[Panic anxiety, joint hypermobility and chromosome 15q changes].
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Chromosome Aberrations↗
Biomedical subjects
R Rosenberg
Publications and source records attributed to R Rosenberg.
[Current drug treatment. Effects of antidepressive agents in nervous and stress-related disorders].
Antidepressants have a much broader range of indication than the name suggests. The efficacy of antidepressant treatment of nervous and stress-related disorders has been documented in several controlled trials, both in comparison with placebo and with other antidepressants. Most studies have included testing in panic disorder, with or without agoraphobia, and obsessive compulsive disorder, but there is empirical evidence for the efficacy of the drugs in most anxiety disorders. Antidepressants with a preference for serotonergic neurotransmission (i.e. clomipramine and SSRIs (serotonin specific reuptake inhibitors) are particularly effective in the treatment of panic disorder and obsessive compulsive disorder. Owing to their more favourable side effect profile as compared with classical antidepressants, the SSRIs are considered to be the drugs of first choice, except for generalised anxiety disorder, where the efficacy of venlafaxine has been most thoroughly documented. Studies comparing different antidepressant are warranted. So are studies elucidating the relative benefits of drug treatment and psychotherapy, but, with the concept of modern anxiety treatment, there is no principal objection to combining the two treatment methods.
Agoraphobia↗
Nitric oxide modulates lithium-induced conditioned taste aversion.
Nitric oxide (NO) has been shown to affect the behaviour in animal models of depression, anxiety and avoidance learning. Lithium has marked effect in avoidance learning, an effect that can be modulated via the 5-HT system. Experiments were carried out using the conditioned taste aversion (CTA) paradigm to investigate whether administration of NO-modifying drugs, serotonergic drugs and lithium, alone or in combination, induced or affected a CTA. The NO-precursor L-arginine (L-Arg), the non-specific inhibitor of NOS and guanylate cyclase, methylene blue (MB) and the specific NOS inhibitor 7-Nitroindazole (7-NI) all produced CTAs in a dose-dependent fashion. Furthermore, we found that L-Arg counteracted the CTAs induced by LiCl or MB but failed to modulate the CTA produced by 7-NI. The administration of the selective 5-HT1A agonist, 8-OH-DPAT, counteracted the CTAs produced by MB and 7-NI. In contrast, depletion of 5-HT by p-Chlorophenylalanine did not affect the aversions produced by MB and 7-NI, but counteracted the CTA produced by L-Arg. Our results suggest that NO plays a role in the acquisition of the CTA induced by LiCl. Furthermore, the results suggest that the 5-HT1A receptor plays an important role in the CTA induced by MB and 7-NI, thus indicating a possible interaction between the 5-HT and NO systems.
8-Hydroxy-2-(di-n-propylamino)tetralin↗
The ERK signaling cascade inhibits gonadotropin-stimulated steroidogenesis.
The response of granulosa cells to luteinizing hormone (LH) and follicle-stimulating hormone (FSH) is mediated mainly by cAMP/protein kinase A (PKA) signaling. Notably, the activity of the extracellular signal-regulated kinase (ERK) signaling cascade is elevated in response to these stimuli as well. We studied the involvement of the ERK cascade in LH- and FSH-induced steroidogenesis in two granulosa-derived cell lines, rLHR-4 and rFSHR-17, respectively. We found that stimulation of these cells with the appropriate gonadotropin induced ERK activation as well as progesterone production downstream of PKA. Inhibition of ERK activity enhanced gonadotropin-stimulated progesterone production, which was correlated with increased expression of the steroidogenic acute regulatory protein (StAR), a key regulator of progesterone synthesis. Therefore, it is likely that gonadotropin-stimulated progesterone formation is regulated by a pathway that includes PKA and StAR, and this process is down-regulated by ERK, due to attenuation of StAR expression. Our results suggest that activation of PKA signaling by gonadotropins not only induces steroidogenesis but also activates down-regulation machinery involving the ERK cascade. The activation of ERK by gonadotropins as well as by other agents may be a key mechanism for the modulation of gonadotropin-induced steroidogenesis.
Animals↗
Genomic medicine and the individual patient-byte to bedside: a call for papers.
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Delivery of Health Care↗
Implications of occult metastatic cells for systemic cancer treatment in patients with breast or gastrointestinal cancer.
