linked to bladder oncogenesis. Translocations occurred in chromosomes 1, 2, 3, 4, 5, 6, 7, 8, 9, 11, 13, 14, 15, 16, 17, 19, 20, 21, 22, X and Y. G-banding analysis revealed rearrangements involving chromosomes 9q and 17p, and the location of the ab11 oncogene and the p53 gene, respectively. The availability of this bladder cancer cell line will provide a useful tool for the further study of bladder carcinoma oncogenesis and gene therapy.

Aged↗
PubMedDate not supplied

Depressions of bereavement.

The clinical significance of the depressions of bereavement is controversial. Although evidence suggests that most of these depressions remit spontaneously, some of them do require professional attention. Using a trained, non-professional screener, a study to screen for depressions of bereavement at 6 and 12 months after loss of a spouse was performed to determine the rate of depression and its characteristics. The relative value of using a dimensional assessment of depression (20-item Center for Epidemiologic Studies Depression [CES-D] Scale) and a structured diagnostic schedule for depression (Structured Clinical Interview for the DSM [SCID]) as telephone screening measures was evaluated. We found that while the CES-D overestimated, the SCID more precisely reflected the true rate of depression as determined in a subsample. The criterion for depression in this analysis was a diagnostic interview by a psychiatrist using DSM-III criteria and the Hamilton Rating Scale for Depression (HRSD). The study confirmed the existing literature on the high rate of depressions at 6 months (32% of bereaved spouses) and 12 months (27% of bereaved spouses) after a loss. These depressions were more common in widows than widowers. Past personal history (PPH) of depression and family history (FH) of depression were common among bereaved spouses, but did not enhance the risk of depression. Most of these depressions lasted considerably longer than 1 month. Anxiety, restlessness, and psychomotor retardation were prominent; melancholia was occasionally observed; and intense grief was associated with the depression.

Adaptation, Psychological↗
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Adrenal function predicts demoralization after losses.

Stressful experiences can cause disturbances in the hypothalamic-pituitary-adrenocortical axis and the sympathetic-adrenomedullary system. The authors hypothesized that assessments of adrenal function made in the circumstances of stressful losses would predict outcome 1 or 2 years later. The authors collected 24-hour urinary free cortisol, serum cortisol, and 24-hour urinary catecholamines 2 months after intake and used these measures as predictors of depression, anxiety, hopelessness/helplessness, unresolved grief, self-rated health, and help-seeking behavior on follow-up at 13 and 25 months. Adrenal function in the circumstances of a loss predicted only demoralization scores (hopelessness/helplessness) on follow-up.

Adrenal Insufficiency↗
PubMedDate not supplied

Efficacy of imiquimod 5% cream in the treatment of recalcitrant warts in children.

Long-lasting cutaneous warts are a therapeutic challenge, especially widespread or symptomatic recalcitrant warts in children. It can be speculated that natural immunity to these human papillomavirus (HPV)- induced lesions is extremely poor. Therefore ideally treatment should focus on increasing local immune response. Recently imiquimod, a topical immune modifier, has been successfully used in the treatment of external genital warts. Our purpose is to report on our experiences with imiquimod 5% cream applied to therapy-resistant, long-lasting (duration 2-7 years) common warts in children. In 18 children, imiquimod cream was self-applied by the patients or by their parents to the warts twice a day. Assessment for response and occurrence of adverse effects was performed every 4 weeks until clinical cure. Follow-ups could be arranged in 14 of the 18 patients 1-2 years after total clearance. Sixteen of 18 patients experienced total clearance of their warts; 2 showed partial improvement but were lost to follow-up. The mean duration of treatment was 5.8 months. Two of the 14 patients in whom a follow-up was performed showed a small number of new warts after a period of at least 1 year without recurrence. Our data demonstrate that the topical application of imiquimod 5% cream is an effective treatment for long-lasting cutaneous warts in children.

Adjuvants, Immunologic↗
PubMedDate not supplied

Intrathecal labor analgesia with bupivacaine and sufentanil: the effect of adding 2.25 microg epinephrine.

