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Biomedical subjects

D J Rossouw

Publications and source records attributed to D J Rossouw.

At least 19 recordsLinked to original sources

Has the character of gastric cancer changed? A descriptive study of a 10-year period.

Over the 10-year period January 1976-December 1985, 446 patients with histologically verified adenocarcinoma of the stomach were treated at Tygerberg Hospital. Coloured patients made up 63.4% of the study population and a significant increase in the annual proportion of this group was observed. Coloured men comprised 47.6% of the total group. The mean age of white and coloured patients differed significantly (68.9 v. 56.5; P less than 0.001). The symptom complex was essentially similar in the two racial groups and in general the character of the symptoms had no bearing on the prevalence of resection. Although antral tumours were most common in whites and in coloureds, there was a significant increase in tumours located in the fundus in whites. The resection rate remained unchanged over the 10-year period. Only 4 cases of early gastric cancer were detected during this period without any signs of an increased yield of early lesions over time. This audit revealed no beneficial changes over time, which is in stark contrast with reports from Japan regarding the proportion of curable lesions.

Adenocarcinoma

Lupus nephritis. Part I. Histopathological classification, activity and chronicity scores.

Renal biopsy has made a major contribution to the understanding and management of patients with lupus nephritis. In a 5-year retrospective study the renal morphology of 55 biopsies from 51 patients with lupus nephritis was classified according to World Health Organisation criteria. In addition, semi-quantitative activity and chronicity scores were documented. The findings were similar to series from other parts of the world. Of the biopsies reviewed, 6 were class II, 13 class III, 32 class IV and 4 class V. In situations of overlap, segmental proliferative features determined the class to which a biopsy specimen was assigned. Twenty-five of the patients, all WHO class IV, showed activity scores in the severe range. Most of the activity score features were common and easily recognised but necrotising angiitis was only seen in 1 patient. Haematoxylin bodies were difficult to document and the nature and value of the haematoxylin body is questioned.

Adult

Cyclosporin as a treatment for interstitial lung disease of unknown aetiology.

Ten patients with progressive, symptomatic interstitial lung disease of unknown aetiology who were treated with cyclosporin A were reviewed. Five had clinical and histopathological features of cryptogenic fibrosing alveolitis and five a progressive restrictive lung disease characterised by interstitial infiltration with lymphocytes and minimal fibrosis, which could not be classified precisely. Three patients with lymphocytic infiltration showed a response to initial treatment with cyclosporin A alone at high dosage, but toxicity precluded further treatment. All 10 patients then received low doses of cyclosporin A and prednisone. Three of the patients with cryptogenic fibrosing alveolitis and all five patients with lymphocytic infiltration responded with a reduction in dyspnoea or an increase in vital capacity, or both; cyclosporin A appeared to be effective, or at least to have a corticosteroid potentiating effect. A high incidence of side effects occurred, though these do not necessarily prohibit the long term use of cyclosporin A when it is indicated clinically. Cyclosporin A may be effective in the treatment of interstitial lung disease of unknown aetiology. Further studies are required to determine the long term outcome of treatment.

Adult

Electron microscopic analysis of the specific granule content of human atria. An investigation of the role of atrial pressure and atrial rhythm in the release of atrial natriuretic peptide.

Knowledge about the stimulus for the release of atrial natriuretic peptide (ANP) from human atria is incomplete. Atrial stretch is known to be a stimulus and atrial tachyarrhythmias are thought to be another. The effects of atrial size (by two-dimensional echocardiography) and atrial fibrillation on the atrial specific granule content of human atria were studied to gain insight into the secretory mechanisms of ANP. An electron microscopic analysis of the atrial granule content was used to study 12 patients--5 with mitral stenosis and sinus rhythm, 3 with mitral stenosis and atrial fibrillation and 4 controls. Granules were counted using a free count and montage method. This is the first report of such a morphometric analysis in humans. Granule counts were significantly raised in the patients with mitral stenosis compared with controls (P less than 0.014). This observation probably reflects a high turnover state induced by elevated atrial pressures. Further support for this conclusion is provided by the demonstration of a positive correlation between granule counts and left atrial size (r = 0.86; P less than 0.01). The tendency for higher counts in patients with atrial fibrillation may be related to the rhythm disturbance itself, but clinical and echocardiographic data suggest more severe atrial pressure overload in this group.