The early and clinically occult spread of viable tumour cells to the organism is becoming acknowledged as a hallmark in cancer progression, since abundant clinical and experimental data suggest that these cells are precursors of subsequent distant relapse. Using monoclonal antibodies against epithelial cytokeratins or tumour-associated cell membrane glycoproteins, individual carcinoma cells can be detected in cytological bone marrow preparations at frequencies of 10(-5) to 10(-6). Prospective clinical studies have shown that the presence of such immunostained cells in bone marrow is prognostically relevant with regard to relapse-free and overall survival, even in malignancies that do not preferentially metastasise to bone. As current treatment strategies have resulted in a substantial improvement of cancer mortality rates, it is noteworthy to consider the intriguing options of immunocytochemical screening of bone marrow aspirates for occult metastatic cells. Besides improved tumour staging, such screening offers opportunities for guiding patient stratification for adjuvant therapy trials, monitoring response to adjuvant therapies (which, at present, can only be assessed retrospectively after an extended period of clinical follow-up), and specifically targeting tumour-biological therapies against disseminated tumour cells. The present review summarises the current data on the clinical significance of occult metastatic cancer cells in bone marrow.
Bone Marrow Neoplasms↗
The Danish PET/depression project: PET findings in patients with major depression.
BACKGROUND: It is hypothesized from previous positron emission tomography (PET) studies of patients with major depression that dysfunction of regions of the limbic system and the frontal lobes in close connection with the basal ganglia is involved in the pathophysiology of major depression. METHODS: By means of PET and 15O labelled radioactive water we determined an index of the neuronal activity by mapping the cerebral blood flow distribution of 42 unselected in-patients suffering from moderate to severe depression and 47 healthy controls controlling for age and gender. The PET maps were co-registered to magnetic resonance images of the anatomy of the brain. RESULTS: The functions-of-interest analysis revealed significant gender differences in cerebral blood flow and changes in the relative distribution of the blood with increasing age. The patients had increased activity of the hippocampus and the cerebellum compared to the healthy controls when corrected for these confounders and the influence of antidepressant medication. Furthermore, data in the Danish Psychiatric Central Register showed that the patients studied were representative of the population of depressed patients admitted to the hospital during the study period. CONCLUSION: Our main finding is increased blood flow to the hippocampus, even when controlling for a number of confounders. This is in accordance with a rapidly expanding literature suggesting an important role for this structure in major depression.
Adolescent↗
Structural brain abnormalities in unselected in-patients with major depression.
OBJECTIVE: Several studies have indicated an increased frequency of cerebral atrophy and white matter lesions in patients with major depression, especially in older age groups. METHOD: Forty-four representative in-patients with major depression in which neurological disorders were clinically excluded, and 49 age- and gender-matched controls were MR scanned. RESULTS: Unexpectedly, two of the patients had severe brain pathology which could account for their psychiatric symptoms. Analysis of the remaining patients (mean age 42 years) did not reveal an increased frequency of cerebral atrophy. The number of white matter lesions increased with age to an odds ratio greater than 3 for patients aged 50, but this was not statistically significant. CONCLUSION: Brain atrophy and white matter lesions did not occur with significantly increased frequency in these relatively young unselected depressives, but the finding of severe brain pathology stresses the importance of brain imaging in late-onset psychiatric disorders.
Adult↗
Fatty acid bile acid conjugates (FABACs)--new molecules for the prevention of cholesterol crystallisation in bile.
BACKGROUND: Cholesterol gall stones are a frequent disease for which at present surgery is the usual therapy. Despite the importance of bile acids it has become evident that phospholipids are the main cholesterol solubilisers in bile. Even phospholipid components, such as fatty acids, have anticrystallising activity. AIM: To synthesise fatty acid bile acid conjugates (FABACs) and study their effects on cholesterol crystallisation in bile in vitro and in vivo. METHODS: FABACs were prepared by conjugation of cholic acid at position 3 with saturated fatty acids of variable chain length using an amide bond. Cholesterol crystallisation and its kinetics (crystal observation time, crystal mass) were studied in model bile, pooled enriched human bile, and fresh human bile using FABACs with saturated fatty acids of varying chain length (C-6 to C-22). Absorption of FABACs into blood and bile was tested in hamsters. Prevention of biliary cholesterol crystallisation in vivo was tested in hamsters and inbred mice. RESULTS: FABACs strongly inhibited cholesterol crystallisation in model as well as native bile. The FABACs with longer acyl chains (C-16 to C-22) were more effective. At a concentration of 5 mM, FABACs almost completely inhibited cholesterol crystallisation in fresh human bile for 21 days. FABACs were absorbed and found in both portal and heart blood of hamsters. Levels in bile were 2-3 times higher than in blood, indicating active secretion. Appreciable levels were found in the systemic circulation 24-48 hours after a single administration. Ingested FABACs completely prevented the formation of cholesterol crystals in the gall bladders of hamsters and mice fed a lithogenic diet. CONCLUSIONS: FABACs are potent inhibitors of cholesterol crystallisation in bile. They are absorbed and secreted into bile and prevent the earliest step of cholesterol gall stone formation in animals. These compounds may be of potential use in cholesterol gall stone disease in humans.