BACKGROUND AND OBJECTIVES: Epinephrine, 25 microg and 200 microg, has been found to prolong the duration of intrathecal labor analgesia when added to an opioid. In our hospital we use the standard epidural mixture, prepared by the pharmacist, containing epinephrine 1:800,000; i.e., 1.25 microg/mL for both spinal and epidural labor analgesia. We wanted to evaluate whether such a low dose, depending on its effect on duration or quality of analgesia, should be maintained or deleted in future mixtures. METHODS: Forty-five term parturients were randomly assigned to receive 1.8 mL intrathecally of a mixture containing bupivacaine 0.125% and sufentanil 0.75 microg/mL with or without epinephrine 1.25 microg/mL. The quality and duration of analgesia, side effects, and obstetric/neonatal outcome were compared. RESULTS: For both combinations, the onset until the first painless contraction was between 5 and 6 minutes. Most patients were pain free during the second uterine contraction. The duration of complete analgesia was 93.2 +/- 24.2 minutes in the epinephrine group and 79.3 +/- 18.1 minutes for patients not receiving epinephrine (P = .014). The quality of the block, bupivacaine consumption, side effects, and obstetric/neonatal outcome were not different between groups. CONCLUSIONS: It was concluded that epinephrine in a dose as low as 2.25 microg significantly prolonged the duration of intrathecal analgesia of bupivacaine-sufentanil by 15 minutes. No other differences were noticed. Diluting the commercially available bupivacaine 0.5% with epinephrine 1:200,000 may avoid the need of freshly prepared epinephrine solutions.

Adult↗
PubMedDate not supplied

Diagnostic criteria for traumatic grief.

This article reviews the rationale for the development of diagnostic criteria for Traumatic Grief. Traumatic Grief is a new nosologic entity that a panel of experts recently proposed. It is a direct descendent of the concept of pathologic grief, and it has roots in attachment behavior, separation distress, and traumatic distress. We present consensus, diagnostic criteria for Traumatic Grief and discuss them in relation to another recently proposed set of criteria. In conclusion, we recommend the development of empirically tested, consensus, diagnostic criteria for Traumatic Grief. Diagnostic criteria would facilitate early detection and intervention for those bereaved persons afflicted by this disorder and lead to additional studies of the prevalence, the nature, and the treatment of the disorder.

Diagnostic Techniques and Procedures↗
PubMedDate not supplied

Comorbid anxiety and affective disorder in alcohol-dependent patients seeking treatment: the first Multicentre Study in Germany.

The goals of this study were to describe demographic variables, drinking history, and the 6-month prevalence of Axis I comorbidity among alcohol-dependent subjects in GERMANY: The variables: amount of alcohol consumption, age at onset of the first alcohol consumed, age at onset of daily alcohol consumption, age at onset of withdrawal symptoms and number of detoxifications were related to the different comorbid disorders and gender. In this study, 556 patients from 25 alcohol treatment centres were enrolled between 1 January 1999 and 30 April 1999. After a minimum of 10 days of sobriety patients who fulfilled ICD-10 and DSM-IV criteria of alcohol dependence were interviewed for data collection using the Mini-DIPS (German version of the Anxiety Disorders Interview Schedule) and a standardized psychosocial interview. The 6-month prevalence of comorbid Axis I disorders was 53.1%. Among the patients with comorbidity, affective and anxiety disorders were most frequent. Comorbid stress disorder was associated with an early start of drinking, an early beginning of withdrawal symptoms, highest number of detoxifications, and the highest amount of alcohol consumed. Female patients with anxiety disorder consumed more alcohol and started earlier than females without this comorbid disorder. The data do not answer the question of the pathogenesis of comorbid disorders and alcoholism, but indicate that stress disorders in alcoholic patients and anxiety disorders in female alcoholics influence the course and severity of alcoholism.

Adult↗
PubMedDate not supplied

An epidemiological review of the mortality of bereavement.

Epidemiological literature revealing excess mortality in the newly widowed is reviewed. The risk varies by age and sex. Younger persons and men are at higher risk. There are manifold specific causes of death characterized by conditions manifest in middle and late life. Cause specificity also varies by sex. Methodological problems in this literature are mitigated by application of varied methodology and replication of basic findings. Socioeconomic status and "social" stress are not well controlled as independent variables. Nevertheless, they probably do not explain the large relative risk of mortality among the bereaved. Pathogenetic mechanisms resulting from a loss are probably twofold: physiologic changes associated with the loss response and behavioral changes that comprise health maintenance or chronic disease management. Because of its important as a health problems, as a fundamental human reaction, and as a research strategy for the basic psychosomatic hypothesis, bereavement is a prime target of investigation.