Adult

Multiple endocrine neoplasia type IIb: a clinicopathological report.

The clinicopathological findings in a 12-year-old boy with multiple endocrine neoplasia type IIb (MEN-IIb) are presented. He demonstrated the characteristics of a Marfanoid habitus and had mucosal neuromas of the lips, tongue, eyelids, and cornea. The enlarged right thyroid lobe showed an increased thallium-201 chloride uptake, and the serum calcitonin level was markedly raised. A total thyroidectomy was performed. Histopathological examination showed an infiltrating medullary carcinoma of the thyroid (MCT) and metastatic spread to supraclavicular lymph nodes. Special stains, immunocytochemistry, and electron microscopy revealed mucin-containing follicular structures lined by calcitonin-positive and thyroglobulin-negative tumour cells. Ultrastructurally the mucosal neuromas consisted of proliferating perineurial and Schwann cells. The serum calcitonin level fell below 300 pmol/L, and his stools returned to normal postoperatively. Because the incidence of MCT in MEN-IIb is virtually 100%, a total thyroidectomy in high risk patients--even before clinical evidence of malignant tumours--may be the only hope of cure.

Child

Digital papular calcific elastosis: a histopathological, histochemical and ultrastructural study of 20 patients.

In 1960, 5 patients were reported with a condition termed "degenerative collagenous plaques of the hands". Ultraviolet light and chronic pressure seem to be the inciting factors. Clinically, it is characterized by keratotic, translucent papules, in linear array, on the radial border of the hands. Histology shows hyperkeratosis and dermal elastosis. The current study documented the histopathological, histochemical and ultrastructural features of 20 patients with this condition and considered the differential diagnoses. The findings were in accordance with those of previous studies, but peculiar, basophilic elastotic masses (BEMs), were a prominent finding. Ultrastructurally, elastic tissue appeared in the form of degenerated non-fragmented and fragmented elastic fibres, degenerated fibres showing foci of increased density, with or without a fibrillar component and as amorphous, structureless material. BEMs arose almost exclusively from degenerated elastic tissue and contained calcium. Disintegrated collagen may be incorporated in the amorphous material and, subsequently, form a minor part of BEMs. Solar elastosis, and its variants, show some similarity to degenerative collagenous plaques of the hands, but lack the constant presence of these calcified angular elastotic masses. BEMs show resemblance to elastic globes, and elastotic bodies found in elastotic nodules of the anthelix and cartilage-hair hypoplasia. In the clinical setting of "degenerative collagenous plaques of the hands", BEMs seem to be unique and due to their extensive presence serve as a non-specific marker for this condition. Digital papular calcific elastosis therefore seems to be more appropriate nomenclature.

Aged

Spontaneous rupture of adult Wilms' tumor.

Wilms' tumor is uncommon in adults, and spontaneous retroperitoneal hemorrhage as the presenting sign of renal malignancy also is rare. A 22-year-old man with spontaneous rupture of a Wilms' tumor, who died within 5 months, is described. The factors that probably contributed to his rapid demise included preoperative tumor spilling, unfavorable histology, and the omission of radiotherapy owing to poor patient compliance. Although Wilms' tumor is known to have a poorer prognosis in adults than in children, the reason for this is not known. Due to the limited number of cases reported, the optimal treatment for adult Wilms' tumor remains to be defined. However, the recent literature indicates that radical surgery combined with maximal radiotherapy dosage and modification of the chemotherapy schedules used in children may be required to improve the prognosis for adults with Wilms' tumor.

Adult

Lafora-body disease with optic atrophy, macular degeneration and cardiac failure.

