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Biomedical subjects

J Lindholm

Publications and source records attributed to J Lindholm.

At least 19 recordsLinked to original sources

The prognostic value of cytometric DNA analysis in early stage tongue cancer.

In spite of a small size and seemingly localised properties T1 tongue cancer does recur after surgical treatment, locally and/or in regional lymph-nodes, in 30-40% of the patients, and 50% of patients with recurrent disease die because of their cancer. If these patients could be identified by analysis of relevant parameters on the primary biopsy reflecting the biological properties of the tumours more extensive treatment regimes could be given selectively. In 47 primary biopsy specimens from patients with T1N0M0 squamous cell carcinoma of the mobile tongue the aberration in cellular DNA content was significantly higher in the group of tumours which recurred after surgical treatment compared with the non-recurrent group. Tumours in females recurred more frequently than in males. No significant correlation between recurrence and grade of histological differentiation or tumour thickness could be found. Image cytometry DNA analysis provides an objective and reproducible assessment of the nuclear DNA content which could facilitate selection of adequate treatment strategies.

Adult

Morphometry and prognosis in cancer of the pancreatic head.

The histological slides of 39 cases of cancer of the pancreatic head were analysed using an interactive image analyser system. Some 14 cases were classified as periampullary, 25 as ductal pancreatic cancer. All cases had undergone radical tumor resection according to Whipple's procedure. Morphometric data, tumor size and metastatic nodal involvement were correlated to prognosis. Univariate statistical analysis showed that the classical differentiation between ductal and periampullary cancer was a weaker prognosticator than morphometric variables. In fact, multivariant statistical analysis showed that the morphometric variable irregularity was the best prognosticator (p = 0.0001). No other variable added significant prognostic information. Irregularity is a newly developed variable describing the nuclear shape corrected for roundness. We conclude that morphometry can be of essential prognostic information for the clinician in cancer of the pancreatic head.

Carcinoma, Intraductal, Noninfiltrating

Endocrine function in patients with Cushing's disease before and after treatment.

OBJECTIVE: To estimate the value of some commonly used tests in diagnosing Cushing's disease and to assess the outcome after treatment. DESIGN: Follow-up of a consecutive group of patients for 4.1 to 109.6 months, median 34.4. PATIENTS: Forty-six patients assumed to have ACTH dependent hypercorticism (of 50 patients with Cushing's syndrome) were included. Forty-five underwent transsphenoidal neurosurgery. Ten were treated preoperatively with radiotherapy. MEASUREMENTS: Pituitary, adrenal, thyroid and gonadal function, radiology and pituitary histology were evaluated. RESULTS: One main finding was a significant correlation between the urinary excretion of cortisol before and during administration of dexamethasone. Thus patients with modestly elevated urinary cortisol excretion had an apparently normal suppression. The urinary cortisol values during the dexamethasone test were significantly related to the peak plasma cortisol concentrations at the 30-minute ACTH tests. Computed tomography failed to identify an adenoma in 10 of the 19 patients who were histologically proved to harbour a corticotroph adenoma. At 6 months after radiotherapy, clinical and biochemical improvement was noted in none. Cure was achieved in 36 after neurosurgery. Eventually, adrenalectomy was needed in eight patients. Sixteen patients developed persisting adrenal insufficiency after neurosurgery so that the total number of patients on permanent steroid substitution was 24. Post-operative thyroid and gonadal insufficiency (in men and women of fertile age) was found in 36 and 49%, respectively. CONCLUSIONS: The diagnostic value of measuring the cortisol excretion during dexamethasone administration appears doubtful. The outcome after neurosurgical treatment for Cushing's disease is not entirely satisfactory. Further studies are needed to decide whether adrenalectomy as the first line of therapy should be considered relevant in some patients with Cushing's disease.

Adenoma

Pituitary histology in Cushing's disease.

OBJECTIVE: We assessed pituitary histology in patients with Cushing's disease. DESIGN: Systematic histological assessment of pituitary tissue removed at surgery. PATIENTS: Thirty-six consecutive patients cured from Cushing's disease by transsphenoidal neurosurgery. MEASUREMENTS: Microscopical examination of all available tissue removed at operation. RESULTS: After selective removal of tissue supposed to represent an adenoma in 25 patients this could be histologically verified in 18. In the 11 patients who had undergone a total hypophysectomy an adenoma could be demonstrated in three patients only, despite a systematic search of the entire pituitary gland. Only in 21 of the 36 cured patients (58%) could an adenoma be verified. CONCLUSIONS: Combining the present results with previous reports there is strong reason to believe that in some patients with Cushing's disease no histological lesion in the pituitary is verifiable.

