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Biomedical subjects

B Strauss

Publications and source records attributed to B Strauss.

At least 37 records · Page 2Linked to original sources

Best hope or last hope: access to phase III clinical trials of HER-2/neu for advanced stage breast cancer patients.

Breast cancer is a major public health problem, with a 12% incidence among women. The over-expression of the proto-oncogene HER-2/neu is associated with 30% of breast and ovarian cancers that are very aggressive and do not respond to standard therapeutic regimens. Entrance into clinical trials can represent the best hope and even the last hope for these patients. Entrance, however, is based on satisfying eligibility criteria. In examining advanced stage breast cancer patients' access to phase III clinical trials for HER-2/neu, two specific arguments regarding eligibility will be addressed. First, if research is to provide the utilitarian goal of the 'greatest good to the greatest number', delineation of the population receiving the 'good', rather than a homogeneous sub-set of this population, must be addressed, along with patients' values and goals, very relevant to determining a 'good life', how to achieve it, and whether a treatment is a part of that process. Second, the 'good' being generated should involve realistic, practical values of quality ways of living with advanced breast cancer and not just increased survival, or cure. Arguments for relaxing criteria are based on an accurate versus over-simplified interpretation of utilitarian principles and concepts of human flourishing. Only through addressing these issues can the true 'good' of clinical trials and research be given to the greatest number of people.

Antibodies, Monoclonal↗

[Are the children of fatherless families more frequently emotionally disturbed in adult life?].

It has been the subject of numerous debates recently whether children who grew up without fathers suffer more than others under the long-term consequences of their fatherless childhood. In 1994 we conducted a large-scale population-based investigation over a hundred subjects who had grown up without father to establish standardized norms for various psychometric questionnaires that were also relevant to this issue. This allows us to contribute to the discussion with some concrete data, which correspond without exception with the dominant trend of other research results. Whereas there was evidence to support the view that some children of fatherless families do indeed suffer from increased emotional disturbance in later life, there were also indications that others even profited emotionally from their fatherless childhood. In the area of bodily complaints the results were confounded to a high degree with gender differences, showing that women are more frequently negatively affected, and men more positively.

Adolescent↗

Stabilization of the intermediate in frameshift mutation.

A mismatch repair, proofreading deficient mutant of Escherichia coli lost a C from a C8 run at a rate 10 times higher than the loss of A from an A8 sequence in the same double mutant. This greater frameshift instability of a homopolymeric run of C's may be due to stabilization of a stacked intermediate. Gain of a (CA) unit in a similarly constructed (CA)15 sequence occurred at a rate about 1/3 that previously reported for a (CA)14 construct losing a (CA) repeat unit.

Base Sequence↗

[Validation of the Inventory for Interpersonal Problems (IIP). Results of a representative study in East and West Germany].

The Inventory of Interpersonal Problems (IIP) was developed in the USA in the late 1970s and in the mean time has become a well-established instrument applied in numerous clinical studies in German speaking countries under the name "Inventar zur Erfassung interpersonaler Probleme". The test manual was published in German in 1994, but without the corresponding standardisation for a German-speaking population. The present study fills this gap. In a representative study the IIP was completed by 2025 West Germans and 1022 East Germans aged 14-92 years. The representative norms are given and the psychometric dimensions of the questionnaire adjusted for this sample. As a contribution to testing validity the results were also related to the scores of a number of other tests completed by the same sample (Giessen Test--GT; Giessener Beschwerdebogen--GBB; Fragebogen zur Lebenszufriedenheit--FLZ; Angstbewältigungsinventar--ABI and the Fragebogen zum erinnerten elterlichen Erziehungsverhalten [FEE]). The relevant results will be reported.

Adolescent↗

Three year followup of bone mineral density change in premenopausal women with systemic lupus erythematosus.

