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Biomedical subjects

J Haas

Publications and source records attributed to J Haas.

At least 19 recordsLinked to original sources

Immunological and clinical response to immunosuppressive treatment in paraneoplastic cerebellar degeneration.

OBJECTIVE: To report the clinical and immunological response to immunosuppressive treatment with cyclophosphamide in two patients with paraneoplastic cerebellar degeneration. DESIGN: Case reports. Clinical and immunological follow-up data available for 4 1/2 years in the first patient and for 2 years in the second patient. SETTING: A 1500-bed university hospital and a 1200-bed university teaching hospital. INTERVENTION: Cyclophosphamide intermittent treatment. MAIN OUTCOME MEASURE: Clinical disability. RESULTS: One of the patients, who was treated from an early stage, recovered completely. The other patient showed a partial clinical response. While the two patients were receiving a maintenance regimen with cyclophosphamide, the conditions of both patients remained stable for at least 2 years. In both patients, intrathecal antibody synthesis declined considerably. CONCLUSION: Early induction of immunosuppressive therapy with cyclophosphamide should be tried in treating patients with paraneoplastic cerebellar degeneration.

Cerebellar Diseases

A correlation of cell cycle perturbations with chemosensitivity in human ovarian cancer cells exposed to cytotoxic drugs in vitro.

To test the association between cytotoxicity and in vitro cell cycle perturbations we systematically studied cell cycle perturbations after exposing human ovarian cancer cells to nine commonly used cytotoxic agents. Three principal patterns of cell cycle alterations were observed: a sequential S-G2/M block after exposure to the non-phase-specific agents cis-platinum, 4-hydroperoxy-cyclophosphamide, and mitomycin C (Group I); an isolated G2/M block after exposure to the G2/M phase-specific drugs etoposide and vincristine and the non-phase-specific agent doxorubicin (Group II); and an isolated S block following exposure to the S phase-specific agents 5-fluorouracil, methotrexate, and cytosine arabinoside (Group III). Overall, there was no direct correlation between the degree of cell cycle perturbations and chemosensitivity. However, when the three subgroups of non-phase-specific agents, S phase-specific agents, and G2/M-specific agents were analyzed separately, positive correlations between the magnitude of cell kinetic alterations and chemosensitivity were observed. Cell kinetic alterations appeared to precede cytotoxicity.

Antineoplastic Agents

Benzimidazolones and renzapride facilitate acetylcholine release from guinea-pig myenteric plexus via 5-HT4 receptors.

The effects of the 5-HT4 receptor agonists BIMU 8, BIMU 1, renzapride and of the 5-HT1p receptor agonist 5-hydroxyindalpine on basal and electrically evoked outflow of tritium were studied in guinea-pig longitudinal muscle myenteric plexus preparations preincubated with [3H]choline. Muscle contractions were recorded simultaneously. BIMU 8 caused a calcium dependent and tetrodotoxin sensitive increase in basal [3H]outflow that was assumed to represent release of [3H]acetylcholine. In addition, BIMU 8 enhanced the release of [3H]acetylcholine and twitch contractions evoked by submaximal electrical stimulation. Ondansetron (1 mumol/l) did not change the effects of BIMU 8, but DAU 6285 and tropisetron (each 1 mumol/l) competitively antagonized the various facilitatory effects of BIMU 8 with pA2 values of 7.0-7.2 (DAU 6285) and 7.0-7.3 (tropisetron). The phosphodiesterase inhibitors IBMX and rolipram did not increase the effects of BIMU 8. BIMU 1 and renzapride also concentration-dependently increased basal release of acetylcholine, and release and contractions caused by submaximal stimulation. The effects of BIMU 1 and renzapride were competitively antagonized by 1 mumol/l tropisetron (pA2 6.6-7.1). The EC50 values for the increase in the evoked [3H]acetylcholine release and contractions were closely similar. 5-Hydroxyindalpine did not change basal release and slightly inhibited the evoked release of [3H]acetylcholine. Release of acetylcholine and contractions elicited by submaximal stimulation were strongly inhibited by (+)-tubocurarine which indicates that nicotine ganglionic transmission is involved in this kind of release. The results suggest that BIMU 8, BIMU 1 and renzapride stimulate 5-HT4 receptors at cholinergic interneurones and thereby facilitate nicotinic ganglionic transmission in the myenteric plexus.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholine

Pathology of tumor-stroma interaction in melanoma metastatic to the skin.

