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Biomedical subjects

A Lang

Publications and source records attributed to A Lang.

At least 91 records · Page 5Linked to original sources
PubMed1997

Interferon-alpha-2C and LD ara-C for the treatment of patients with CML: results of the Austrian multi-center phase II study.

Small pilot studies of patients with CML have reported on encouraging response rates after treatment with interferon-alpha (IFNalpha) in combination with low-dose cytosine arabinoside (LD ara-C). We therefore initiated a multi-center phase II trial in order to investigate the efficacy and tolerability of this combination in newly diagnosed patients with Ph-positive chronic myelogenous leukemia (CML). Eighty-four patients were treated with IFN-alpha-2c at daily subcutaneous doses of 3.5 MU and LD ara-C added subcutaneously for 10 days every month at a dose of 10 mg/m2, following an initial reduction of WBC to less than 20 x 10(9)/l with hydroxyurea (HU). Within a median observation period of 28 (5-59) months the patients received a median of 7 (1-35) IFNalpha and LD ara-C cycles. Treatment was stopped due to side effects in 16 cases (19%) and to primary or secondary treatment failure in 38 cases (45%). In 45 patients (54%) complete hematological response (CHR) was achieved; in 39 patients (46%) cytogenetic responses including 15 (18%) complete cytogenetic responses (CHR) were observed. Median duration of cytogenetic responses was 15 months. Relapses were seen in 8/15 patients (53%) with complete cytogenetic remission (CCR), in 3/6 patients (50%) with partial cytogenetic response and in 9/18 patients (50%) with minor cytogenetic response. In conclusion, the combination of IFNalpha and LD ara-C resulted in encouraging rates of hematological and cytogenetic responses in patients with CML with low to moderate toxicity.

Adolescent↗
PubMed1997

Relation of exploratory behavior of rats in elevated plus-maze to brain receptor binding properties and serum growth hormone levels.

Forty-five male Wistar rats were selected according to their behavior in the elevated plus-maze. They were separated as follows: animals with low exploratory activity ('anxious'), an 'intermediate' group and animals having high exploratory activity ('non-anxious'). Various receptor binding studies and hormonal assays were also performed in these selected rats. The affinity of 5-hydroxytryptamine 5-HT2A receptors in the frontal cortex was lower in the 'anxious' rats compared to home-cage controls and 'non-anxious' animals. Moreover, the number of cholecystokinin (CCK) receptors in the hippocampus was significantly elevated in the 'anxious' group compared to home-cage control animals. The blood levels of growth hormone (GH) were significantly lower in the 'non-anxious' rats compared to 'anxious' counterparts. In conclusion, it seems likely that the decreased exploratory activity of rats is related to the increased 5-hydroxytryptamine (5-HT) and CCK mediated neurotransmission in the brain. The different serum levels of GH in the selected rats probably reflect alterations in the activity of 5-HT and CCK.

Animals↗
PubMed1997

Schistosoma mansoni-related morbidity on Ukerewe Island, Tanzania: clinical, ultrasonographical and biochemical parameters.

One thousand six hundred and ninety-five inhabitants of 3 rural villages on Ukerewe Island, Lake Victoria, Tanzania, were examined by clinical, parasitological, ultrasonographic and--in part--serological means to evaluate Schistosoma (S.) mansoni-related morbidity on a community level. Villagers frequently complained of typical colitis symptoms (abdominal pain 80.1%, bloody stools 43.1%, diarrhoea 35.1%); haematemesis, on the other hand, was rare (and reports doubtful in most cases). 16.9% of the population had been given praziquantel previously. Overall S. mansoni prevalence was 86.3%, with a median egg output of 176 eggs per gram (e.p.g.) and maximum output of 17,984 e.p.g. Children and adolescents were infected more severely than adults, men more severely than women. Pretreated individuals excreted significantly fewer ova (median 124 vs 192e.p.g., P < 0.001). Hepatomegaly (determined by ultrasonography) was present in 35%, splenomegaly in 80%. Organomegaly was significantly related to egg output. Pretreated persons had lower rates of splenomegaly and left lobe hepatomegaly. Low-degree periportal fibrosis was common, while severe grades of fibrosis (MANAGIL score II and III) were present in about 6%. About 10% had other abnormalities on liver sonography (irregular parenchymal texture and/or shape); these person passed significantly more S. mansoni ova than others. Clear sonographic signs of portal hypertension were seen in 2.1%. Serum procollagen-IV-peptide and gamma-glutamyl-transferase levels were increased in persons with severe periportal fibrosis, irregular liver texture of portofugal collateral vessels. Thus, S. mansoni infection in the western part of Ukerewe Island is frequent and often severe, leading to a high prevalence of gastrointestinal symptoms. Hepatosplenic involvement does occur, although symptomatic cases of portal hypertension were not identified beyond doubt. The overall level of schistosomal morbidity is thus considered intermediate. Serum procollagen-IV-peptide may be a promising marker of schistosomal liver disease. Our data suggest that S. mansoni infection may also be related to diffuse liver parenchyma alterations in this area.

