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Biomedical subjects

S Kos

Publications and source records attributed to S Kos.

At least 19 recordsLinked to original sources

Platelet adhesion enhances the glycoprotein VI-dependent procoagulant response: Involvement of p38 MAP kinase and calpain.

In the final stages of activation, platelets express coagulation-promoting activity by 2 simultaneous processes: exposure of aminophospholipids, eg, phosphatidylserine (PS), at the platelet surface, and formation of membrane blebs, which may be shed as microvesicles. Contact with collagen triggers both processes via platelet glycoprotein VI (GPVI). Here, we studied the capacity of 2 GPVI ligands, collagen-related peptide (CRP) and the snake venom protein convulxin (CVX), to elicit the procoagulant platelet response. In platelets in suspension, either ligand induced full aggregation and high Ca(2+) signals but little microvesiculation or PS exposure. However, most of the platelets adhering to immobilized CRP or CVX had exposed PS and formed membrane blebs after a prolonged increase in cytosolic [Ca(2+)](i). Platelets adhering to fibrinogen responded similarly but only when exposed to soluble CRP or CVX. By scanning electron microscopic analysis, the bleb-forming platelets were detected as either round, spongelike structures with associated microparticles or as arrays of vesicular cell fragments. The phosphorylation of p38 mitogen-activated protein kinase (MAPK) elicited by CRP and CVX was enhanced in fibrinogen-adherent platelets compared with that in platelets in suspension. The p38 inhibitor SB203580 and the calpain protease inhibitor calpeptin reduced only the procoagulant bleb formation, having no effect on PS exposure. Inhibition of p38 also downregulated calpain activity. We conclude that the procoagulant response evoked by GPVI stimulation is potentiated by platelet adhesion. The sequential activation of p38 MAPK and calpain appears to regulate procoagulant membrane blebbing but not PS exposure.

Blood Platelets↗

Cognitive dysfunction following subcortical infarction.

OBJECTIVE: To determine the association between computed tomographic scan findings of subcortical infarction, periventricular lucency, and ventricular enlargement and a patient's performance on a range of neuropsychological tests. DESIGN: Prospective study of patients in whom computed tomographic scanning identified discrete areas of subcortical lucency that were consistent with multiple subcortical infarcts and in whom there was no evidence for additional cerebral computer tomographic pathology. SETTING: Hospital practice that included both inpatients and ambulatory patients. PATIENTS: One hundred forty-seven consecutive appropriate computed tomographic scans were identified. Sixty-two patients were excluded because of concomitant medical disorders, and eight refused participation. We describe 77 patients. MAIN OUTCOME MEASURES: Performance on a battery of neuropsychological tests. RESULTS: The number of infarcts but not the volume of infarction, periventricular lucency, and cerebral ventricular enlargement but not cortical atrophy were significantly associated with impaired performance on neuropsychological tests. The number of infarcts correlated with impaired performance on tests, and this impaired performance was thought to be dependent on the function of frontal systems, while periventricular lucency and ventricular enlargement correlated with impaired performance on a wider range of tests, including tests that depended on memory and language. CONCLUSIONS: The number of infarcts, periventricular lucency, and ventricular enlargement are the computed tomographic head scan parameters that correlated with severity of impaired performance on neuropsychological tests in patients with subcortical infarction. Cognitive impairment is presumed to be the result of cortical disconnection following disruption of the connections between the subcortical regions and the frontal cortex.

Aged↗

The effect of low-dose cyclical etidronate and calcium on bone mass in early postmenopausal women.

This 2-year study was carried out in 36 healthy women of mean age 53.9 +/- 3.8 (SD) years and 3.4 +/- 2.3 years postmenopausal. Bone mineral density (BMD) in the spine, measured by single-energy quantitative computed tomographic scanning, gave a mean initial value of 110 +/- 26 mg/ml. The women were divided randomly into group 1 (n = 11), calcium 600 mg/day; group 2 (n = 15), calcium plus etidronate sodium 400 mg/day for 14 days every 3 months; and group 3 (n = 10), calcium plus etidronate plus phosphate, the 14-day etidronate course being preceded by phosphate 1 g twice daily for 3 days. During the first year of the study BMD decreased by 6.0 +/- 5.8% (p < 0.005) in group 1 subjects and increased by 4.5 +/- 7.8% (p < 0.005) in the combined etidronate-treated groups (difference between control and treated p < 0.001). Inclusion of phosphate in the regimen did not affect the response to etidronate. In the second year there was no significant mean change in BMD in any of the three groups. However, whilst there was little change in BMD values for most of the group 1 subjects, there was considerable variation in individual response within the etidronate-treated groups, with some subjects gaining and some losing bone. The change in BMD during the second year in the subjects as a whole was highly correlated with the change in plasma calcium after 3 months of treatment (r = 0.60, p < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Bone Density↗

Metastatic carcinoma in the neck: a clinical computerized tomography scan and ultrasound study.