A 17-year-old boy was admitted to hospital in acute cardiac failure and psychosis. The clinical course, EEG records and tissue diagnosis, including biopsies of brain, skin, skeletal muscle, peripheral nerve and liver were compatible with Lafora-body disease (LBD). Unusual features were those of optic atrophy and macular degeneration, signs generally regarded as negative criteria for the diagnosis of this disease. We also present the findings on endomyocardial biopsy which was performed because cardiac failure as an early symptom of LBD has not been previously described. The patient died in status epilepticus a few months after discharge from hospital.

Adolescent

The adult respiratory distress syndrome in association with diabetic keto-acidosis. A case report.

A 41-year-old man presented in stupor, with ketoacidosis and acute severe respiratory failure. He had a history of alcohol abuse and had been on insulin therapy for diabetes secondary to chronic pancreatitis for 11 years. the condition was rapidly progressive and the patient died within 5 hours of presentation of profound hypoxia and hypotension despite aggressive therapy. Autopsy confirmed the clinical diagnosis of 'shock lung'. None of the more commonly associated precipitating factors of adult respiratory distress syndrome could be detected clinically or at autopsy and the pathogenesis of the condition remains elusive.

Adult

Nephroblastoma in an ovotestis of a true hermaphrodite: a case report.

We describe a patient who presented with a painful mass in the left inguinoscrotal region, gynecomastia, perineal hypospadias with chordee and a bifid scrotum with a small gonad in the right hemiscrotum. At operation the left mass was found to be an ovotestis with hemorrhage in a corpus luteum cyst. A rudimentary uterus and fallopian tube were situated next to the ovotestis. The right gonad also was an ovotestis with a tiny focus of small cell malignancy that was suggestive of nephroblastoma.

Adult

Experimental reclamping of free-flap pedicles: the effect of prolonged stasis on the anastomoses and clamp sites.

The effect of static blood in direct contact with areas of microvascular anastomoses and previous clamp application for prolonged periods of time has been investigated. The free groin flap was used as a model in 27 white rabbits. The flap pedicle vessels were reclamped proximal to the anastomoses and areas of previous clamp application for periods of time varying between 30 minutes and 4 hours after 15 minutes of blood flow over these areas. A 100 percent patency rate was achieved despite the long periods of reclamping. Histologically, minor intimal damage was visible in the immediate period following anastomoses and clamping of the vessels. After 2 weeks, despite a thickened myofibroblastic intimal lesion, an intact endothelial layer was observed. No evidence of thrombosis could be demonstrated in either period. We postulate that vessels carefully treated and with technically well-performed anastomoses can be regarded as "normal" vessels after 15 minutes of blood flow over the anastomoses and clamp sites. We suggest that when required, microvascular clamps may then be reapplied without risk for prolonged periods of time despite static blood being in contact with these areas.

Animals

Liposarcoma. An ultrastructural study of 15 cases.

Fifteen liposarcomas from 13 patients were examined by electron microscopy. These included nine primary tumors, four recurrent tumors after primary surgery or irradiation, and two metastatic lesions. Twelve of the liposarcomas were located in the thigh, and 11 were of the myxoid variety. All neoplasms were composed of cells having the ultrastructural characteristics of some stage of lipoblastic differentiation, i.e., lipid droplets, micropinocytotic vesicles, glycogen, external lamina, intermediate filaments, Golgi apparatuses, rough and smooth endoplasmic reticulum, and mitochondria. The nuclear-cytoplasmic ratio and nuclear pleomorphism were related inversely to the size and number of lipid droplets. Lipoblasts were frequently in close association with capillaries and pericytes, and in four cases lipid droplets were found in pericytes. Multivacuolated, mitochondria-rich lipoblasts, resembling brown fat cells, also were seen. Most tumors contained lipid-free, poorly differentiated mesenchymal cells that showed a continuum of morphologic differentiation to cells that closely resembled early lipoblasts that contained nonmembrane-bound lipid vacuoles. Fibrolipoblasts, cells containing lipid droplets and abundant rough endoplasmic reticulum, were observed only in well-differentiated liposarcomas. Some soft tissue sarcomas contain vacuolated cells that simulate lipoblasts by light microscopy but prove to be reactive or malignant fibroblasts, histiocytes, or smooth muscle cells ultrastructurally. Therefore, use of electron microscopy may be necessary to establish the line of differentiation in these neoplasms.

