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Biomedical subjects

D Schmidt

Publications and source records attributed to D Schmidt.

At least 451 records · Page 25Linked to original sources

[Malignant peripheral neuroepithelial tumors in childhood].

The different therapy modalities and course of disease of 42 patients with a malignant peripheral neuroepithelial tumor are retrospectively analyzed. Therapy was completed in 31 children, 25 of whom had a primary localized tumor and 6 a disseminated neuroepithelioma. 17 of the children with a localized illness survive disease free in contrast to no survivor in the group with a disseminated tumor. The effective chemotherapy combining vincristine, adriamycin, ifosfamide and actinomycin D must be complemented by an efficacious local control because malignant peripheral neuroepithelioma tend to recur locally. The prospective analysis of newly diagnosed patients and a standardized therapy regimen will show if malignant peripheral neuroepithelioma represents a distinct tumor entity, different from a Ewings-Sarcoma.

Adolescent↗

[Total or partial withdrawal of antiepileptic drugs].

Total withdrawal of antiepileptic drugs leads to a mean relapse rate of approximately 50 p. 100 in adults and 25 p. 100 in children. The relapse rates are lowest in patients with benign epilepsies of childhood and epilepsies with absence seizures only and those with a short duration of epilepsy. Relapse rates are higher in patients with complex partial seizures, absences with generalized tonic-clonic seizures, juvenile myoclonic epilepsy, patients with several types of seizures, high seizure frequency prior to control, in patients with neurological, psychiatric or social handicaps and in those with emotional ambivalence towards the reduction. Guidelines for slow and safe withdrawal are given. Reduction should be actively encouraged only in patients with absence seizures or benign focal epilepsy and those with epilepsy of short duration. Slow partial withdrawal is recommended in uncontrolled epilepsy because in 80 p. 100 of the patients it results in a decrease in seizure frequency and side effects or both.

Anticonvulsants↗

Activity of phospholipase A compared in serum of patients with pancreatic and nonpancreatic diseases.

Phospholipase A (PLA) activity was measured with a semi-automated photometric test system that is based on liberation of fatty acids from phosphatidylcholine by phospholipases A1 (EC 3.1.1.32) and A2 (EC 3.1.1.4). We studied 528 serum samples from 86 patients whose lipase activities were increased owing to pancreatitis, pancreatic carcinoma, and extrapancreatic diseases. PLA activity showed no correlation with lipase or amylase activities or with the primary cause of the disease, but was clearly related to prognosis. Noncomplicated acute pancreatitis was characterized by "normal" PLA activities (0-10 U/L), whereas the values (50-137 U/L) were highest in necrotizing pancreatitis and septicemia with a lethal outcome. Changes in lipase and phospholipase A activities exhibited completely different time courses in the various diagnostic groups.

Acute Disease↗

Flow cytometric analysis of nephroblastomas and related neoplasms.

A total of 59 cases of nephroblastoma and related neoplasms were studied by flow cytometry of paraffin-embedded tissue. According to clinical prognosis, cases were subdivided into three groups: Group 1 (low risk) consisted of congenital mesoblastic nephroma (n = 13) and cystic, partially differentiated nephroblastoma (n = 2). Group 2 (intermediate risk) comprised the various subtypes of "typical" nephroblastoma (n = 24) including cases of fetal rhabdomyomatous nephroblastoma (n = 4). In group 3 (high risk) there were cases of anaplastic nephroblastoma (n = 3), clear cell sarcoma of the kidney or "bone metastasizing renal tumor of childhood" (n = 7), and malignant rhabdoid tumor of the kidney (n = 6). The three clinically different groups of tumors also varied in the proportion of cases with aneuploid tumor DNA stemlines, in S-phase fractions, and in proliferation indices (PI = S + G2 + M). Group 1 was generally characterized by a small number of cases with aneuploid tumor DNA stemlines and low values for S-phase fractions and PI, whereas Group 3 showed the largest number of cases with aneuploid tumor DNA stemlines and high values for S-phase fractions and PI. Group 2 was in between. It is concluded that flow cytometry on paraffin-embedded tissue from pediatric tumors may be a useful adjunct in determining prognosis, and that the subdivision of nephroblastomas and related neoplasms into three prognostically different groups is warranted.

Aneuploidy↗

The influence of seizure type on the efficacy of plasma concentrations of phenytoin, phenobarbital, and carbamazepine.

Plasma concentrations of phenytoin, phenobarbital, or carbamazepine were monitored prospectively during successful single-drug therapy in 78 patients who had various types of epileptic seizures. Mean plasma concentrations necessary for complete control of tonic-clonic seizures alone were as follows: phenytoin, 14 micrograms/mL (n = 28); phenobarbital, 18 micrograms/mL (n = 10); and carbamazepine, 5.5 micrograms/mL (n = 2). Epilepsy with simple or complex partial seizures alone or together with tonic-clonic seizures was completely controlled at the following plasma concentrations: phenytoin, 23 micrograms/mL (n = 25); phenobarbital, 37 micrograms/mL (n = 5); and carbamazepine, 7 micrograms/mL (n = 7). Higher plasma concentrations of phenytoin, phenobarbital, and carbamazepine are necessary for control in epilepsy with simple or complex partial seizures compared with epilepsy with tonic-clonic seizures alone. The efficacy of plasma concentrations of phenytoin, phenobarbital, and carbamazepine varies with the type of seizure.