Adenoma

Hyponatraemia in acute brain disease.

Hyponatraemia (HN) can result from a wide range of mechanisms, and therapy must be individualized. Two theories of the origin of HN in acute brain disease have prevailed. The first is the cerebral salt wasting syndrome (CSWS), where excessive natriuresis caused by some unknown cerebral natriuretic factor lowers the total sodium pool of the body and hence the plasma concentration. The second theory is the syndrome of inappropriate secretion of antidiuretic hormone (SIADH), where an increase in total body water is caused by unphysiological secretion of ADH, lowering the concentration of sodium in the plasma. A third possibility is 'sodium shift', i.e. a displacement of sodium from the extracellular to the intracellular space with a simultaneous movement of potassium in the opposite direction. The morbidity and mortality associated with HN only arise in cases where the rate of development of HN was 0.5 mmol h-1 or more. Symptoms respond promptly when the HN is quickly corrected with furosemide and 3% sodium chloride.

Acute Disease

Staging of soft-tissue sarcomas. Prognostic analysis of clinical and pathological features.

In a retrospective study of all 137 patients with soft-tissue sarcoma treated by surgery between 1972 and 1984, the clinical course was related to several host and tumour features, including the Surgical Staging System of Enneking, Spanier and Goodman (1980). Only patients free from metastasis with untreated primary lesions on admission were included. According to the Surgical Staging System, nine tumours were IA, 18 IB, 38 IIA and 72 IIB. Only 12 patients underwent amputation; 125 were treated by local surgery. The mean follow-up time was ten years (minimum five). For the whole series the probability of seven-year survival was 0.65; 42 patients (31%) died from tumour disease. All these had metastases and 24 also had local recurrence. The local recurrence rate was 36%. Multivariate analysis identified large tumour size and high histological grade as significant risk factors for metastatic disease and tumour-related death. Sex, age, tumour site, surgical margin and local recurrence showed no correlation with survival. The prognostic contribution of compartmentality was virtually nil. Histological grade combined with tumour size was found to give better prognostic information than that obtained by the Surgical Staging System.

Adult

A morphometric filter improves the diagnostic value of morphometric analyses of frozen histopathological sections from mammary tumours.

Frozen sections of 202 consecutive breast tumour cases were analyzed by morphometric quantitation of nuclear features. Nuclei were selected at random. Conventional light microscope examination of the paraffin-embedded specimens revealed 144 cases of cancer and 56 benign tumours. Using multivariate discriminant analysis of morphometric features, all but two of the benign cases and 79% of the malignant tumours were correctly classified. When a morphometrically based dynamic filter set to exclude 'non-diagnostic' nuclei was used, the correctly classified malignant cases rose to 86% Morphometry is a fast, reproducible and efficient method that can be used in conjunction with the histomorphological diagnosis of mammary frozen sections. The combination of systematic sampling and an objective dynamic filter may be a powerful approach to quantitative analyses of tumours from other sites. However, it is also likely that efficiency can be improved by combining nuclear morphometric features with structural, histochemical and molecular biological data. The combination of traditional histomorphological examination with quantitative information may well increase the diagnostic accuracy in individual patients.

Breast Neoplasms

Bone disorder in men with chronic alcoholism: a reversible disease?

Disturbances in bone metabolism and histology have been recognized in chronic alcoholism. It has not been established whether they are reversible and the cause remains unclear. We studied various serum and urine variables (including serum PTH, calcium, D-vitamins, and osteocalcin concentrations), bone mineral content, and bone histomorphometrics in men who at present abused alcohol and compared the results to those from men who previously had abused alcohol but who had abstained from alcohol for at least 2 yr and from normal men. No significant differences were found in bone mineral content at the two measuring sites (distal forearm, lumbar spine) between drinkers, abstainers, and controls though a considerable proportion of both current drinkers and abstainers had subnormal values. Bone formation rate and turnover (expressed by the activation frequency) was significantly reduced in the current drinkers who also had lower serum PTH, 1,25-dihydroxycholecalciferol, and osteocalcin concentrations. Men who had abstained from alcohol consumption for at least 2 yr had results similar to those from normal men, suggesting that the disturbances in bone metabolism in men abusing alcohol are reversible. The decrease in bone turnover in the drinkers may be explained by the observed reduction in plasma PTH concentration or a direct toxic effect of ethanol on bone tissue leading to a deficient recruitment of osteogenic cells.

