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Biomedical subjects

H Maurer

Publications and source records attributed to H Maurer.

At least 55 records · Page 3Linked to original sources
PubMed1994

Renal toxicity of ifosfamide in pilot regimens of the intergroup rhabdomyosarcoma study for patients with gross residual tumor.

PURPOSE: The purpose of this review is to characterize the nephrotoxicity noted in newly diagnosed patients under 21 years of age after treatment with ifosfamide-containing chemotherapy regimens and local irradiation for localized gross residual rhabdomyosarcoma or undifferentiated sarcoma. PATIENTS AND METHODS: From 1987 to 1991, 194 previously untreated patients received vincristine and ifosfamide plus dactinomycin or etoposide for 1-2 years. Ifosfamide was given at 1.8 g/m2/day for 5 days with sodium mercaptoethane sulfonate, or 9 g/m2 of ifosfamide per course. The three-drug regimen was repeated every 3-4 weeks. RESULTS: Twenty-eight patients (14%) developed renal toxicity: 19 had renal tubular dysfunction (RTD) characterized by low serum phosphate (< or = 3 mg/dl) or bicarbonate (< 20 or = mEq/L) levels, five had decreased glomerular function (DGF), and four had both RTD and DGF. When nine or more courses of ifosfamide (> 72 g/m2) were given, children < 3 years of age had a higher incidence of RTD than did children > or = 3 years of age (34% versus 6%; p < 0.001). A similar age difference was observed even when eight or fewer courses (< or = 72 g/m2) were given (p = 0.03). A matched case-control comparison showed that renal abnormalities at diagnosis, chiefly hydronephrosis, also increased the risk of renal tubular injury by ifosfamide by a factor of 13 (p < 0.001). Patients with DGF tended to be older than those with RTD, and all but one received > 72 g/m2 of ifosfamide. CONCLUSIONS: Patients who are < 3 years of age who receive more than eight courses (> 72 g/m2) of ifosfamide and who have a preexisting renal abnormality have an increased risk of RTD and DGF. The renal function of patients being considered for ifosfamide treatment must be carefully monitored. Ifosfamide should be avoided in patients with renal abnormalities at diagnosis unless the potential benefit clearly exceeds the risk of further renal impairment.

Acute Kidney Injury↗
PubMed1994

Erythropoiesis, but not thrombocytopoiesis, is affected by the presence of a large amount of subcutaneously implanted bone marrow.

The concept that megakaryocytopoiesis is regulated in part by the number of megakaryocytes themselves, separately from its regulation by the number of platelets, is referred to as autoregulation. Its occurrence has been implied from animal models that demonstrate compensated megakaryocytopenia. In that condition, normal platelet production can occur even though numbers of megakaryocytes are substantially reduced, and individual megakaryocytes exhibit changes consistent with their being stimulated. The present experiments were undertaken to determine whether the converse situation, namely suppression of megakaryocytopoiesis by an excess of megakaryocytes, could be created. The experimental model consisted of C57Bl mice in which as many as 10 isogeneic femurs were implanted subcutaneously 10 weeks before analysis. The implanted femurs contained hematopoietic marrow morphologically. They incorporated radioiron, but only about 40% as much as an equal number of normal femurs, so hematopoiesis did not regenerate to the full potential of the implanted marrows. After implantation of nine or 10 femurs, thrombocytopoiesis was normal as judged by platelet counts, mean platelet volumes, numbers of megakaryocytes in tibial marrow, and megakaryocyte sizes. Hematocrits were increased, but plasma erythropoietin levels were normal. The implants showed a 15- to 20-hour incorporation of radioiron of 9.4 +/- 0.5%. Iron incorporation into endogenous bones and spleen was reduced, demonstrating that erythropoiesis was redistributed. The total incorporation of iron into all hematopoietic tissue was slightly increased, but red-cell iron incorporation was normal, implying that there was more ineffective erythropoiesis than normal. Leukocyte counts, differentials, and tibial cellularity were normal. After implantation of three or six femurs, no abnormalities of hematopoiesis were detected, even though the implants incorporated iron in proportion to their number. Thus, erythropoiesis was adjusted by the excess of total marrow caused by nine or 10 subcutaneously implanted femurs. This is about the maximum of implanted marrow that is feasible with this model, and the failure to observe suppression of megakaryocytopoiesis may have been due to an inability to achieve a large enough number of megakaryocytes to elicit a detectable response. Alternatively, autoregulation of megakaryocytes may depend more on the marrow concentration of megakaryocytes than on the total body content.