Metastatic cervical lymph node involvement is a major determinant of treatment planning and prognosis of upper aerodigestive tract tumours. If the metastatic tumor invades the carotid artery wall then complete tumour excision is not possible unless carotid artery ligation or replacement is planned. A prospective study was performed to assess the role of palpation, computerized tomography (CT) and B-mode ultrasound scanning in the detection of metastatic cervical lymph node involvement in patients with upper aerodigestive tract tumours. In particular, detection of carotid artery wall invasion by tumour was examined. Thirty-two neck dissection specimens were available for histopathological confirmation of findings. Palpation under general anaesthesia was 87.5% sensitive and 87.5% specific in the detection of involved nodes. If a positive finding was defined as detection of a node greater than 15 mm in largest diameter, CT scanning was 78.6% sensitive and 93.8% specific, and the sensitivity of ultrasound was 81.3% and specificity was 84.6%. Ultrasound scanning was sensitive in excluding carotid artery wall invasion, identifying five out of five cases with one false positive and no false negative reports. The combination of palpation under general anaesthesia and B-mode ultrasound imaging provides a sensitive means of detecting the presence of metastatic cervical lymphadenopathy and invasion of the carotid artery wall.

Carotid Arteries↗

Frontal signs following subcortical infarction.

Subcortical cerebral infarction is associated with impaired performance on tests of cognitive function which are sensitive to frontal lobe damage. In a cohort of 82 patients with multiple subcortical cerebral infarcts diagnosed on the basis of CT scan appearances, physical signs presumed to be sensitive to frontal lobe dysfunction were elicited. Associations between physical findings and CT scan changes were determined. The snout reflex was present in 38 patients and correlated significantly with the number of lesions, the presence of periventricular lucency and the presence of ventricular enlargement, while the grasp reflex occurred in 33 and correlated with the number of lesions and the presence of ventricular enlargement, and gait impairment in 54 correlated with the number of lesions and the presence of ventricular enlargement. It is assumed that multiple subcortical infarcts disrupt frontal association pathways, resulting in frontal disconnection which produces frontal cognitive dysfunction and frontal release signs.

Aged↗

[Work capacity evaluation in nonspecific lung diseases in a polyclinic section for lung diseases and tuberculosis].

Describing the structure of a chest clinic in a large city requirements for a high level on the field of medical assessing in patients with non-specific lung diseases are formulated. 1. It must be sure, that all patients suffering from lung diseases are referred to a pneumologist. 2. Opportunities for optimal diagnosis must be given (knowledge and experiences of physicians and nurses; medical equipments of a high technical standard). 3. A scientific-based treatment must be guaranteed. Under optimal conditions it is possible to shorten the duration of disablement and to avoid the hospitalization in some cases.

Ambulatory Care↗

Perineural spread of cutaneous head and neck cancer. Its orbital and central neurologic complications.

The ability of cutaneous squamous cell carcinoma of the face to cause ophthalmoplegia or central nervous system dysfunction via perineural spread is not well recognized. Five patients presenting to a general neurology unit are described in whom partial or complete ophthalmoplegia developed following fifth and seventh cranial nerve involvement by cutaneous squamous cell carcinoma. Two patients subsequently developed a contralateral hemiparesis; and one, multiple cranial nerve palsies as the tumor spread centrally. Normal radiologic findings or complete healing of the primary skin lesion caused delay in the diagnosis in three of the patients. When ophthalmoplegia or central nervous system dysfunction develops as a consequence of perineural spread of cutaneous facial cancer, management is palliative.

Aged↗

Ophthalmic manifestations of perineural spread of facial skin malignancy.

Facial skin malignancy, when complicated by perineural spread (PNS), can lead to devastating orbital, intracranial and paranasal sinus involvement, the management of which requires a multidisciplinary approach and which itself may be devastating. Adequate surgical excision with frozen section control, and specific inspection of histological specimens for perineural invasion, are essential to avoid this problem. This report presents four patients who manifested such involvement, and emphasises the importance of recognition of such ominous symptoms as facial pain, paraesthesiae and weakness. Thorough neuro-ophthalmic examination is mandatory to detect signs of nerve involvement which may indicate perineural spread both at the initial assessment of primary tumour and at suspected recurrence. In this series, the most common sensory and motor nerves affected were, respectively, single, small branches of the ophthalmic and facial nerves.

Aged↗

Measurement of bone in the os calcis: a clinical evaluation.