OBJECTIVE: To measure the change in bone mineral density (BMD, g/cm2) in a female population with systemic lupus erythematosus (SLE) over 3 years, to identify factors predictive of bone loss, including the role of corticosteroid and disease related variables, and to determine the predictive value of urinary collagen crosslinks for bone loss. METHODS: All premenopausal women with SLE who participated in a cross sectional study of BMD in 1994 were invited to undergo a standardized interview, examination, medical record review, and BMD measurement of the lumbar spine and femoral neck by dual energy x-ray absorptiometry. RESULTS: Thirty-two women participated with a mean (SEM) age of 35.2 (1.5) years, duration of SLE of 7.0 (0.8) years, and mean (range) time to followup of 3.2 (2.9-3.4) years. Twenty-one subjects were exposed to corticosteroids during the study period with a mean (range) daily dose of prednisolone of 11.1 (2.8-22.9) mg. There was no significant change over the 3 years in BMD at the lumbar spine (1.161+/-0.122 vs. 1.169+/-0.022; p = 0.39) or femoral neck (0.944+/-0.023 vs. 0.955+/-0.020; p = 0.47) for the group as a whole, or when subjects were divided according to corticosteroid exposure. However, in the corticosteroid exposed subgroup, patients treated with > or = 7.5 mg/day (n = 14) lost lumbar spine BMD (-0.50%/yr) in contrast to those receiving <7.5 mg/day, who gained 1.06%/yr (p = 0.02). Furthermore, no participant receiving <7.5 mg/day lost lumbar spine BMD, while 57% of patients receiving > or =7.5 mg/day lost lumbar spine BMD (p = 0.01). In the corticosteroid exposed subgroup only, subjects who did not exercise regularly lost femoral neck BMD, while those who did gained femoral neck BMD (-0.54%/yr vs. 1.39%/yr; p = 0.02). Disease related variables (disease severity, activity, duration, functional capacity) and baseline urinary collagen crosslink levels were not predictive of BMD change. CONCLUSION: Loss of lumbar spine and femoral neck BMD in this premenopausal female SLE population was minimal for the group as a whole; however, a daily dose of prednisolone of > or =7.5 mg was associated with loss of lumbar spine BMD. In corticosteroid exposed patients, regular exercise was protective of femoral neck BMD loss. A single baseline measurement of urinary collagen crosslinks was not predictive of bone loss.

Absorptiometry, Photon↗

The Australian Multicenter Trial of Growth Hormone (GH) Treatment in GH-Deficient Adults.

GH treatment in adults with GH deficiency has numerous beneficial effects, but most studies have been small. We report the results of an Australian multicenter, randomized, double-blind, placebo-controlled trial of the effects of recombinant human GH treatment in adults with GH deficiency. GH deficiency was defined as a peak serum GH of < 5 mU/liter in response to insulin-induced hypoglycemia. Patients were randomly assigned to receive either GH (0.125 U/kg per week for 1 month and 0.25 U/kg per week for 5 months) or placebo. After 6 months, all patients received GH. The primary end points were biochemical responses, body composition, quality of life, and safety. One hundred sixty-six patients (72 females and 91 males) with a mean age of 40 +/- 1 yr (+/- SEM; range 17-67 yr) were recruited. Serum insulin-like growth factor-I (IGF-I) increased from a standard deviation score of -2.64 +/- 0.27 (range -8.8 +3.82; n = 78) to +1.08 +/- 2.87 (range -7.21 to +6.42) at 6 months in the GH/GH group; 38% of the whole group were above the age-specific reference range following treatment [17.6% and 68.9% with subnormal (< 2 SD) or normal (+/- 2 SD) pretreatment levels, respectively]. Fasting total cholesterol (P = 0.042) and low-density lipoprotein cholesterol (P = 0.006) decreased over the first 6 months. Fat-free mass increased in the first 6 months whether measured by bioelectrical impedance (P < 0.001) or dual energy x-ray absorptiometry (DEXA; P < 0.001). Total-body water increased in the first 6 months whether measured by bioelectrical impedance (P < 0.001) or deuterium dilution (P = 0.002). Fat mass measured by DEXA (P < 0.001), skinfold thicknesses (P < 0.001), and waist/hip ratio (P = 0.001) decreased in the first 6 months. Most changes in body composition were complete by 3 months of treatment and maintained to 12 months. Whole-body bone mineral density (BMD) (by DEXA) was unaffected by GH treatment. Self-reported quality of life was considered good before treatment, and beneficial treatment effects were observed for energy, pain, and emotional reaction as assessed by the Nottingham Health Profile. In the initial 6 months, adverse effects were reported by 84% of patients in the GH and 75% in the placebo group, with more symptoms relating to fluid retention in the GH group (48% vs. 30%; P = 0.016). Such symptoms were mild and resolved in 70% of patients despite continued treatment. Resting blood pressure did not change over the initial 6 months. In summary, GH treatment in adults with GH deficiency resulted in 1) prominent increases in serum IGF-I at the doses employed, in some cases to supraphysiological levels; 2) modest decreases in total- and low-density lipoprotein cholesterol, together with substantial reductions in total-body and truncal fat mass consistent with an improved cardiovascular risk profile; 3) substantial increases in lean tissue mass; and 4) modest improvements in perceived quality of life. The excessive IGF-I response and side-effect profile suggests that lower doses of GH may be a required for prolonged GH treatment in adults with severe GH deficiency.