Adult↗

Clobazam for refractory focal epilepsy. A controlled trial.

The effect of 1,5-benzodiazepine clobazam was assessed in a double-blind add-on trial in 20 patients with chronic complex partial seizures uncontrolled by maximally tolerable daily dosage of standard antiepileptic drug therapy. The number of seizures was lower during the three months of active treatment. At the end of the third month, eight (40%) of the patients had a seizure reduction by more than 75%, including four patients (20%) who had complete control. Tolerance to the antiepileptic effect of clobazam was noted in 56% of the patients, and mild transient sedation occurred in 40% of the patients. Despite these drawbacks, clobazam is an effective add-on drug for individual patients with refractory focal epilepsy.

Adolescent↗

Alternative single anticonvulsant drug therapy for refractory epilepsy.

Fifty-nine patients with chronic generalized tonic-clonic or partial seizures refractory to the maximally tolerated daily dosage of single-drug therapy with carbamazepine, phenytoin, phenobarbital, or primidone subsequently received single-drug therapy with another one of these primary anticonvulsant drugs. Alternative single-drug therapy resulted in complete seizure control or more than 75% seizure reduction for 18 patients (31%). Side effects disappeared in 16 patients (27%). Patients with a good therapeutic response often had epilepsy of recent onset. Alternative single-drug therapy is beneficial for chronic refractory epilepsy and should be considered before a second drug is permanently added.

Adult↗

Cellular differentiation and prognosis in embryonal rhabdomyosarcoma. A report from the Cooperative Soft Tissue Sarcoma Study 1981 (CWS 81).

Sixty-four cases of embryonal rhabdomyosarcoma (eRMS) were investigated for cellular differentiation by light microscopy. Of these 64 cases 20 were studied by means of immunohistochemistry. Histologically, three subgroups could be distinguished: primitive (less than 10% rhabdomyoblasts), intermediate (10-50% rhabdomyoblasts) and well differentiated (greater than 50% rhabdomyoblasts) eRMS. Vimentin-positive cells predominated in the primitive eRMS. Intermediate eRMS showed large proportions of desmin-positive cells but vimentin containing cells were also numerous. Myoglobin could only be demonstrated in well differentiated eRMS. Primitive and well differentiated eRMS mainly occurred in the head and neck area, whereas intermediate eRMS were predominantly located in the abdomen. Stage III and IV tumours predominated in cases of primitive eRMS, whereas lower stages were noted in cases of intermediate and well differentiated eRMS. Response to chemotherapy, evaluated after seven weeks of treatment, was achieved in 10/15 (66%) cases of primitive, in 16/19 (84%) cases of intermediate and 5/5 cases of well differentiated eRMS. It is concluded from the current study that the three subgroups of eRMS differ not only by cytological differentiation but also by site of predilection, stage at time of diagnosis and response to chemotherapy.

Abdominal Neoplasms↗

Potent vasopressin antagonists lacking the proline residue at position 7.

As part of a program to design potent antidiuretic vasopressin antagonists and to define the minimum effective pharmacophore requirements for vasopressin (VP) antagonist activity, we studied the importance of the C-terminal tripeptide of a previously reported peptide antagonist of arginine-vasopressin (AVP,1). The proline residue at position 7 in AVP is proposed to impart a conformational constraint to the peptide backbone that is essential for V2-receptor agonist activity. Since the structure-activity relationships for VP agonists and antagonists are different, we investigated the effect of proline on antagonist activity, by synthesizing analogue 3 lacking this residue. This analogue was found to retain a high degree of antidiuretic antagonist activity. Since deletion of the Gly residue at position 9 of the antagonist did not adversely affect VP antagonist potency, several vasopressin antagonist analogues (4-7 and 9) that lacked both the Pro and Gly residues were also studied. These, too, were found to block vasopressin V2-receptor activity. Our results indicate that neither the proline nor glycine residues are essential for antagonism of the V2 receptor.

Animals↗

Vasopressin antagonist analogs modified at position 7.

Vasopressin antagonist analogs having alanine or glycine at position 7 were essentially equipotent with analogs with proline, N-methylalanine or sarcosine at position 7. This demonstrates that the conformational constraint imposed by an N-alkyl residue at position 7 is not necessary for binding of antagonist to the receptor, the exact opposite of what is seen in agonists. This suggests that antagonists bind to the receptor in a manner which is very different from that of agonists.

Animals↗