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Biomedical subjects

M Kane

Publications and source records attributed to M Kane.

At least 55 records · Page 3Linked to original sources

Unsafe injections.

In many developing countries use of unsterilized or improperly sterilized needles and syringes is common and causes millions of cases of viral hepatitis B and C as well as contributing to the spread of human immunodeficiency virus (HIV) and other bloodborne pathogens. To combat this problem, WHO has stimulated the development of the "auto-destruct" syringe and encourages all donors, international agencies, and health departments to include a supply of such syringes with all vaccines supplied for emergency purposes. In addition, health providers and the public need to be educated about the risk of inappropriate and unsterile injections.

Blood-Borne Pathogens↗

Integration of hepatitis B vaccination into national immunisation programmes. Viral Hepatitis Prevention Board.

Hepatitis B is a major public health problem even though safe and effective vaccines have been available for over 10 years. Because hepatitis B infection is largely asymptomatic with long term complications occurring after many years it has not received the attention it deserves. Strategies to immunise those at high risk have failed to control the disease. Delegates to the World Health Assembly of the World Health Organisation recommended in May 1992 that all countries should integrate hepatitis B vaccination into their national immunisation programmes by 1997. Some western European countries remain unconvinced that the burden of disease warrants the expense of universal vaccination. However, epidemiological data and economic evaluation show that universal hepatitis B vaccination is cost effective in countries with low endemicity and that it will control hepatitis B, reinforcing the necessity for action.

Cost-Benefit Analysis↗

Mechanical, acoustic and electromagnetic evaluation of the semi-implantable middle ear hearing device (SIMEHD).

The properties of the partially implantable middle ear hearing device (SIMEHD) were extensively studied. The internal unit was subjected to 5,000 cycles of bending at a force of 75 g (gravity) without failure. An accurate measurement of the force output of the SIMEHD was obtained (14-25 dynes/mA). This force is too small to cause any damage to the ossicular chain. The force resulting from electromagnetic interference over a wide frequency range (500 khz -1 Giga (10(9)) Hz) was measured and noted to be within the margin of safety. The frequency response plots (500-8,000 Hz) were also obtained and revealed an excellent ability to amplify middle and high-frequency sounds.

Acoustics↗

Semi-implantable middle ear electromagnetic hearing device for sensorineural hearing loss.

A semi-implantable middle ear electromagnetic hearing device (SIMEHD) is proposed for limited clinical trial in adult patients to evaluate the implantable hearing device for moderate to severe sensorineural hearing loss. Food and Drug Administration (FDA) investigational device exemption (IDE) approval has been granted (May 1996) for clinical trials. The implant unit has been evaluated acutely and chronically in animals (cats) with excellent results. Five cats undergoing chronic implantation were allowed to survive an average of 9.6 months, showing that the SIMEHD is biocompatible, functional and without untoward complications. All implant units recovered from the cats were functional, except for wire breakage of the internal antenna. A new antenna was redesigned for human implantation. The SIMEHD system consists of an external and internal unit. The external unit consists of a microphone, audio amplifier, modulator, radio frequency (RF) amplifier, antenna and battery. The internal unit is composed of a receiving antenna, hybrid electronic circuit, air core driving coil, and a target magnet cemented to the incus. All materials in contact with the body are biocompatible and expected to survive indefinitely. The implant unit is miniaturized and manufactured with existing fabrication technology by our industrial collaborator, Wilson Greatbatch, Ltd. The specific aims and major tasks of the proposed research are: a) to evaluate reliability, safety and efficacy of the SIMEHD system in a selected group of patients diagnosed with sensorineural hearing loss, due mainly to presbycusis or aging of the inner ear; and b) to obtain objective and subjective evaluation of audiologic and psychoacoustic performance as compared to the acoustic hearing aid. This paper describes the design, illustrates the actual device (newest prototype) and details the technique for surgical implantation in the attic and mastoid antrum in humans.

Adult↗

External unit for a semi-implantable middle ear hearing device.

A miniaturized, low-power external unit has been developed for the clinical trials of a semi-implantable middle ear electromagnetic hearing device (SIMEHD) which uses radio-frequency telemetry to couple sound signals to the internal unit. The external unit is based on a commercial hearing aid which provides proven audio amplification and compression. Its receiver is replaced by an application-specific integrated circuit (ASIC) which: 1) adjusts the direct-current bias of the audio input according to its peak value; 2) converts the audio signal to a one-bit digital form using sigma-delta modulation; 3) modulates the sigma-delta output with a radio-frequency (RF) oscillator; and 4) drives the external RF coil and tuning capacitor using a field-effect transistor operated in class D. The external unit functions as expected and has been used to operate bench-top tests to the SIMEHD. Measured current consumption is 1.65-2.15 mA, which projects to a battery lifetime of about 15 days. Bandwidth is 6 kHz and harmonic distortion is about 2%.

Ear, Middle↗

Meiotic pachytene arrest in MLH1-deficient mice.

