PubMed Health⌕ Search

Biomedical subjects

T H Fagerlund

Publications and source records attributed to T H Fagerlund.

10 recordsLinked to original sources
PubMed2001

[Future pain treatment].

BACKGROUND: The recent rapid progress in pain research is due in large part to advances in genetics and cell and molecular biology. We now know that chronic pain (hypersensitivity due to inflammation or nerve injury) and acute nociceptive pain are different and must be treated accordingly. We will continue to reveal sophisticated mechanisms underlying different kinds of pain that can be targeted to inhibit nociceptive transmission and produce analgesia. METHODS: This review is based upon literature collected through the authors' own reading and through PubMed searches. New hopes for future pain treatments are discussed. Further, the impact of genetic factors on pain sensitivity and pain modulation are discussed, and conceivable therapeutic approaches based on genetic techniques are mentioned. RESULT: At the level of the peripheral nerve, many novel targets have recently been identified: the tetrodotoxin-resistant sodium channel, the vanilloid receptor and different calcium channels are very interesting. In the spinal cord, different approaches can be used: to either block excitatory input or to increase inhibitory control or to do both at the same time. The mechanisms for hypersensitivity are being identified and offer multiple possible targets for novel analgesics. INTERPRETATION: Many interesting targets for analgetics has emerged during that last few years, lending great hope for new and better (i.e. with less side effects) analgesic drugs in the future.

Analgesia↗
PubMed2001

No pain relief from codeine...? An introduction to pharmacogenomics.

Drug treatment remains a mainstay of medicine. In some situations a drug unexpectedly has no effect, or unforeseen serious side effects occur. For the patient this represents a dangerous and potentially life-threatening situation. It certainly is a distressing experience for the doctor. At the societal level, adverse drug reactions represent a leading cause of disease and death. Genetic variation often underlies these unexpected situations. Pharmacogenetics is the term used about genetically determined variability in the metabolism of drugs. Pharmacogenomics usually refers to drug discovery based on knowledge of genes, but it is a discipline that offers insight into aetiologic mechanisms, and possible prevention and treatment. There is a trend towards a definition of pharmacogenomics that includes both pharmacogenetics and pharmacogenomics as defined above. Our article is an introduction to pharmacogenomics, using the broader definition. Biotechnological methods cannot be understood without a grasp of basic medical genetics, and we provide a brush-up on the fundamentals. We then outline pharmacogenetics, giving examples of genetically based variation in drug metabolising enzymes, drug receptors and drug transporting proteins. Modern biotechnology would be unthinkable without the aid of computers, and we briefly touch upon the field of bioinformatics. Finally, we give an overview of pharmacogenomics in the narrower sense. The rapidly growing field of pharmacogenomics is going to influence our everyday practice of medicine in the immediate future.

Adult↗
PubMed1997

Malignant hyperthermia susceptibility, an autosomal dominant disorder?

A large series of Swedish nuclear families, in which malignant hyperthermia (MH) reactions had occurred during anaesthesia, have been examined with respect to malignant hyperthermia susceptibility. In vitro contracture tests (IVCT) of muscle strips were conducted to diagnose MH status. Included in this series were some families where only one of the parents was tested by IVCT, while in 79 of the families both parents were tested by IVCT. Six known mutations in the gene encoding the calcium release channel of sarcoplasmic reticulum in skeletal muscle (the RYR1 gene), believed to cause MHS in man, were searched for in 41 nuclear families. The present paper focuses on findings in eight families, where both parents were malignant hyperthemia negative (MHN), while at least one child was either malignant hyperthermia susceptible (MHS) or malignant hyperthermia equivocal (MHE). There was no suggestion of non-paternity. The RYR1 mutations investigated were Arg163Cys, Gly341Arg, Ile403Met, Arg614Cys, Gly2433Arg and Arg2434His. No family had any of the six RYR1 mutations searched for.

Adolescent↗
PubMed1997

Discordance between malignant hyperthermia susceptibility and RYR1 mutation C1840T in two Scandinavian MH families exhibiting this mutation.

The ryanodine receptor 1 (RYR1) mutation C1840T has been reported to segregate with malignant hyperthermia (MH) susceptibility in several families. We have investigated several Scandinavian MH families with respect to five different RYR1 mutations reported to cause predisposition to MH, and we here report on two of the families in which the C1840T mutation was detected. In these two families there was recombination between MH susceptibility and this mutation in one and three individuals, respectively. These findings may suggest that it is necessary to reconsider the specificity of the IVCT and the role of C1840T as a cause of MH susceptibility in some families exhibiting this mutation.

