Screening mammogram microcalcification due to basal cell carcinoma of the skin.

Basal cell carcinoma is the most common skin malignancy worldwide, typically presenting as a pearly or translucent papule. Histologically, approximately 21% contain areas of microcalcification. We report a case of a woman presenting with microcalcification on screening mammography that was suspicious. Repeated core biopsies did not obtain microcalcification, and a diagnostic excision of breast tissue and overlying skin revealed an intradermal basal cell carcinoma containing the microcalcification. No breast malignancy was present. We believe this is the second such reported case in the literature and the first to be reported in Europe.

11-gauge vacuum assisted directional biopsy of breast calcifications, using upright stereotactic guidance.

To assess the use of a prototype vacuum assisted biopsy device on a standard upright mammography unit, using a slightly modified digital stereotactic add-on component. A group comprised of 42 sequential patients, who had been recalled from an asymptomatic mammographic screening programme, were studied. All 42 were recalled for assessment of small clusters of microcalcification, graded as indeterminate. Group 1 (21 patients) were biopsied using 14-gauge automated large core needle biopsy. Group 2 (21 patients) were biopsied using 11-gauge vacuum assisted biopsy. Both groups had mammographic guidance on the same upright mammographic unit (Siemens 3000), with Opdima Digital Stereotactic add-on. A total of 86% of specimen radiographs in Group 2 patients (vacuum assisted biopsy) showed successful sampling of the calcifications, compared to 62% of Group 1 patients (14-gauge automated large core biopsies). This study shows that vacuum assisted biopsy is possible using upright stereotactic mammography units. The technique shows promise as a biopsy tool, offering larger cores compared to 14-gauge automated large core biopsy, while requiring less space and lower purchase price compared to dedicated prone biopsy tables. The technique also offers access to biopsy in patients with posterior lesions and for patients who cannot tolerate prone positioning.

A comparison of invasive breast cancer detected in a screened population with invasive breast cancers detected at rapid access diagnostic facilities.

The objective of this study was to assess the impact of rapid access breast diagnostic facilities on the benefit of mammographic breast screening. Invasive cancers were compared for maximum diameter in two groups: group A--70 patients, with screen detected breast cancer aged 50-65, mean age 55.8; group B--46 patients, with symptomatic breast cancer aged 50-65, mean age 56.7. Group A patients had all been invited for screening and included interval cancers and cancers in lapsed attenders. Group B patients were detected at rapid access diagnostic facilities. In group A (screened) the invasive cancers had a mean diameter of 17.8 mm, with a median of 15 mm. Group B (unscreened) consisted of invasive cancers with a mean diameter of 25.2 mm, and a median of 25 mm. Thirty-two (46%) of the screened cancers were found to be less than 15 mm compared to 5 (11%) of the unscreened cancers, using the Wilcoxon Rank Sum Test, P<0.001. Although rapid access modern diagnostic facilities for breast cancers offer the ability to detect early cancers (11% in this survey), screen detected invasive cancers remain significantly smaller even when interval cancers and cancers in lapsed attenders are included.

Basal ganglia neuronal nitric oxide synthase mRNA expression in Parkinson's disease.

Expression of nitric oxide synthase (NOS) mRNA in post mortem brain was studied in putamen, globus pallidus and subthalamic nucleus (STN) of neurologically normal control subjects and patients with Parkinson's disease (PD) using in situ hybridization histochemistry. In PD, a significant increase in NOS mRNA expression was observed in the dorsal two-thirds of the STN with respect to the ventral one-third of the STN. A significant increase in NOS mRNA expression per cell in the medial medullary lamina of the globus pallidus was also observed in PD. NOS mRNA expression was significantly reduced in PD putamen. These findings provide evidence of increased activity of STN neurotransmitter systems in PD and demonstrate for the first time in any species that basal ganglia nitric oxide systems can be selectively regulated in response to changes in dopaminergic input.

Selective increase in somatostatin mRNA expression in human basal ganglia in Parkinson's disease.