Germ line mutations in DNA mismatch repair genes including MLH1 cause hereditary nonpolyposis colon cancer. To understand the role of MLH1 in normal growth and development, we generated mice that have a null mutation of this gene. Mice homozygous for this mutation show a replication error phenotype, and extracts of these cells are deficient in mismatch repair activity. Homozygous mutant males show normal mating behavior but have no detectable mature sperm. Examination of meiosis in these males reveals that the cells enter meiotic prophase and arrest at pachytene. Homozygous mutant females have normal estrous cycles and reproductive and mating behavior but are infertile. The phenotypes of the mlh1 mutant mice are distinct from those deficient in msh2 and pms2. The different phenotypes of the three types of mutant mice suggest that these three genes may have independent functions in mammalian meiosis.

Adaptor Proteins, Signal Transducing↗

The detection of picoplankton 16S rDNA in cases of drowning.

Picoplankton belonging to the Synechococcus genus in cyanobacteria (approximately 1 micron in size) are found ubiquitously in Lake Biwa, Japan. However, they could not be morphologically discriminated from other bacteria by microscopy. In this study we attempted to use picoplankton for the diagnosis of drowning by PCR analysis of the 16S ribosomal DNA (rDNA). We designed primers complementary to the variable regions of 16S rDNA of the picoplankton we had sequenced. A comparison was made of the PCR products from the three picoplanktons, five other cyanobacteria, Melosira (diatom), Staurdstrum (green alga), bacteria from Lake Baikal, and humans. The picogram order of template DNA from picoplankton was specifically amplified by the primers. When the template of picoplankton was mixed with human lung tissue, at least 10 ng of template DNA was needed to obtain a PCR product. The isolation of the picoplankton from human lung tissue increased the sensitivity of PCR more than a hundred-fold. The specific PCR products of the picoplankton were obtained from formalin-fixed drowning tissue. Molecular biological diagnosis of drowning was successful using picoplankton 16S rDNA.

Animals↗

Global DTP manufacturing capacity and capability. Status report: January 1995.

A recently completed survey of 63 manufacturers of diphtheria-tetanus-pertussis (DTP) vaccine and its components in 42 countries shows that there is potentially a large excess installed capacity for DTP production. However, many manufacturers are not producing to capacity, and demand and supply for this vaccine are not matched in individual countries. About half of all countries producing DTP vaccine and its components do not have fully functional national control systems, and some countries are performing none of the critical functions for an effective control of quality. Thus, potential for export of excess capacity is limited. The data collected indicate much homogeneity in the preparation of diphtheria and tetanus toxoids. Nearly all manufacturers use the same seeds and similar purification methods, but there is variability in whether purification is done before or after conversion of toxin to toxoid. About 10% of all manufacturers do not meet WHO-defined standards of purity for these toxoids. There is much more heterogeneity in the pertussis seed strains and the methods of purification used. The formulation of DTP vaccine differs considerably among producers. Potency testing is not being done by the WHO-recommended method by about 50% of manufacturers on lots of diphtheria and tetanus toxoids for release. Testing of irreversibility of conversion of toxin to toxoid, a WHO-specified safety test, is also not being done on each lot of diphtheria toxoid by 15% of manufacturers surveyed nor on each lot of tetanus toxoid vaccine by 30% of manufacturers surveyed. Access to technology to develop new DTP-based combination vaccines will be delayed if these manufacturers cannot ensure consistent high quality vaccine for their target populations. The results and conclusions suggest areas for future activities to strengthen the supply and quality of DTP and DTP-based combination vaccines.

Chemistry, Pharmaceutical↗

[Value of selective prescription of preanesthetic laboratory tests].

The aim of this study was to determine the comparative value of routine or selective ordering of preoperative tests. 400 ASA I, II, III patients were enrolled in the study. Two periods were considered: a retrospective period where the patients (n = 200) underwent routine preoperative tests and a prospective period where the patients (n = 200) had only preoperative tests according to the results of questioning and clinical examination. During the retrospective period 1.408 tests were effected with 44 abnormal results. During the prospective period, the abnormal results among 855 prescribed tests were: 0.8% in ASA I patients, 7.5% in ASA II and 5.9% in ASA III patients. The ASA I patients had an average of 3.47 +/- 1.28 tests each, ASA II patients 4.50 +/- 1.21 and ASA III 7.50 +/- 1.50. No complication inducing sequelae or death could be linked to lacking tests. The mean cost of tests was reduced by 50 percent.

Adolescent↗

Pemoline-induced autoimmune hepatitis.

We present a case of pemoline-induced autoimmune hepatitis in a 46-yr-old woman who received the drug for management of her multiple sclerosis. The autoimmune nature of the hepatitis is based on elevation of her anti-nuclear antibodies, anti-thyroid antibodies, IgA, and IgM globulins. These features of autoimmunity disappeared with normalization of her liver-associated enzymes and have remained negative for at least 6 months after completion of prednisone therapy.

Antibodies, Antinuclear↗

Microsatellite instability, mismatch repair deficiency, and genetic defects in human cancer cell lines.