Adult↗
PubMedDate not supplied

Psychological correlates of growth hormone response to stress.

A stressful interview was conducted in 52 older people to determine whether a stress provoked change in growth hormone (GH) is correlated with anxiety and "defensiveness." The interview was referred to events surrounding the potential loss of a spouse hospitalized two months previously: in 29 instances, the spouse had died before this interview. GH was measured before and, in 23 subjects, during the interview. After the interview, in addition to GH, anxiety was measured using the Taylor Manifest Anxiety Scale (MAS), and defensiveness using the Crowne Marlowe Social Desirability Scale (SD). An elevation of at least 2.0 ng/ml in GH was used to classify subjects as GH responders (Rs) and nonresponders (NRs). Although the Rs and NRs had similar mean scores on defensiveness (SD), the Rs scored higher on anxiety (MAS) (14.9 vs. 10.2, p less than 0.05). Using a median cutoff with anxiety (MAS) alone, only 59% of the Rs were correctly classified as Rs. However, combining both scales in a discriminant function analysis (DFA) improved the ability of either scale alone to distinguish the Rs from the NRs. Using the DFA, 73% of the 29 NRs were correctly classified and 70% of the 23 Rs were correctly classified (p less than 0.005). With higher levels of defensiveness (SD), relatively low levels of anxiety were needed to provoke a GH response. This finding supports previous studies of GH response to stress and provides a multivariate model for the interaction of anxiety and "defensiveness."

Anxiety↗
PubMedDate not supplied

Urinary-free cortisol excretion in relation to age in acutely stressed persons with depressive symptoms.

We examined the relationship between age and urinary excretion of free cortisol in acutely stressed middle-aged and elderly persons. We observed that elderly persons under stress excreted larger amounts of urinary-free cortisol than did middle-aged persons; Pearson's r between age and cortisol = 0.38, p less than 0.05. When the sample was stratified by severity of depressive symptoms, the relationship between age and cortisol excretion was strongly accentuated among those with severe depressive symptoms (r = 0.62, p = 0.01) and diminished among those with milder symptoms (r = 0.25, N.S.). Potentially confounding factors such as diet, use of medications, and physical stature were controlled and did not explain the observations. The high depression scores in this acutely stressed sample were indicative of a higher severity of stress response and also a higher risk of occurrence of depressive syndromes. The depressive syndromes did not resemble depressive disorder of an endogenous nature.

Adjustment Disorders↗
PubMedDate not supplied

Conscious and unconscious coping with loss.

Sixty-seven persons were identified 1 to 2 months after the death or life-threatening illness of their spouse and followed for 25 months. Intake measures included a) a revised Ways of Coping Scale, a structured assessment of ego defenses, sociodemographic information, and other baseline variables. Fifty-six completed follow-up. Outcome measures included deaths, hospitalization, self-rated health, depressive symptoms, symptoms of anxiety, and separation distress. In our analyses, bereavement was used as a covariate and found to be unrelated to outcome. Low self-ratings on coping by making a change and problem-focused planning predicted higher scores on separation distress at 13 months (p < or = .05). Participants who used less problem-focused planning were at risk for higher depression scores 13 months after the stressful event (p < or = .05). Low ego-defensive work and high neurotic ego-defensive ratings predicted high depression scores at 13 months (p < or = .05). At 25 months, coping by self-blame was inversely related to scores on separation distress (p < or = .05). Coping variables predicted neither scores on anxiety symptom scales nor the outcomes of hospitalization or death over the 25-month study period. These observations counter some prevailing clinical assumptions about coping with a loss and emphasize the value of empirical studies of coping as a mediator of outcome during the stress of a loss.

Adaptation, Psychological↗
PubMedDate not supplied

Molecular analysis of the effect of topical imiquimod treatment of HPV 2/27/57-induced common warts.

