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Biomedical subjects

K K Jain

Publications and source records attributed to K K Jain.

At least 55 records · Page 3Linked to original sources
PubMed2000

Evaluation of mitoxantrone for the treatment of multiple sclerosis.

Mitoxantrone (Novantrone((R))), an antineoplastic agent, has been approved for treating patients with secondary progressive multiple sclerosis (MS). Mitoxantrone, which is usually categorised as an immunosuppressant drug, is now also considered to be a specific immunomodulator. Autoimmune mechanism of pathogenesis of MS is the basis of immunosuppressive therapeutic approaches to MS whereas immunoregulatory abnormalities including defective IFN-alpha production provide the rationale for immunomodulating therapies. Clinical trials have shown that mitoxantrone had a statistically significant impact on reduction of relapse rate and delay in disability progression in these patients. Advantages of mitoxantrone as therapy for MS are: (1) considerable information is available about its pharmacokinetics, metabolism and toxicology from previous use in oncology; (2) it requires administration only once in three months which is not only convenient for the patient but also cost-effective; (3) mitoxantrone is one of the two drugs to be approved for secondary progressive MS (the other is IFN-beta1) which offers an advantage over IFN-beta1a preparations and glatiramer acetate which are indicated only for relapsing remitting MS. However, the duration of therapy is usually limited to two to three years because the maximum cumulative dose recommended is 120 mg/m(2) due to concern for possible cardiotoxicity. Potential market value of the mitoxantrone, based on the cost of treatment per patient and the number of patients likely to be treated in the first year of introduction, is US$210 million.

Animals↗
PubMed2000

Evaluation of memantine for neuroprotection in dementia.

Memantine, a non-competitive NMDA antagonist, has been approved for use in the treatment of dementia in Germany for over ten years. The rationale for use is excitotoxicity as a pathomechanism of neurodegenerative disorders. Memantine acts as a neuroprotective agent against this pathomechanism, which is also implicated in vascular dementia. HIV-1 proteins Tat and gp120 have been implicated in the pathogenesis of dementia associated with HIV infection and the neurotoxicity caused by HIV-1 proteins can be blocked completely by memantine. Memantine has been investigated extensively in animal studies and following this, its efficacy and safety has been established and confirmed by clinical experience in humans. It exhibits none of the undesirable effects associated with competitive NMDA antagonists such as dizocilpine. The efficacy of memantine in a variety of dementias has been shown in clinical trials. Memantine is considered to be a promising neuroprotective drug for the treatment of dementias, particularly Alzheimer's disease for which there is no neuroprotective therapy available currently. It can be combined with acetylcholinesterase inhibitors which are the mainstay of current symptomatic treatment of Alzheimer's disease. Memantine has a therapeutic potential in numerous CNS disorders besides dementias which include stroke, CNS trauma, Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), epilepsy, drug dependence and chronic pain. If memantine is approved by the FDA for some of these indications by the year 2005, it can become a blockbuster drug by crossing the US$1 billion mark in annual sales.

Alzheimer Disease↗
PubMed2000

An assessment of levetiracetam as an anti-epileptic drug.

A brief review of epilepsy as a disease, anti-epileptic drugs (AEDs) and methods of evaluation of AEDs are presented as a background for the assessment of levetiracetam which has been approved by the FDA as add-on therapy for the treatment of partial seizures with or without secondary generalisation in adults. The exact mechanism of action of levetiracetam is not known but its action differs from that of other anti-epileptic drugs. A specific binding site for levetiracetam has been identified and is possibly related to anticonvulsant activity. Levetiracetam offers an effective and broad spectrum treatment of epileptic seizures, partial as well as generalised epilepsy. Levetiracetam has been shown to be effective in genetic and kindled animal models of epilepsy and against chemoconvulsant-induced partial epileptic seizures. Levetiracetam has a near perfect pharmacokinetic profile, with rapid absorption following oral administration, excellent bioavailability, quick attainment of steady-state concentrations, linear kinetics and minimal plasma protein binding. Levetiracetam does not interact with commonly used drugs and other AEDs. In recent Phase III clinical trials, the responder rate was 39.4 - 42.1% on 3000 mg dose, compared with placebo rates of 10.9 - 16.7%. Levetiracetam has a favourable safety profile and the most frequently reported adverse events were somnolence, asthenia and dizziness. Overall, levetiracetam is considered to have several advantages over current AEDs.

Animals↗
PubMed2000

Applications of biochip and microarray systems in pharmacogenomics.