Levels of the neurotransmitter somatostatin (SS) have previously been shown to be reduced in the cortex and hippocampus of demented parkinsonian patients and patients with Alzheimer's disease. In situ hybridisation histochemistry (ISHH) was performed with an 35S tail-labelled oligonucleotide DNA probe to human SS mRNA, to examine its expression within the striatum, medial medullary lamina (MML) and reticular thalamic nucleus in Parkinson's disease (PD) and in matched controls. A chronic unilaterally MPTP-lesioned L-DOPA-naive primate model was also examined for comparison of SS mRNA expression with that in human L-DOPA treated PD subjects. Quantitation of SS mRNA expression on emulsion dipped sections revealed a significant increase (82%) in the MML of the globus pallidus in PD (56.5 microm2 of silver grain/cell, n = 9 cases) compared to controls (26.3 microm2/cell, n = 13 cases, p < 0.01, Student's t-test), paralleling the increase previously observed by this group for NOS mRNA. SS mRNA expression was higher in the dorsolateral than ventromedial putamen in controls (p < 0.001; DL: 24.89 +/- SEM 1.35; VM: 17.96 +/- SEM 2.63; n = 14) but this gradient was lost in PD cases (p > 0.05; DL: 22.68 +/- 1.94; VM: 22.17 +/- 2.94; n = 10). These findings suggest specific modification of basal ganglia SS-ergic pathways in PD.

Glutamate decarboxylase-67 messenger RNA expression in normal human basal ganglia and in Parkinson's disease.

Expression of glutamate decarboxylase-67 messenger RNA was examined in the basal ganglia of normal controls and of cases of Parkinson's disease using in situ hybridization histochemistry in human post mortem material. In controls glutamate decarboxylase-67 messenger RNA expression was detected in all large neurons in both segments of the globus pallidus and in three neuronal subpopulations in the striatum as well as in substantia nigra reticulata neurons and in a small sub-population of subthalamic neurons. In Parkinson's disease, there was a statistically significant decrease of 50.7% in glutamate decarboxylase-67 messenger RNA expression per neuron in the lateral segment of the globus pallidus (controls: mean 72.8 microns2 +/- S.E.M. 8.7 of silver grain/neuron, n = 12; Parkinson's disease: mean 35.9 microns2 +/- S.E.M. 9.7 of silver grain/neuron, n = 9, P = 0.01, Student's t-test). In the medial segment of the globus pallidus, there was a small, but non-significant decrease of glutamate decarboxylase-67 messenger RNA expression in Parkinson's disease (controls: mean 100.6 microns2 +/- S.E.M. 7.2 of silver grain/neuron, n = 11; Parkinson's disease: mean 84.8 microns2 +/- S.E.M. 13.0 of silver grain/neuron, n = 7, P = 0.1, Student's t-test). No significant differences in glutamate decarboxylase-67 messenger RNA were detected in striatal neuronal sub-populations between Parkinson's disease cases and controls. These results are the first direct evidence in humans that there is increased inhibitory drive to the lateral segment of the globus pallidus in Parkinson's disease, as suggested by data from animal models. We therefore provide theoretical support for current experimental neurosurgical approaches to Parkinson's disease.

Preproenkephalin and preprotachykinin messenger RNA expression in normal human basal ganglia and in Parkinson's disease.

Striatal expression of preproenkephalin and preprotachykinin messenger RNA was studied in normal controls and in patients with Parkinson's disease using in situ hybridization histochemistry. In controls, preproenkephalin messenger RNA was expressed in a population of medium-sized neurons of mean cross-sectional area 165 microns 2, accounting for 66% of striatal medium-sized neurons, whereas preprotachykinin messenger RNA was expressed in a population of medium-sized neurons of mean cross-sectional area 204 microns 2 (23% larger than those expressing enkephalin, P < 0.05), accounting for 58% of medium-sized striatal neurons. Much lower levels of both preproenkephalin messenger RNA and preprotachykinin messenger RNA were expressed by large neurons in the globus pallidus and substantia nigra reticulata. In addition, preproenkephalin messenger RNA was expressed at low levels by neurons in the subthalamic nucleus. In Parkinson's disease cases, there was a statistically significant increase in preproenkephalin messenger RNA expression in the body of the caudate (109% increase, P < 0.05) and in the intermediolateral putamen (55% increase, P < 0.05) due to an increase in the level of gene expression per neuron rather than an increase in the number of neurons expressing preproenkephalin messenger RNA. Similar increases were observed in other putaminal subregions and in the putamen as a whole, but these did not reach statistical significance. No change in preprotachykinin messenger RNA expression was detected. These findings demonstrate selective up-regulation of a striatal neuropeptide system in Parkinson's disease compatible with increased activity of the "indirect" striatopallidal pathway, which is thought to play a crucial role in the pathophysiology of akinesia and rigidity in this condition.