Tumor invasion and metastasis formation largely depend on tumor-stroma interaction. In the present study morphological correlates of tumor-stroma interaction were examined in 344 melanoma lesions metastatic to the skin. In particular, the presence of simple infiltration into the surrounding dermis or subcutis without evident stromal reaction, the incorporation of pre-existent dermal collagen or subcutaneous fat cells into the tumor bulk, and the formation of a peritumoral capsule or intratumoral fibrous septa were evaluated. Our results showed that simple infiltration into the surrounding tissue as well as the incorporation of pre-existent stroma tissue without destruction is associated with poor outcome, whereas capsule and fibrous septa are favorable prognostic signs, particularly in subcutaneous lesions. Remarkably, simple infiltration is a prognostic indicator independent of the location of the metastasis (locoregional or distant), as shown by multivariate analysis. These data indicate that morphological aspects of tumor-stroma interaction in metastatic skin lesions of melanoma may reflect biological behavior of the tumor cells, may facilitate a pathological subclassification of metastatic melanoma in addition to clinical data, and are directly related to the patient's outcome.

Adult

Computer simulations of histologic patterns in melanoma using a cellular automaton provide correlations with prognosis.

Computer simulations have been used frequently in the life sciences to investigate the mechanisms of morphologic pattern formation. The cellular automaton program SMN5 is designed to simulate tumor growth and to estimate biologic properties by comparing real tumor patterns with computer-simulated reference patterns. This method was applied to 195 cases of primary melanoma of the skin. S-100-stained sections were evaluated by image analysis and compared statistically to a reference set of 4000 simulated patterns. Estimates of tumor cell proliferation, motility, cell loss, cohesion, stroma destruction, and intercellular signals (autocrine and paracrine factors affecting growth, motility, and cell loss) were calculated. Twelve of 18 estimated parameters correlated significantly with tumor progression, as indicated by vertical tumor thickness (linear regression analysis: p < or = 0.05), and 13 of 18 parameters carried prognostic significance (log rank test: p < or = 0.05). Poor prognosis was associated particularly with a pronounced increase in the estimates of proliferation, tumor cell motility, and stromal degradation. Poor prognosis was also associated with a decrease in the estimates of cell loss, tumor cell cohesion, and paracrine growth factor dependence. In multivariate analysis using Cox's proportional hazard model, stromal degradation and motility showed prognostic information in addition to conventional prognostic parameters. The study shows that analytical comparison of real tumors with computer-simulated patterns of a cellular automaton facilitates a functional interpretation of tumor morphology, which carries prognostic significance in cutaneous melanoma.

Computer Simulation

Comparative analysis of intrathecal antibody synthesis and DNA amplification for the diagnosis of cytomegalovirus infection of the central nervous system in AIDS patients.

