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Biomedical subjects

C D Mackenzie

Publications and source records attributed to C D Mackenzie.

At least 19 recordsLinked to original sources
PubMed1999

Patellar tendon augmentation after removal of its central third limits joints tissue changes.

The central third of the patellar tendon is commonly used to reconstruct the injured anterior cruciate ligament. Some studies have noted changes in joint tissues following this procedure. It has been postulated that these changes may be associated with increased stress on the remaining tendon following harvest of the graft. In our study, the central third of the patellar tendon was excised in three groups of rabbits. The central tendon defects in two of the three groups were fitted with different augmentation devices to augment the host tendon during the healing process. All rabbits followed a daily treadmill exercise regimen for 12 weeks following the operation. Biomechanical testing of the tendon revealed that in nonaugmented tendons the cross-sectional area and the length of the patellar tendon significantly increased 112 and 16%, respectively. There was histological evidence of host-tendon remodeling throughout the cross section and extensive fibrosis in the infrapatellar fat pad. Augmentation of the tendon significantly reduced these changes, with the least change noted in the group with the greatest augmentation. The rabbits with augmentation devices retained tendon dimensions similar to those of the contralateral intact tendon, and tendon remodeling occurred only in the defect area. The rabbits with augmentation devices exhibited little to no fibrosis of the fat pad. Structural properties of augmented and nonaugmented tendons were similar despite the size differences, indicating higher tissue quality in the augmented tendons. This study suggested that complications of the knee joint (i.e., tendon proliferation and fat pad fibrosis) noted after anterior cruciate-ligament reconstruction with the autogenous patellar tendon may be limited by the implantation of an augmentation device.

Animals↗
PubMed1998

Blunt impact causes changes in bone and cartilage in a regularly exercised animal model.

The goal of this study was to document the effect of blunt-impact trauma on the knee in a small animal model that incorporated a known level of physical exercise after impact. We hypothesized that a single blunt impact to the patellofemoral joint, of a magnitude comparable with our earlier studies, would result in degenerative changes to cartilage and to subchondral bone of the patella. Blunt impacts were delivered to rabbit patellofemoral joints without producing bone fracture, and biomechanical and histological analyses were performed on joint tissues at various times. At 12 months, the subchondral bone plate was thicker on the impacted side than on the unimpacted side and than that of the controls at comparable locations (near where surface fissures were found on the impacted side). The instantaneous modulus of cartilage was significantly less on the impacted side than that of controls at 3, 6, and 12 months after impact. The relaxed modulus of cartilage on the unimpacted side increased with time after impact and was significantly greater than that of controls at 12 months. These facts suggest that in this exercise model, the contralateral limb should not be considered a control. The retropatellar cartilage on the impacted side was significantly less thick than that of controls at 12 months, and histological analyses of the cartilage and bone indicated early-stage osteoarthrosis in the impacted joint. Thus, in this animal model a single subfracture blunt impact produced degeneration of joint tissues.

Animals↗
PubMed1998

Octreotide decreases connective tissue formation and improves vascular changes associated with hepatic schistosomiasis.

In clinical practice, Octreotide has its greatest impact in the management of bleeding varices. The present work is the first one which was undertaken to investigate the possible use of Octreotide as an antifibrotic agent and to study its effect on hepatic vasculature in Schistosoma mansoni infection. The material of this investigation consisted of two groups of albino mice (A&B) subdivided each, into normal control, infected control, Octreotide treated, Praziquantel treated and Octreotide with Praziquantel treated subgroups. Groups A & B were sacrificed at the 8th week and the 18th week post infection respectively. By analysis of the obtained results, Octreotide has induced reduction of the portal pressure, the weight of the spleen and the liver, the number of liver egg load, granuloma size and cellularity, and of the degree of hepatic fibrosis quantified by serum PIIINP, serum laminin and tissue collagen using sirius red dye assay. Moreover, the biochemical state of hepatocytes has been improved. The subgroups treated with Octreotide in association with Praziquantel revealed better results than the subgroups treated with Praziquantel alone. Data were analysed in terms of histological extent of liver fibrosis in sections stained with Masson trichrome and sirius red, hepatocytic and sinusoidal changes at an ultrastuctural level and by immunohistochemical demarcation of endothelial cells of blood vessels through the determination of factor VIII related antigen. The promising results detected in this study may encourage to further investigate the positive findings of this drug with the intention of its possible application on a clinical level.