Adolescent↗
PubMed1997

The ten test.

The authors describe a new test for clinical sensibility, initiated in response to the need of the senior author for a rapid, reliable method to evaluate sensibility. Using this test, the patient develops a ratio between normal light moving touch and diminished moving touch. Subsequent determinations can detect serial changes. The ratios obtained can be compared with a standard scale of sensibility with a high degree of validity and reliability. The interexaminer and intraexaminer results obtained are reliable and repeatable. Statistical evaluations substantiating the validity of the test are presented. Simplicity and depend-ability recommend this test for use in a busy clinical setting.

Humans↗
PubMed1997

Colonic wall thickness measured by ultrasound: striking differences in patients with cystic fibrosis versus healthy controls.

BACKGROUND: Colonic strictures represent an advanced stage of fibrosing colonopathy in patients with cystic fibrosis. AIMS: To clarify whether ultrasonography can identify patients with an early stage of fibrosing colonopathy and to determine clinical factors that influence bowel wall thickening. PATIENTS: Ninety patients with cystic fibrosis, median age 10 years, and 46 healthy controls, median age 13 years, were investigated. METHODS: Bowel wall thickness was measured by ultrasound in a prospective study. RESULTS: In cystic fibrosis, wall thickness of both small intestine and colon was significantly (p < 0.0001) higher than in controls; 81% of patients with cystic fibrosis had a maximum colon wall thickness at any site of 2 mm or more, a value that was never reached by controls. The maximum colon wall thickness was 6.5 mm. Bowel wall thickness was unchanged at re-examination after one year. There was no progression even with high dose pancreatic supplements. There was no association between bowel wall thickness and clinical features such as previous meconium ileus, intestinal resection, distal intestinal obstruction syndrome, abdominal pain, or pancreatic enzyme dose. CONCLUSIONS: There is genuine intestinal involvement in cystic fibrosis; in a few cases this could lead to fibrosing colonopathy.

Adolescent↗
PubMed1997

Immunization of cystic fibrosis patients with a Pseudomonas aeruginosa O-polysaccharide-toxin A conjugate vaccine.

Healthy, non-colonized cystic fibrosis (CF) patients (N = 26) were immunized with an octavalent Pseudomonas aeruginosa O-polysaccharide-toxin A conjugate vaccine. Vaccination was well tolerated and induced anti-lipopolysaccharide (LPS) antibodies of a high affinity capable of promoting the opsonophagocytic killing of P. aeruginosa by human peripheral lymphocytes. In contrast, anti-LPS antibodies acquired after natural infection possessed a very low affinity and were non-opsonic. To determine if immunization could prevent or delay infections due to P. aeruginosa, the infection rate among immunized patients was compared retrospectively to age and gender-matched controls. After 6 years of clinical follow-up, 15/20 (75%) of control and 8/23 (35%) of immunized subjects were classified as infected (p = 0.022). The persistence of high-affinity antibodies among immunized patients correlated with a significantly lower rate of infection after 4-6 years of observation. Infection of immunized patients was correlated with a dramatic decline in total antibody titer between year 2 and 3 of follow-up. Smooth, typeable strains of P. aeruginosa predominated among immunized patients. In contrast, rough, nontypeable strains were most frequently isolated from nonimmunized patients. Mucoid P. aeruginosa strains were isolated from 6 nonimmunized patients versus only I immunized subject.

ADP Ribose Transferases↗
PubMed1997

Perceptions of suicide risk and the helpfulness of intervention strategies: a comparison of students and mothers.

College students (n = 132) and mothers (n = 64) listened to simulated hotline calls and rated level of suicide risk and the helpfulness of interventions. Students also rated their intent to take action in a similar situation; mothers rated their child's intent to take action. Students, more than mothers, perceived emotional problems to be associated with risk; mothers, more than students, perceived changes in behavior to be associated with risk. Students and mothers generally agreed regarding the helpfulness of different interventions, rating talking as most helpful. However, students, more than mothers, perceived social distraction as helpful. Mothers were generally accurate in their perceptions of their children's intended actions. Results suggest the need for additional research on the skills adolescents bring to crisis situations.