We evaluated 49 paired cerebrospinal fluid (CSF) and serum samples of 35 patients infected with the human immunodeficiency virus type 1 (HIV-1) for laboratory evidence of cytomegalovirus (CMV) infection. The patients were grouped according to clinical criteria as probable CMV encephalitis/polyradiculomyelitis, CMV retinitis, cerebral toxoplasmosis, progressive multifocal leukoencephalopathy, HIV-1-related cognitive/motor complex, HIV-1-associated myelopathy, and other neurological diseases. Paired CSF and serum samples were analysed for CMV deoxyribonucleic acid (DNA) by polymerase chain reaction (PCR), quantitative intrathecal synthesis of immunoglobulin G (IgG) antibodies specific for recombinant phosphoprotein 150 (pp150) of CMV and CMV-specific serum IgM. Intrathecal synthesis of pp150-specific IgG was detected in 26% of patients (9/35), serum IgM was found in 23% of patients (8/35), and PCR of CSF was positive in 11% of patients (4/35). Detection of CMV-specific DNA in CSF preceded the intrathecal antibody synthesis in three patients for whom serial samples were available. PCR results of the CSF became negative in one patient with CMV polyradiculomyelitis after successful therapy with 9-[2-hydroxy-1-(hydroxymethyl) ethoxymethyl] guanine (DHPG). PCR has a higher diagnostic specificity in the acute phase of CMV infection than intrathecal antibody synthesis. The serum IgM response to CMV cannot be used to monitor a compartmentalized immune response in the central nervous system while an intrathecal immune response seems to be associated with recovery either spontaneously or as a result of treatment.

AIDS-Related Opportunistic Infections

[Premature labor and fetal fibronectin in cervical and vaginal secretions].

This study aimed to determine whether quantitative measurements of fetal fibronectin in cervical vaginal secretions reflect the prognosis for imminent premature delivery. 166 patients, who were pregnant from between 25 and 36 weeks, were included in the study over a six months' period. Group A included 60 women with premature contractions, which ceased after tocolytic therapy. Group B consisted of 25 women, who delivered prematurely within 1 week. Group C contained 22 patients, with confirmed PROM and group D contained 24 patients in whom PROM was suspected, but not confirmed. The control group (group E) consisted of 35 patients with uneventful pregnancies. Fetal fibronectin levels in groups B and C differed significantly from those in the other groups. Therefore, the positive predictive value of elevated fetal fibronectin levels for premature delivery was 86.1%.

Amniotic Fluid

Reproductive effects of inorganic borates on male employees: birth rate assessment.

The purpose of this study was to investigate the potential for reproductive effects of inorganic borate compounds on male employees. The standardized birth ratio (SBR) methodology was used to assess fertility among male employees, using live births as the measured end point. The ratio of female to male births was also assessed. Data were collected via questionnaires and telephone follow-up interviews. Medical insurance records were assessed for nonresponders. Exposures were assessed using three semiquantitative categories. We found a statistically significant increase in fertility as measured by live births among the employees of the inorganic borate facility. There does not appear to be any decrease in fertility due to exposures either as analyzed by the borate exposure categories or over time, which is an indirect measure of exposures. We found a nonstatistically significant increase in the percentage of female offspring. This increase was due, not to a deficiency of male offspring, but rather to a marked increase in the numbers of female offspring. This increase in percentage female offspring does not appear to be related to exposures to inorganic borates. Based on the data, exposures to inorganic borates do not appear to adversely affect fertility in this population.

Birth Rate

In vivo comparison of zidovudine resistance mutations in blood and CSF of HIV-1-infected patients.

Several mutations are associated with resistance to zidovudine (3'-azido-3'-deoxythymidine, AZT) in cultured human immunodeficiency virus type 1 (HIV-1) isolates. Little is known as to what extent drug resistance occurs in vivo and whether its development within the CNS differs from that in peripheral blood. We therefore performed comparative nucleotide sequence analysis of the HIV-1 reverse transcriptase (RT) gene in proviral DNA obtained from blood and CSF of three patients, all of whom had progressed to AIDS under long-term zidovudine treatment. Six to 11 individual proviral copies per patient and compartment were analyzed by polymerase chain reaction (PCR)-mediated direct sequencing. In all samples, mutations associated with zidovudine resistance could be identified. They occurred in multiple HIV-1 copies in both blood and CSF, indicating that molecular determinants of resistance are reflected in most individual proviruses in vivo. Comparable positions and frequencies of mutations in isolates derived from both compartments do not argue for independent development of zidovudine resistance in CSF.

Acquired Immunodeficiency Syndrome

Knowledge discovery in GenBank.