Animals↗
PubMed1998

Effect of octreotide on the pathology of hepatic schistosomiasis.

In clinical practice, octreotide (CAS 83150-76-9) has its greatest impact in the management of bleeding varices. The present work is the first one which was undertaken to investigate the possible use of octreotide as an antifibrotic agent and to study its effect on hepatic vasculature in Schistosoma mansoni infection. The material of this investigation consisted of two groups of albino mice (A, B), subdivided each into normal control, infected control, subgroups treated with octreotide, praziquantel (CAS 55268-74-1), and a combination of octreotide and praziquantel. Groups A and B were sacrificed at the 8th week and the 18th week post infection, respectively. By analysis of the obtained results, octreotide induced a reduction of the portal pressure, the weight of the spleen and the liver, the liver egg load (number of eggs) granuloma size and cellularity, and of the degree of hepatic fibrosis quantified by serum N-terminal peptide of type III procollagen in serum, serum laminin and tissue collagen using a Picrosirius red dye assay. Moreover, the biochemical state of hepatocytes has been improved. The subgroups treated with octreotide in association with praziquantel revealed better results than the subgroups treated with praziquantel alone. These obtained data were analysed in terms of histological extent of liver fibrosis in sections stained with Masson trichrome and sirius red, hepatocytic and sinusoidal changes at an ultrastructural level and by immunohistochemical demarcation of endothelial cells of blood vessels through the determination of factor VIII-related antigen. The promising results detected in this study may encourage to further investigate the positive findings of this drug with the intention of its possible application on a clinical level.

Animals↗
PubMed1997

Dirofilaria immitis: heartworm infection alters pulmonary artery endothelial cell behavior.

The pathogenesis of filariasis has generally been attributed to either physical presence of the adult parasites or the host's immune response to the parasites. However, the spectrum of filariasis cannot be entirely explained by these causes, and other mechanisms must be operative. It is now evident that factors released by filarial parasites likely contribute to the pathogenesis of filarial diseases. Adult heartworms (Dirofilaria immitis) reside in the right heart and pulmonary artery, so the pulmonary artery should be exposed to the highest concentration of filarial factors. We tested the hypothesis that endothelium-dependent relaxation is altered in the in vitro pulmonary artery from heartworm-infected dogs. Relaxation responses to endothelium-dependent vasodilators (methacholine, bradykinin, substance P, and A-23187) and the nonendothelium-dependent vasodilator nitroglycerin and contractile responses were measured in rings of pulmonary artery from control and heartworm-infected dogs. Endothelium-dependent relaxation was assessed in the presence and absence of inhibitors of nitric oxide synthase, cyclooxygenase, and guanylate cyclase. Responses to methacholine, substance P, and A-23187, but not to bradykinin, nitroglycerin, norepinephrine, or KCl, were depressed in pulmonary artery from heartworm-infected dogs when compared with control, suggesting that changes in endothelial cell and not vascular smooth muscle behavior are involved in altered relaxation. The mechanism of endothelium-dependent relaxation in control pulmonary artery appears to involve nitric oxide in the case of methacholine and both nitric oxide and a cyclooxygenase product in the case of bradykinin and A-23187. The mechanism of endothelium-dependent relaxation in pulmonary artery from heartworm-infected dogs was not clearly elucidated. These data provide no evidence that heartworm infection globally influences either endothelial cell receptor function or the vascular smooth muscle guanylate cyclase guanosine 3',5'-cyclic monophosphate system, making it likely that changes in intracellular signaling are primarily responsible for the observed alteration of endothelium-mediated relaxation. Alteration of endothelial cell function by filarial parasites may be an important component in the pathology associated with filariasis.

