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Biomedical subjects

D J Ferguson

Publications and source records attributed to D J Ferguson.

At least 145 records · Page 8Linked to original sources

A controlled trial of extended radical versus radical mastectomy. Ten-year results.

In view of increasing debate over possible benefit of more complete surgery compared to conservative procedures, a randomized controlled trial contrasting the then standard Halsted radical (RDL) operation with the more complete extended radical (EXT) mastectomy was initiated in 1973. Between November 1973 and July 1982, 123 women younger than 70 years of age and at clinical Stages I and II were enrolled. Of the total series, 112 were treated by the same surgeon and confirmed pathologically as having invasive mammary carcinoma. In this more homogeneous subgroup, the 10-year survival rates (and standard errors) were for RDL, 60% (+/- 7%) and for EXT, 74% (+/- 6%) (P value for comparison of survival curves = 0.13). In patients from this subgroup with central-medial tumors, comprising 62% of the total, survival after RDL at 10 years was 60% (+/- 8%), and after EXT 86% (+/- 6%) (P = 0.025). In the remaining patients with lateral tumors, survival rates were unaffected by treatment: 58% (+/- 13%) and 56% (+/- 11%), respectively (P = 0.62). Comparison of a nonrandomized series of 266 RDL and 124 EXT patients treated between 1960 and 1978 found differences consistent with those of the randomized study, although not statistically significant.

Aged↗

Tissue cyst rupture in mice chronically infected with Toxoplasma gondii. An immunocytochemical and ultrastructural study.

The incidence and effect of tissue cyst rupture in the brains of mice chronically infected with Toxoplasma gondii was studied by immunocytochemistry and electron microscopy. Cyst rupture was extremely rare (2 of 750 tissue cysts) irrespective of the interval post-infection. The event was associated with a rapid cell-mediated immune response, giving rise to microglial or inflammatory nodules. Macrophages were observed to engulf and degrade the cystozoites and cyst debris. Initially, the nodules contained large amounts of immunologically reactive material, but this was degraded with the majority (94%) of lesions containing no recognizable parasites or Toxoplasma antigens. There was little evidence of parasite multiplication or new cyst formation associated with cyst rupture. This study shows that although intermittent cyst rupture occurs, in immunocompetent individuals the immune response limits the potential damage from the release of large numbers of infective organisms to small microglial/inflammatory nodules.

Animals↗

Erythrocytes alter the pattern of renal hypoxic injury: predominance of proximal tubular injury with moderate hypoxia.

1. The distribution of morphological injury was assessed qualitatively and quantitatively in the perfused rat kidney in vitro at controlled rates of oxygen delivery in the presence of low concentrations of erythrocytes. 2. In control kidneys (total oxygen delivery approximately 32 mumol/min per kidney) no injury was seen in the medullary thick ascending limb of Henle's loop (MTAL) whilst 11 +/- 5(SD)% of proximal tubules sustained damage. 3. Mild hypoxia (total oxygen delivery approximately 28 mumol/min per kidney) produced little or no injury to MTAL, namely 6 +/- 4(SD)% and 3 +/- 3% of tubules damaged, respectively. In contrast, both groups sustained extensive damage to proximal tubules, averaging 46 +/- 13% (P less than 0.01 vs control) and 84 +/- 14% (P less than 0.001 vs control), respectively. This damage was equally distributed between the superficial and deep cortex. 4. Comparison with morphometric data obtained previously from cell-free-perfused rat kidneys [P.J. Ratcliffe, Z. H. Endre, S. J. Scheinman, J. D. Tange, J. G. G. Ledingham & G. K. Radda (1988) Clinical Science 74, 437-448] showed that (a) erythrocytes prevent hypoxic damage to the MTAL at mild and moderate levels of hypoxia; (b) when oxygen delivery rates are matched between cell-free- and erythrocyte-perfused kidneys, proximal tubular injury is greater in the presence of erythrocytes; (c) when arterial partial pressure of oxygen is matched between cell-free- and erythrocyte-perfused kidneys, the degree of proximal tubular injury is similar. 5. The data suggest that the proximal tubule and not the MTAL is the nephron segment most at risk of hypoxic injury in vitro.

Acute Kidney Injury↗

An ultrastructural study of mitosis and cytokinesis in normal 'resting' human breast.