Adult↗

Functional expression of human p21(WAF1/CIP1) gene in rat glioma cells suppresses tumor growth in vivo and induces radiosensitivity.

This study reports the successful growth suppression of a rat glioblastoma model (RT-2) both in vitro and in vivo by the insertion of p21(WAF1/CIP1), a negative cell cycle regulatory gene, into the tumor cells. Greater than 95% of the tumor cells expressed p21 protein after being infected with pCL based p21 retrovirus at 4x M.O.I. (multiplicity of infection). The p21-infected cells showed a 91% reduction in colony forming efficiency and a 66% reduction in growth rate. More prominent p21 staining was found in cells exhibiting histologic evidence of senescence. Intracranial implantation of the infected cells showed complete disappearance of the p21-infected cells at day 10 and long-term survival of the animals compared to controls. Injection of pCLp21 virus into tumor established in situ showed tumor necrosis and gene expression. In a clonogenic radiation survival assay, a 93% reduction of surviving colonies of p21-infected cells was seen in comparison to vector-infected control cells and to p53-infected cells after exposure to 8 Gy (800 rads).

Animals↗

Comparison of preoperative innervation pattern and postreconstructive urodynamics in the exstrophy-epispadias complex.

A primary neurogenic component is often being postulated to be responsible for unfavourable postoperative results of bladder growth and continence in the exstrophy-epispadias complex. On the other hand, we have seen favourable clinical situations and urodynamic follow-up after primary reconstruction employing the 'Erlangen technique' without evidence of primary dysinnervation. Since there are only few data available on this issue, we decided to apply immunocytochemistry and histochemistry for neuronal markers as a further step to elucidate this problem. Transmural biopsies were obtained during reconstructive surgery from the bladder dome and trigone of 22 children between September 1994 and June 1995. Indirect immunocytochemistry for vasoactive intestinal polypeptide (VIP), neuropeptide Y (NPY), substance P (SP) calcitonin gene-related product (CGRP) and protein gene product (PGP) 9.5, a universal marker for neuronal tissue and histochemistry for nicotinamide adenine dinucleotide phosphate diaphorase (NADPHd), was performed on 14-micron cryostat sections. During the same period of time, control biopsies from 6 healthy bladders of an age-compatible group were subjected to the same examination. In addition, 19 patients were examined urodynamically after reconstruction in order to compare postoperative bladder function with the preexisting innervation pattern. No evidence of dysinnervation was found either morphologically or urodynamically in cases of isolated epispadias and classical exstrophy. Cases of exstrophies after failed reconstruction had muscular innervation deficiencies but increased sub and intraepithelial innervation. This group, according to morphological changes, also demonstrated bladder wall instability, decreased bladder compliance and absent detrusor contractions during micturition. All cloacal exstrophies had an extremely uneven innervation pattern with noticeable calibre differences of nerve fibres and bundles with simultaneously increased innervation density. Functionally these bladders were marked by small capacity and decreased compliance and absent detrusor function. All exstrophies in conjunction with an anal atresia or with a caudal regression syndrome (so-called 'transition forms') had a nearly universal pathological innervation pattern, compatible with cloacal exstrophies and had equally unfavourable functional findings. Cloacal exstrophies and 'transition forms' seemed to have primarily a completely different pattern of innervation when compared to normal bladders. Prognosis of bladder function in these children remains unclear.