Alcoholism

Prognostic significance of tumor cell morphometry, histopathology, and clinical parameters in advanced ovarian carcinoma.

The prognostic value of clinicopathologic data and tumor cell morphometry was assessed in 49 consecutive patients with advanced epithelial ovarian carcinoma (Stage III-IV as defined by the International Federation of Gynaecologists and Obstetricians [FIGO]). Single-variant analysis proved that nuclear area at the 10th, 50th, and 90th percentiles and nuclear density were the strongest prognostic factors. To assess difference in prognostic influence between morphometric and clinicopathologic factors, Cox regression analysis was carried out and revealed nuclear density and age as prognostically significant (p less than 0.0003 and p less than 0.0004, respectively). Choice of chemotherapy, FIGO stage, histologic grade, and mitotic activity index (MAI) were not of additional prognostic importance. Objective measurement of morphometric factors is simple, highly reproducible, and adequate for routine work and promises to be of clinical value in therapeutic decision-making in advanced ovarian carcinoma.

Adult

The influence of growth hormone on sleep in adults with growth hormone deficiency.

Eight patients with isolated growth hormone deficiency (IGHD), 20-30 years old were studied with polysomnography before and after 6 months of treatment with growth hormone (GH). During GH treatment total sleep time decreased and REM sleep time increased significantly. Delta sleep time (stage 3 + 4) did not change significantly. All patients reported improved well-being and none wished to discontinue the treatment with growth hormone. These findings suggest that GH has an effect on sleep. The effect of increased REM sleep in humans is incompletely understood, but sleep recordings may be one way of directly monitoring the effect of GH on the central nervous system.

Adult

Growth hormone-deficient young adults have decreased deep sleep.

The sleep in young adults with severe isolated growth hormone deficiency (IGHD) was examined by polysomnography. There was a significant decrease in delta sleep time (= stages 3 + 4, slow wave sleep, 'deep sleep'), especially in stage 4. The total sleep time was significantly increased compared to age- and sex-matched normal subjects. The increase in total sleep time was related to an increase in stage 1 and stage 2 sleep. There was no significant difference in total rapid eye movement (REM) sleep time, but when correcting for the very long sleep time in the IGHD subjects, the cumulated REM time within the first 390 min of sleep was significantly less than in the normal subjects.

Adolescent

Control cells for image cytometric DNA analysis of esophageal tissue and the influence of preoperative treatment.

The nuclear DNA content of 4,960 normal cells in 30 esophagectomy specimens was assessed by image cytometry. In relation to intermediate squamous epithelial cells, the mean transmission values were 25.6% higher for basal squamous epithelial cells, 10.1% higher for fibroblasts and 16.2% lower for lymphocytes. The interslide coefficient of variation (CV) was similar for intermediate and basal squamous epithelial cells, 20.2% and 18.9%, respectively, while fibroblasts and lymphocytes displayed lower interslide CVs, 10.5% and 8.8%, respectively. In spite of their high interslide CVs, the mean DNA values of intermediate and basal squamous epithelial cells had the highest intraslide correlation. This correlation indicates that the preparative and analytical differences between slides that result in alterations in mean DNA values affect squamous epithelial cells of similar origin, size and shape in an analogous manner. Basal squamous epithelial cells replicate their DNA and contain more than the diploid amount; therefore, normal intermediate squamous epithelial cells are suggested as control cells to define the 2c reference value for further DNA studies on squamous epithelial lesions of the esophagus. Preoperative irradiation, with or without chemotherapy, did not alter the DNA values of the investigated control cells.

Adenocarcinoma

Variability in plasma oestrogen concentrations in men with a myocardial infarction.