The parenchyma of the normal "resting" human breast was examined by electron microscopy to characterize the cells undergoing mitosis and the mechanism by which the normal tissue architecture is maintained during this process. In this study of 112 mitotic cells, it was found that the mitotic cells were luminally positioned, polarised epithelial cells with no evidence of myoepithelial cell division. Ultrastructurally, the nuclear and cytoplasmic changes were consistent with previous reports of mitosis in other tissues. However, unlike all previous reports, two specific orientations of the nuclear spindle and thus the planes of cytokinesis were observed. In a few cases the spindle formed parallel to the lumen and division resulted in two luminally positioned daughter cells. However, in the majority of mitotic cells the spindle was approximately at right angles to the lumen and this orientation resulted in a luminally and a basally positioned daughter cell. It is proposed that the abnormally positioned basal daughter cell could develop into a myoepithelial cell or undergo deletion (apoptosis). Thus the two orientations of mitosis may explain the mechanism by which the epithelial and myoepithelial cell populations were maintained by a single progenitor cell without disrupting the integrity of the tissue architecture.

Adolescent↗

Lower limb compression using inflatable splints to prevent hypotension during spinal anaesthesia for caesarean section.

The efficacy of pneumatic compression of the lower limbs using inflatable leg splints in prevention of hypotension during spinal anaesthesia was assessed in an open study of 46 patients undergoing elective caesarean section. All patients received 15 ml/kg of Hartmann's solution before spinal anaesthesia and were tilted to the left to minimise aortocaval compression. Splints were rapidly inflated to a pressure of 5.3 kPa immediately after institution of the block in treated patients. Blood pressure was measured by a cuff method at 1-min intervals until the commencement of surgery. Hypotension was less common (P less than 0.05) and less severe (P less than 0.05) in splint-treated patients, but the incidence was unacceptably high in both treated (48%) and control (83%) groups.

Adult↗

Ultrastructural and immunocytochemical study of a case of invasive cribriform breast carcinoma.

A case of recurrent invasive cribriform carcinoma of the breast mimicked the histological and mucin staining characteristics of adenoid cystic carcinoma. The diagnosis was based on negative immunocytochemical staining for laminin and ultrastructural evidence of luminal differentiation by cells lining the cystic spaces. Accurate characterisation of this type of breast tumour can be facilitated by retrospective immunocytochemical or ultrastructural examination, or both.

Adenocarcinoma↗

A morphological study of the effect of treatment with the antibiotic ceftazidime on experimental staphylococcal endocarditis and aortitis.

The morphological effects of antibiotic therapy with either single or repeated (8 hourly) injections of ceftazidime were examined in rabbits with experimentally induced staphylococcal endocarditis and aortitis. At 3 h after initiating treatment, many of the bacteria, irrespective of the location of the colony, showed evidence of abnormal ultrastructural changes of the cytoplasm and/or cell wall. By 8 h many degenerate lysed bacteria were present. By 24 h, in rabbits which received a single injection, bacterial colonies contained many normal and dividing bacteria. In comparison, bacterial colonies at 24 h in rabbits receiving repeated injections consisted of large masses of lysed bacteria with only a few viable appearing thick-walled 'persistent' cells. At 48 and 72 h, no viable appearing bacteria were observed although they could be isolated by culture methods. Treatment was associated with an increased inflammatory cell response at the surface of the vegetation and within the vasculature. In the later stages there was evidence of healing with endothelialization of the lesions. It would appear, therefore, that ceftazidime penetrates efficiently into the vegetations with only a short transitory phase at sub-bactericidal concentrations. The few 'persistent' bacteria appear to be protected from the host defences by the surrounding thrombus which prevents their eradication.

Animals↗

[Local immune reaction in human intestinal spirochetosis].

The pathogenetic and clinical importance of intestinal spirochaetes in man is still unresolved. In 12 patients mainly presenting with mild diarrhoea, light and electron microscopy demonstrated massive spirochaetal infestation of the colonic mucosa (spirochaetosis). There were several hitherto unreported features: spirochaetes adhered not only to the surface epithelium of the intestine but were also present within epithelial cells and subepithelial macrophages; many partially degranulated mast cells were noted within the epithelium; there was a marked increase of IgE plasma cells within the lamina propria. In control biopsies intraepithelial mast cells were absent and IgE cells occurred only sporadically. Penetration of the microorganisms into the intestinal mucosa may be responsible for this unusual immune response. Spirochaetes, symptoms and findings disappeared after antibiotic therapy. The authors therefore suggest that intestinal spirochaetosis can cause clinical symptoms in man, and that spirochaetes should not invariably be considered harmless commensals.

Colonic Diseases↗

Loop mattress suture.

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Dermatologic Surgical Procedures↗

An ultrastructural study of the early development and tissue cyst formation of Toxoplasma gondii in the brains of mice.