Imiquimod is effective in the treatment of genital warts and clinical studies suggest activity against common warts as well. We have analyzed the effect of topical imiquimod on gene expression and virus load in human papilloma virus (HPV) 2/27/57-induced common warts. mRNA was extracted from keratinocyte culture, from normal skin, from three untreated common warts and from three common warts treated topically with 5% imiquimod cream twice daily. Differential gene expression was demonstrated by RT-PCR and by cDNA microarray hybridization. We further analyzed viral DNA content in scales from three superficially pared imiquimod-treated warts by real-time PCR. Comparison of normal skin with wart tissue revealed that HPV 2/27/57 infection led to an induction of IL-6, IL-10 and interferon-gamma inducible protein (IP10) and to an up-regulation of TGF-beta. We could further detect expression of PCTAIRE-3, WNT2B, frizzled-3, notch-2, notch-4 and BRCA2 in normal skin and common warts. Analysis of imiquimod-treated warts demonstrated that imiquimod enhanced IL-6 expression and induced IL-8, GM-CSF, MRP-8 and MRP-14. It could also be shown that imiquimod led to an infiltration of wart tissue with macrophages and to a strong decrease of viral copy number in warts within 3 months of treatment. Our data thus provide molecular proof of principle for imiquimod treatment of cutaneous common warts.

Administration, Topical↗
PubMedDate not supplied

Identifying ICU patients who would not benefit from total parenteral nutrition.

This study attempted to improve patient selection for total parenteral nutrition (TPN) by identifying ICU patients whose prognoses were so hopeless that they would not or would no longer benefit from TPN. Computerized trend analysis of daily Apache II scores, corrected for the presence, number, and duration of major organ system failures was used to predict individual hospital outcome among 50 intensive care unit patients treated with TPN. Thirteen of the 18 deaths were correctly predicted without any false predictions. During the study, the results of predictions were not used to influence clinical decision making. If TPN was withheld in the five patients predicted to die before starting TPN, or withdrawn in the eight patients when they were predicted to die, $28,350 or 11.5% of the cost of TPN during the study period would have been saved. This hypothetical study shows that elimination of inappropriate treatment of patients with hopeless prognosis with the aim of avoiding the prolongation of the process of dying and unnecessary suffering is a compassionate patient-selection strategy that can result in major savings in healthcare resources.

Decision Making, Computer-Assisted↗
PubMedDate not supplied

Continuous enteral feeding: a major cause of pneumonia among ventilated intensive care unit patients.

Continuous enteral feeding is widely practiced in intensive care units (ICU). We found that pneumonia developed in 54% of 24 ventilated patients on continuous enteral feeding for more than 3 days. This appeared to affect only patients with a persistently high morning (7:00 am) gastric pH, with 12 of 13 (92%) patients developing pneumonia. In 11 patients the causative organisms were cultured initially from the stomach, oropharynx and trachea before pneumonia supervened. This effect was distinct from that found with the prophylactic use of antacids or H2-receptor antagonists. The mortality (46%) of this group of patients was 1.6 times greater than the expected mortality predicted by the Apache II Severity of Disease Classification System.

Adolescent↗
PubMedDate not supplied

Fasting early morning rise in peripheral insulin: evidence of the dawn phenomenon in nondiabetes.

The dawn phenomenon, a tendency for glucose to rise between 0500 and 0800 h in subjects with diabetes, is also reflected as an increase in insulin required to maintain normoglycemia during closed-loop insulin infusion. Individuals without diabetes have minimal or absent rises in early morning glucose. To test the hypothesis that the absence of early morning glucose increases in subjects without diabetes is due to an increase in insulin levels, we measured insulin levels from 2400 to 0800 h in four male and two female volunteers. Subjects were on an unrestricted diet with three main meals and one bedtime snack at 2100 h. Blood samples were collected continuously in hourly pools by a constant-rate withdrawal pump. We observed the following: (1) hourly integrated concentration of glucose was stable from 2400 to 0800 h (range of mean plasma values, 94.5-97.3 mg/dl), and (2) hourly integrated concentration of insulin increased from the 0300-0400 (4.6 microU/ml) to the 0700-0800-h pool (6.2 microU/ml) (P less than 0.05). The observed increase in insulin in the early morning hours despite stable levels of glucose indicates a temporally increased insulin need in nondiabetic individuals similar to that found in individuals with diabetes. The mechanism underlying this increased insulin need may be similar in diabetes and nondiabetes, with the ensuing rise in glucose being dependent on the availability of compensatory insulin.

Adult↗