Tissue pH as an indicator of mRNA preservation in human post-mortem brain.

The relationship between pH and mRNA preservation in post-mortem human brain was examined using in situ hybridization histochemistry and Northern hybridization with oligonucleotide probes in a large group of human subjects, including control and neuropathological cases. Tissue pH was found to correlate strongly with preservation of four mRNA species in three brain areas. Tissue with low pH, assumed to result from prolonged terminal hypoxia, contained reduced or absent mRNA, while tissue with higher pH was found to contain quantifiable amounts, the values for pathological brain samples being comparable to those for control material of similar pH. Measurement of tissue pH provides a simple means to screen post-mortem brain for mRNA preservation and is suggested as a means to match material in case-control studies of human neurodegenerative disease.

Nitric oxide synthase mRNA expression in human subthalamic nucleus, striatum and globus pallidus: implications for basal ganglia function.

The distribution of NOS mRNA within human basal ganglia was investigated using in situ hybridisation histochemistry (ISHH). Greater than 95% of subthalamic nucleus neurons were NOS mRNA-positive, between 1.5% and 2% of striatal neurons were positive and scattered NOS mRNA-positive neurons were detected in the medial, but not lateral globus pallidus. Levels of NOS mRNA expression per neuron were considerably higher in the striatum than in the pallidum or subthalamus. These findings have implications for basal ganglia function and disease states.

51Cr-EDTA/99Tcm-MDP ratio: a simple non-invasive method for assessing renal osteodystrophy.

We have used 99Tcm-MDP to develop a measure of overall skeletal activity for use in renal disease. The method utilizes the relative clearances of 99Tcm-MDP and 51Cr-EDTA from the blood after simultaneous injection. This is expressed as a ratio and the upper limit in normals is 1.4. This ratio has been evaluated in 42 patients with chronic renal failure and compared with appearances of left-hand radiographs. The ratio was elevated in these patients and the level corresponded to the degree of severity of the subperiosteal resorption. Similarly, there was a close correlation between the ratio values and the serum alkaline phosphatase measurements and parathyroid hormone values. Thirty-three patients had sequential studies performed at intervals of up to 2 years. Twenty-one patients showed no change on clinical, biochemical or bone scan evaluation. Of these, only one patient showed a change in ratio value of greater than 20%. Twelve patients showed evidence of change based either on clinical, biochemical or bone scan alteration and all 12 patients showed changes in ratio values greater than 20%. The 51Cr-EDTA/99Tcm-MDP ratio appears to offer not only a single plasma sample method for the detection and evaluation of renal bone disease, but our results also suggest that it may be valuable in the follow-up of these patients.

A single plasma sample method to assess disease activity in patients with bone metastases from carcinoma of the prostate.

A single blood sample method was used to measure total skeletal activity during routine radionuclide bone scans in 114 patients with known carcinoma of the prostate. The method is based on the measurement of radioactivity in plasma after administration of 99mTc MDP and 51Cr EDTA, providing an assessment of total skeletal activity independent of renal function. The results showed a significant elevation of skeletal activity in patients with untreated bone metastases when compared with patients with no metastatic spread. Significant elevation with increasing extent of metastases was also shown, the highest activity being in patients with diffuse metastatic spread (superscan). Patients with treated metastatic disease showed significantly lower skeletal activity than patients with untreated bone metastases. The method requires the use of two radiopharmaceuticals injected as a mixture and potential errors may arise from pharmaceutical instability. In addition, elevation of total skeletal activity may be caused by coexistent metabolic bone disease. The results suggest that the measure may provide quantitative information in the assessment of the activity of bone metastases from prostatic carcinoma.