The ultrastructural features of the early development and tissue cyst formation of Toxoplasma gondii were examined in the brains of mice at various intervals from 7 days to 22 months post inoculation (PI). At 11 days PI toxoplasmas, with the ultrastructural features of the proliferative (endozoite) form, were identified undergoing multiplication within both inflammatory and neural cells. Early tissue cyst formation was also observed, predominantly within neurons. By 21 days PI the proliferative forms had disappeared and only developing tissue cysts containing densely packed cystozoites were present. The proportion of dividing cystozoites decreased with increasing size and age of the cysts. The wall of the tissue cyst developed as an adaptation of the lining of the parasitophorous vacuole. In the majority of older cysts, numerous tubular structures were present beneath the cyst wall. All the cysts observed were retained within intact host cells. The only morphological change with increasing age was that a proportion of the older cysts contained loosely packed cystozoites in an electron lucent ground substance. There was no evidence of any degenerative changes within the cystozoites.

Animals↗

The host-parasite relationship of Toxoplasma gondii in the brains of chronically infected mice.

The host parasite relationship in the brains of asymptomatic mice chronically infected with Toxoplasma gondii was examined at 3, 6 and 12 months post-infection (PI) using electron microscopy. The parasites were located in large numbers within tissue cysts which ranged in size from 10-50 microns in diameter. The cysts were predominantly found in the grey matter. The toxoplasms were enclosed by a cyst wall consisting of a membrane, with irregular invaginations, and an underlying layer of homogeneous osmiophilic material. A detailed examination of 50 cysts revealed that all the cysts were present within intact host cells irrespective of their size or the period PI. The majority of host cells could be positively identified as neurons by the presence of synapses. No extracellular cysts were observed. It is probable that the intracellular location of the cysts protects them from recognition and attack by the host immune system.

Animals↗

Spirochaetosis of the human rectum associated with an intraepithelial mast cell and IgE plasma cell response.

In two patients presenting with mild intestinal symptoms, rectal spirochaetosis was the only morphological abnormality diagnosed by light microscopy. A re-evaluation of the morphological changes using electron microscopy and immunohistochemistry showed certain unusual features: the microorganisms were observed within epithelial cells and in subepithelial macrophages; there were numerous partially degranulated intraepithelial mast cells; and there was a marked increase in the proportion of IgE plasma cells within the lamina propria. Mucosal penetration by the organisms may be responsible for the unusual immune response. In one patient, treatment with antibiotics eliminated the spirochaetes and resulted in a clinical improvement. Spirochaetes should not always be considered as harmless commensals in the colon.

Adult↗

Experimental staphylococcal endocarditis and aortitis. Morphology of the initial colonization.

The initial colonization, by Staphylococcus aureus, of the catheter damaged aortic valve and aorta of the rabbit, was examined by light and electron microscopy at 15 min, 3 h and 24 h post inoculation (PI). At 15 min PI, the majority of bacteria (80%) were located on the lateral surfaces of the thrombic vegetations while 20% were attached directly to the connective tissue of the aortic valve and aorta in areas where the endothelial lining was disrupted. By 3 h the bacteria on the thrombic vegetations were covered by fibrin. At this time, the bacteria both within the vegetations and on the surface of the vasculature were undergoing multiplication to form small groups. The precipitation of thrombus around the bacteria attached to the surface of the aorta to form microscopic infected vegetations had occurred by 24 h PI. The colonizing bacteria did not elicit any phagocytic response. The colonization of the cardiovasculature by Staph. aureus did not necessarily require pre-existing vegetations.

Animals↗

Chromosomal localization of genes by scanning electron microscopy using in situ hybridization with biotinylated probes: Y chromosome repetitive sequences.

The feasibility of using scanning electron microscopy (SEM) to identify the position of specific DNA sequences was examined using a Y chromosome 'specific' probe (pHY2.1). Tests were carried out on chromosome spreads hybridized in situ with biotinylated pHY2.1. Chromosomal sites of hybridization of the probe were localized by an indirect immunohistochemical procedure which resulted in a gold product which could be amplified by silver precipitation. In the SEM, the specific location of the probe was easily identified due to the enhanced signal produced by the gold-silver complex. The probe was localized both on the long arm of the Y chromosome and within interphase nuclei. It was found that SEM was more sensitive than light microscopy since the probe could be identified without silver amplification. With refinements to the technique, SEM could provide a useful method for high resolution localizing of unique DNA sequences (i.e. single copy genes).

Biotin↗