We describe various methods designed to discover knowledge in the GenBank nucleic acid sequence database. Using a grammatical model of gene structure, we create a parse tree of a gene using features listed in the FEATURE TABLE. The parse tree infers features that are not explicitly listed, but which follow from the listed features. This method discovers 30% more introns and 40% more exons when applied to a globin gene subset of GenBank. Parse tree construction also entails resolving ambiguity and inconsistency within a FEATURE TABLE. We transform the parse tree into an augmented FEATURE TABLE that represents inferred gene structure explicitly and unambiguously, thereby greatly improving the utility of the FEATURE TABLE to researchers. We then describe various analogical reasoning techniques designed to exploit the homologous nature of genes. We build a classification hierarchy that reflects the evolutionary relationship between genes. Descriptive grammars of gene classes are then induced from the instance grammars of genes. Case based reasoning techniques use these abstract gene class descriptions to predict the presence and location of regulatory features not listed in the FEATURE TABLE. A cross-validation test shows a success rate of 87% on a globin gene subset of GenBank.

Algorithms

Treatment of multiple sclerosis with 15 +/- deoxyspergualin. Design of a controlled study with close MRI-monitoring.

The rationale and design of a prospective randomized double blind study of 15 +/- Deoxyspergualin in the treatment of Multiple Sclerosis are presented. The study was started in autumn 1992 and will include more than 200 patients who will be randomized either to DSG low dose or DSG high dose or placebo. Average number of contrast enhancing lesions in monthly cranial MRIs during the first six months of treatment and change in EDSS at the end of the two-year study period will be the main efficacy parameters.

Adolescent

Results of surgical treatment of 1028 cervical cancers studied with volumetry.

BACKGROUND AND METHODS: The clinical staging system of cervical cancer according to the International Federation of Gynecology and Obstetrics (FIGO) entails a large measure of subjectivity. This study analyzed the results of 1028 patients with cervical cancer at three reference centers. All patients had radical surgery, and all surgical specimens were processed as histologic giant sections with precise volumetry of the tumor. RESULTS: The interpretation of the histologic findings of parametrial invasion, vascular involvement, and lymph node involvement was found to differ somewhat among the three centers. However, all these findings were associated with tumor size. Survival rates correlated more consistently with tumor volume than with clinical or histologic stage. Five-year survival rates ranged from 91% for patients with tumors smaller than 2.5 cm3 to 70% for those with tumors 10-50 cm3. The 5-year survival rate of 24 patients with tumors larger than 50 cm3 (71% of whom had lymph nodes with positive findings) was 48%. Survival rates were identical among the three centers for patients with tumors smaller than 10 cm3, despite different degrees of surgical radicality. In contrast, more radical surgery was associated with significantly better survival rates in patients with larger tumors. CONCLUSIONS: The results of this study indicate that volumetry of the tumor permits a more accurate assessment of therapeutic results in patients with cervical cancer than does the FIGO classification. Pretherapeutic assessment of tumor volume is possible with magnetic resonance imaging. It seems that maximum parametrial resection is not necessary for patients with smaller tumors (smaller than 10 cm3), but truly radical surgery in patients with bulky tumors achieves better results than those usually expected in Stage IIb cervical cancer and at least comparable to those of radiation therapy.

Adult

Prognostic importance of human papillomavirus type 16 DNA in cervical cancer.

Human papillomavirus (HPV) type 16 DNA is frequent in invasive cervical cancers. Among 43 patients with invasive cervical cancer, HPV-16-positive tumors spread to the parametrial and pelvic lymph nodes significantly more often than did HPV-16-negative tumors (P less than 0.05). Demonstration of HPV-16 DNA in invasive cervical cancers may be an additional prognostic factor for this disease.

Adult

Prenatal diagnosis by amniocentesis in 82 pregnancies after in vitro fertilization.

