High-resolution confocal microscopy using synchrotron radiation.

A confocal scanning light microscope coupled to the Daresbury Synchrotron Radiation Source is described. The broad spectrum of synchrotron radiation and the application of achromatic quartz/CaF2 optics allows for confocal imaging over the wavelength range 200-700 nm. This includes UV light, which is particularly suitable for high-resolution imaging. The results of test measurements using 290-nm light indicate that a lateral resolution better than 100 nm is obtained. An additional advantage of the white synchrotron radiation is that the excitation wavelength can be chosen to match the absorption band of any fluorescent dye. The availability of UV light for confocal microscopy enables studies of naturally occurring fluorophores. The potential applications of the microscope are illustrated by the real-time imaging of hormone traffic using the naturally occurring oestrogen coumestrol. (The IUPAC name for coumestrol is 3,9-dihydroxy-6H-benzofurol[3,2-c][1]benzo-pyran-6-one (Chem. Abstr. Reg. No. 479-13-0). The trivial name will be used throughout this paper.

Effect of joint position and ligament tension on the MR signal intensity of the cruciate ligaments of the knee.

Six cadaveric lower extremities were imaged with T1-weighted spin-echo pulse sequences with the knees extended and flexed to 90 degrees. Magnetic resonance signal intensities of the anterior cruciate ligament (ACL) and posterior cruciate ligament (PCL) were compared. Changing from extension to flexion resulted in decreased signal intensity in six of six ACLs and five of six PCLs. Two of the knees were then imaged with and without tension applied to the ACL. Both specimens showed a decrease in signal intensity with tension, followed by an increase in signal intensity with release of the tension. Finally, in three of the limbs the ACL was surgically reconstructed and then imaged with and without tension applied to the tendon graft. Signal intensity decreased with tension and increased with release of the tension in all three specimens. Thus, joint position and changes in ligament tension affect the signal intensity of the ACL and PCL, generally resulting in a signal intensity decrease with tension.

Clinics without walls. Alternative practice structures for physicians in independent practice.

Clinics Without Walls will function as integrated medical practice business organizations for the purpose of carrying out ventures approved by their boards of directors, including the delivery of patient care services under contract to managed care organizations or others. The networks will be responsible for receiving revenue for contracted services and for paying expenses. Patient care should be enhanced by this structure, which will result in improved communications and information exchange among participating physicians and greater patient access to convenient, decentralized medical facilities. Patients and physicians will likely benefit from the expanded services made available through shared network resources. As mentioned above, the MMA and the Hennepin and Ramsey county medical societies are currently developing a detailed Clinics Without Walls prototype that will be made available for implementation during the first half of 1993.

Twin cities health care mergers, acquisitions, and affiliations. Implications for independent physician practices.

"The health care system in Minnesota, especially in the Twin Cities area, is currently undergoing change that can best be characterized as a consolidation of providers into larger and larger groups (multispecialty clinics, hospital/physician mergers, and expanded HMOs and PPOs). These changes are intended to produce economies of scale, less duplication of services, and better control of costs and quality of health care. Where does this leave the more traditional, smaller multispecialty or single-specialty practices often referred to as 'independents'?... How can independent groups respond to these trends in order to survive in the new health care marketplace?"

Haemodynamic considerations in the management of patients with subarachnoid haemorrhage.

Cerebral vasospasm occurs, following subarachnoid haemorrhage, in the majority of patients and is accompanied by cerebral ischaemia in 30%. The objectives of this article are to review (1) the effects of subarachnoid haemorrhage and vasospasm on cerebral blood flow (CBF); (2) the effects of induced hypotension and hypocapnia on CBF in these patients; (3) current therapy for cerebral ischaemia from vasospasm. The medical literature was searched using Index Medicus; for the period 1983-90 this search was done on a computer with the CD-ROM version of Index Medicus, Silver Platter. Papers were selected on the basis of validity and applicability to clinical practice; animal studies are included when human data is lacking. Cerebral vasospasm may decrease cerebral blood flow, disturb autoregulation and place the patient at risk for delayed cerebral ischaemia. Intraoperative induced hypotension and hypocapnia can decrease CBF further, although effects of either on outcome have not been evaluated. Calcium antagonists are effective for both the prevention and the treatment of delayed cerebral ischaemia. Of the mechanical treatments, systemic-arterial hypertension has the firmest scientific foundation, although this is frequently combined with haemodilution and blood volume expansion. There is a need for randomized clinical trials to assess the efficacy of these latter treatments.

Red blood cell and adipose tissue fatty acids in mild inactive multiple sclerosis.