Bone mineral content (BMC) was measured in the os calcis of 232 normal subjects aged 17-82 years. The mean reproducibility (coefficient of variation) of the measurement was 1.8%. Substantial bone loss occurred between the ages of 20 and 50 years, and in females the menopause was associated with additional bone loss. There was no significant difference in the rate of bone loss in females and males, but the mean BMC was greater at all ages in males than in females. We also compared os calcis BMC with spinal bone mineral density (BMD), measured by quantitative computed tomographic (CT) scanning, in 85 subjects: 33 were normal controls, 19 had osteoporosis defined by the presence of one or more pathological fractures, and in the remainder the CT examination was performed at the patient's request. Os calcis BMC correlated with spinal BMD in both females (r = 0.69, p less than 0.001) and males (r = 0.84, p less than 0.001). However, the os calcis BMC did not reliably predict spine values around the CT "fracture threshold" of 90-100 mg/cm3 and did not correlate with osteoporotic fracture as well as did spinal BMD. It is concluded that measurement of the os calcis BMC is of limited clinical usefulness for the early diagnosis of osteoporosis.

Adolescent↗

How useful is pre-operative computerized tomography scanning in staging rectal cancer?

This study evaluates prospectively the reliability of computerized tomography (CT) in the pre-operative staging of 80 patients with rectal cancer. The scans were performed and reviewed by one radiologist without knowledge of either the operative findings or the final clinicopathological stage of the tumours. Fourteen of 60 patients (23%) who had a potentially curative resection were correctly staged by CT. The tumour was understaged in 28 patients (47%) and was overstaged in 18 patients (30%). CT did not identify the one patient with histological demonstration of invasion of an adjacent organ was equivocal or incorrect in 10 others on the question of adjacent organ invasion. CT failed to define accurately local tumour spread confined to the rectal was (positive predictive value (PPV) 23%), identify venous invasion (PPV 35%) or involved regional lymph nodes (PPV 42%). However, the negative predictive value for excluding synchronous liver metastases was 90%, and 11 patients who subsequently developed histologically confirmed local recurrence were all correctly diagnosed on CT. These findings suggest that pre-operative examination of patients with rectal cancer by CT is not routinely justified specifically for purposes of staging the disease.

Aged↗

Lethal extrapulmonary mycobacteriosis.

A 60 yr old previously healthy man was treated for gradually elevating fever and rash followed by leucopenia and mycosis of the gastrointestinal tract; he died within 6 weeks of the first symptoms appearing. Histologic examination revealed disseminated tuberculosis of paratracheal lymph nodes, liver, spleen and bone marrow with the presence of acid fast bacilli by smear examination. Multiple colonies of the same strain of Mycobacterium kansasii were isolated by bacteriological examination of lymph node and spleen tissue. Neither macroscopical nor histological examination showed any evidence of lung tuberculosis. The final diagnosis of the described acute disease and rapid death was stated as generalized extrapulmonary mycobacteriosis, which is a rare observation.

Humans↗

Bone mass is low in relatives of osteoporotic patients.

STUDY OBJECTIVE: To determine whether the failure to attain normal bone mass in young adulthood contributes to the later development of osteoporotic fractures. DESIGN: Case-control study. SETTING: Referral-based bone clinic at a large teaching hospital. PATIENTS: Sequential sample of 35 asymptomatic relatives, aged 19 to 59 years, of patients with osteoporotic fractures, and 24 patients with osteoporotic fractures. MEASUREMENTS AND MAIN RESULTS: Bone mineral density in the spine was measured by quantitative computed tomographic scanning. Bone mineral content in the os calcis was measured in 19 of the relatives of osteoporotic patients by single-photon absorptiometry. The values for bone mineral density in the spine were corrected to age 50 years with the regression equation derived from the normal values in the controls. The values were lower in relatives of osteoporotic patients than in controls. In men, the mean values (+/- standard deviation [SD]) for relatives were 91 +/- 16 mg/cm3, and for controls, 129 +/- 21 mg/cm3 (P less than 0.001). In women, the mean values for relatives were 96 +/- 17 mg/cm3 and for controls, 126 +/- 19 mg/cm3 (P less than 0.001). In the osteoporotic patients, the corrected mean value for men was 53 +/- 12 mg/cm3, and for women, 77 +/- 20 mg/cm3. The os calcis values did not correlate with the spine values and were mostly well within the normal range. CONCLUSIONS: Mean bone mass is lower in apparently healthy young and middle-aged adult relatives of osteoporotic patients than in normal persons with no family history of osteoporosis. Our findings suggest that the failure to attain an adequate peak bone mass may play an important role in the later development of osteoporotic fractures. Relatives of osteoporotic patients should be advised to have measurements of bone mass taken. This measurement should be taken at the spine, because peripheral sites do not appear to provide adequate information about early osteoporosis.

Adolescent↗

Properties of low-molecular-weight acid phosphatases isolated from cytosol and chromatin of rat liver.

1. Acid phosphatases (orthophosphoric-monoester phosphohydrolases, acid optimum, EC 3.1.3.2) of low molecular weight were isolated from cytosol and chromatin of rat liver cells. The cytosolic enzyme was homogeneous on SDS-polyacrylamide-gel electrophoresis at pH 8.3 (mol. wt. 16 000+/-3000). Both enzymes showed similar electrophoretic mobility and molecular weight but they differed in substrate specificity, response to inhibitors and susceptibility to SH-protecting reagents.

Acid Phosphatase↗