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Biomedical subjects

R Pfeiffer

Publications and source records attributed to R Pfeiffer.

At least 55 records · Page 3Linked to original sources
PubMed1995

Dopaminergic defect of enteric nervous system in Parkinson's disease patients with chronic constipation.

Clinical studies suggest that gut disorders are common in Parkinson's disease, but the morphological basis is unknown. Depletion of dopamine-containing neurons in the central nervous system is a basic defect in Parkinson's disease. We compared colonic tissue from 11 patients with advanced Parkinson's disease, 17 with adenocarcinoma (normal tissue was studied), and five who underwent colectomy for severe constipation. Immunohistochemistry was used to stain myenteric and submucosal neurons for dopamine, tyrosine hydroxylase, and vasoactive intestinal polypeptide (VIP). Each class of neurons was quantified as a percentage of the total neuronal population stained for the marker protein gene product 9.5. Nine of the 11 Parkinson's disease patients had substantially fewer dopaminergic myenteric neurons than the other subjects (mean 0.4 [SE 0.2] vs 6.9 [2.3] in controls and 5.7 [2.0] in constipated subjects). There was very little difference between the groups in numbers of tyrosine-hydroxylase and VIP neurons. Two Parkinson's disease patients had similar distributions of all types of neurons, including dopaminergic myenteric neurons, to the controls. High-performance liquid chromatography showed lower levels of dopamine in the muscularis externa (but not mucosa) in four Parkinson's disease patients than in four controls (7.3 [5.1] vs 24.2 [4.6] nmol per g protein), but levels of dopamine metabolites were similar in the two groups. The identification of this defect of dopaminergic neurons in the enteric nervous system in Parkinson's disease may lead to better treatment of colorectal dysfunction in this disease.

Adenocarcinoma↗
PubMed1995

Pharmaceutical solids: a strategic approach to regulatory considerations.

PURPOSE: This review describes a conceptual approach to the characterization of pharmaceutical solids. METHODS: Four flow charts are presented: (1) polymorphs, (2) hydrates, (3) desolvated solvates, and (4) amorphous forms. RESULTS: These flow charts (decision trees) are suggested as tools to develop information on pharmaceutical solids for both scientific and regulatory purposes. CONCLUSIONS: It is hoped that this review will lead to a more direct approach to the characterization of pharmaceutical solids and ultimately to faster approval of regulatory documents containing information on pharmaceutical solids.

Chemical Phenomena↗
PubMed1994

Inhibition of calmodulin-dependent myosin light-chain kinase by growth-hormone-releasing factor and vasoactive intestinal peptide.

In view of the ability of calmodulin to bind vasoactive intestinal peptide (VIP) and growth-hormone-releasing factor (GRF) with high affinity [Stallwood, Brugger, Baggenstoss, Stemmer, Shiraga, Landers and Paul (1992) J. Biol. Chem. 267, 19617-19621], the effects of these neuropeptides on a model calmodulin-dependent enzyme, myosin light-chain kinase (MLCK), were studied. Both peptides were potent inhibitors of MLCK activity. The inhibition of enzyme activity by VIP and GRF was progressively overcome with increasing calmodulin concentrations, with no inhibition observed at a saturating calmodulin concentration. Nanomolar concentrations of MLCK blocked the formation of calmodulin-[125I-Tyr10]VIP complexes. These data provide support for a functional role of VIP and GRF binding by calmodulin.

Amino Acid Sequence↗
PubMed1994

Immunogenetic and serological investigations in nonpregnant and in pregnant women with a history of recurrent spontaneous abortions. German RSA/IVIG Study Group.

In the context of a controlled multicenter study on intravenous immunoglobulin (IVIG) treatment of patients with a history of unexplained recurrent spontaneous abortions (RSA), a number of controversial immunological parameters were evaluated prior to and during pregnancy with respect to their diagnostic and/or prognostic significance. A total of 390 serum samples from 52 patients were investigated. Sharing of 2 or more HLA (A, B, DR, DQ) antigens was significantly more frequent in RSA couples than in controls. The rate of cytotoxic or Fc-receptor (FcR)-blocking antibodies was not significantly lower in RSA patients than in individuals with normal pregnancies. Both tumor necrosis factor-alpha (TNF-alpha) levels and IgG anticardiolipin antibodies (IgG-ACA) were significantly increased in the patient group. While the occurrence of HLA sharing, cytotoxic/FcR-blocking antibodies and IgG-ACA did not correlate with the outcome of pregnancy, TNF-alpha levels were found to be significantly higher in patients with subsequent miscarriage than in those with successful pregnancy. IgG-ACA, if present, significantly decreased during the course of successful pregnancy but remained high in patients with subsequent abortion. It is concluded that the diagnostic and/or prognostic value of HLA sharing and cytotoxic/FcR-blocking antibodies has been overestimated while TNF-alpha and ACA levels are potential diagnostic markers and/or exhibit prognostic significance in subgroups of RSA patients.