The fatty acid profiles of phosphatidyl ethanolamine (PE) and phosphatidyl choline (PC) of the red blood cells of 30 patients with mild inactive multiple sclerosis (MS) and 30 healthy controls were studied by gas chromatography. The groups were well matched for factors likely to influence tissue lipid levels, including diet. The MS patients showed a significant reduction in PE eicosapentaenoic acid (p = 0.009) especially in women, and an increase in both PE dihomo-gamma-linolenic acid (p = 0.004) and PC stearic acid (p = 0.04). No reduction in linoleic acid was observed in either the PC or PE fractions of the MS subjects. A similar study of the fatty acid profile in adipose tissue in 26 MS and 35 healthy controls found no detectable eicosapentaenoic acid in either group. However, whereas docosahexaenoic acid was not detectable in any MS patient, 40% of the controls had measurable levels varying from to 0.1 to 0.3% of total estimated fatty acid (p = 0.0003). No reduction in linoleic acid in MS subjects was observed. Supplementation with oral fish body oil demonstrated that n-3 fatty acids were incorporated into red blood cells over 5 weeks and this occurred equally in MS and controls. The effects of oral supplementation on adipose tissue were studied after 1 and 2 years. Whereas many fatty acids such as linoleic acid were raised at 1 year, but did not rise subsequently, eicosapentaenoic acid and docosahexaenoic acid continued to rise through the 2-year period.(ABSTRACT TRUNCATED AT 250 WORDS)

Relation between apocrine differentiation and receptor status, prognosis and hormonal response in breast cancer.

The release of a gross cystic disease fluid protein (GCDFP 15) by tumour explants grown in tissue culture was used to measure apocrine differentiation in 117 women with breast carcinoma. GCDFP 15 was detected by radioimmunoassay in the media from 90% of tumours (range 2-2100 ng/ml, mean 41). Tumour secretion of GCDFP 15 was higher in oestrogen receptor rich (over 20 fmol/mg) tumours (P less than 0.05) but did not correlate with any other prognostic factors or with survival. Response to hormonal therapy was assessable by UICC criteria in 33 women (6 partial responses, 8 stable disease, 19 progression). Responders had significantly higher tumour oestrogen receptor levels (P less than 0.005) but a lower GCDFP 15 secretion than non-responders (P less than 0.02). Apocrine differentiation in breast cancer may be a marker for oestrogen receptor positive tumours that do not respond to hormonal therapy.

An analysis of factors predisposing to neurological injury in patients undergoing coronary bypass operations.

In a prospective study of 312 patients undergoing elective coronary bypass surgery we evaluated 50 preoperative, intraoperative and postoperative factors with the aim of identifying predisposing causes for perioperative neurological morbidity. Factors which showed a significant association with the development of neurological complications included the duration and severity of heart disease before surgery; the presence of extracoronary vascular disease; history of cardiac failure; history of diabetes; difficulty in terminating bypass; intraoperative mean arterial pressure levels of less than 40 mmHg; a large drop in haemoglobin level during surgery; prolonged stay in the intensive therapy unit after operation; and abnormalities of blood pressure control in the postoperative period. The significance of these findings is discussed and a comparison made with data available from previous studies.

A double-blind controlled trial of long chain n-3 polyunsaturated fatty acids in the treatment of multiple sclerosis.

A trial of n-3 polyunsaturated fatty acids in the treatment of multiple sclerosis has been conducted over a 5 year period. Ambulant patients (312) with acute remitting disease were randomly allocated to treatment or placebo. Both groups were given dietary advice to increase the intake of n-6 polyunsaturated fatty acids and the treatment group in addition received capsules containing n-3 polyunsaturated fatty acids. Analysis of clinical outcome at the end of 2 years of treatment was made in terms of the duration, frequency and severity of relapses and the number of patients who had improved or remained unchanged. The results showed no significant difference at the usual 95% confidence limits but there was a trend in favour of the group treated with n-3 polyunsaturated fatty acids in all parameters examined.

Hyperbaric oxygen and multiple sclerosis: final results of a placebo-controlled, double-blind trial.

The long term results are reported of a trial involving 120 patients with chronic multiple sclerosis who were randomised to receive either 100% oxygen at 2 atmospheres absolute (ATA) for 90 minutes daily for 20 sessions or placebo therapy with air using a simulated compression procedure. The previous finding of subjective improvement in bowel/bladder function at the end of treatment was not confirmed by objective urodynamic assessment. The treatment did not alter disease progression as measured by the Kurtzke disability status scale nor did it alter the rate of acute relapse. There was less deterioration in cerebellar function at one year in the treated patients as measured by the Kurtzke functional systems scale. No other differences were found between the two groups. Psychometric tests and measurements of lymphocyte sub-populations showed no treatment related effects. Evoked potential studies showed no improvements but there was a significant reduction in amplitude of the visual evoked potential in the treated patients at the end of therapy. This might indicate a reversible degree of retinal damage induced by oxygen toxicity.

Neuro-ophthalmological complications of coronary artery bypass graft surgery.

In a prospective study of neurological complications of coronary bypass surgery, detailed pre- and post-operative bedside ophthalmological evaluation was undertaken in 312 patients. Post-operative neuro-ophthalmological complications developed in 80/312 (25.6%) patients and included: areas of retinal infarction (17.3%); retinal emboli (2.6%); visual field defects (2.6%); reduction of visual acuity (4.5%) and Horner's syndrome (1.3%). Neuro-ophthalmological complications were not observed in a control group of 50 patients undergoing major peripheral vascular surgery. Ten of 75 patients reviewed at 6 months still had detectable neuro-ophthalmological abnormalities, but functional disability occurred only in those with persistent visual field defects. Multivariate analysis revealed that extra-coronary vascular disease, severe and prolonged duration of heart disease prior to operation, and large drop in haemoglobin level during surgery may predispose to neuro-ophthalmological complications.