A DNA microarray system is usually comprised of DNA probes formatted on a microscale on a glass surface (chip), plus the instruments needed to handle samples (automated robotics), to read the reporter molecules (scanners) and analyse the data (bioinformatic tools). Biochips are formed by in situ (on chip) synthesis of oligonucleotides or peptide nucleic acids (PNAs) or spotting of DNA fragments. Hybridisation of RNA- or DNA-derived samples on chips allows the monitoring of expression of mRNAs or the occurrence of polymorphisms in genomic DNA. Basic types of DNA chips are the sequencing chip, the expression chip and chips for comparative genomic hybridisation. Advanced technologies used in automated microarray production are photolithography, mechanical microspotting and ink jets. Bioelectronic microchips contain numerous electronically active microelectrodes with specific DNA capture probes linked to the electrodes through molecular wires. Several biosensors have been used in combination with biochips. PNA biosensors commonly rely on the immobilisation of a single-stranded DNA sequence (the 'probe') onto a transducer surface for hybridisation with the complementary ('target') strand to give a suitable electrical signal. Other sensors are cell-based immunobiosensors with engineered molecular recognition, integrated biosensors based on phototransistor integrated circuits and sensors based on surface plasmon resonance. Microarray technologies offer enormous savings in time and labour as compared to standard gel-based microsatellite methods. Reading of the information and its management by bioinformatics is necessary because of the enormous amount of data generated by the various technologies using microarrays. Standardised procedures are essential for compatible data production, quality control and analysis. Expression monitoring is the most biologically informative application of this technology at present. Microarray technology has important applications in pharmacogenomics: drug discovery and development, drug safety and molecular diagnostics. DNA chips will facilitate the integration of diagnosis and therapeutics, as well as the introduction of personalised medicines.

Animals↗
PubMed2000

Applications of proteomics in oncology.

Genomics has expanded the field of molecular oncology, and proteomics is complementing genomics in the fields of elucidation of pathophysiology, gene function, molecular diagnosis and anticancer drug discovery. This trend is reflected in the establishment of the Human Tumour Gene Index by the National Cancer Institute (NCI), which is now followed by the Tissue Proteomics Initiative. Laser capture microdissection (LCM) provides an ideal method for extraction of cells from specimens in which the exact morphologies of both the captured cells and the surrounding tissue are preserved. Proteomic technologies can be applied for the further characterisation and analysis of proteins. LCM can also be combined with the protein chip technology. Proteomic technologies have been used for the study of cancer of various organs including the liver, prostate, breast, bladder and oesophagus. Some of the anticancer strategies are directed against proteases that facilitate several steps in cancer progression. Proteomic mapping of blood vessels in normal and malignant tissues can be used to identify tissue-specific markers on the endothelium that serve as potential targets for in vivo drug delivery. Studies of global protein expression in human tumours have led to the identification of various polypeptide markers, potentially useful as diagnostic tools. Genes that encode proteins that are overexpressed in tumours are being identified. Demonstration of tissue or cell type specific expression of some nuclear matrix proteins has led to the search for tumour specific nuclear matrix proteins. There is considerable activity in the commercial sector to develop diagnostic tests, as well as to facilitate anticancer drug discovery using proteomic technologies. Continued refinement of techniques and methodologies to determine the abundance and status of proteins in vivo holds great promise for future study of normal cells and associated neoplasms.

Animals↗
PubMed2000

An assessment of zonisamide as an anti-epileptic drug.

A brief review of epilepsy as a disease, anti-epileptic drugs and methods of evaluation of anti-epileptic drugs are presented as a background for assessment of zonisamide, which has been approved by the FDA as add-on therapy for the treatment of partial seizures with or without secondary generalisation in adults. Chemically, zonisamide is classified as a sulphonamide and is unrelated to other anti-epileptic drugs. The mode of action of zonisamide remains unclear, but likely mechanisms are blockade of sodium and T-type calcium channels. It is also shown to have some neuroprotective effect against hypoxia and ischaemia. It has a liner pharmacokinetics with excellent oral bioavailability. Zonisamide has been approved for use in Japan for ten years prior to approval in USA and Europe. Clinical experience with zonisamide in Japan has documented its efficacy in the treatment of partial seizures (partial-onset generalised tonic-clonic, simple partial and/or complex partial seizures) and to a more variable extent, generalised tonic-clonic, generalised tonic (mainly seen in symptomatic generalised epilepsies including Lennox-Gastaut Syndrome) and compound/combination seizures. The efficacy and safety was confirmed in trials conducted in USA and Europe in adults as well as children. Zonisamide compares favourably with other newly introduced drugs and has the potential for development as a monotherapy for epilepsy.

Adolescent↗
PubMed1994

Cutaneous vasculitis associated with granulocyte colony-stimulating factor.

BACKGROUND: Several cases of cutaneous vasculitis have been reported in patients treated with granulocyte colony-stimulating factor (G-CSF). OBJECTIVE: The purpose of this study was to determine the prevalence of cutaneous vasculitis in patients receiving G-CSF therapy, causal relation to the drug, and possible pathomechanisms. METHODS: Review of the literature, retrieval of cases from the safety database of the manufacturer of G-CSF, and global assessment of the causal relation of the drug to adverse drug reactions were done. RESULTS: Eighteen cases of cutaneous vasculitis were found, of which only three have been published. A skin biopsy was done in 12 and showed leukocytoclastic vasculitis. Although cutaneous vasculitis was rare in patients treated for neutropenia associated with malignant disease and chemotherapy, it occurred in 6% of the patients with chronic benign neutropenias. Cutaneous vasculitis usually followed the increase of absolute neutrophil count (ANC) and subsided after the decrease of ANC. There was no recurrence if ANC was kept below 800/mm3. The course of G-CSF was completed in most patients. CONCLUSION: Cutaneous vasculitis should be recognized as an adverse reaction to G-CSF with low morbidity. It can be managed by reduction of dose or discontinuation of G-CSF therapy and use of topical steroids.