Adolescent↗
PubMed1996

Soft tissue sarcoma metastasis from clonal expansion of p53 mutated tumor cells.

Although soft tissue sarcoma has a high incidence of p53 mutations, it is not clear if such alterations facilitate tumor growth and metastasis. In this study, fresh autologous normal lymphocytes, normal muscle, primary and metastatic sarcoma tissues from a single synovial sarcoma patient were examined for p53-related alterations that potentially associated with sarcoma tumor development and metastasis. Normal tissues contain two wild-type p53 alleles. Primary sarcoma had one chromosome 17p p53 allelic deletion without apparent p53 mutation in the other allele. However, metastatic tumor had deletion of one p53 allele with an exon 5 codon 135 missense mutation in the other allele. This p53 gene point mutation in the metastasis was associated with the production of mutated p53 protein. A small clone of cells harboring the identical p53 gene point mutation was identified in the primary tumor using mutant allele specific PCR amplification, albeit at levels much less than in the metastatic sarcoma. This single patient example indicate that soft tissue sarcoma metastasis can develop from clonal expansion of primary tumor cells bearing p53 mutations.

Base Sequence↗
PubMed1996

Interferon alpha-2c therapy of patients with chronic myelogenous leukemia: long-term results of a multicenter phase-II study. Austrian Biological Response Modifier (BRM) Study Group.

In a prospective multicenter phase-II trial 80 patients with Philadelphia (Ph)-positive chronic myelogenous leukemia (CML) were treated with recombinant interferon (IFN) alpha-2c, administered subcutaneously at an absolute dose of 3.5 megaunits (MU)/day. Complete hematological remission was achieved in 29 (39%) and partial hematological remission in 26 (35%) of the 74 patients evaluable for response. Major cytogenetic responses were observed in ten (13%) and minor cytogenetic responses in 11 patients (15%). Median duration of cytogenetic response was 33 months (range, 2-90); relapses were seen in all of the 11 patients with minor and in three of the ten patients with major cytogenetic responses. Median survival estimates for pretreated (n = 19) and untreated (n = 58) patients were 51 months (95% confidence interval [CI], 30-72) and 77 months (95% CI, 43-111), and the survival probabilities at 5 years were 45% and 54% for the two groups, respectively. Hematological response after 3 months of treatment demonstrated a clear-cut discriminative capacity with 5-year survival probabilities of 100%, 67% and 24% for patients achieving CHR (n = 6), PHR (n = 34), and less than PHR (n = 35), respectively. Landmark analysis at 12, 18, and 24 months after start of IFN therapy and an analysis treating time to cytogenetic response as a time-dependent covariate showed that cytogenetic response was associated with longer survival. The impact of a low-dose IFN regimen on survival in CML patients is unclear and requires further clarification by randomized clinical trials. Early hematological and cytogenetic response to IFN-alpha treatment identifies patients with a favorable long-term prognosis.

Adolescent↗
PubMed1996

Uncoupling of the pathways which link MAP kinase to c-fos transcription and AP-1 in response to growth stimuli.

The v-Src oncoprotein induces mitogenesis and transformation of cells through multiple effects on diverse signalling pathways that are influenced by the cellular context in which v-Src is expressed. Here we have examined the effects of a temperature-sensitive (ts) v-Src on transcription of the c-fos proto-oncogene, in serum-deprived and growing Rat-1 fibroblasts. We have also considered the role of mitogen-activated protein (MAP) kinase, a known mediator of ternary complex formation at the c-fos serum response element (SRE), which results in transcriptional enhancement in response to growth factors. In cells exponentially growing in the presence of serum, activation of v-Src stimulated MAP kinase and c-fos transcription. In cells made quiescent by serum deprivation, however, v-Src did not induce a c-fos transcriptional response, nor was there stimulation of ternary complex formation, despite normal activation of MAP kinase. Thus, activation of MAP kinase and stimulation of c-fos transcription and ternary complex formation are uncoupled in the absence of serum growth factors. Stimulation of c-fos by v-Src in growing cells, however, coincided with formation of a complex with an oligonucleotide spanning the c-Sis-inducible element (SIE) upstream from the SRE, suggesting that the signal transduction and activator of transcription (STAT) family of transcription factors, which bind here, may function in response to the v-Src oncoprotein. During these studies, we also observed that addition of fresh serum growth factors to growing Rat-1 fibroblasts expressing ts v-Src at the restrictive temperature resulted in substantially impaired activation of MAP kinase. This interference with normal growth factor signalling implies that catalytically inactive Src acts in a dominant negative manner by blocking normal activation of MAP kinase, although not at the expense of c-fos transcription. Thus, serum-induced c-fos transcription can also occur in an MAP kinase-independent manner.

