CURRENT CONCEPTS IN PERIPHERAL NERVE INJURY REPAIR.

Even though reconstructive surgery of the nerves underwent significant progress due to experimental and clinical research over the past 40 years, injuries to the peripheral nerves still remain a great challenge for microsurgery. Literature results of these procedures are often evaluated as very good but the final result is often characterized by an achievement of only a useful and not full function, which is rather rare. It is not only a simple suture; the success is also based on functional regeneration and interconnection of the nerve fibres. This is limited by correct surgical technique, the age of the patient, delay from the time of injury and the mechanism or localization of the injury. Some injuries even now remain untreatable (such as the most severe brachial plexus injuries or long traction injuries of the peroneal nerve). Apart from standard neurolysis and epi- or perineural suture with or without nerve grafts, distal nerve transfers (in case of proximal injuries) and end-to-side neurorrhaphy (mainly in trauma of sensitive nerves) have recently been frequently used. The future is however based on influence of nerve regeneration at the cellular level using substances with growth potential. The main prerequisite of successful surgery is however early indication of surgical revision in a specialized centre.

Completely Endoscopic Approach Using a Skeeter Drill to Treat Bilateral Congenital Choanal Atresia in a 33 Week Born Pre-term Baby.

Choanal atresia (CA) is a relatively rare condition manifesting with respiratory distress. Endoscopic approaches have superseded transnasal and transpalatal approaches. We present a case of a premature baby of 1.10 kg, who developed respiratory distress and was diagnosed with bilateral CA. A nasal airway was created endoscopically using a skeeter drill.

Cellular pharmacology and biological activity of 5-carboranyl-2'-deoxyuridine.

PURPOSE: The intracellular uptake and metabolism of 5-carboranyl-2'-deoxyuridine was investigated in primary human lymphocytes and in a T lymphoblastoid cell line using unlabeled and tritium labeled compound. The cytotoxicity and antiviral activity of the compound and stability to enzyme degradation was determined. METHODS AND MATERIALS: A novel method for radiolabeling the 5-carboranyl moiety of pyrimidine nucleosides was developed. Cells were exposed to unlabeled and tritium labeled 5-carboranyl-2'-deoxyuridine and the intracellular uptake and egress of the compound determined by high pressure liquid chromatography. The viability and growth of normal and malignant cells, including human and rat gliomas, in the presence of the compound was determined. RESULTS: Substantial levels of 5-carboranyl-2'-deoxyuridine-5'-monophosphate are formed intracellularly and this major metabolite can be detected in cells 48 h after removal of the parent compound from the medium. No significant phosphorylation to the 5'-diphosphate or triphosphate of 5-carboranyl-2'-deoxyuridine was detected. Furthermore, radiolabeled 5-carboranyl-2'-deoxyuridine was not incorporated into deoxyribonucleic acid. 5-carboranyl-2'-deoxyuridine was essentially nontoxic to human lymphocytes as well as human or rat glioma cells, and had no marked effect in human lymphocytes acutely infected with human immunodeficiency virus type 1. CONCLUSION: The results demonstrate for the first time that 5-carboranyl-2'-deoxyuridine is phosphorylated intracellularly and suggest that it should be considered for further studies as a potential sensitizer for boron neutron capture therapy.

Structure-activity relationships of pyrimidine nucleosides as antiviral agents for human immunodeficiency virus type 1 in peripheral blood mononuclear cells.

The structure-activity relationships of several pyrimidine nucleosides related to 3'-azido-3'-deoxythymidine (AZT) were determined in human immunodeficiency virus type 1 (HIV-1) infected human peripheral blood mononuclear cells. These studies indicated that nucleosides with a 3'-azido group on the sugar ring exhibited the most potent antiviral activity. Substitution at C-5 with H, CH3, and C2H5 produced derivatives with the highest potency, whereas alkyl functions greater than C2, including bromovinyl substitution reduced the antiviral potency significantly. Changing the 3'-azido function to an amino or iodo group reduced the antiviral activity. Replacement of the uracil ring by cytosine or 5-methylcytosine produced analogues with high potency and low toxicity. Modification of the 5'-hydroxy group markedly reduced the antiviral activity. Similarly, various C-nucleoside analogues related to AZT and 2',3'-dideoxycytidine were inactive and nontoxic. From these systematic studies 3'-azido-2',3'-dideoxyuridine (5a), 3'-azido-5-ethyl-2',3'-dideoxyuridine (5c), and 3'-azido-2',3'-dideoxycytidine (7a) and its 5-methyl analogue (7b) were identified as potent and selective anti-HIV-1 agent in primary human lymphocytes.

