Mode of transmission and histology of M. leprae infection in nude mice

Athymic (nude) mice were experimentally infected with Mycobacterium leprae via the alimentary and respiratory tracts and through the skin. Animals were allowed to inhale aerosols of M. leprae or had bacilli instilled into the nostrils or directly into the lungs. Others were fed M. leprae by gastric tube or had bacilli placed on the tongue. Attempts were also made to transmit M. leprae from infected footpads by Aedes aegyptii mosquitoes. The most successful infections resulted from nasal instillations and from bacilli inoculated onto the tongue surface: in these cases heavy systemic infections occurred. M. leprae was also shown to survive passage through the alimentary tract and bacilli recovered from the faeces were capable of causing infection in recipient nude mice. The possible epidemiological significance of these findings for the transmission of leprosy in man is discussed.     

Airborne infection with Mycobacterium leprae in mice.

Although the portal of entry and mode of spread of M. leprae in human leprosy are still uncertain, it is widely held that direct person-to-person skin contact is important. This assumption has ignored the fact that patients with highly bacilliferous leprosy have nasal as well as dermal infection and that, since M. leprae is shed predominantly from the nose, leprosy might be an airborne infection. The present study was designed to investigate this possibility with mice exposed to airborne infection with M. leprae. The conditions are described in which thymectomised-irradiated CBA strain mice exposed to M. leprae aerosols sustained an immediate lung retention of 1 X 10(5) bacteria. Fourteen to 24 months later, 33% (10 of 30) of the mice had countable numbers of acid-fast bacilli (greater than 2 X 10(4)) with the characteristics of M. leprae in one or more homogenates prepared from ears, foot pads, nose or lungs. Evidence is presented from the distribution of M. leprae that the infection had arisen from systemic spresd of bacilli initially entering the lungs rather than from multiplication of organisms locally retained there, or in the nose, at the time of airborne infection. The relevance of these results to the possible route of infection of leprosy in man is discussed.     

Complications resulting from spurious fields produced by a microwave applicator used for hyperthermia

Microwave hyperthermia applicators are generally characterized at two or three frequencies. These frequencies usually are at the extremes of the applicator's operating range. However, such applicators are often used at arbitrary frequencies within their range. The most common reason for choice of frequency is to achieve acceptable coupling in the clinical configuration with a given patient. Occasionally a spurious transmission pattern will result from the frequency chosen that can lead to undetected high power densities well away from the target volume. In the present report, such a situation is discussed. The transmission pattern resembled "horns" reported at the field edge of certain accelerators. This pattern resulted in the inability to heat the target volume and the production of thermal blisters outside that volume. Such an occurrence underscores the need to characterize the transmission characteristics of a microwave hyperthermia applicator at all the frequencies used.     

Multiple Micronutrients,Including Zinc,Selenium and Iron,Are Positively Associated with Anemia in New Zealand Aged Care Residents

Anemia is a significant comorbidity for older adults not fully attributable to iron deficiency. Low-grade inflammation and other micronutrient deficiencies also contribute. This cross-sectional study examined the relationships between nutrient and non-nutrient factors with hemoglobin and anemia in 285 residents (>65 years) of 16 New Zealand aged-care facilities. Blood samples were analyzed for hemoglobin, ferritin, sTfR, hepcidin, zinc, selenium, and interleukin-6 (IL-6), (with ferritin, sTfR, zinc and selenium adjusted for inflammation). Linear regression models examined the relationships between micronutrient biomarkers (iron, zinc, selenium, vitamin B-12 and D), age, sex, and health factors with hemoglobin. Thirty-two percent of participants exhibited anemia, although <2% had either depleted iron stores or iron deficiency. Plasma zinc and selenium deficiencies were present in 72% and 38% of participants, respectively. Plasma zinc and total body iron (TBI) were positively associated (p < 0.05) with hemoglobin, while gastric acid suppressing medications, hepcidin, and interleukin-6 were inversely associated. These relationships were maintained after the application of anemia cut-offs. These findings emphasize the importance of considering multiple micronutrient deficiencies as risk factors for anemia.     

Effects of lorazepam upon recollective experience in recognition memory

The effects of lorazepam (2 mg) and placebo upon recognition memory with and without conscious recollection were assessed in a cross-over study with normal volunteers. When recognising a word from study lists presented before and 1, 3 and 5 h after drug administration, subjects were required to indicate whether they could consciously recollect the word's prior occurrence or recognised it on the basis of knowing; in the absence of conscious recollection. Lorazepam only impaired word recognition which was accompanied by conscious recollection, and further, the level of this impairment correlated significantly with each of three different indices of subjects' arousal at the time of presentation of each list. Recognition in the absence of conscious recollection was not impaired but somewhat heightened by lorazepam, and these effects did not significantly relate to any index of arousal. These findings are interpreted as providing further support for the notion that recognition entails two distinct components, one based on contextual and associative information and related to conscious recollection, the other possibly based on a traceless perceptual or semantic memory system and related to feelings of knowing in the absence of conscious recollection. Implications are drawn for a contextual-encoding/retrieval account of lorazepam-induced amnesia.     