Anesthesia↗
PubMed1996

[Analgesic effect of ketamine in a patient with neuropathic pain].

We report the effect of a single daily dose of ketamine in a 54 year old woman with fibromyalgia and severe post-traumatic neuropathic pain. A number of different approaches for pain relief had been tried with little effect. An intramuscular test dose of 0.4 mg/kg ketamine combined with 0.05 mg/kg midazolam lead to analgesia which lasted for almost two days. Long-term analgesia was also obtained by 250 mg/kg ketamine hydrochloride taken orally in the form of capsules every night at bedtime. The patient has now used this dose for nine months. Ketamine is an NMDA receptor antagonist. A single sub-anaesthetic dose of ketamine causes a long-term depression of pain intensity in some, but not in all, patients suffering chronic pain. This effect is distinctly different from the short-lasting (10-30 min) analgesic effect in cases of acute nociceptive pain. The long-term depression of the intensity of chronic pain states may be due to a reversal of NMDA receptor-dependent long-term potentiation of synapses in central pain pathways. By giving ketamine as a single dose at night the mental side-effects are reduced or avoided.

Administration, Oral↗
PubMed1996

Recombination between the postulated CCD/MHE/MHS locus and RYR1 gene markers.

Malignant hyperthermia (MH) susceptibility is considered a subclinical myopathy or a pharmacogenetic trait, and is believed to be closely associated with central core disease (CCD). Data support the notion that MH susceptibility is heterogeneous, with the ryanodine receptor I (RYR1) locus on chromosome 19 being one locus harboring a gene that can cause MH susceptibility. The gene for CCD is believed to reside in the locus on chromosome 19. In the family presented here, a girl has CCD, and several close relatives are MH susceptible (MHS). DNA studies conducted on available family members uncovered recombination between the MH susceptibility locus and RYR1 markers. Consequently, if one postulates that the CCD gene in this family resides in the same locus as the MH susceptibility gene, an additional CCD locus different from the RYR1 locus must also be postulated.

Alleles↗
PubMed1995

A search for three known RYR1 gene mutations in 41 Swedish families with predisposition to malignant hyperthermia.

Eight mutations in the gene (the RYR1 gene) encoding the calcium release channel of sarcoplasmic reticulum (SR) in skeletal muscle are so far known to be very closely linked to malignant hyperthermia susceptibility in man and are regarded to be causative. We have examined 41 Swedish families where malignant hyperthermia had occurred in at least one member during anaesthesia, with respect to three of the known mutations. The mutations were Arg163Cys; Ile403Met and Arg614Cys (also known as the "pig mutation"). In three (i.e. 7%) of the families we detected the Arg614Cys mutation, and this was the only one of the mutations searched for that was observed. This indicates that other mutations than those searched for in this study must cause malignant hyperthermia susceptibility in most Swedish malignant hyperthermia susceptible families.

Adult↗
PubMed1995

A simple method to detect the RYR1 mutation G1021A, a cause of malignant hyperthermia susceptibility.

To search for the mutations RYR1 G1021A in families where malignant hyperthermia (MH) episodes have occurred, we have used an amplification-created restriction sites (ACRS) technique to detect the mutation. The previously described single-stranded conformation polymorphism (SSCP) technique was laborious and time consuming, but necessary to detect the mutation, whereas the method described here discriminates quickly and efficiently between homozygotes with the mutation, heterozygotes and homozygotes without the mutation.

Base Sequence↗
PubMed1993

Mutations in the ryanodine receptor gene in central core disease and malignant hyperthermia.

Central core disease (CCD) of muscle is an inherited myopathy which is closely associated with malignant hyperthermia (MH) in humans. CCD has recently been shown to be tightly linked to the ryanodine receptor gene (RYR1) and mutations in this gene are known to be present in MH. Mutation screening of RYR1 has led to the identification of two previously undescribed mutations in different CCD pedigrees. One of these mutations was also detected in an unrelated MH pedigree whose members are asymptomatic of CCD. The data suggest a model to explain how a single mutation may result in two apparently distinct clinical phenotypes.

Adolescent↗