Animals↗
PubMed1993

Interleukin-3, interleukin-6, granulocyte-macrophage colony-stimulating factor and erythropoietin cord blood levels of preterm and term neonates.

The cascade of known haematopoietic growth factors controlling granulomonopoiesis and erythropoiesis includes interleukin-3 (IL-3), interleukin-6 (IL-6), granulocyte-macrophage colony-stimulating factor (GM-CSF), and erythropoietin (EPO). Elevated endogenous IL-3 and IL-6 cord blood levels in infection-free premature and mature neonates may reflect their possible role for expansion of haematopoietic progenitor cells, granulocytes and monocytes. Within the erythroid lineage a synergistic action of IL-3, IL-6 and EPO can be assumed. To identify the regulatory role in fetal haematopoietic expansion cord blood plasma levels of these haematopoietic growth factors were assessed in 19 premature and 20 mature infants using commercial enzyme-linked immunosorbent assay and enzyme-amplified sensitivity immuno assay test kits. Peripheral blood IL-3, GM-CSF and EPO were studied in 5 and 10 premature infants respectively. Compared with cord blood levels we found a decline in EPO levels but no decrease of IL-3 and GM-CSF during the 1st month of life. We conclude that postnatal decrease in plasma burst-promoting activity levels in preterm infants is mainly explained by low postnatal EPO levels.

Erythropoietin↗
PubMed1992

Ascending myelitis after intensive chemotherapy and radiation therapy in children with cranial parameningeal sarcoma.

In 1977, a program of early, wide-field radiation therapy (RT) to the central nervous system and repeated lumbar intrathecal (IT) medications along with systemic chemotherapy was begun by the Intergroup Rhabdomyosarcoma Study (IRS) for patients younger than 21 years of age with cranial parameningeal sarcoma and a high risk of meningeal extension. From 1977 until 1987, 149 eligible patients with high-risk cranial parameningeal sarcoma were enrolled in IRS trials. None had evidence of lower extremity or sphincter impairment at diagnosis. Five of the 149 (3.4%) had ascending myelitis at 5.5 to 9 months after the initiation of therapy, with loss of sphincter control and inability to walk; this progressed to severe flaccid quadriparesis and necessitated long-term ventilatory support in 4. All five had received vincristine, dactinomycin, cyclophosphamide, and doxorubicin; four also had received cisplatin and three also had received etoposide. All patients received 4770 to 5500 cGy to the primary tumor, and four patients received 3000 cGy of cranial RT. Three patients received cervical RT and two received spinal RT. The patients also received four to seven courses of IT methotrexate, hydrocortisone, and cytosine arabinoside. Three patients died: one after local tumor recurrence with central nervous system extension and two without known recurrence. In one of the latter patients, the results of an autopsy showed necrosis of the cervical spinal cord and caudal medulla. Although the exact cause of this complication is unclear, no additional cases have been reported to the IRS since the protocol was revised in 1987 to reduce the doses of the IT drugs and to limit them to four courses each.

Adolescent↗
PubMed1992

A prospective study of nonrhabdomyosarcoma soft tissue sarcomas in the pediatric age group.