The 5-HT1 receptor agonist RU-24969 decreases 5-hydroxytryptamine (5-HT) release and metabolism in the rat frontal cortex in vitro and in vivo.

K+-stimulated release of [3H]-5-hydroxytryptamine ( [3H]-5-HT) from rat frontal cortex slices was decreased by the 5-HT receptor agonists 5-methoxy-n1N-dimethyltryptamine and 5-methoxy-3(1,2,3,6,-tetrahydro-4-pyrindinyl)-1H-indole (RU-24969) (1 X 10(-5)M). RU-24969 (10 mg kg-1, i.p.) decreased extracellular 5-HT and its metabolite 5-hydroxyindoleacetic acid measured in vivo by use of intracerebral dialysis combined with high performance liquid chromatography and electrochemical detection. The decrease in extracellular 5-hydroxyindoleacetic acid in vivo after RU-24969 (10 mg kg-1, i.p.) was also observed by in vivo voltammetry. The non-selective 5-HT antagonist metergoline prevented the RU-24969-induced decrease in 5-HT release and metabolism in vivo while the 5-HT2 receptor antagonist R-55669 (ritanserin) did not. The results support the view that RU-24969 stimulates a 5-HT1 receptor that is involved in the autoregulation of 5-HT release and metabolism.

Increased behavioural response to 5-methoxy-N,N-dimethyltryptamine but not to RU-24969 after intraventricular 5,7-dihydroxytryptamine administration.

Chemical lesioning of the 5-hydroxytryptamine neurones in the brain with 5,7-dihydroxytryptamine (200 micrograms i.c.v., 14 or 21 days previously) resulted in an enhanced behavioral response following administration of the 5-hydroxytryptamine receptor agonist 5-methoxy-N,N-dimethyltryptamine (2.5 mg/kg). The increase in the behavioural response showed a positive correlation with the decrease in whole brain 5-hydroxytryptamine levels. In contrast, there was no increase in the hyperlocomotion produced by the 5HT1 receptor agonist RU-24969 (3.5 mg/kg). The results are discussed in relation to the proposed 5-hydroxytryptamine receptor subtypes.

Chromium 51 EDTA/technetium 99m MDP plasma ratio to measure total skeletal function.

A method is described for the quantitation of total skeletal activity during bone scans. The method requires a single plasma sample only, taken at the time of imaging. The ratio of % injected dose of 51Cr EDTA to that of 99Tcm MDP is calculated from this sample following combined injection of the two radiopharmaceuticals. The 51Cr EDTA level corrects for the glomerular filtration of 99Tcm MDP. Using this method, which only requires a gamma counter, significant differences from normal controls have been shown in patients with osteomalacia, renal osteodystrophy, Paget's disease and hypercalcaemia. The method provides routine quantitative data to add to the imaging information in the bone scan.

Ventricular function in thyrotoxicosis complicated by atrial fibrillation.

The radionuclide gated ventriculogram was used to study the association between thyrotoxic atrial fibrillation and underlying ischaemic heart disease. Comparison between ten patients with atrial fibrillation induced by thyrotoxicosis which reverted to sinus rhythm after return to a euthyroid state, and ten age-matched controls with treated hyperthyroidism who never developed atrial fibrillation, showed no significant difference in the incidence of underlying ischaemic heart disease. This study suggests that further investigation for underlying coronary arterial disease is not indicated in simple, reversible, thyrotoxic atrial fibrillation.

Clinical indications for optimal use of the radionuclide brain scan.

427 radionuclide brain scans, performed in 1981 at Guy's Hospital Nuclear Medicine Department, were reviewed retrospectively to define clinical circumstances in which the study provided useful information. It was concluded that the radionuclide brain scan was the appropriate first line investigation in patients with known non-cerebral malignancy, in whom the possibility of cerebral metastases exists; and in patients with a low to moderate probability of subdural haematoma. The radionuclide brain scan can provide a valuable alternative to computed tomography studies:--(1) in patients without known underlying disease who develop localising signs; (2) in patients with focal fits; (3) in patients with underlying vascular disease and gradual onset of localising signs; and (4) in patients with suspected inflammatory conditions of the central nervous system. Outside these groups, the radionuclide brain scan rarely provided useful information.