Adolescent↗

[Category distribution and prognostic significance of operationalized psychodynamic diagnosis. Initial experiences with "OPD-1" in inpatient psychotherapy].

The paper describes the application of the system of "operationalized psychodynamic diagnosis" (OPD) which was developed in a multicentric effort during the recent years. The system is used for the classification of videotape-recorded interviews with 30 patients prior to inpatient psychotherapy. The classification system allows the diagnostic assessment of the patients' illness behaviour, their interpersonal relationships, their conflicts, psychic structure and their symptoms. The aim of the study was a description of the patient group as well as a test of the relationship between diagnostic features and treatment outcome following several months of inpatient group psychotherapy. The study confirms the practicability of the OPD-system and shows that the description of the patient group seems to be plausible and valid. Single diagnostic categories seem to be useful for the prognosis of treatment outcome, especially structural features, but also characteristics of the patients' illness behaviour and their sensitivity for conflicts.

Adolescent↗

Prevalence of reduced bone mineral density in systemic lupus erythematosus and the role of steroids.

OBJECTIVE: To determine the prevalence of reduced bone mineral density (BMD) in a large female cohort of systemic lupus erythematosus (SLE) and to determine the role of steroids and disease related variables. METHODS: All females with SLE managed by rheumatologists affiliated with a single center were invited to undergo BMD measurement of the lumbar spine and left femoral neck by dual energy X-ray absorptiometry (DEXA), standardized examination, and medical record review. RESULTS: Ninety-seven females with a mean (SD) age of 44.2 (14.9) years were studied. Low bone mass [defined as BMD > 1 standard deviation (SD) below young adult mean] was present in 44.3 and 42.1% at the lumbar spine and femoral neck, respectively. Osteoporosis (defined as BMD > 2.5 SD below young adult mean) was present in 13.4 and 6.3% at the lumbar spine and femoral neck, respectively. Steroid usage showed a strong inverse relationship with BMD in the lumbar spine, but a less strong relationship in the femoral neck. CONCLUSION: The findings of high prevalence of reduced BMD and association with steroid therapy have important implications for the routine management of SLE.

Absorptiometry, Photon↗

[Choking under pressure: Positive public expectations and performance in a motor task].

According to Baumeister (e.g. 1985) "choking under pressure" means showing a suboptimal performance when under pressure, despite a high motivation to perform well. Factors that can exert pressure on performers ("pressure variables") include competition, the reward to be gained, the expectation of negative consequences, the presence of spectators etc. However, "choking" can also occur when public expectations (e.g., of the audience) are positive. Baumeister et al. (1985) showed this in two experiments. In the present study an experimental design (a 2 x 2 design) was developed to examine this question in a sport context. Under various conditions of public expectations ("positive" vs "no") and private expectations ("positive" vs "negative"), 60 university students repeatedly had to do a motor task on a rowing ergometer. The main results were: When the public expects success, but not the performing person, then the level of performance decreases. Under the condition of "public expectation of success" a better performance was only shown when the private and the public expectations corresponded with each other.

