These results indicate that both the choice of species combination as well as the choice of the donor organ studied can be crucial in the reproducibility, validity, and probably the relevance of xenograft testing. The vexatious results often encountered in a variety of mouse strains should lead to caution in the use of mouse models in general. Perhaps it is fair to say that the authors of mouse studies should indicate some particular reason for choice of the combination of rat-to-mouse transplant rather than mouse-to-rat as their primary model, or utilize the reciprocal species combination as a control. In regard to choice of organ xenograft transplant, the primarily vascularized heart xenograft is an excellent model. In contrast to skin, isolated pancreas islet, and some other xenograft organ models, the primarily vascularized heart model is a valid one and shows little variance in mean survival with a given treatment in the mouse. If a choice of rat-to-mouse or other species xenograft to mouse recipients is necessary or desirable, the primarily vascularized heart should be used as the organ of choice. In the emerging field of xenograft testing, the reproducibility, validity, and relevance of these xenograft models will be crucially important in deriving information useful for expansion of xenografting and to higher animals ultimately into clinical practice. There is little doubt that the rodent studies in both xenografts and allografts have provided a wealth of the immunological and surgical information that was obtained in a cost-effective manner with minimal ethical problems.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1994

Techniques of chronic plasmapheresis and antibody depletion in small animals.

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Animals↗

PubMed1993

[Ibuprofen 800 mg in the treatment of arthrosis of the fingers or rhizarthrosis].

Sixty outpatients with osteoarthritis of the interphalangeal joints of the hands or trapezo metacarpal joints were included in a multicentre, randomised, double-blind, parallel-group study. Patients were assigned to ibuprofen 800 mg (n = 30) or a placebo (n = 30) in two daily doses after morning and evening meals, for 14 days. Patients were assessed at entry and after one and two weeks' treatment. On D7, overall efficacy assessments performed by the investigator and patient using a four-point scale and overall spontaneous pain evaluated by the patient showed changes in favor of ibuprofen 800 mg. On D14, all selected evaluation criteria showed improved results with ibuprofen compared to placebo (p < 0.01). Three patients in the ibuprofen 800 mg group and one in the placebo group experienced adverse events during the study. Neither the incidence nor the type of adverse events were significantly different in the two groups. The algofunctional index recently developed by R.L. Dreiser and evaluated during this study correlated significantly with spontaneous global pain and with physician and patient efficacy ratings on D7 and on D14, but should nevertheless be subjected to a further validation study.

Adult↗

PubMed1993

[Treatment of acromegaly with sustained-release lanreotide. A new somatostatin analog].

The recovery of acromegaly is not obtained in about 50 percent of cases treated with radiotherapy and/or transsphenoidal surgery. Somatostatin analogs prescribed in such cases are effective but need either several subcutaneous injections a day or continuous infusions with pumps. Long-acting formulations of the new somatostatin analog lanreotide should avoid such drawbacks. Nine acromegalics, not cured by pituitary surgery (associated with radiotherapy in 7) received on IM injection of a long acting formulation of lanreotide twice a month for one year. Basal evaluation included: clinical examination, routine analyses, gall bladder ultrasonography, hormonal investigation of pituitary function including GH and IgF-1 measurements, visual field evaluation and pituitary scanning. A similar evaluation was performed on months 6 and 12 of treatment. The clinical symptoms of acromegaly progressively improved during therapy. Plasma GH levels decreased significantly (P < 0.01) from 24.2 +/- 2.1 to 9.3 +/- 1.2, 6.4 +/- 1.4 and 7.9 +/- 1.1 micrograms/l on months 3, 6 and 12, respectively. Plasma IgF-1 levels were normalized, decreasing from 676 +/- 40 to 331 +/- 30, 350 +/- 36, and 317 +/- 29 ng/ml on months 3, 6 and 12, respectively. Plasma lanreotide levels remained stable throughout the treatment. Side-effects included slight and transient diarrhoea and abdominal cramps which disappeared after 6 months of treatment. No gallstones appeared during treatment. These results show that one injection, twice a month, of a long-acting formulation containing 30 mg lanreotide is able to control the evolutivity of acromegalies not cured by pituitary radiotherapy and/or transsphenoidal surgery. Such formulations are well tolerated and avoid the drawbacks of either several subcutaneous injections a day or continuous infusions of somatostatin analogs.

Acromegaly↗

PubMed1993

Increased production of apolipoprotein A-I associated with elevated plasma levels of high-density lipoproteins, apolipoprotein A-I, and lipoprotein A-I in a patient with familial hyperalphalipoproteinemia.