Animals↗
PubMed1996

A comparative study of histological conditions suitable for both immunofluorescence and in situ hybridization in the detection of Herpesvirus and its antigens in chicken tissues.

Our objective was to identify an optimal single set of conditions for use in both indirect immunofluorescence assays (IFA) and in situ hybridization (ISH) to detect viral proteins and nucleic acids in avian lymphoid and neural tissues. Various fixatives were evaluated for use with IFA to detect turkey Herpesvirus (HVT) glycoprotein B (gB) and ISH to identify HVT mRNA in chicken tissues. A precipitating fixative (acetone) was compared to crosslinking fixatives [buffered glutaraldehyde-picric acid (BGPA), 10% formalin, and 4% paraformaldehyde] for both IFA and ISH using spleen, thymus, bursa, sciatic plexus, and brachial plexus of 28-day-old chickens. Four percent paraformaldehyde was found to be the optimal fixative for preservation of all chicken tissues examined with both IFA and ISH. Glass slide preparation, incubation temperatures, and tissue processing were each individually evaluated for ISH and IFA. Silylated slides provided the best retention of tissue sections for both procedures. For IFA, 37 degrees C was the ideal incubation temperature tested, whereas the optimal incubation temperature tested for ISH was 47 degrees C. Of the blocking agents compared, Evans blue dye prevented background fluorescence to a greater extent than either calf serum or bovine serum albumin. These findings provide a technical basis for investigations into various aspects of the molecular pathology of avian diseases.

Animals↗
PubMed1993

A clinical classification and grading system of the cutaneous changes in onchocerciasis.

Although onchocerciasis is one of the most important diseases of the skin and eye in the tropical world, to date there has been no formal consensus regarding the description and terminology of skin lesions. Furthermore, the contribution of cutaneous pathology to the morbidity and socio-economic effects of the disease has been largely neglected. We present a clinical classification and grading system for recording the cutaneous changes of onchocerciasis, and propose that this system be used as a standard method of description to convey clinical information between workers in all endemic areas to assist local and comparative research.

Acute Disease↗
PubMed1993

Antibody responses to Onchocerca volvulus in Ecuadorian Indians and blacks.

In Ecuador, previous epidemiological studies of onchocerciasis affecting a population consisting of Blacks of African origin and Amerindians of the Chachi tribe, have demonstrated different frequencies of clinical disease manifestations in each racial group. To explore the possibility of differential antibody responses to O. volvulus antigens in this population, a subset of sera from these two groups of Ecuadorians with onchocerciasis was analyzed for antibody to O. volvulus antigens using ELISA and Western blot techniques. Significantly higher levels of immunoglobulin against O. volvulus were demonstrated in Chachi Indians compared to native Blacks of African origin: total Ig (p = 0.049), IgG (P = 0.002) IgG4 (p = 0.019) and IgA (p = 0.035). Western blot analysis of sera from 41 persons demonstrated more intense and more frequent recognition of low molecular weight parasite antigens in the Chachi compared to a similar group of male and female Ecuadorian Blacks. These data suggest that the intensity of antibody responses to O. volvulus antigens may reflect the influence of racial factors in the pathogenesis of onchocerciasis in Ecuador.

Adult↗
PubMed1991

The conditions required for the maintenance of Onchocerca lienalis microfilariae in vitro.

Microfilariae of the bovine parasite Onchocerca lienalis were maintained in vitro using a tick cell line as a feeder layer, and under the conditions provided would develop to the sausage stage. A number of media supported this achievement with CMRL 1066 producing the highest yields, particularly when used in conjunction with either medium 199, HAM's F-12, RPMI 1640 or Mark's M20. The addition of inactivated foetal calf serum (iFCS) suppressed development; on the other hand, the addition of tryptose phosphate broth (TPB) enhanced it. The pH range of the medium preferred by the developing worms was 7.35-7.85, and the most favourable osmolality lay in the range 360 to 390 mosM/kg. Insect-derived hormones did not improve yields of developed larvae nor promote moulting to the second larval stage. The culture conditions described in this work, which favour parasite survival and development, provide further insights into the physiological requirements of filariae as well as guide lines to achieving successful in vitro maintenance of Onchocerca sp. A morphological examination of the developing larvae was carried out at electron microscopical level.