Nonrhabdomyosarcoma soft tissue sarcomas in infants and children are rare malignancies with most of the clinical data gained by retrospective analysis. In 1986, a prospective multicentered study was initiated by the Pediatric Oncology Group (POG) with a total of 75 cases now entered for epidemiologic examination. Median age of presentation was 12 years (range, newborn to 20 years). The male to female ratio was 2.3 to 1. The most common soft tissue tumor was synovial cell sarcoma (32/75, 42%), followed by fibrosarcoma (10/75, 13%), malignant fibrous histiocytoma (9/75, 12%), and malignant neurogenic tumors (8/75, 10%). Sixty-five percent of all tumors presented on the extremities (44% lower extremity, 21% upper extremity). Tumors of the trunk accounted for 28% (abdomen 15%, thorax 13%), whereas head and neck tumors were 7%. By TNMG classification, 16% presented as stage I, 21% as stage II, 33% as stage III, and 30% as stage IV. Age at presentation did not affect clinical site or stage. All upper extremity tumors presented with localized disease, whereas lower extremity tumors presented with regional nodal disease in 7% and metastatic disease (pulmonary) in 23% of the cases. Seventy-eight percent of the abdominal tumors were metastatic at diagnosis; the other 22% had extensive regional disease. In the thorax 78% had localized lesions with 22% having extensive regional disease. Ninety percent of synovial cell sarcomas were on the extremities: 84% localized disease and 12% metastatic spread at presentation. Sixty percent of the fibrosarcomas presented on the extremities with 80% having localized disease and 20% metastatic spread. Only 25% of the neurogenic tumors presented with localized disease, whereas 50% had metastases at the time of diagnosis.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1991

Immunohistochemical study of childhood rhabdomyosarcomas and related neoplasms. Results of an Intergroup Rhabdomyosarcoma study project.

The authors assessed a panel of immunohistochemical stains against 109 pediatric solid tumors, primarily rhabdomyosarcomas, under the auspices of the Intergroup Rhabdomyosarcoma Study. Fresh tumor tissue received from participating organizations was divided into portions that were either frozen or fixed in formalin, alcohol, or B5. Immunostaining was performed by the avidin-biotin complex method using monoclonal antibodies to desmin, neurofilaments, vimentin, cytokeratin, and leukocyte common antigen on cryostat sections. Tissue was also embedded in paraffin and stained with antimuscle-specific actin (MSA) and polyclonal antibodies to desmin, creatine kinase M subunit (CKM), myoglobin, and neuron-specific enolase (NSE). Antidesmin staining of cryostat sections was the most sensitive indicator of rhabdomyosarcoma (58 of 62 specimens positive). Results with this reagent in alcohol-fixed and formalin-fixed tissue were similar (46 of 56 positive versus 43 of 56 positive, respectively) and comparable with results with anti-MSA in formalin-fixed tissue (43 of 55 positive). However, the proportion of cells stained by antidesmin was higher in alcohol-fixed tissue than in formalin-fixed tissue. Staining with antimyoglobin and anti-CKM was much less satisfactory, with positivity rates of 17 of 37 and 11 of 57, respectively, in formalin-fixed rhabdomyosarcomas. Immunostaining of muscle markers revealed evidence of myogenesis in six undifferentiated sarcomas and in two sarcomas with inadequate histologic study on hematoxylin-eosin-stained sections. However, positivity was also noticed in samples of fibromatosis, Wilms' tumor, ectomesenchyoma, peripheral primitive neuroectodermal tumor, renal rhabdoid tumor, myositis ossificans, malignant fibrous histiocytoma, and embryonal sarcoma of the liver. The authors conclude that combined use of antidesmin and anti-MSA enhances the diagnosis of childhood sarcomas, especially when employed with other techniques such as electron microscopic study.

Actins↗
PubMed1991

Prognostic factors in 951 nonmetastatic rhabdomyosarcoma in children: a report from the International Rhabdomyosarcoma Workshop.