Animals↗
PubMed1996

Incidence of extramural venous invasion in colorectal carcinoma: findings with a new technique.

In reported studies of extramural venous invasion (EVI) by colorectal carcinoma (CRC) in which conventional preparations involving a sectioning plane perpendicular to the tumor were used, an incidence as high as 36% has been found for unselected surgical material from patients operated on for cure. However, with this preparation technique, not all of the veins that exit the bowel wall roughly at right angles can be examined adequately. We investigated whether preparation of the adjacent vascular connective tissue with tangential sectioning might not result in different EVI rates. A total of 100 unselected surgical specimens of the bowel bearing 103 CRCs were prepared using a previously undescribed method, and EVI was found in 54.1% of the cases considered to have been treated curatively. To assess EVI fully, a complete study of all the vessels draining the tumor would be required yet the conventional preparation technique is associated with the distinct possibility of sampling error, because only a few vessels in each block are sectioned in the longitudinal axis. This sampling error might well be the explanation for the considerably higher incidence of EVI in our cases than in the reports in the literature. In all patients with EVI, the possibility of hematogenous metastases exists, and this has a significant bearing on the question of selecting patients for adjuvant chemotherapy.

Carcinoma↗
PubMed1996

Successful treatment of primary extramedullary leukemia (EML) of the uterus with radical surgery, chemotherapy, autologous bone marrow transplantation (BMT) and prophylactic local irradiation.

Extramedullary myeloid cell tumors are rare manifestations of acute nonlymphocytic leukemia (ANLL). While many advances in diagnosis have been made, dilemmas remain concerning the treatment of this disease. In primary extramedullary leukemia (EML) most reports agree upon a local therapy followed by systemic chemotherapy such as is used for ANLL. However, further prophylactic local or systemic therapy with stem cell support remains controversial. A 20-year-old patient was diagnosed as having granulocytic sarcoma (GS) of the uterus without evidence of ANLL in 1991. After resection of the tumor at the uterine cervix and chemotherapy with daunorubicin 50 mg/m2 (days 1-3) and cytosine-arabinoside 200 mg/m2 (days 1-7) in September 1991, complete remission was achieved. In October 1991 cytosine-arabinoside 1000 mg/m2 every 12 h from day 1 to day 6 and amsacrine 200 mg from day 5 to day 7 were given as consolidation. Two years later relapse occurred in the adnexae. After radical hysterectomy, the same induction and consolidation chemotherapy was administrated. Subsequently, cytoxane 60 mg/m2 and fractionated total body irradiation (6 x 200 cGy) were given as conditioning and the previously cryopreserved bone marrow was reinfused. Finally, after hematopoietic engraftment, prophylactic local irradiation (4500 cGy) to the pelvis was given resulting in a disease-free long-term survival of more than 36 months after relapse. Although this experience is confined to one patient, it may contribute to the design of prospective therapeutic studies in patients with primary EML.

Adult↗
PubMed1996

[Significance of arterial anastomoses of the distal calf and proximal foot for compensation of peripheral arterial occlusive disease].

The vascular anatomy of the distal calf and proximal foot was studied in 16 preparations obtained by corrosion. Arterial anastomoses between the different vessels are frequently observed and were also detected by digital subtraction arteriography in 14 patients with peripheral arterial occlusive disease. The comparison between anatomy and arteriography revealed that performed anastomoses in the malleolar and proximal foot region are important for compensating crural arterial occlusions. The Ramus communicans posterior, the Ramus perforans of the fibular artery and the Rete calcaneare play an important role. Whereas in other vascular territories collaterals dominate for compensation of occlusions performed anastomoses are of crucial importance at the malleolus.

Aged↗
PubMed1995

Beneficial effects of co-administration of catechol-O-methyltransferase inhibitors and L-dihydroxyphenylalanine in rat models of depression.

The administration of catechol-O-methyltransferase inhibitors alone changed neither the behavior of the rats in two animal models of depression, the forced swimming test (entacapone and tolcapone) or in the learned helplessness paradigm (tolcapone), nor the locomotor activity. L-Dihydroxyphenylalanine (L-DOPA) and carbidopa treatment as such decreased motility but did not improve the behavior in the antidepressant tests. Co-administration of catechol-O-methyltransferase inhibitors and L-DOPA/carbidopa increased the performance of rats in both tests without increasing locomotor activity. Catechol-O-methyltransferase inhibitors could be beneficial as adjunct drugs of L-DOPA not only in Parkinson's disease but also in the coincident depressive illness.