Several studies have reported high levels of oestrogens--especially oestradiol--in plasma in men surviving an acute myocardial infarction (AMI). We have measured plasma levels of the two major oestrogens, oestrone and oestradiol, for three days during the acute AMI and at three months after discharge. Patients admitted to a coronary care unit with ischaemic heart disease without proof of an infarction and patients without evidence of heart disease served as controls. We found significantly higher oestrone levels during the acute infarction than at three months afterwards and also higher than in men without AMI. Men who died shortly after admission had grossly elevated plasma oestrone concentrations. As oestrone levels were correlated to excretion of catecholamines and cardiac enzyme levels in plasma and as circulating levels of oestrone are influenced by ACTH, the hyperoestronaemia may reflect stress-induced increased adrenocortical activity. Plasma oestradiol concentrations in men with AMI decreased significantly during the first three days after admission. In men given no medication oestradiol concentrations did not differ significantly from those in the control groups. Three months after the infarction, the median plasma oestradiol (but not oestrone) concentrations were significantly elevated, but not if only data from men given no medication were considered.

Adult

Improved method for mapping gastric intestinal metaplasia using selective histochemical morphometry.

A gastrectomy specimen containing two tubular adenomas from a 67-year-old woman was mapped by an improved method using selective histochemical staining. The specimen was divided into 83 blocks measuring 4.0 cm x 0.5 cm. Sections from the blocks were stained with alcian blue (pH 2.5) to detect mucin. Alcian blue-stained fields were easily identified and measured with the aid of a MOP 30 interactive digital image analyzer. The total area of gastric mucosa analyzed in the 83 sections measured 3,270.9 sq mm while the area occupied by alcian blue-stained goblet cells measured 755.9 sq mm (23.1% of the total area). Intestinal metaplasia was present in 46 of 83 blocks. Both the mean size of alcian blue-positive fields per section as well as the number of alcian blue-positive fields per section were significantly larger in the antral zone I and the intermediate zone II than in the fundal zones III, IV and V. The highest proportion of gastric mucosa with intestinal metaplasia was not found around the two gastric adenomas, but elsewhere. There was no significant difference in the proportion of intestinal metaplasia between the greater and lesser curvatures, further challenging the belief that intestinal metaplasia is always greatest along the lesser curvature. The method described will permit future studies of the possible association between intestinal metaplasia and dysplasias and adenocarcinomas of the stomach.

Aged

A morphometric method to discriminate normal from dysplastic/carcinoma in situ squamous epithelium in the human esophagus.

The possibility to differentiate normal squamous epithelium from dysplastic/cis in the human esophagus by means of quantitative morphometry was investigated in surgical specimens from 31 consecutive patients. The epithelium was divided into three equal zones, and a total of 186 areas was investigated. Of all variables employed, the interzonal variation between the three epithelial layers was the one showing the highest degree of efficiency (95%) in discriminating normal esophageal epithelium from dysplastic/cis lesions. Nuclear density, nuclear area, nuclear irregularity, nuclear parallelity and nuclear ovality were the most efficient discriminatory individual morphological variables. A 100% sensitivity in discriminating normal squamous epithelium from dysplastic/cis through morphometric evaluation was achieved by considering nuclear area in the superficial zone, nuclear perpendiculairty in the intermediate zone, nuclear density in the total epithelial thickness and interzonal variation of these variables. On the other hand, the specificity in discriminating dysplasia/cis lesions from normal squamous epithelium was only 96.8%. This was due to the fact that one case, by visual impression considered as dysplasia, was morphometrically recorded as normal. The view of that case showed that our initial visual impression of a dysplastic lesion proved to be erroneous, and today that case would be recorded as a reactive lesion due to chronic inflammation.

Analysis of Variance

Mapping intestinal metaplasia by histochemistry and morphometry.

A gastrectomy specimen housing an adenocarcinoma of intestinal type was divided into 60 blocks. Sections were stained with Alcian blue pH 2.5 (to detect foreign mucins). Alcian blue fields were quantitated with a MOP 30 connected to a computer. The mucosa analysed in the 60 sections measured 3788.3 mm2 and that occupied by Alcian blue stained goblet cells 300.9 mm2 (or 7.9% of the total mucosal area). The number of Alcian blue positive fields was significantly larger in the intermediate zone followed by the antral zone, the lowest value was found in the corpus. However, the gastric mucosa with Alcian blue positive cells was larger in the antrum than in the intermediate zone due to the fact that the area of the fields with Alcian blue positive cells was significantly larger in the antrum than in the intermediate zone. The size and number of Alcian blue positive fields were significantly larger along the greater than along the smaller curvature. All measurements were done by a trained technician. The method (using histochemistry, morphometry and skilled technical assistance) will be applied to study the distribution of intestinal metaplasia in gastrectomy specimens from populations with disparate incidences of gastric carcinoma.

Adult