Abortion, Habitual↗
PubMed1994

Gastrointestinal dysfunction in Parkinson's disease. A report of clinical experience at a single center.

We describe our clinical experience in the evaluation of gastrointestinal symptoms in patients with Parkinson's disease. Dysphagia, heartburn, medication-related nausea, and constipation were the predominant symptoms. Although all of the patients localized their dysphagia to the oropharynx and although oropharyngeal dysfunction was common, evaluation revealed significant dysfunction in either the esophageal body or lower esophageal sphincter in many--gastroesophageal reflux-related disease being especially common. Studies of anorectal sphincter and pelvic floor function in those patients with constipation demonstrated a high incidence of abnormal external anal sphincter dysfunction. We conclude, first, that dysphagia in patients with Parkinson's disease should not be assumed to result solely from oropharyngeal dysfunction but deserves detailed evaluation and, second, that constipation in Parkinson's disease is commonly consequent on anorectal sphincter and pelvic floor dysfunction.

Abdominal Pain↗
PubMed1992

[Secretion of hCG by mononuclear cells--a specific and essential reaction in pregnancy?].

Mononuclear cells in peripheral blood secrete immunoreactive hCG (ir-hCG) when they are stimulated in in-vitro culture with the proteinkinase C - activator phorbol-myristat-acetate (TPA). We examined the ir-hCG secretion in 61 fertile and 191 pregnant women and 38 men. Mononuclear cells of pregnant women secrete after TPA stimulation significantly more ir-hCG than mononuclear cells on non-pregnant but fertile women. This effect can be detected as early as 23rd days of a menstrual cycle which is accompanied by conception and persisted over the entire duration of a pregnancy. Maximal effects were observed in the 7th to 19th and 30th to 34th weeks of pregnancy. An artefact caused by adhesive serum-hCG could be excluded. The elevated potential of the mononuclear cells to be stimulated remained intact for about 14 days after termination of a normal pregnancy in the first trimester. An ir-hCG secretion similar to that seen in nonpregnant women was found in patients with early abortion. The possible physiological importance of the in-vivo secretion of beta-HCG during pregnancy is discussed.

Abortion, Incomplete↗
PubMed1992

Optimization of levodopa therapy.

While there is no single correct starting dose for levodopa therapy, many individuals can be started on either the 25/100 or controlled-release formula, following the general rule not to attempt to titrate carbidopa-levodopa to the point of "normality," which can lead to toxicity. The physician should also determine the proper use of any adjunctive medications; such combined therapy has become the standard approach to treatment. Following the initial period of therapy, emerging difficulties require a reassessment of therapeutic approaches, such as dosage adjustment or introduction of a dopamine agonist. Other possible adverse effects--such as gastrointestinal disorders, orthostatic hypotension, levodopa-induced psychosis, sleep disturbances or parasomnias, or drug interactions--also require carefully monitored individual treatment. Nonpharmacologic concerns can help the Parkinson's disease patient achieve and maintain optimal functioning, including daily exercise, physical therapy, and involvement with support groups.

Antiparkinson Agents↗
PubMed1990

Comparative study on lymphocyte subpopulations in cancer patients after immunostimulation with propionibacteria and in renal transplant patients after combined immunosuppression.

In two groups of patients the influence of unspecific immunostimulation (group 1) and combined immunosuppression (group 2) on lymphocyte subpopulations was studied. Patients constituting group 1 suffered from gastric and colorectal carcinoma, respectively, and were preoperatively treated with 10 mg whole cell preparation of immunostimulating Propionibacterium avidum KP-40 (Köln-Propioni, strain 40). Patients of group 2 were submitted to combined immunosuppressive therapy and treated with antilymphocyte globulin, prednisone, and azathioprine subsequent to renal transplantation. Immunostimulation with P. avidum KP-40 resulted in a significant increase (p less than or equal to 0.01) of the natural killer (NK) cell population, whereas total leukocyte and lymphocyte counts as well as helper and suppressor T lymphocyte subsets did not evidently differ from control values. On the contrary after immunosuppression all subsets of lymphocytes as well as NK cells significantly decreased.

Azathioprine↗
PubMed1989

Status of dopamine in bovine pineal glands and the stimulation of N-acetyltransferase activity by D2-dopaminergic receptor agonists in the rat pineal glands in culture.