A total of 951 newly diagnosed patients with nonmetastatic rhabdomyosarcoma (RMS) under 21 years of age from four different cooperative study groups were analyzed to identify the most important pretreatment tumor characteristics in predicting survival. The patient characteristics considered were tumor invasiveness (T), tumor size, status of locoregional lymph nodes, and primary site. The cooperative groups and studies analyzed were: SIOP [RMS-75 (1975-1984)], the Intergroup Rhabdomyosarcoma Study [IRS-II (1978-1982)], Federal Republic of Germany [CWS-81 (1981-1986)] and Italy [RMS-79 (1979-1986), each study involving a different therapeutic protocol. Patient characteristics identified as having a significant relationship to survival by univariate analysis were (favorable features given in brackets): tumor invasiveness [T1], tumor size [less than or equal to 5 cm], status of locoregional lymph nodes [clinically negative], and primary site [orbit and genitourinary non-bladder prostate (GU-non-BP) sites]. T2 tumors tended to have large size (greater than 5 cm), to be associated with positive nodes, and to have a different distribution by primary site than T1 tumors. A multivariate Cox regression analysis of the pooled data identified tumor invasiveness (T), primary site, and the interaction between T and primary site as significant predictive factors for survival. The prognosis of orbital tumors was consistently favorable regardless of T status, whereas the prognosis for "other sites" was consistently unfavorable. International cooperation in this study has permitted the identification of good and poor risk patient subgroups, permitting the focusing of therapeutic protocols to particular risk groups and setting the stage for common future therapeutic protocols for rare subgroups of patients.

Child↗
PubMed1990

Transcutaneous carbon dioxide pressure for monitoring patients with severe croup.

In a prospective investigation of 17 children with severe croup, we analyzed the effect of epinephrine inhalations and mild sedation with chloral hydrate on transcutaneous carbon dioxide pressure (tcPCO2), pulse oximetry measurements, and croup scores. There was a highly significant reduction (p less than 0.001) in the tcPCO2 values and croup scores after inhalation of epinephrine. The changes in the tcPCO2 values correlated with the clinical findings. Mild sedation also significantly improved the croup scores but failed to influence the tcPCO2 values. There was not statistically significant difference in pulse oximetry saturation, fraction of administered oxygen, heart rate, or respiratory rate before and after inhalation of epinephrine or chloral hydrate administration. Monitoring tcPCO2 appears to be a reliable and objective tool for managing patients with upper airway obstruction, whereas croup scores may be misleading.

Blood Gas Monitoring, Transcutaneous↗
PubMed1990

Bioequivalence of sodium monofluorophosphate with sodium fluoride and compatibility with calcium.

The study was conducted in a triple cross-over on 12 healthy Caucasian volunteers (4 males and 8 females) of an age between 23 and 44 years. The following products were given in a single oral dose in fasting state. 1. Solution of 29.18 mg of sodium fluoride in 80 ml of water (reference NaF solution). 2. Solution of 100 mg sodium monofluorophosphate (CAS 10163-15-2) in 80 ml of water (Na2FPO3 solution). 3. Tablets with 100 mg sodium monofluorophosphate and 1250 mg calcium carbonate (Na2FPO3 + Ca tablets). The three products were equivalent in fluorine content (13.2 mg). The bioavailability of fluorine was evaluated on the basis of the plasma levels and of the urinary excretion of fluoride. After administration of the products, fluoride appeared in blood with a lag time smaller than 0.05 h and invaded the blood with a t1/2 from 0.07 to 0.12 h. The Cmax of fluoride in plasma was 412-466 ng/ml at a tmax of 0.5-0.7 h. The AUCs of fluoride after Na2FPO3 solution and after Na2FPO3 tablets were within the 0.80-1.20 bioequivalence limits with regard to the AUC after NaF solution. The three products can therefore be considered bioequivalent according to the Westlake criteria. In the 24 h following the administration, the urinary excretion of fluoride accounted for 51 +/- 10%, 46 +/- 6% and 47 +/- 8% of the administered dose, respectively for NaF solution, Na2FPO3 solution and Na2FPO3 + Ca tablets. The difference between the three products was statistically not significant and confirms their bioequivalence.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1990

Relative bioavailability of fluoride from monofluorophosphate tablets after single oral administration.