Animals↗
PubMed1991

Identification of related DNA sequences in Borrelia burgdorferi and two strains of Leptospira interrogans by using polymerase chain reaction.

The suitability of a polymerase chain reaction assay for Borrelia burgdorferi in epidemiological studies of infected tick populations was evaluated by using 28 strains of Leptospira interrogans and lysates of fixed adult Ixodes tick tissues. Two false positives representing leptospires were differentiated from B. burgdorferi by using an oligonucleotide probe.

Animals↗
PubMed1991

Surface area calculation for Onchocerca volvulus microfilariae.

The pathogenesis of tissue damage in filarial infections involves the generation of inflammatory mediators by interaction of parasite surfaces with the host immune response. In the presence of a heavy parasite burden, the tremendous potential for development of adverse local or systemic inflammatory responses may be appreciated by knowledge of the cumulative surface area represented by circulating microfilariae. The approximate surface area of a single microfilariae of Onchocerca volvulus was calculated using mathematical formulae for standard geometrical shapes and values derived from serial measurements of electron micrographs. Numerical values for the surface area represented by large numbers of microfilariae are given and compared to surface areas of the host which can harbor many millions of microfilariae.

Animals↗
PubMed1990

Delayed eye and other consequences from exposure to methyl isocyanate: 93% follow up of exposed and unexposed cohorts in Bhopal.

A follow up study three years after exposure to methyl isocyanate in 93% of exposed survivors and "control" residents in 10 Bhopali communities showed an excess of eye irritation, eyelid infection, cataract, and a decrease in visual acuity among the exposed people. Breathlessness was twice as common in the heavily exposed clusters as those with lower exposure, a trend that could not be explained by different age or smoking patterns (OR 2.05, 95% CI 1.36-3.08). Case referent analysis of outpatient attendances at Bhopal Eye Hospital, considering patients with severe refractive errors and astigmatism as "controls," showed a 40% increased risk of trachoma, 36% increased risk of other lid infections, and 45% increased risk of irritant symptoms among previously exposed people. "Bhopal eye syndrome" may thus include full resolution of the initial interpalpebral superficial erosion, a subsequent increased risk of eye infections, hyperresponsive phenomena (irritation, watering, and phlyctens), and possibly cataracts. It remains to be confirmed whether this reflects a more generalised disease as a consequence of previous exposure to methyl isocyanate or whether it is only the eye that is affected.

Accidents, Occupational↗
PubMed1989

Onchocerciasis in Ecuador, 1980-1986: epidemiological evaluation of the disease in the Esmeraldas province.

An increase in both the prevalence (68.3%) and intensity of infection (106.2%) occurred in the Ecuadorian onchocercal focus during the 6 year period, 1980 to 1986. In 1986, a higher prevalence of infection was noted in males (53.6%) than females (33.1%), but a greater rate of increase of infection over the 6 years was seen in females than males (75.7% vs 61.9% respectively). In all endemic areas, the Chachi race had a higher prevalence of infection as well as higher increase rate of infection than the Black. In the hyperendemic and hypoendemic areas the highest increase of infection was seen in the Chachi female and Chachi male respectively. The prevalence of infection in 1986 was greater than that in 1980 for all ages, with the greatest increase of infection in the 1-4 year age groups. There was an average increase of 106.2% in the microfilarial skin density with an increase seen in all age groups. A higher microfilariae density increase was seen in the hypoendemic (100.0%) than the hyperendemic (66.5%) areas. The Blacks showed a greater microfilarial density increase than the Chachi (155.1% vs 70.7% respectively) with the Black female showing the highest increase (117.6%) in the hyperendemic area and the Black male showing the highest (155.6%) in the hypoendemic area. Along the Rio Cayapas, high microfilarial densities were found in 3 major areas on the river, a reflection of man-vector exposure.