Analysis of Variance↗
PubMed1995

Role of N-methyl-D-aspartic acid and cholecystokinin receptors in apomorphine-induced aggressive behaviour in rats.

We studied the aggressive behaviour induced by repeated treatment with apomorphine, a dopamine agonist (0.5 mg/kg s.c. twice daily, 10 days), in rats. The first signs of defensive aggressiveness appeared on the third day of apomorphine treatment and were generally seen on the 7th day. Aggressiveness induced by a challenge dose of apomorphine (0.5 mg/kg s.c.) on the 11th day was antagonized by haloperidol (0.05 and 0.1 mg/kg i.p.) and clozapine (10 mg/kg i.p.). An antagonist of N-methyl-D-aspartate (NMDA)-gated channels, dizocilpine (MK-801), also blocked the aggressive behaviour at 0.25 and 0.5 mg/kg i.p. but caused ataxia. When dizocilpine (0.25 mg/kg i.p.) and apomorphine were coadministered for 10 days, aggressive behaviour did not develop. At 0.025 mg/kg i.p., dizocilpine even accelerated the appearance of apomorphine-induced aggressive behaviour, which manifested on the 3rd day in all rats. In a separate study, a 7-day treatment with dizocilpine (0.25-1 mg/kg i.p.) of rats, sensitized by a prior 10-day apomorphine treatment, did not reverse the established aggressive behaviour. The coadministration of apomorphine and cholecystokinin (CCK) -A or -B antagonists, devazepide or L-365,260 (0.01-2.5 mg/kg i.p.) respectively, neither affected development of apomorphine-induced aggressive behaviour nor intensity of aggressiveness in the sensitized rats. In binding studies neither density nor affinity of striatal dopamine D2 receptors was changed by acute or chronic apomorphine treatment. The number of [3H]pCCK-8 binding sites in the frontal cortex increased already after a single injection of apomorphine.(ABSTRACT TRUNCATED AT 250 WORDS)

Aggression↗
PubMed1995

Further studies on the role of cholecystokinin-A and B receptors in secretion of anterior pituitary hormones in male rats.

We compared the effects of unselective cholecystokinin (CCK) agonists (caerulein and CCK-8s) and a CCKB agonist CCK-4 on the secretion of thyrotropin (TSH), growth hormone (GH) and prolactin (PRL) in male rats. The subcutaneous (s.c.) administration of caerulein and CCK-8s suppressed dose-dependently TSH and GH levels. In contrast, when given into the 3rd brain ventricle (i.c.v.) caerulein dose-dependently elevated the GH levels. Next the importance of the afferent vagal nerves was studied in the action of caerulein and CCK-4. Subdiaphragmatic vagotomy itself decreased cold-stimulated TSH levels but abolished the suppressing effect of intraperitoneal (i.p.), and apparently also that of the i.c.v. caerulein. GH and PRL levels were altered neither by vagotomy nor caerulein. CCK-4 did not affect hormone levels. Atropine and butylscopolamine (i.p.) themselves did not alter TSH, PRL or GH secretion in intact rats. Neither did they reverse the effect of caerulein on TSH. In conclusion, CCKA receptors dominate in TSH and CCKB receptors in GH regulation. CCKA receptors in the gastrointestinal tract, related to the nervus vagus are mediating the inhibitory effect of caerulein upon TSH secretion but inhibition of GH secretion does not depend on the nervus vagus. CCKB receptors in the brain stem or near the 3rd brain ventricle are responsible for stimulation of GH secretion.

Animals↗
PubMed1995

Effect of silicone sound speed and intraocular lens thickness on pseudophakic axial length corrections.

We compared the sound speeds of SLM-1/UV (990 M/sec at 35 degrees Celsius [degrees C]), SLM-2/UV (1090 M/sec at 35 degrees C), and Perspex CQ poly(methyl methacrylate)(2658 M/sec at 35 degrees C). Methods are presented to determine the correction of axial length (CAL) factors for axial length measurements made on pseudophakes with AMO PhacoFlex Si-18, Si-26 (SLM-1/UV), and AMO PhacoFlex II SI-20 or SI-30 (SLM-2/UV) silicone intraocular lenses (IOLs). A CAL is required to avoid potential errors with secondary IOL power predictions; CALs, which are strongly dependent on the material sound speed and less so on lens thickness, ranged from -0.65 mm to -1.20 mm for SLM-1/UV silicone IOLs and from -0.35 mm to -0.55 mm for SLM-2/UV silicone IOLs. The sound speeds of IOL materials varied insignificantly between ambient room temperature (23 degrees C) and intraocular temperature (35 degrees C).

Artifacts↗