Familial hyperalphalipoproteinemia (FHA) is a heritable trait associated with elevated plasma concentrations of high-density lipoprotein (HDL) cholesterol and possibly with longevity and protection against coronary heart disease (CHD). The metabolic basis and molecular etiology of FHA have not been established in most kindreds. The proband of a kindred with FHA and possible longevity was found to have elevated plasma levels of HDL cholesterol, apolipoprotein (apo) A-I, and lipoproteins containing apo A-I without apo A-II (Lp A-I), but normal levels of apo A-II and lipoproteins containing apo A-I with apo A-II (Lp A-I:A-II). The in vivo kinetics of apo A-I and apo A-II were studied in the FHA proband and in control subjects using both exogenous radiotracer (125I-apo A-I and 131I-apo A-II) and endogenous stable isotope (primed constant infusion of 13C6-phenylalanine) labeling techniques. The production rate (PR) of apo A-I was markedly increased in the FHA subject (28.9 mg/kg.d) compared with the control subjects (12.0 +/- 2.1 mg/kg.d), whereas the apo A-II PR was not substantially increased. The primary sequence of the proband's apo A-I gene, including 1.2 kb of the 5'-flanking sequence, was normal. We conclude that a selective upregulation of apo A-I production is one metabolic cause of FHA, and results in high plasma concentrations of HDL cholesterol, apo A-I, and Lp A-I and possibly in protection from atherosclerotic CHD.

Apolipoprotein A-I↗

PubMed1993

A cross-linking assay allows the detection of receptors for the somatostatin analogue, lanreotide in human breast tumours.

Hypothalamic somatostatin and its synthetic analogues inhibit the cell growth of several tumour models. The somatostatin analogue lanreotide (somatuline or BIM23014C) inhibits both the in vivo and in vitro cell growth of various mammary tumours. In order to evaluate the presence of receptors for lanreotide in breast tissue, samples from 41 female and 2 male patients were analysed by a cross-linking assay. All the samples examined possessed at least one subtype of lanreotide binding polypeptide, however, different polypeptide patterns were observed. The two major complexes had molecular weights of 57 kD and 42 kD. The previously demonstrated antiproliferative activity of lanreotide and the high percentage of positive tumours supports the use of lanreotide in clinical trials. However, the role of each receptor subtype in the control of breast cell proliferation requires further characterisation.

Adult↗

PubMed1993

Ictal 99mTc HM-PAO brain single-photon emission computed tomography in electroencephalographic nonlocalizable partial seizures.

A 9-year-old child with intractable focal epilepsy was studied for possible surgical treatment. Multiple electroencephalographic studies did not localize the epileptic focus. An ictal single-photon emission computed tomography (SPECT) study with technetium 99m-hexamethylpropyleneamineoxime demonstrated a focal area of hyperperfusion. Through three-dimensional, functional to anatomical image-matching techniques, the focus was overlaid on the magnetic resonance image localizing the cortical convolution responsible for the epileptogenic focus. Subdural electroencephalographic studies performed for seizure localization and functional mapping confirmed this location. This case emphasized the usefulness of ictal SPECT scans in patients with seizures nonlocalizable by electroencephalography being evaluated for epilepsy surgery.

Child↗

PubMed1993

Pharmacokinetics and efficacy of a long-acting formulation of the new somatostatin analog BIM 23014 in patients with acromegaly.

The treatment of acromegalics with somatostatin analogs requires continuous sc infusion using pumps or several sc injections daily. Long-acting formulations (BIM-LA) of BIM 23014 (BIM) using delayed microcapsules may provide a more convenient form of therapy. Fourteen acromegalics whose GH secretion had not been normalized by transphenoidal surgery followed, in 10 cases, by pituitary radiotherapy (performed at least 2 yr before the study) were studied. Eight of these patients participated in an initial study of the pharmacokinetics of BIM-LA, after which a 6-month efficacy study was undertaken. The 8 patients in the pharmacokinetic study had an initial blood sample collected for measurements of plasma GH and insulin-like growth factor-I (IGF-I) levels before the im injection of 30 mg BIM-LA, and blood samples were subsequently taken 2, 4, 6, and 8 h after injection and then twice a week for a month. Plasma IGF-I levels were measured on days 4, 14, 20, and 30 after the injection. Assays of plasma GH, IGF-I, and BIM levels were performed by RIAs. The results showed that plasma GH levels were markedly reduced from 26.0 +/- 2.0 to 2.5 +/- 0.2 micrograms/L 2 h after BIM-LA injection and remained lower than 5 micrograms/mL for the 11 following days. Plasma GH levels increased to 5.5 +/- 1.2 micrograms/L on day 14 and returned to basal values 23 days after injection. Similarly, plasma IGF-I decreased from an initial level of 656 +/- 43 to 324 +/- 23 ng/mL on day 4 and remained close to the normal range for the following 10 days. Plasma BIM levels reached a peak 2 h after the injection (7.2 +/- 2.3 ng/mL) and remained higher than or close to 1 ng/mL until the 14th day after injection. This initial study showed that a single injection of 30 mg BIM-LA effectively suppressed GH and IGF-I secretion for at least 14 days, in accordance with the kinetics of the drug in plasma. Based on the results of this initial study, 30 mg BIM-LA were injected twice monthly for 6 months in all 14 patients. All of the subjects had a basal evaluation before treatment with BIM-LA and were then subjected to assessment of clinical, pituitary, and hormonal parameters. Patients were evaluated after 3 and 6 months of treatment on the same basis as that previously used when starting the BIM-LA therapy. Plasma BIM levels were measured monthly. Clinical signs of acromegaly improved during the treatment.(ABSTRACT TRUNCATED AT 400 WORDS)

