Viability and functionality of bovine chromaffin cells encapsulated into alginate-PLL microcapsules with a liquefied inner core.

Implantation of adrenal medullary bovine chromaffin cells (BCC), which synthesize and secrete a combination of pain-reducing neuroactive compounds including catecholamines and opioid peptides, has been proposed for the treatment of intractable cancer pain. Macro- or microencapsulation of such cells within semipermeable membranes is expected to protect the transplant from the host's immune system. In the present study, we report the viability and functionality of BCC encapsulated into microcapsules of alginate-poly-L-lysine (PLL) with a liquefied inner core.

Intrathecal grafting of porcine chromaffin cells reduces formalin-evoked c-Fos expression in the rat spinal cord.

Chromaffin cells from the adrenal gland secrete a combination of neuroactive compounds including catecholamines, opioid peptides, and growth factors that have strong analgesic effects, especially when administered intrathecally. Preclinical studies of intrathecal implantation with xenogeneic bovine chromaffin cells in rats have provided conflicting data with regard to analgesic effects, and recent concern over risk of prion transmission has precluded their use in human clinical trials. We previously developed a new, safer source of adult adrenal chromaffin cells of porcine origin and demonstrated an in vivo antinociceptive effect in the formalin test, a rodent model of tonic pain.

A new method for encapsulation of living cells: preliminary results with PC12 cell line.

A new method is described for encapsulation of living cells. PC12 rat adrenal pheochromocytoma cells, which have been shown to synthesize, store and release dopamine were employed. The particles are made first and the cells then incorporated in a gentle mechanical procedure.

[Management of intractable cancer pain: from intrathecal morphine to cell allograft].

The durable effectiveness of intrathecal morphine administration is well established for the management of intractable cancer pain, after failure of systemic opioids, secondary to the persistence of non-reversible undesirable side effects. Many patients are referred to late in the disease course. This conservative method to control pain of malignant origin must not be reserved for last resort treatment for terminal patients.

One-year chromaffin cell allograft survival in cancer patients with chronic pain: morphological and functional evidence.

The control of chronic pain through transplantation of chromaffin cells has been reported over the past few years. Analgesic effects are principally due to the production of opioid peptides and catecholamines by chromaffin cells. Clinical trials have been reported with allografts consisting of whole-tissue fragments implanted into the subarachnoid space of the lumbar spinal cord (14,19,36).

Does intrathecal morphine in the treatment of cancer pain induce the development of tolerance?

Objective: This retrospective study was designed to investigate whether chronic lumbar intrathecal administration of morphine leads to the development of opioid tolerance in patients suffering from intractable cancer pain.

Methods: Between 1978 and 1995, 159 patients with refractory cancer pain were treated with intrathecal morphine in our Multidisciplinary Pain Center. The treatment consisted of preservative-free morphine administered through an access port as a single bolus.

[Centralized preparation in the pharmacy of dilute solutions of ganciclovir: (Cymevan): work load change and economic potential].

The production of ganciclovir doses by a hospital pharmacy having the necessary facilities to reconstitute anticancer drugs would be of the utmost relevance regarding both protection of the nursing staff and therapeutic safety. As this activity is also economically worthwhile a large number of our colleagues would like to implement it. The aim of this work has was to take advantage of a 40 weeks production of ganciclovir dose by the pharmacy at Rangueil hospital in Toulouse so as to answer some of the questions raised by such a project.

Effect of intraperitoneal insulin delivery on growth hormone binding protein, insulin-like growth factor (IGF)-I, and IGF-binding protein-3 in IDDM.

Low plasma insulin-like growth factor (IGF)-I despite high circulating growth hormone (GH) in insulin-dependent diabetes mellitus (IDDM) indicate a hepatic GH resistance. This state may be reflected by the reduction of the circulating GH binding protein (GHBP), corresponding to the extracellular domain of the GH receptor, and the reduction of insulin-like growth factor binding protein (IGFBP)-3, major IGF-I binding protein, upregulated by GH. We carried out two studies.

Insulin therapy and GH-IGF-I axis disorders in diabetes: impact of glycaemic control and hepatic insulinization.

In Type 1 diabetes, high circulating growth hormone (GH) in conjunction with low plasma insulin-like growth factor-I (IGF-I) is indicative of a hepatic GH-resistance profile since the liver is the main source of circulating IGF-I. The reduction in specific growth hormone binding protein (GHBP), corresponding to the extracellular domain of the GH receptor, provides an indirect indication of the hepatic density of GH receptors, as does the reduction in IGFBP-3, the major IGF binding protein, which is GH-dependent. Type 1 diabetes is also associated with high levels of IGFBP-1, a binding protein down-regulated by insulin.

Differential regulation of serum growth hormone (GH)-binding protein during continuous infusion versus daily injection of recombinant human GH in GH-deficient children.

Serum GH-binding protein (GHBP) was evaluated in 2 randomly divided groups of prepubertal children presenting with idiopathic GH deficiency and receiving recombinant human GH, either continuously by sc infusion (group 1) or as 1 daily sc injection (group 2). After the first 6 months, group 1 switched from continuous infusion to daily injections for the following 6 months. There was no significant difference in clinical data, GH values, or GHBP levels between the 2 groups before treatment.

[Nosocomial infections in an urological department. Incidence and etiological factors].

The authors report a prospective study with active request of data for nosocomial infections (NI) in an urological department during six months. From 453 patients, 43 developed an NI (incidence = 9.5%): urinary tract infections (53.

CSF baclofen levels after intrathecal administration in severe spasticity.

The pharmacokinetic parameters in the CSF of baclofen given to 4 patients as an intrathecal bolus are reported. Considerable inter-individual variability in the parameters was observed. The elimination half-life ranged from 0.

Chronic intrathecal baclofen administration for control of severe spasticity.

Baclofen, the most effective drug for treating spasticity, is a specific agonist of gamma-aminobutyric acid-B receptors, and is very abundant in the superficial layers of the spinal cord. Given orally, baclofen does not easily penetrate the blood-brain barrier, and is distributed equally to the brain and spinal cord. Direct intrathecal administration was given in order to change the distribution of the drug by preferentially perfusing the spinal cord.

The stability of morphine in isobaric and hyperbaric solutions in a drug delivery system.

Intrathecal preparations of morphine for use in intractable pain must contain no preservatives. They are generally formulated in saline (isobaric) or dextrose (hyperbaric) which raises questions of stability. The behaviour of morphine in hyperbaric and isobaric solutions stored in a reservoir for implantation has been examined and the effect of temperature and the time of contact of morphine with the different components of the reservoir as well as the sterilization procedure have been investigated.

CSF morphine levels after lumbar intrathecal administration of isobaric and hyperbaric solutions for cancer pain.

The objectives of this study were to compare the pharmacokinetic properties and the duration of analgesia following intrathecal administration (L5-S1) of 2 mg morphine in 2 forms: (1) an isobaric (NaCl 0.9%) and (2) a hyperbaric solution (7% dextrose). The study was carried out on 5 cancer patients with severe, intractable pain in the lower half of the body.

Spinal versus intraventricular chronic opiate administration with implantable drug delivery devices for cancer pain.

Early publications have separately reported the efficacy, specificity and conservative character of direct spinal and intraventricular morphine analgesia in the treatment of intractable cancer pain. The objectives of this study are to compare efficacy and safety of these sites of local administration in order to determine the indication for each, the clinical effects of different opiates and the choice of various drug administration devices.