In a previous study, we identified in the bovine pineal gland two [3H]spiroperidol-binding sites with KD values of 0.18 and 2.1 nM and Bmax values of 37 and 630 fmol/mg protein, respectively. In this study, the status of dopamine in the bovine pineal glands was delineated further by measuring the relative concentrations of dopamine and norepinephrine and the relative concentrations of serotonin and melatonin. Furthermore, the presence of 4.0 +/- 0.6 micrograms/dopamine/gm tissue encouraged us to delineate the effects of select dopaminergic receptor agonists and antagonists on the synthesis of melatonin in vivo and on the activity of N-acetyltransferase in the rat pineal gland in culture. The acute administration of haloperidol (3 mg/kg intraperitoneally [ip]) or sulpiride (200 mg/kg ip) increased the concentration of melatonin in the pineal gland from 160.6 +/- 8.18 to 327.6 +/- 45.43 and 306.5 +/- 40.53 pg/gland, respectively. Dopamine exhibited dual effects on the activity of N-acetyltransferase, inhibiting the basal activity at 0.1 microM and stimulating it at 10 microM, and the later effect was blocked by propranolol. D2-dopaminergic receptor agonists such as bromocriptine (4.0 microM) or LY-171555 (10.0 microM) partially attenuated the norepinephrine-induced stimulation of N-acetyltransferase, and these attenuating effects were reversed by D2-dopaminergic antagonists such as haloperidol (10 microM) or domperidone (10 microM). The results of these studies are interpreted to indicate that for the synthesis of melatonin, the pineal D2-dopaminergic receptors may function independently from those of the beta 1-adrenergic receptor sites. Furthermore, the said D2-dopaminergic receptor are amenable to down regulation since the activity of N-acetyltransferase remained unaltered (0.0717 vs. 0.0729 nmol/gland/h) following chronic treatment (4 mg/kg ip/day for 30 days) with bromocriptine.

Acetyltransferases↗
PubMed1988

Is there any clinical relevance of serial determinations of serum carcinoembryonic antigen in small cell lung cancer patients?

Carcinoembryonic antigen (CEA) serum concentrations were serially determined by an enzyme immunoassay before, during, and after chemotherapy and radiotherapy in 129 male patients with small cell lung cancer (SCLC). Pretherapeutic CEA concentrations were as follows: 2.5 ng/ml or less for 37% of the patients; greater than 2.5 but less than or equal to 5 for 27%; and greater than 5 for 36%. Before therapy, CEA levels in patients with extensive disease (median value, 5.8 ng/ml) were higher than those in patients with limited disease (3.0 ng/ml; P less than 0.01). Median survival in patients with pretherapeutic CEA titers of 5 ng/ml or less (median survival, 14.3 months) was significantly longer than in patients with CEA levels greater than 5 but less than or equal to 10 and CEA levels greater than 10, respectively (8.3 and 9.7 months; P less than 0.01). Patients with pretherapeutic CEA levels greater than 10 ng/ml showed a significant decrease (P less than 0.01) of CEA while reaching partial remission (PR) or complete remission (CR). In five of 16 evaluable patients, a continuous increase of CEA titers was seen starting at least 3 months before relapse could be defined by clinical, radiologic, or endoscopic means. However, the number of patients for whom CEA serum determinations reliably indicate stage of disease and outcome of therapy is small (at best, 10% of all SCLC patients), and pretherapeutic CEA level cannot be used for individual prognosis. Moreover, it is still uncertain whether earlier detection of relapse in SCLC can improve the therapeutic results. So far, the clinical relevance of serial CEA serum determinations in SCLC patients is rather low.

Adult↗
PubMed1988

Subsequent development of acute non-lymphocytic leukemia in patients treated for Hodgkin's disease.

A nested case control study was carried out to investigate the association between treatment of patients with Hodgkin's disease (HD) and the risk of developing acute non-lymphocytic leukemia (ANLL). Seven Cancer Centers of the International Cancer Patient Data Exchange System of the UICC participated. A study cohort was selected consisting of 1,681 nonpretreated patients with HD, diagnosed from 1972 through 1978, and followed up through 1984. The median follow-up time was 66 months. Eighteen cases of leukemia were observed in the cohort. The risk of development of ANLL was significantly greater for male than for female patients. The treatment characteristics associated with an increased risk of developing ANLL were extensive radiotherapy, splenectomy and the chemotherapy combination of vincristine, procarbazine and mechlorethamine.

Acute Disease↗
PubMed1988

Cryptococcal meningoencephalitis with parkinsonian features.

The subacute onset of parkinsonism in a patient with cryptococcal meningoencephalitis is described. The prompt resolution of the extrapyramidal dysfunction with antifungal agents suggests direct involvement of basal ganglia structures by the cryptococcal infection. Rapid development of parkinsonism in immunocompromised individuals should prompt investigation for an infectious etiology.

Aged↗
PubMed1987

Subcutaneous heparin injection in the upper arm as a method of avoiding lymphoceles after lymphadenectomies in the lower part of the body.

The authors have measured the concentration of biologically active heparin in the drainage fluid after ilioinguinal, pelvic and retroperitoneal lymphadenectomy. After s.c. heparin administration in the thighs high levels of heparin were found in the drainage fluid of all patients (up to 0.89 IU/ml). After s.c. heparin application in the upper arms, no measurable concentrations of heparin were detected. Lymph loss in these patients was considerably lower. According to this experience, subcutaneous application of heparin into the upper arms is to be recommended in patients who undergo lymphatic surgery of the lower part of the body.

Heparin↗