Acromegaly↗

PubMed1993

Therapeutic use and perspectives of synthetic peptides in oncology.

Several native peptides can regulate tumour cell proliferation. After binding to specific membrane receptors they have the ability to stimulate or inhibit directly cell growth. Peptides can also control the regulation of endocrine or paracrine growth factor secretion. Agonist and antagonist molecules have been synthesized for therapeutic purposes. Hypothalamic neuropeptides are used in oncology. GnRH agonists lead to biochemical castration which is useful in treatment of hormone-dependent tumours (breast and prostate). Somatostatin analogues are beneficial in the treatment of gut neuroendocrine tumours and have demonstrated an antitumoural effect in experimental studies. Cytostatic agents, such as Gastrin Releasing Peptide antagonists, may be of interest as an adjuvant to chemotherapy or surgery in small cell lung cancer and other malignancies. The role of peptides in antigenic presentation, cell proliferation control and the metastatic process suggests a new therapeutic potential for these compounds. Progress in biotechnology could provide specific tools to screen new molecules and increase the understanding of mechanisms of action. Improvement in drug delivery techniques will allow for more convenient routes of administration.

Gonadotropin-Releasing Hormone↗

PubMed1993

[The logic of the desire. A new look at induced abortion].

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Abortion, Illegal↗

PubMed1993

[Peptide growth factors in the prostate].

Growth and development of the prostate depend on androgen action and other factors. Androgens act directly by specific nuclear receptors and induce or control many effects mediated by peptide growth factors on both epithelial and stromal cells. The major important peptide growth factors detected in the prostate are Fibroblast Growth Factors, Transforming Growth Factors, and Epidermal Growth Factor. These factors are not prostate specific. They are produced by epithelial or stromal cells and regulate the growth of these two cell compartments through autocrine or paracrine pathways. Overproduction of these factors or modification in affinity or number of cell receptors may participate in the two main prostatic pathologies: benign hyperplasia or adenocarcinoma. Recently, other factors have been evidenced in the prostate: Interleukine 6, Nerve Growth Factor or Insulin-like Growth factors. The study of the localization and the effects of these factors may be crucial to understand the prostatic development and diseases and may suggest new targets for therapy.

Adenocarcinoma↗

PubMed1993

Linkage disequilibrium between the fragile X mutation and two closely linked CA repeats suggests that fragile X chromosomes are derived from a small number of founder chromosomes.

In order to investigate the origin of mutations responsible for the fragile X syndrome, two polymorphic CA repeats, one at 10 kb (FRAXAC2) and the other at 150 kb (DXS548) from the mutation target, were analyzed in normal and fragile X chromosomes. Contrary to observations made in myotonic dystrophy, fragile X mutations were not strongly associated with a single allele at the marker loci. However, significant differences in allelic and haplotypic distributions were observed between normal and fragile X chromosomes, indicating that a limited number of primary events may have been at the origin of most present-day fragile X chromosomes in Caucasian populations. We propose a putative scheme with six founder chromosomes from which most of the observed fragile X-linked haplotypes can be derived directly or by a single event at one of the marker loci, either a change of one repeat unit or a recombination between DXS548 and the mutation target. Such founder chromosomes may have carried a number of CGG repeats in an upper-normal range, from which recurrent multistep expansion mutations have arisen.

Alleles↗

PubMed1993

Effect of depleting CD3+ cells from DR- donor bone marrow to facilitate kidney graft tolerance in recipients given total lymphoid irradiation.

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Actins↗