Spatial heterogeneity of the effects of calcitonin gene-related peptide (CGRP) on the microvasculature of ligaments in the rabbit knee joint

1. Experiments were performed in anaesthetized rabbits to examine the effects of calcitonin gene-related peptide (CGRP) and the CGRP antagonist CGRP_8–37 on blood flow to the medial collateral ligament of the knee joint.
2. Topical application of CGRP (10⁻¹³ to 10⁻⁹  mol) to the exposed external surface of eight knee joints resulted in dose-dependent dilatation of vessels in both the ligament and the joint capsule. The magnitude of this response varied significantly in different regions of the medial collateral ligament, with the 10⁻⁹  mol dose of CGRP giving the maximum response (101.5±25.3% increase) at the femoral insertion site of the medial collateral ligament and lowest (23.1±8.8%) at the tibial insertion site.
3. Topical application of CGRP_8–37 (0.1, 1 and 10  nmol) produced dose-dependent constriction of vessels in the ligament and the joint capsule in five knees, with a trend towards the greatest effect occurring at the femoral insertion site (45.8±8.1% reduction in blood flow). With the 10  nmol dose, the vasoconstrictor response at the femoral insertion site differed significantly (P<0.05) from the responses obtained at the tibial insertion and joint capsule sites.
4. Topical application of CGRP_8–37 (0.1, 1 and 10  nmol) to four chronically denervated knees produced substantially smaller vasoconstrictor responses at all sites. At the femoral insertion site, where 10  nmol CGRP_8–37 normally produces a 45.8±8.1% reduction in blood flow (n=8), ten days following denervation this response was reduced to 6.5±6.1%, this difference being significant (P=0.01).
5. Adrenaline was applied topically to augment blood vessel tone, in order to establish how effectively co-administration of CGRP would offset this increase in tone. Adrenaline (10⁻¹⁰  mol) produced vasoconstriction at all sites (n=6). In the capsule this vasoconstriction was virtually abolished when CGRP (10⁻⁹  mol) was co-administered with adrenaline but in the ligament vasodilatation occurred at all sites. This vasodilatation was significantly greater at the femoral insertion site compared to the tibial insertion and mid ligament sites (P<0.05 for both) and the capsule (P<0.01).
6. Topical application of substance P (10⁻¹⁰ or 10⁻⁹  mol) failed to elicit dilatation of ligament blood vessels.
7. These results suggest that endogenous CGRP may play an important role in regulating blood flow to different structures in and around the knee joint.

     

Chromosome 11q13 markers and D-type cyclins in breast cancer

Summary One in six primary human breast cancers has DNA amplification centered on the cyclin D1 gene (CCND1) on chromosome 11q13. This genetic abnormality is preferentially associated with estrogen-receptor positive tumors and may define a sub-class of patients with an adverse prognosis. AlthoughCCND1 has the credentials of a cellular oncogene, being a target for chromosomal translocation and retroviral integration, the 11q13 amplicon encompasses several other markers andCCND1 is not the only candidate for the key gene on the amplified DNA. To assess their relative importance, we have constructed a physical map of the amplified DNA and compared the extent and frequency of amplification across the region. Since it is likely that the gene providing the selective force for amplification will be expressed at elevated levels, we have also examined expression of both RNA and protein. By these criteria, cyclin D1 remains the strongest candidate for the key oncogene on the amplicon and we are currently investigating the functional consequences of its over-expression.Presented by Gordon Peters at the 16th Annual San Antonio Breast Cancer Symposium, San Antonio TX, USA, November 4, 1993; Minisymposium on Molecular Genetics in Breast Cancer.     

Conducting qualitative research in the health sector: researcher issues and dilemmas.

This article contributes to bridging the gap between research activity and the practical implementation of management decision making in the health sector by reflecting upon some of the issues and dilemmas for researchers, whether academics or managers, in conducting qualitative research in this sector. The article presents the methodological issues addressed by a team of researchers engaged on a project about manager learning and development in an NHS Trust, and highlights concerns about ethical issues that emerged from the research process. The study had involved a series of interviews with senior managers and clinical staff, doctors, nurses and therapists, and it addressed issues surrounding change within the organization, the impact on individuals' jobs, and the resultant learning and development required and undertaken. The article emphasizes that engaging in reflection on the research process is valuable and suggests that it should become a mainstream part of such research. It concludes that there is an important role of qualitative management research in the health sector and that for it to be acceptable and valued, it must be operationally sensitive, ethically robust and methodologically rigorous.     

Reinforced responding of the 11-day-old rat pup: synergistic interaction of D1 and D2 dopamine receptors.

Reinforced responding of 11-day-old rat pups was assessed after blockade of D1 and D2 dopamine receptors. Initially, rat pups were trained to traverse a straight alley for nipple attachment reward. Rat pups were than injected IP with either the D1 antagonist SCH 23390 (0.01, 0.015, 0.03, or 0.1 mg/kg), the D2 antagonist sulpiride (15 or 50 mg/kg), or a combination of SCH 23390 (0.015 mg/kg) and sulpiride (15 mg/kg). The approach performance of drug-treated pups was then compared to vehicle-treated pups on both reinforcement and extinction trials. Sulpiride (15 mg/kg) did not affect either the extinction or reinforced responding of 11-day-old rat pups. In contrast, SCH 23390-treated pups showed significantly longer response latencies than the vehicle controls in both extinction and reinforcement conditions. Combined treatment with SCH 23390 and sulpiride produced the longest response latencies. Analyses of "best score" and frequency data indicated that the drug-induced decline in responding was due to effects on both reward processes and motor capability. The combined results indicate that D1 and D2 receptors interact complexly to affect reinforced responding.