Granulocyte Colony-Stimulating Factor↗
PubMed1994

High-pressure neurological syndrome (HPNS).

High-pressure neurological syndrome (HPNS) is a condition encountered in diving beyond a depth of 100 m. Manifestations include headache, tremor, myoclonus, neuropsychiatric disturbances and EEG changes. Convulsions are seen only in experimental animals. Most of the changes are reversible on surfacing but some such as memory disturbances may linger on for long periods. Excessive atmospheric pressure is the most important factor in the pathogenesis of HPNS. Neurotransmitter changes occur of which serotonin appears to be a more likely mediator because of the resemblance of HPNS to serotonin syndrome. Anesthetics and anticonvulsants have been used in experimental animals but are unsuitable for use in human divers. Breathing gas mixtures such as heliox have enabled the extension of depth of diving without HPNS. Use of 5-HT1A receptor antagonists may provide an interesting approach to prevention of HPNS.

Animals↗
PubMed1993

Investigation and management of loss of efficacy of an antiepileptic medication using carbamazepine as an example.

Cases reported as loss of efficacy (secondary failure) of carbamazepine (CBZ) for epilepsy were analysed to determine the cause. In these cases, seizures previously controlled with CBZ, recurred or increased in frequency. The following causes were identified in 131 cases where adequate information was available: use for types of epilepsy where this drug is not recommended, lowering of the blood levels of the drug on switching over from branded to a generic CBZ, change in the galenic form, drug interactions, progression of the underlying brain pathology such as a brain tumor, and unexplained increase in the blood levels of the drug. In cases where the increase in seizures was transient no special measures or changes in therapy were required. Unexplained failure occurred only in seven cases (5.3%). Based on this information, a flow chart was designed to evaluate such a problem step by step and to take appropriate measures. Only when true therapeutic failure is identified, should another antiepileptic drug be substituted for CBZ. Similar approach can be used for other antiepileptic drugs.

Algorithms↗
PubMed1986

Incision of the brain with the Varipulse carbon dioxide laser: a preliminary study for potential application in neurosurgery.

Incisions were made into the rat brain using the Varipulse carbon dioxide laser; they were compared with those made by using an equal amount of energy in the continuous mode of the same laser. Histological examination of the cross sections of the incisions was done. The Varipulse CO2 laser, in comparison with the continuous wave CO2 laser, caused less damage to the tissues surrounding the incision. A 500 Z (peak power, 500 watts) NIIC carbon dioxide laser (Cooper Laser Sonics, Santa Clara, California) equipped with a microcomputer was used with a pulse repetition rate of 200 to 400 and a pulse width of 0.1 second. A focused spot of 0.2 mm and a constant speed of incision of 5 mm/second was used for both types of lesions. The potential usefulness of the Varipulse CO2 laser in neurosurgery, as well as the precautions to be observed during its use, are discussed.

Animals↗
PubMed1985

A prospective randomized comparison of epirubicin and doxorubicin in patients with advanced breast cancer.

Fifty-four patients with advanced breast cancer who had failed prior non-anthracycline combination chemotherapy were randomized to treatment with either epirubicin 85 mg/m2 or doxorubicin 60 mg/m2 intravenously every three weeks. Of 52 evaluable patients, 25% (six of 24) treated with epirubicin, and 25% (seven of 28) treated with doxorubicin experienced major therapeutic responses. The median duration of response to epirubicin was 11.9 months compared to 7.1 months with doxorubicin. Cardiotoxicity was monitored by serial multigated radionuclide cineangiocardiography performed at rest and after exercise. Laboratory evidence of cardiotoxicity was defined as a decrease in resting left ventricular ejection fraction of greater than 10% from the baseline value, or a decrease of 5% or greater with exercise compared with the resting study performed on the same day. Fifteen patients treated with epirubicin and 18 patients treated with doxorubicin had at least two determinations of left ventricular ejection fraction and were evaluable for laboratory cardiotoxicity. Using methods of survival analysis, the median doses to the development of laboratory cardiotoxicity were estimated to be 935 mg/m2 of epirubicin and 468 mg/m2 of doxorubicin. Four patients treated with epirubicin and five treated with doxorubicin developed symptomatic congestive heart failure. The median cumulative dose at which congestive heart failure occurred was 1,134 mg/m2 of epirubicin compared with 492 mg/m2 of doxorubicin. Fewer episodes of nausea and vomiting were observed in patients receiving epirubicin. Epirubicin is a new anthracycline with reduced cardiac toxicity, but preserved efficacy in the treatment of patients with advanced breast cancer.

Actuarial Analysis↗