Animals↗
Double-imaging mammography.
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Breast Neoplasms↗
NHLBI workshop report: endothelial cell phenotypes in heart, lung, and blood diseases.
Endothelium critically regulates systemic and pulmonary vascular function, playing a central role in hemostasis, inflammation, vasoregulation, angiogenesis, and vascular growth. Indeed, the endothelium integrates signals originating in the circulation with those in the vessel wall to coordinate vascular function. This highly metabolic role differs significantly from the historic view of endothelium, in which it was considered to be merely an inert barrier. New lines of evidence may further change our understanding of endothelium, in regard to both its origin and function. Embryological studies suggest that the endothelium arises from different sites, including angiogenesis of endothelium from macrovascular segments and vasculogenesis of endothelium from microcirculatory segments. These findings suggest an inherent phenotypic distinction between endothelial populations based on their developmental origin. Similarly, diverse environmental cues influence endothelial cell phenotype, critical to not only normal function but also the function of a diseased vessel. Consequently, an improved understanding of site-specific endothelial cell function is essential, particularly with consideration to environmental stimuli present both in the healthy vessel and in development of vasculopathic disease states. The need to examine endothelial cell phenotypes in the context of vascular function served as the basis for a recent workshop sponsored by the National Heart, Lung, and Blood Institute (NHLBI). This report is a synopsis of pertinent topics that were discussed, and future goals and research opportunities identified by the participants of the workshop are presented.
Animals↗
[Conservative therapy of incontinence].
Conservative therapy of faecal incontinence includes normalisation of colonic function, restauration of damaged anal skin and exercising methods. The most successful of those seems to be Biofeedback with good short time results up to 92% patients without further complaints, the long time results still being up to 67%. Prognosis depends on neuropathy, age and ability of perception and compliance. Passive electrostimulation replaces the damaged nerve and therefore has to be done lifelong. Increasing anal resting pressure seems to be a possible result.
Aged↗
Performance of screening mammography among women with and without a first-degree relative with breast cancer.
BACKGROUND: Although it is recommended that women with a family history of breast cancer begin screening mammography at a younger age than average-risk women, few studies have evaluated the performance of mammography in this group. OBJECTIVE: To compare the performance of screening mammography in women with a first-degree family history of breast cancer and women of similar age without such history. DESIGN: Cross-sectional. SETTING: Mammography registries in California (n = 1), New Hampshire (n = 1), New Mexico (n = 1), Vermont (n = 1), Washington State n = 2), and Colorado (n = 1). PARTICIPANTS: 389 533 women 30 to 69 years of age who were referred for screening mammography from April 1985 to November 1997. MEASUREMENTS: Risk factors for breast cancer; results of first screening examination captured for a woman by a registry; and any invasive cancer or ductal carcinoma in situ identified by linkage to a pathology database, the Surveillance, Epidemiology, and End Results program, or a state tumor registry. RESULTS: The number of cancer cases per 1000 examinations increased with age and was higher in women with a family history of breast cancer than in those without (3.2 vs. 1.6 for ages 30 to 39 years, 4.7 vs. 2.7 for ages 40 to 49 years, 6.6 vs. 4.6 for ages 50 to 59 years, and 9.3 vs. 6.9 for ages 60 to 69 years). The sensitivity of mammography increased significantly with age (P = 0.001 [chi-square test for trend]) in women with a family history and in those without (63.2% [95% CI, 41. 5% to 84.8%] vs. 69.5% [CI, 57.7% to 81.2%] for ages 30 to 39 years, 70.2% [CI, 61.0% to 79.5%] vs. 77.5% [CI, 73.3% to 81.8%] for ages 40 to 49 years, 81.3% [CI, 73.3% to 89.3%] vs. 80.2% [CI, 76.5% to 83.9%] for ages 50 to 59 years, and 83.8% [CI, 76.8% to 90.9%] vs. 87.7% [CI, 84.8% to 90.7%] for ages 60 to 69 years). Sensitivity was similar for each decade of age regardless of family history. The positive predictive value of mammography was higher in women with a family history than in those without (3.7% vs. 2.9%; P = 0.001). CONCLUSIONS: Cancer detection rates in women who had a first-degree relative with a history of breast cancer were similar to those in women a decade older without such a history. The sensitivity of screening mammography was influenced primarily by age.
