Defining moments in medicine. Pathology.
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Biomedical subjects
Publications and source records attributed to P B Herdson.
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We present the case of a 39-year-old male who died with three significant and separate shotgun wounds. During the investigation, the possibility of murder was considered, but reconstruction of the case and post-mortem findings led to a coronial conclusion that the death was a suicide, accounted for by the type of weapon used and the stamina of the deceased.
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Ninety-three cases of malignant melanoma of the uveal tract diagnosed in Auckland between April 1960 and July 1984 were reviewed to determine the significant pathological factors for predicting prognosis. Six factors correlating with outcome were: extension of the tumour into and through sclera or into optic nerve, tumour size, cell type, mitotic rate, pigmentation, vascularity.
We have reviewed our experience of lupus nephropathy in Auckland over a 15 year period during which time 70 biopsies were obtained from 56 patients with systemic lupus erythematosus. Based on appearances by light microscopy, the biopsies were categorised as mesangial, focal, diffuse or membranous lupus nephritis. Immunofluorescence, where performed, was positive in all instances, including those biopsies showing only mesangial disease by light microscopy. By electronmicroscopy, biopsies with mesangial disease by light microscopy usually had deposits confined to the mesangium, while more severe forms of disease usually had deposits present both around the loops and in the mesangium. Clinical renal abnormalities were uncommon in the mesangial group, usual in the focal group and ubiquitous in the diffuse group. Notably, four of the 18 patients who had no clinical renal or urinary abnormalities, had focal or diffuse disease, indicating a small but definite risk of missing significant renal disease if a biopsy is not performed.
To investigate the pathogenesis of the reperfusion defect which develops in ischaemic myocardium, intravascular casts were prepared by injection of methyl methacrylate into the coronary arteries of isolated heparinised rat hearts. Using a scanning electron microscope, the vascular morphology following 60 min of global ischaemia at 37 degrees C was compared to that of non-ischaemic control hearts injected immediately after stopping perfusion with oxygenated Krebs-Henseleit buffer. Complete casts were obtained from control hearts and from all parts of ischaemic hearts except the subendocardial half of the left ventricular wall of ischaemic hearts where the blood vessels were not filled. At the border between the perfused subepicardial and unperfused left subendocardial regions, the resin which filled the radial penetrating arteries and their branches projected from the filled capillary plexus to an extent proportional to their diameter. Intravascular events such as erythrocyte plugging and thrombosis were excluded as causative factors by the use of a cell-free perfusate. Also, there was no morphological evidence that endothelial cell swelling or constriction of any particular population of vessels was involved. The observed pattern of vascular occlusion suggests that, during global ischaemia, blood vessels in the endocardial half of the left ventricular myocardium lose their ability to be reperfused because of extravascular compression.
The practical value of measuring the ratio of potassium ion (K+) to sodium ion (Na+) in myocardium as an indicator of early inapparent infarction in sudden cardiac death was assessed using a series of 29 human hearts from selected coroner's autopsies together with experimental material from dogs, including infarcts of 5 min to 4 h duration. Samples for electrolyte analysis were derived from a transverse slice of each heart, taken through both ventricles midway between base and apex, all slices being completely subdivided into a numbered sequence of blocks. Ratios were mapped and compared with macroscopic enzyme staining and histological stains for injured muscle. Detailed examination of coronary arteries was performed on all human cases. Measurement of the K+/Na+ ratio did not detect all human cases of proven acute coronary occlusion and did not unequivocally demonstrate experimental infarcts less than 2 h old. Moreover, all ratios fell with increasing duration of autolysis, emphasizing the need for multiple sampling so that each heart may serve as its own control. As a routine test, therefore, the method is both impracticable and unreliable and as previously used has been subject to misinterpretation.
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The clinical course and levels of anti-glomerular basement membrane (GBM) antibody were compared in 20 patients with Goodpasture's syndrome treated with plasma exchange and immunosuppression (8 patients), immunosuppression alone (4 patients) or no specific therapy (8 patients). There was a more rapid fall in the level of anti-GBM antibody and pulmonary hemorrhage was less protracted in the 8 patients treated with plasma exchange and immunosuppression. In this group, 1 patient who presented with severe renal failure showed a marked improvement of renal function and there was no progression of disease in the 4 with milder renal involvement. 2 of the 4 patients treated with immunosuppression alone, and only 2 of the 8 patients who received no specific therapy, maintained normal renal function. In the group which received no specific therapy, 1 of the 6 patients who progressed to renal failure had mild renal involvement initially. There was a significant correlation between the level of anti-GBM antibody and the severity of the morphological changes seen at renal biopsy but not between the level of anti-GBM antibody and the severity of lung hemorrhage. The course and outcome of the disease in those patients not treated, or treated with immunosuppression alone, was better than that described in early reports of this disease, while those patients with plasma exchange and immunosuppression fared even better. An adequately stratified controlled trial of immunosuppression and plasma exchange versus immunosuppression alone is in order.
To study the 'no-reflow' phenomenon is ischemic myocardium, the effects of ischemia and selective embolic blockade of capillaries, precapillaries and terminal arterioles were compared in isolated rat hearts. Hearts received oxygenated Krebs-Henseleit buffer for 10 min via an aortic cannula, and then coronary perfusion was stopped. The pattern and extent of reperfusion after 15-90 min of global ischemia and after the injection of 9, 15 or 55 mu diameter microspheres were determined from the distribution of injected 6.7% fluorescein isothiocyanate-dextran in frozen transverse sections of the ventricles. Following ischemia, progressively larger subendocardial regions surrounding the left ventricle could not be reperfused. In contrast, embolic occlusion of capillaries, precapillaries or terminal arterioles caused a transmural reduction in perfusion and a fine linear or herringbone pattern of fluorescence. Sixty min of ischemia followed by microsphere injection had no effect on the subendocardial zone of no-reflow but much reduced the intensity of fluorescence elsewhere. Thus thrombosis, erythrocyte plugging and occlusion of capillaries, precapillaries or terminal arterioles are unlikely to be primary causes of the reperfusion defect which develops in ischemic myocardium.
Fluorescein-isothiocyanate dextran (FITC-dextran; MW approximately 70,000) was used in isolated rat hearts to compare normal vascular perfusion of ventricular myocardium with the pattern and extent of reperfusion following 60 minutes of global ischemia. Its gross distribution in frozen transverse sections through the ventricles was similar to that of sodium fluorescein. However, unlike 0.1% sodium fluorescein, 6.7% FITC-dextran has a viscosity similar to that of blood, and its much higher molecular weight prevents its diffusion beyond the ischemically injured vessels. Furthermore, staining by the alcoholic periodic acid-Schiff technique enabled tracer distribution to be confirmed microscopically and distinguished competent from incompetent vessels in paraffin embedded material.
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