Adolescent↗
PubMed1989

Onchodermatitis--correlation between skin disease and parasitic load in an endemic focus in Ecuador.

Onchocerciasis is a chronic parasitic infection in which infiltration of the skin by microfilariae has been associated with a number of different pathological changes. This survey compared the prevalence of different forms of skin disease in two villages, one of which was located within the endemic zone for onchocerciasis (Zapallo Grande), in a lowland rain forest area of western Ecuador. The commonest skin diseases in both villages were scabies, pyoderma and pityriasis versicolor. In addition changes closely correlated with the presence of microfilariae in skin snips were found in Zapallo Grande--such as atrophic gluteal changes, and acute and chronic papular dermatitis. The only other skin disease associated with onchocerciasis was widespread tinea corporis due to T. rubrum. The Amerindians in the endemic onchocerciasis area were more likely than Negroes to have generalized atrophic changes of the skin, whereas in the latter group significant numbers of individuals had no obvious skin lesions but large numbers of microfilariae were detected in skin snips. Acute papular dermatitis was common in both groups and in biopsied lesions microfilariae could usually be identified within the epidermis or close to the dermo-epidermal junction. One patient had developed severe reactive onchodermatitis (Sowda). Swabs taken from onchocercal skin lesions showed no evidence of skin surface carriage of Staphylococcus aureus. Changes classically associated with onchocerciasis such as pretibial hypopigmentation (leopard skin) and hanging groin were notably absent in this population.

Adolescent↗
PubMed1989

Identification of Mycobacterium leprae antigens in tissues of leprosy patients using monoclonal antibodies.

Five monoclonal antibodies (MAbs) directed against antigens of Mycobacterium leprae were tested for their ability to bind to components of tissue sections prepared from biopsies taken from patients with various forms of leprosy. Immunoperoxidase was the most successful marker system used, although immunofluorescence and alkaline phosphatase were also successful in certain cases. Positivity was high with all five antibodies successfully staining those sections containing a bacterial index of 3+ or more; sections with 0 bacterial counts also had areas staining positively with two of the MAbs. The positive staining in the tissues was confined to areas infiltrated by inflammatory cells; however it was not identifiable as being associated with individual bacteria. These findings suggest that immunostaining with specific monoclonal antibodies can help to identify leprosy in diagnostic samples in which acid-fast bacilli are not identifiable by standard histochemical means. Immunohistochemical techniques are likely to be valuable in studies of the distribution of M. leprae antigens and their association with individual tissue elements.

Adolescent↗
PubMed1989

Rapid recovery of lung histology correlates with clearance of influenza virus by specific CD8+ cytotoxic T cells.

Previous studies have shown that influenza nucleoprotein (NP)-specific cytotoxic T-cell clones do not prevent influenza infection of mice but lead to a more rapid viral clearance and recovery of the host. Here we examine the histology of the lung to see if viral clearance by cytotoxic T cells (Tc) correlates with recovery of pulmonary pathology or if it is in any way deleterious. Intransasal (i.n.) A/X31 virus infection of BALB/c mice produces lung tissue changes lasting 8-10 days in BALB/c mice, with the most severe abnormalities appearing between Days 4 and 6 (e.g. loss of epithelium, airway obliteration, peribronchiolar and perivascular cell accumulation). The transfer of Tc clone T9/13 into i.n.-infected BALB/c mice induces a transient enhanced loss of epithelium on Day 4, while by Day 6 epithelial abnormalities are much reduced in the lung compared to control infected mice. This correlates with a significant reduction in lung virus titres by Day 6; by Day 8 virus is cleared in Tc recipients and lung histology is normal. Another Tc clone (T5/5) with greater cytolytic activity resulted in significant recovery of the lung tissues by Day 4. Tc clones also resulted in enhanced perivascular infiltration of cells and variation in the infiltrating cell type. Quantification in our system required careful attention to the level of the airway assessed. These histological findings showing an enhanced tissue recovery support the previous assessment of reduced lung viral levels following the transfer of Tc cells, and show that a transient increase in lung pathology can occur.

Animals↗