Adult↗
[Treatment of panic attacks: antidepressive agents and/or cognitive therapy?].
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Antidepressive Agents↗
Paromomycin: no more effective than placebo for treatment of cryptosporidiosis in patients with advanced human immunodeficiency virus infection. AIDS Clinical Trial Group.
To evaluate the efficacy of paromomycin for the treatment of symptomatic cryptosporidial enteritis in human immunodeficiency virus-infected adults, we conducted a prospective, randomized, double-blind, placebo-controlled trial before the widespread introduction of highly active antiretroviral therapy (HAART). Seven units under the auspices of the AIDS Clinical Trials Group enrolled 35 adults with CD4 cell counts of < or = 150/mm(3). Initially, 17 patients received paromomycin (500 mg 4 times daily) and 18 received matching placebo for 21 days. Then all patients received paromomycin (500 mg q.i.d.) for an additional 21 days. Clinical definitions of response were measured by an average number of bowel movements per day in association with concurrent need for antidiarrheal agents that was lower than that before study entry. There was no treatment response during the placebo-controlled phase of the study according to protocol-defined criteria (P=.88). Three paromomycin recipients (17.6%) versus 2 placebo recipients (14.3%) responded completely. Rates of combined partial and complete responses in the paromomycin arm (8 out of 17, 47.1%) and the placebo arm (5 out of 14, 35.7%) of the study were also similar (P=.72). The clinical course of cryptosporidiosis was quite variable. Paromomycin was not shown to be more effective than placebo for the treatment of symptomatic cryptosporidial enteritis. However, inadequate statistical power prevents definitive rejection of the usefulness of paromomycin as therapy for this infection.
AIDS-Related Opportunistic Infections↗
[The GCP-unit at the Aaarhus University Hospital].
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Clinical Trials as Topic↗
The effect of acute citalopram on extracellular 5-HT levels is not augmented by lithium: an in vivo microdialysis study.
A substantial number of patients do not respond sufficiently to antidepressant drugs and are therefore often co-medicated with lithium as an augmentative strategy. Since lithium has been demonstrated to affect 5-HT neurotransmission, we examined the effect of acute and subchronic lithium on 5-HT levels after a challenge with citalopram. We found that subchronic administration of lithium increases extracellular 5-HT baseline level and decreases the extracellular 5-HIAA baseline. However, we found no evidence that the effect of acute citalopram on extracellular 5-HT levels is augmented by acute or subchronic lithium.
Animals↗
Biologic characteristics of interval and screen-detected breast cancers.
BACKGROUND: Interval breast cancer is defined as a cancer that is detected within 12 months after a negative mammogram. The failure of mammography to detect breast cancer depends on testing procedures, radiologist interpretation, patient characteristics, and tumor properties. Although errors by radiologists explain some interval cancers, another explanation is that the tumor is rapidly growing and was too small to be detected on the last mammogram. To determine whether markers of tumor growth rate are associated with risk of an interval cancer, we conducted a population-based study with the use of data collected statewide by the New Mexico Mammography Project. METHODS: Among women who received a mammographic examination from 1991 throughout 1993, we ascertained records of all patients with breast cancer diagnosed within 12 months of a negative screening mammographic examination (interval cancers) and corresponding tumor samples, when available. We selected an age- and ethnicity-matched comparison group of control patients with screen-detected breast cancers diagnosed during the same period. In tumor samples, p53, bcl-2, and Ki-67 were examined immunologically and the apoptotic index was assessed histologically. We used logistic regression to determine whether interval cancers were associated with selected demographic, radiologic, and biologic characteristics. RESULTS: It is more likely that mammography did not detect tumors with a high proportion of proliferating cells (>20%) than tumors with a low proportion of proliferating cells (<5%) (odds ratio [OR] = 4.09; 95% confidence interval [CI] = 1.14-14.65). The OR for mammographic failure was 2.96 (95% CI = 1.07-8.20) among cancers that expressed p53 compared with cancers that did not. Interval cancers also had fewer apoptotic cells. Approximately 75% of interval cancers appear to have tumors with 5% proliferating cells or more. Younger women had a higher proportion of rapidly proliferating and aggressive cancers. CONCLUSION: Rapidly growing and aggressive tumors account for a substantial proportion of mammographic failure to detect breast cancer, especially among younger women, who have a high proportion of aggressive cancers.
Adult↗