Synthesis and structure-activity relationships of 6-substituted 2',3'-dideoxypurine nucleosides as potential anti-human immunodeficiency virus agents.

In order to study the structure-activity relationships of 2',3'-dideoxypurine nucleosides as potential anti-HIV agents, various 6-substituted purine analogues have been synthesized and examined in virus-infected and uninfected human peripheral blood mononuclear cells. N6-methyl-2',3'-dideoxyadenosine (D2MeA, 7a) was initially synthesized from adenosine via 2',3'-O-bisxanthate 3. As extension of this reaction to other N6-substituted compounds failed, a total synthetic method utilizing 2',3'-dideoxyribose derivative 9 was used for the synthesis of other purine nucleosides. An acid-stable derivative of N6-methyl-2',3'-dideoxyadenosine, 2'-fluoroarabinofuranosyl analogue 32 (D2MeFA), has been synthesized from the appropriate carbohydrate 24 by condensation with N6-methyladenine 23. Among these compounds, N6-methyl derivative (D2MeA) 7a proved to be one of the most potent antiviral agents. The order of potency for the 6-substituted compounds was NHMe greater than NH2 greater than Cl approximately N(Me)2 greater than SMe greater than OH approximately NHEt greater than SH greater than NHBn approximately H. The results suggest that a bulk tolerance effect at the 6-position of the 2',3'-dideoxypurine nucleoside may dictate the antiviral activity of these compounds. Acid-stable analogue 32 (D2MeFA) was found to be 20-fold less potent than the parent compound. Both D2MeA and D2MeFA were resistant to calf intestine adenosine deaminase. The presence of a fluorine atom in the carbohydrate moiety greatly increased stability to acid, making D2MeFA a potential orally active antiviral agent that could be useful for the treatment of retroviral infections in humans.

Tissue Raman spectroscopy for the study of radiation damage: brain irradiation of mice.

Radiotherapy is routinely employed in the treatment of head and neck cancers. Acute cell death, radiation-activated chemical cascades, and the induction of genes coding for protective factors like cytokines are considered to be the major processes involved in radiation damage and repair. It should be possible to follow these processes by monitoring the biochemical interactions initiated by radiation. We have carried out Raman spectroscopy studies on tissue from mice subjected to brain irradiation to identify the biochemical changes occurring in tissue and brain as a result of radiation injury. These studies show that brain irradiation produces drastic spectral changes even in tissue far removed from the irradiation site. The changes are very similar to those produced by the stress of inoculation and restraint and the administration of an anesthetic drug. While the changes produced by stress or anesthetics last for only a short time (a few hours to 1 or 2 days), radiation-induced changes persist even after 1 week. The spectral changes can be interpreted in terms of the observation of new spectra that are dominated by bands due to proteins. The results thus support the hypothesis that various protective factors are released throughout the body when the central nervous system (CNS) is exposed to radiation.

Medically unexplained symptoms and somatisation in ENT.

BACKGROUND: Somatisation has been described as the perception of a physiological event influenced by emotion. METHOD: A review of the medical literature was carried out using the following Medical Subject Headings: somatisation (which identified 357 articles), medically unexplained symptoms (749 articles), unexplained or idiopathic dizziness (142 articles), tinnitus (360 articles), catarrh (1068 articles) and globus pharyngeus (3114 articles). RESULTS: Up to 40 per cent of out-patient attendances have medically unexplainable symptoms. In ENT clinics, this includes patients with dizziness, tinnitus, 'pseudo' eustachian tube dysfunction, being 'unable to hear', catarrh and postnasal drip, atypical facial pain, globus pharyngeus, and functional dysphonia. Medical explanations of these symptoms often differ from patients' perceptions. Demonstrating normal test results and providing reassurance have little effect on patients' doubts and anxieties. Consultations that recognise the symptoms and their impact, and offer a tangible and involving explanation are more likely to satisfy and empower patients. CONCLUSION: The treatment of medically unexplained symptoms has changed in recent years; there is now more emphasis on psychological factors due to an association with anxiety and depression.