The instability of short repetitive sequences in tumor DNA can result from defective repair of replication errors due to mutations in any of several genes required for mismatch repair. Understanding this repair pathway and how defects lead to cancer is being facilitated by genetic and biochemical studies of tumor cell lines. In the present study, we describe the mismatch repair status of extracts of 22 tumor cell lines derived from several tissue types. Ten were found to be defective in strand-specific mismatch repair, including cell lines from tumors of the colon, ovary, endometrium, and prostate. The repair defects were independent of whether the signal for strand specificity, a nick, was 5' or 3' to the mismatch. All 10 defective cell lines exhibited microsatellite instability. Repair activity was restored to 9 of these 10 extracts by adding a second defective extract made from cell lines having known mutations in either the hMSH2 or hMLH1 genes. Subsequent analyses revealed mutations in hMSH2 (4 lines) and hMLH1 (5 lines) that could explain the observed microsatellite instability and repair defects. Overall, this study strengthens the correlation between microsatellite instability and defective mismatch repair and the suggestion that diminuition in mismatch repair activity is a step in carcinogenesis common to several types of cancer. It also provides an extensive panel of repair-proficient and repair-deficient cell lines for future studies of mismatch repair.

Adaptor Proteins, Signal Transducing↗

Induction of antigen-specific T and B cell immunity in colon carcinoma patients by anti-idiotypic antibody.

Polyclonal goat anti-idiotypic Abs directed against anti-human gastrointestinal carcinoma mAb GA733 were administered to 13 colon cancer patients who had their primary tumor and lymph node metastases removed before immunotherapy. Patients received four s.c. doses (0.5 to 8 mg each) of alum-precipitated anti-idiotypic Ab. Seven of the 13 patients produced anti-anti-Ids that bound specifically to the GA733 epitope on tumor cells and shared idiotopes with mAb GA733. In four of the seven responding patients, anti-Id therapy specifically modulated T cell responses. In two patients who did not demonstrate GA733 Ag/anti-Id-reactive T cells before therapy, anti-Id administration induced CD4+, MHC class II-dependent T cells that specifically proliferated in culture in response to stimulation with either anti-Id or GA733 Ag. In two other patients who did demonstrate Ag/anti-Id-reactive T cells before therapy, anti-Id administration transiently induced lymphocytes that suppressed the proliferative responses of cultured pretherapy lymphocytes to stimulation with anti-Id or GA733 Ag. Nine of the 13 treated patients showed no evidence of disease after 39 to 86 mo of observation. Five of these patients developed Ag-specific Ab3 and one had, in addition, a T cell response.

Adult↗

Epidemiology of hepatitis B infection in North America.

Although the USA is considered an area of 'low' endemicity for hepatitis B infection, the incidence of new cases, the prevalence of carriers, and the burden of acute and chronic disease place hepatitis B among the most important communicable diseases. It is estimated that 300,000 new cases of hepatitis B infection occur each year. These acute infections lead to 350-450 fulminant deaths, 27,000-42,000 chronic carriers and ultimately 4000-5500 deaths per year from cirrhosis and primary liver cancer. Most reported cases occur among young adults, many of whom belong to 'high risk' groups defined by lifestyle or occupation. In 1991, sexual transmission was the predominant mode of transmission (41% of cases by heterosexual activity; 14% by homosexual activity); percutaneous drug use was also important (12% of cases). Infection in healthcare workers represented only 2% of reported cases, and is the only group where falling incidence is due to vaccine use. However, 26% of cases occur in people who deny belonging to any 'high risk group'. Public health officials in the USA concluded that the 'high risk group' immunization strategy would not lead to the control of hepatitis B infection on a population basis. In 1992, it was recommended that all newborns in the USA receive hepatitis B vaccine as part of their routine immunization schedule.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Global programme for control of hepatitis B infection.

The hepatitis B virus (HBV) has infected more than 2000 million persons alive today and 350 million persons are chronically infected carriers of the virus, at high risk of death from active hepatitis, cirrhosis and primary hepatocellular cancer. Each year approximately 1 million people die from the acute and chronic sequelae of HBV infection, making it one of the major causes of morbidity and mortality in man. In May 1992, the World Health Assembly, the governing body of the World Health Organization, endorsed recommendations stating that countries with an HBV carrier prevalence of 8% or more should have hepatitis B vaccine integrated into their national immunization programmes by 1995 and that all countries should have such immunization in place by 1997. At present, 50 countries have a national policy of including hepatitis B vaccine as a routine part of their infant immunization programme--up from 25 countries in 1990. These countries represent 32% of the world's 145 million newborns, but 56% of the world's carriers. Several countries of 'low' endemicity are also recommending hepatitis B immunization of all newborns or adolescents (or both), realising that the strategy of 'high-risk group' immunization has failed to control HBV infection even in areas of low endemicity and that addition of hepatitis B vaccine to routine immunization schedules is highly cost-effective. All countries should establish working groups to examine the burden of disease due to HBV infection and the cost-effectiveness of adding hepatitis B vaccine to routine and/or adolescent immunization programmes.

Adolescent↗