Adolescent

A nosocomial outbreak of Crimean-Congo haemorrhagic fever at Tygerberg Hospital. Part III. Clinical pathology and pathogenesis.

Crimean-Congo haemorrhagic fever (CCHF) was diagnosed in 8 patients; 7 were staff members at Tygerberg Hospital who had been infected by a patient in whom the disease had not initially been diagnosed. Two patients, the initial case and a staff member, died and 4 became seriously ill. The immunopathogenesis of CCHF appears to be multifactorial. Certain features were common to all patients--leucopenia, thrombocytopenia, elevated liver enzyme values and low serum total protein levels. Ultrastructural changes in and around skin capillaries, including intracytoplasmic endothelial tuboreticulated bodies, were found. Virus-like particles were found on electron microscopy. Important individual factors related to prognosis were identified. The patients who survived all mounted a good antibody response, and manifested no coagulation defect extensive enough to explain the haemorrhagic tendency. In the patients who died no evidence of antibody production was detected; both developed diffuse intravascular coagulation and in 1 evidence of immune complex formation and complement consumption was found. Hepatorenal failure and cardiovascular collapse characterized the terminal period. Early clinical recognition of CCHF with specific attention to factors amenable to treatment may vastly improve the prognosis.

Adult

Experimental paraquat poisoning--histological, electron microscopic and autoradiographic changes in the lung.

Paraquat is a potent and widely used herbicide which acts as a specific pulmonary toxin and causes lung fibrosis in man and animals. Some controversy still exists concerning the details of the morphogenesis of the pulmonary lesions. The lungs of rats exposed to intravenous injections of paraquat and sacrificed 6-24 days later were examined by light and electron microscopy. Autoradiography was used to detect possible paraquat accumulation in the lung 5 hours after a single intravenous injection. The findings on microscopy suggested an acute phase of damage to alveolar lining epithelium followed by epithelial regeneration. The most pronounced light and electron microscopic findings were: signs of disruption of the alveolar wall; type II alveolar epithelial hyperplasia; mobilization of mononuclear cells, and migration and accumulation of fibroblast-like cells in the intra-alveolar and interstitial spaces. After three equally spaced intravenous injections of paraquat signs of interstitial connective tissue proliferation could be seen. Autoradiography showed low-grade radioactivity over the alveolar wall, indicating possible active uptake of paraquat by alveolar epithelium; this coincides with in vitro evidence of an active transport mechanism for paraquat by alveolar epithelial cells.

Animals

The effect of paraquat on the in vitro activity of cytosol, mitochondrial and microsomal enzyme systems.

Subcellular fractions (mitochondria, microsomes and cytosol) were prepared from the lungs of rabbits and rats to investigate the effects of paraquat (Aldrich Laboratories) on the activity of some cytosol and mitochondrial dehydrogenases and on the microsomal respiration and reduced pyridine nucleotide oxidation rate. The normal basal oxygen consumption of rabbit lung microsomes was 1,9 +/- 0,3 nmol O2/mg microsomal protein/min, and the oxidation rates of reduced nicotinamide-adenine dinucleotide phosphate (NADPH) and reduced nicotinamide-adenine dinucleotide (NADH) were 4,29 +/- 0,53 and 4,0 +/- 0,55 nmol/mg microsomal protein/min respectively. One molecule of oxygen can therefore oxidize two molecules of NADPH or NADH, and the generated hydrogen peroxide is probably immediately broken down by the catalase activity of the normal lung microsomal preparation. When Aldrich paraquat (1,0 mM) was added to microsomes metabolizing NADPH (0,5-0,75 mM), both the rate of oxygen consumption and the generation of nicotinamide-adenine dinucleotide phosphate (NADP) were significantly (P less than 0,001) stimulated over the first 5 minutes, and thereafter returned to within basal limits. When microsomes were preincubated with 1,0 mM paraquat before NADPH was added, the oxygen consumption was substantially lower (10,01 +/- 1,01 nmol oxygen/mg microsomal protein/min), while the NADPH oxidation rate was almost similar to the basal rate in the absence of paraquat. This resulted in a striking dissociation in the H/O ratio under these circumstances. The addition of potassium cyanide (KCN) (5.0 mM) prior to paraquat pre-incubation and followed by the addition of NADPH restored the stimulatory effect of paraquat on microsomal respiration and on NADPH oxidation rate.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Biochemical and morphologic changes in rabbit lung following endotracheal instillation of zymosan particles.