The study was conducted on 12 healthy male Caucasian volunteers of an average age of 27.8 +/- 4.0 years with single oral doses of the following products: 1. sodium monofluorophosphate tablets (MFP-tablets, Mono-Tridin); 2. aqueous solution of 23.2 mg of sodium fluoride (NaF solution-reference); 3. aqueous solution of sodium monofluorophosphate (MFP solution). The three products were equivalent in fluorine content with 10.5 mg F. The bioavailability was evaluated on the basis of the plasma levels and of the urinary excretion of fluoride. The study was designed as a triple latin-square crossover and each subject received the three products in three different periods, at empty stomach. After administration of the products, fluoride appeared quickly in blood (lag time between 0.07 and 0.13 h) and invaded rapidly the blood (invasion t1/2 from 0.04 to 0.15 h). The Cmax of fluoride in plasma was 439 ng/ml at tmax of 1.08 h after MFP tablets, 430 ng/ml at a tmax of 0.51 h after NaF solution and 403 ng/ml at tmax of 0.62 h after MFP solution. The differences for the Cmax were not statistically significant. The relative bioavailability of fluoride from MFP tablets, estimated from the AUC, was 1.35, and significantly larger than that from the reference NaF solution. Fluoride was eliminated from plasma with an initial fast rate (t1/2 from 0.68 to 1.03 h) and a terminal slower rate (t1/2 from 4.71 to 7.37 h). The plasma levels of fluoride were consistent with a two-compartment open pharmacokinetic model after extravascular administration. In the 24 h following the administration the urinary excretion of fluoride accounted for 50-53% of the administered dose, without significant difference between the three products. The three products were well tolerated and no systemic or gastric adverse reaction was recorded.

Adult↗
PubMed1990

Urinary metabolites of benzbromarone in man.

Benzbromarone [3,5-dibromo-4-hydroxyphenyl)-(2-ethyl-3-benzofuranyl)-ketone) is a widely used uricosuric drug which was reported to be metabolized by successive debromination. Recently, however, it was reported that benzbromarone is not debrominated but hydroxylated at the ethyl side chain. The presented paper describes further studies on the metabolism of the drug in man. The metabolites were identified in urine samples from two different patients intoxicated suicidally with high doses of benzbromarone after cleavage of conjugates, extraction and derivatization by acetylation using gas chromatography-mass spectrometry. The following five metabolites could be identified besides the unchanged benzbromarone (BB): hydroxy-alkyl-BB, oxo-BB, two isomers of hydroxyaryl-BB and hydroxy-methoxy-aryl-BB. Therefore, the following two phase I metabolic pathways can be postulated: successive oxidation of the ethyl side chain and one- and twofold hydroxylation of the benzofuran ring followed by methylation of one of the hydroxy groups. Benzbromarone and its metabolites are excreted in urine partly in a conjugated form. Debrominated metabolites could not be detected, although the concentrations of benzbromarone and its metabolites were very high in the urine samples studied.

Acetylation↗
PubMed1990

Lower eyelid reconstruction with the upper eyelid rotation flap.

A new technique of lower eyelid reconstruction was developed by using an ipsilateral upper eyelid rotation flap. After resection of a tumor in the lower eyelid, it is possible to replace the defect by a full-thickness upper eyelid rotation flap. Knowledge of exact eyelid anatomy is necessary to perform this kind of operation. In addition to the well-known techniques, the rotation flap constitutes a complete anatomic reconstruction of the lower eyelid with no functional loss of the upper eyelid.

Aged↗
PubMed1989

Primary extrarenal Wilms' tumor in children.

We report three additional cases of primary extrarenal Wilms' tumor and review those cases previously documented. Analysis of the location, histopathology, treatment, and survival of these cases supports the following conclusions: Wilms' tumor may occur in an extrarenal location without primary renal involvement and must be included in the differential diagnosis of abdominal, pelvic, and inguinal masses; an extrarenal location supports a more frequent occurrence of ectopic metanephric blastema than was previously recognized or origin of Wilms' tumor from a more primitive mesodermal tissue; and the natural history and prognosis of extrarenal and renal Wilms' tumors appears similar.

Abdominal Neoplasms↗