We report on the outcome of 82 amniocenteses (AC) carried out during pregnancies after in vitro fertilization (IVF) from 1-1-1985 to 31-12-1989. The main indication for amniocentesis was a maternal age of greater than or equal to 35 years. In 48 cases, we found an anterior placenta and assumed that this was related to the position in which the uterine embryo transfer was performed. In six pregnancies, we found an abnormal karyotype, including two cases of trisomy 21; the two couples decided for abortion. Four aberrations in the fetal karyotypes were also present in either the mother or the father, the resulting children are healthy. The further course of pregnancies after IVF and AC was characterized by a higher incidence of toxemia, uterine bleeding before the 28th week of gestation, abruptio placentae, and premature deliveries, when compared to the course of pregnancies after spontaneous conception. We believe that these occurrences were not caused by AC, as the incidence was higher in all our pregnancies after IVF (without AC) and has also been reported in pregnancies after ovarian hyperstimulation without IVF. Therefore, we see no reason to renounce AC after IVF. However, the special risks inherent in pregnancies after IVF must always be discussed with the couple.

Adult

Nongenital cancers metastatic to the ovary.

We review our experience with 82 patients with nongenital cancers metastatic to the ovary. All patients were referred for evaluation of an ovarian mass. The patients had primary carcinoma of the breast (n = 28), colon (n = 23), stomach (n = 22), pancreas (n = 7), or gallbladder (n = 2). The overall actuarial 5-year survival rate was 10%. Five-year survival in patients with metastatic colon cancer was significantly higher (23%) than that in patients with metastatic cancer of the breast, stomach, gallbladder, or pancreas, all of whom died within 58 months (P less than 0.05). Patients with unilateral metastatic ovarian involvement had a 5-year survival significantly better than that of those with bilateral involvement (28% vs 5%; p = 0.003). Five-year survival in patients with disease limited to the pelvis was significantly higher than that in those with abdominal spread (22% vs 6%; P less than 0.04). The 5-year survival of patients with residual disease less than 2 cm or greater than 2 cm in diameter was 18% or 4%, respectively (P = 0.002). This pattern applied mainly to differences in patients with primary cancer of the breast or colon (P less than 0.008). These data suggest that an aggressive surgical effort seems to be indicated in colon cancer metastatic to the ovary, as some of these patients may survive 5 years.

Breast Neoplasms

Down syndrome complicated by brain tumors: case report and review of the literature.

This report concerns a 24-year-old male patient with Down syndrome, complicated by a benign but true neoplastic lesion of a differentiated papilloma of the choroid plexus which simultaneously displayed a dysgenetic character. A review of the literature revealed a lack of single case reports of Down syndrome with brain tumors, which may reflect chance occurrence; however, the brain tumors in Down syndrome patients are characterized by their dysontogenetic or dysgenetic character.

Adult

Riboflavin requirements and exercise adaptation in older women.

The effects of exercise training on riboflavin requirements and of riboflavin intake on endurance were examined in 14 women, 50-67 y of age, who participated in a 10-wk, two-period crossover exercise study at two riboflavin intakes, 0.15 micrograms/kJ (0.6 micrograms/kcal) and 0.22 micrograms/kJ (0.9 micrograms/kcal). Subjects exercised 20-25 min/d, 6 d/wk, for 4-wk periods on a cycle ergometer at 75-85% of their maximal heart rate. Riboflavin status was assessed by measuring the erythrocyte glutathione reductase activity coefficient (EGRAC) and urinary riboflavin excretion. Physical performance was evaluated by using a walking treadmill test to determine maximal oxygen capacity (VO2max) and anaerobic threshold by gas exchange (ATGE). Exercise significantly affected riboflavin status as EGRAC increased (P less than 0.001) and riboflavin excretion decreased (P less than 0.01) in both groups. VO2max increased significantly with exercise (P less than 0.01). However, changes in VO2max (L/min) and ATGE with exercise training were not different in the two groups. Riboflavin requirements of older women increased with exercise training, but increased riboflavin intake did not enhance improvements in endurance.

Aged