Adult↗

Repression of the insulin receptor promoter by the tumor suppressor gene product p53: a possible mechanism for receptor overexpression in breast cancer.

There is strong evidence to suggest that insulin and insulin-like growth factor (IGF)-I may be important for tumor growth. Both the insulin and IGF-I receptors (IGF-IR) are overexpressed in breast cancer, and antibody blockade of the IGF-IR inhibits the growth of some breast cancer cell lines. Furthermore, expression of an insulin receptor (IR) in a normal mammary epithelia] cell line causes insulin-dependent transformation. Functional inactivation of p53 is also very frequent in many tumors. In this paper, we investigated whether inactivation of p53 might be involved in the overexpression of the IR in malignancy, specifically breast cancer. We demonstrate a positive correlation between IR and IGF-IR levels and p53 overexpression in primary human breast malignancies. To examine possible mechanisms by which p53 may regulate IR gene expression, we show that p53 can repress the IR promoter and that a dominant-negative p53 (248Q) can de-repress the promoter in cells containing normal p53. The p53 effect was shown to be mediated by C/EBP and Sp1 transcription factors. We also documented that p53-null mice had elevated levels of Sp1, but not C/EBPalpha, and that insulin binding to liver extracts was increased compared to wild-type controls. These results suggest that p53 inactivation may lead to an up-regulation of genes, such as the IR, that are dependent on these transcription factors.

Animals↗

[Psychiatric and sexual sequelae of hysterectomy--a comparison of different surgical methods].

Comparison of Different Surgical Methods: The cardinal question of this prospective longitudinal study was whether different surgical methods of hysterectomy correlate with differences in adaptation and in respect of psychological as well as sexual consequences. A total of 83 patients were investigated immediately prior to surgery as well as 6 weeks later. 61 resp. 58 patients participated in follow-up investigations 6 months and 1 year following surgery. Total hysterectomy was performed vaginally in 16 females, abdominally in 22 patients. 23 patients underwent subtotal C.I.S.H. hysterectomy. 23 females indicated for myoma enucleation formed another group of this study. Besides several psychological variables of potential influence such as personality characteristics, coping, sexual attitudes and partner satisfaction, the study covered psychological as well as physical complaints, life satisfaction and differential characteristics of sexual experiences and behaviour longitudinally. The results indicate that single subgroups differ from each other in several respects. There were no indications of different psychological as well as sexual consequences depending on the surgical method. These findings support the view that consequences of hysterectomies are more likely to be predicted on the basis of psychological traits that existed before the operation, rather than from a medico-technical point of view.

Adaptation, Psychological↗

The interaction between cytotrophoblasts and their derived tumor cells.

Previous experiments demonstrated that human cytotrophoblasts and cells of the choriocarcinoma cell line JAr interact in vitro. As a result of this interaction there is an increased synthesis of CG and hPL, probably as a result of the increased CG and hPL synthesis by the cytotrophoblasts. In the present investigation we studied this interaction in greater detail and found that both cytotrophoblasts and JAr cells undergo changes in their biological properties as a result of this interaction. JAr cells and cytotrophoblasts cocultured for 72 hr were fractionated according to their size by centrifugal elutriation. The number of cells in the fraction which contain the largest cells was very significantly increased as a result of the coculture. This increase was due to an increase in the number of cells of both cell types. This fraction was the most active one in the synthesis of CG and hPL. The synthesis of DNA by the JAr nuclei in this fraction of the cocultured cells was almost completely inhibited but in the parallel fraction of the JAr cells cultivated alone the level of DNA synthesis was equal to that of all other JAr cell fractions. Heterokaryons are formed in the coculture. In these heterokaryons a factor which inhibits DNA synthesis in the cytotrophoblasts may inhibit DNA synthesis in JAr nuclei and at least be partly responsible for the inhibition of DNA synthesis observed.

Animals↗