Neurologic and neuropsychological morbidity following major surgery: comparison of coronary artery bypass and peripheral vascular surgery.

As part of a prospective study of the neurologic and neuropsychological complications of coronary artery bypass graft surgery, 312 patients were compared with a control group of 50 patients undergoing major surgery for peripheral vascular disease. The purpose of comparing the 2 groups was to determine to what extent neurologic complications after heart surgery can be attributed to cardiopulmonary bypass. The 2 groups were similar with respect to age, preoperative neurologic and intellectual status, anesthetic methods, duration of operation, perioperative complications, and time spent in the intensive therapy unit. Certain potential risk factors for cerebrovascular disease were more common in the control than the coronary bypass patients. The important difference between the 2 groups was that only the latter group underwent cardiopulmonary bypass. In this group 191 of 312 (61%) and 235 of 298 (79%), respectively, developed early neurologic and neuropsychological complications. By the time of hospital discharge 17% had neurologic disability and 38% had significant neuropsychological symptoms. In the control group 9 of 50 (18%) developed neurologic complications resulting largely from trauma to lower limb sensory nerves. Two patients developed primitive reflexes. Fifteen of 48 (31%) showed neuropsychological impairment on 1 or 2 subtest scores. Moderate or severe intellectual dysfunction was not seen in the control patients in contrast to the 24% thus affected in the coronary bypass group. The difference in frequency and severity of central nervous system complications between the 2 groups is likely to reflect cerebral injury resulting from cardiopulmonary bypass.

The prognostic value of stress hyperglycaemia and previously unrecognized diabetes in acute stroke.

In a prospective study of 86 patients with acute stroke, blood glucose and HbA1 were estimated within 72 h of onset. The prevalence of previously diagnosed diabetes mellitus was 8% whereas 28% could be assumed to have had unrecognized hyperglycaemia preceeding the acute event as identified by a stable HbA1 raised more than two SD above the mean reference value. Complete functional recovery of the limbs within 4 weeks of the stroke was confined to those patients with a normal admission blood glucose. None of the patients with a raised admission blood glucose regained full functional recovery within 4 weeks. Cumulative mortality at 4 weeks was significantly raised in patients with an elevated blood glucose value irrespective of their HbA1 values (p less than 0.05). The prevalence of unrecognized hyperglycaemia as a risk factor for acute stroke is greater than previously reported in the UK and admission blood glucose concentration is of greatest importance in predicting early mortality and morbidity.

Long-term intellectual dysfunction following coronary artery bypass graft surgery: a six month follow-up study.

As part of a prospective study of neurological and neuropsychological complications of coronary bypass surgery, 259 patients underwent psychometric assessment before operation and at seven days and six months after operation using a battery of 10 standard tests of intellectual function. This report describes the natural history of intellectual dysfunction soon after surgery and the incidence and functional impact of late neuropsychological impairment. The mean neuropsychological scores for the whole group remained unchanged or improved compared with levels before operation for the majority of the 10 tests. Analysis of the test scores for individuals showed that 147 of 259 (57 per cent) patients showed deterioration on at least one test score at six months. The degree of impairment was usually mild. One hundred and thirty of the 147 patients showed mild cognitive dysfunction (score deterioration on one or two tests) and only 17 patients had moderate or severe impairment (score deterioration on three or more tests). Detectable neuropsychological deterioration at six months often did not matter to the patient in functional terms. Seventy-one per cent of these patients had no significant symptoms; 27 per cent had minor symptoms and only 2 per cent were seriously disabled. Of the patients unemployed at six months, in only one case was intellectual impairment the factor preventing return to work. A search for possible predisposing factors for long-term intellectual dysfunction was made using a multivariate analysis of 91 variables for each patient. Cardiac failure before surgery and global impairment of left ventricular function were the only factors showing significant correlation.

Neurological complications of coronary artery bypass graft surgery: six month follow-up study.

As part of a major prospective study of the neurological complications of coronary artery bypass graft surgery patients were reviewed over six months to determine the clinical course and functional impact of early postoperative complications. One hundred and ninety one out of 312 (61%) patients had developed early postoperative disorders. At six months 165 of the 191 patients with early neurological complications were reviewed. Of the 165, 85 still had detectable neurological signs, but these were often minor and of little functional importance. Only 10 patients had neurological disability at six months, and this was major in only four patients, all of whom had suffered major perioperative stroke. No patient with non-disabling neurological complications in hospital became functionally impaired on returning home. Neurological disorders are not a major cause of failure to return to work by six months after coronary artery bypass surgery. Of 139 patients who were of working age and had not returned to work by six months, only four were prevented by neurological injury related to surgery. The long term prognosis for early neurological disorders after coronary artery bypass surgery is usually favourable, except in those patients who have sustained major perioperative stroke.