In order to establish a model of lung disease in which the usefulness of potential antiinflammatory compounds can be evaluated, we have analyzed the biochemical and cellular responses of rabbits to zymosan deposition in their lungs. A suspension of zymosan particles was instilled into the lungs of rabbits using an intratracheal catheter. Because the influx of leukocytes and the transudation of plasma into affected lungs was expected to contribute to the total cellular enzyme and protein levels, lungs were homogenized and assayed after various time intervals for six cellular enzymes and for protein content. After one day, alkaline phosphatase and neutral protease levels were elevated by 90% and 50%, respectively, above normal values. After two and three days, all of the pulmonary enzymes assayed displayed maximal two- to fourfold increases in their levels of activity. After seven days, only the alkaline phosphatase and neutral protease levels remained slightly elevated by 50% and 30%, respectively. Histologic analysis revealed focal and diffuse intraalveolar, interstitial, peribronchiolar, and perivascular accumulations of macrophages, granulocytes, and lymphocytes. Severe pulmonary edema, evident microscopically after one to three days, correlated well with 100% increases in both the wet weight and protein content of the lungs. In control experiments, the intratracheal infusion of saline solution minus zymosan particles resulted in a variety of enzymatic changes in the lungs after three days, which could be distinguished both enzymatically and histologically from those following zymosan deposition; histopathologic analysis revealed a pattern of intravascular congestion with erythrocytes, edematous thickening of alveolar septa, and focal intraalveolar hemorrhages, but with no inflammatory infiltration. In summary, this study demonstrates the time course of an experimental model for acute and chronic lung inflammation, the extent of which may be quantitatively evaluated using cellular enzymatic markers.

Animals

The effect of oxygen and paraquat on the 14C-glucose oxidation of rabbit alveolar macrophages and lung slices.

In this study, we measured the effects of different concentrations of paraquat (0,01 mM and 1,0 mM) on the 1-14CO2 and 6-14CO2 production of rabbit lung slices and isolated alveolar macrophages, in 20% and 95% oxygen phases respectively. A 95% oxygen phase induced an increase in the 6-14C-glucose oxidation of contorol lung slices over a 3-hour period, while the increased activity of the pentose pathway over the first 2 hours started to decline during the third hour of incubation. Paraquat (1,0 mM) in 20% oxygen caused a consistent increase in the 6-14CO2 production by lung slices, but in a 95% oxygen phase gradually inhibited the 6-14C-glucose oxidation over a period of 3 hours. The pentose phosphate pathway was highly significantly stimulated by 1,0 mM paraquat in 20% and 95% oxygen over 3 hours. When isolated alveolar macrophages (viability 95%) were incubated in a 20% and a 95% oxygen phase respectively, both the 6-14C-glucose and 1-14C-glucose oxidation rates were significantly inhibited by 1,0 mM paraquat after 1 hour. Our results confirmed the initial increase in glycolytic metabolism induced by paraquat, but also inhibited by paraquat when lung slices were incubated in a 95% oxygen phase. The fact that the glucose metabolism in alveolar macrophages is more sensitive to paraquat exposure than that of cells in lung slices may be related to the genesis of the intra-aveolar pulmonary lesions described in the literature.

Animals